Culturally and linguistically diverse students in speech-language pathology courses: A platform for culturally responsive services.

PubMed

Attrill, Stacie; Lincoln, Michelle; McAllister, Sue

2017-06-01

Increasing the proportion of culturally and linguistically diverse (CALD) students and providing intercultural learning opportunities for all students are two strategies identified to facilitate greater access to culturally responsive speech-language pathology services. To enact these strategies, more information is needed about student diversity. This study collected descriptive information about CALD speech-language pathology students in Australia. Cultural and linguistic background information was collected through surveying 854 domestic and international speech-language pathology students from three Australian universities. Students were categorised according to defined or perceived CALD status, international student status, speaking English as an Additional Language (EAL), or speaking a Language Other than English at Home (LOTEH). Overall, 32.1% of students were either defined or perceived CALD. A total of 14.9% spoke EAL and 25.7% identified speaking a LOTEH. CALD students were more likely to speak EAL or a LOTEH than non-CALD students, were prominently from Southern and South-Eastern Asian backgrounds and spoke related languages. Many students reported direct or indirect connections with their cultural heritage and/or contributed linguistic diversity. These students may represent broader acculturative experiences in communities. The sociocultural knowledge and experience of these students may provide intercultural learning opportunities for all students and promote culturally responsive practices.

How Useful Are Indices of Personality Pathology when Assessing Domestic Violence Perpetrators?

ERIC Educational Resources Information Center

Gibbons, Peter; Collins, Marjorie; Reid, Corinne

2011-01-01

There has been considerable debate about profiling personality pathology when assessing and treating male perpetrators of domestic violence (DV). This study used the Millon Clinical Multiaxial Inventory (MCMI-III) to explore the severity and diversity of male perpetrator personality pathology and response bias in a group of DV perpetrators being…

Pretreatment tables predicting pathologic stage of locally advanced prostate cancer.

PubMed

Joniau, Steven; Spahn, Martin; Briganti, Alberto; Gandaglia, Giorgio; Tombal, Bertrand; Tosco, Lorenzo; Marchioro, Giansilvio; Hsu, Chao-Yu; Walz, Jochen; Kneitz, Burkhard; Bader, Pia; Frohneberg, Detlef; Tizzani, Alessandro; Graefen, Markus; van Cangh, Paul; Karnes, R Jeffrey; Montorsi, Francesco; van Poppel, Hein; Gontero, Paolo

2015-02-01

Pretreatment tables for the prediction of pathologic stage have been published and validated for localized prostate cancer (PCa). No such tables are available for locally advanced (cT3a) PCa. To construct tables predicting pathologic outcome after radical prostatectomy (RP) for patients with cT3a PCa with the aim to help guide treatment decisions in clinical practice. This was a multicenter retrospective cohort study including 759 consecutive patients with cT3a PCa treated with RP between 1987 and 2010. Retropubic RP and pelvic lymphadenectomy. Patients were divided into pretreatment prostate-specific antigen (PSA) and biopsy Gleason score (GS) subgroups. These parameters were used to construct tables predicting pathologic outcome and the presence of positive lymph nodes (LNs) after RP for cT3a PCa using ordinal logistic regression. In the model predicting pathologic outcome, the main effects of biopsy GS and pretreatment PSA were significant. A higher GS and/or higher PSA level was associated with a more unfavorable pathologic outcome. The validation procedure, using a repeated split-sample method, showed good predictive ability. Regression analysis also showed an increasing probability of positive LNs with increasing PSA levels and/or higher GS. Limitations of the study are the retrospective design and the long study period. These novel tables predict pathologic stage after RP for patients with cT3a PCa based on pretreatment PSA level and biopsy GS. They can be used to guide decision making in men with locally advanced PCa. Our study might provide physicians with a useful tool to predict pathologic stage in locally advanced prostate cancer that might help select patients who may need multimodal treatment. Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Sociocultural and identity predictors of body dissatisfaction in ethnically diverse college women.

PubMed

Rakhkovskaya, Liya M; Warren, Cortney S

2016-03-01

Emerging research suggests that ethnic identity and American identity are associated with mental health in ethnic minorities and European Americans, respectively. Furthermore, although ethnic identity is associated with diminished body dissatisfaction in minority women, the relationship between American identity and body dissatisfaction is unexplored in all ethnic groups. Accordingly, this study examined the relationships among ethnic identity, American identity, thin-ideal internalization, pressures for thinness, and body dissatisfaction in 1018 ethnically diverse college women. Ethnic identity negatively predicted body dissatisfaction for African Americans, and attenuated the relationship between pressures for thinness and body dissatisfaction for African Americans and Asian Americans, but not European Americans or Latina Americans. Results for American identity were inconclusive. Findings suggest that ethnic identity may be a protective factor against eating pathology for Asian American and African American women. Copyright © 2015 Elsevier Ltd. All rights reserved.

The relationships between perfectionism, pathological worry and generalised anxiety disorder.

PubMed

Handley, Alicia K; Egan, Sarah J; Kane, Robert T; Rees, Clare S

2014-04-02

The relationships between perfectionism, pathological worry and generalised anxiety disorder (GAD) were investigated in a clinical sample presenting for treatment of perfectionism. This study explored the utility of perfectionism in predicting pathological worry in a sample of individuals with elevated perfectionism and GAD (n = 36). Following this, the study examined whether perfectionism could predict a principal GAD diagnosis in the full sample (n = 42). Scores on the perfectionism dimensions Concern over Mistakes, Personal Standards, and Clinical Perfectionism significantly predicted pathological worry among participants with GAD after controlling for gender and depression. The perfectionism dimension Doubts about Actions significantly predicted whether individuals from the full sample received a principal diagnosis of GAD. These findings support certain dimensions of perfectionism having significant associations with pathological worry and GAD.

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.

Testing the Predictive Validity and Construct of Pathological Video Game Use

PubMed Central

Groves, Christopher L.; Gentile, Douglas; Tapscott, Ryan L.; Lynch, Paul J.

2015-01-01

Three studies assessed the construct of pathological video game use and tested its predictive validity. Replicating previous research, Study 1 produced evidence of convergent validity in 8th and 9th graders (N = 607) classified as pathological gamers. Study 2 replicated and extended the findings of Study 1 with college undergraduates (N = 504). Predictive validity was established in Study 3 by measuring cue reactivity to video games in college undergraduates (N = 254), such that pathological gamers were more emotionally reactive to and provided higher subjective appraisals of video games than non-pathological gamers and non-gamers. The three studies converged to show that pathological video game use seems similar to other addictions in its patterns of correlations with other constructs. Conceptual and definitional aspects of Internet Gaming Disorder are discussed. PMID:26694472

The relationships between perfectionism, pathological worry and generalised anxiety disorder

PubMed Central

2014-01-01

Background The relationships between perfectionism, pathological worry and generalised anxiety disorder (GAD) were investigated in a clinical sample presenting for treatment of perfectionism. Method This study explored the utility of perfectionism in predicting pathological worry in a sample of individuals with elevated perfectionism and GAD (n = 36). Following this, the study examined whether perfectionism could predict a principal GAD diagnosis in the full sample (n = 42). Results Scores on the perfectionism dimensions Concern over Mistakes, Personal Standards, and Clinical Perfectionism significantly predicted pathological worry among participants with GAD after controlling for gender and depression. The perfectionism dimension Doubts about Actions significantly predicted whether individuals from the full sample received a principal diagnosis of GAD. Conclusions These findings support certain dimensions of perfectionism having significant associations with pathological worry and GAD. PMID:24693946

Using Computer-extracted Image Phenotypes from Tumors on Breast MRI to Predict Breast Cancer Pathologic Stage

PubMed Central

Burnside, Elizabeth S.; Drukker, Karen; Li, Hui; Bonaccio, Ermelinda; Zuley, Margarita; Ganott, Marie; Net, Jose M.; Sutton, Elizabeth; Brandt, Kathleen R.; Whitman, Gary; Conzen, Suzanne; Lan, Li; Ji, Yuan; Zhu, Yitan; Jaffe, Carl; Huang, Erich; Freymann, John; Kirby, Justin; Morris, Elizabeth; Giger, Maryellen

2015-01-01

Background To demonstrate that computer-extracted image phenotypes (CEIPs) of biopsy-proven breast cancer on MRI can accurately predict pathologic stage. Methods We used a dataset of de-identified breast MRIs organized by the National Cancer Institute in The Cancer Imaging Archive. We analyzed 91 biopsy-proven breast cancer cases with pathologic stage (stage I = 22; stage II = 58; stage III = 11) and surgically proven nodal status (negative nodes = 46, ≥ 1 positive node = 44, no nodes examined = 1). We characterized tumors by (a) radiologist measured size, and (b) CEIP. We built models combining two CEIPs to predict tumor pathologic stage and lymph node involvement, evaluated them in leave-one-out cross-validation with area under the ROC curve (AUC) as figure of merit. Results Tumor size was the most powerful predictor of pathologic stage but CEIPs capturing biologic behavior also emerged as predictive (e.g. stage I+II vs. III demonstrated AUC = 0.83). No size measure was successful in the prediction of positive lymph nodes but adding a CEIP describing tumor “homogeneity,” significantly improved this discrimination (AUC = 0.62, p=.003) over chance. Conclusions Our results indicate that MRI phenotypes show promise for predicting breast cancer pathologic stage and lymph node status. PMID:26619259

Does corticobasal degeneration exist? A clinicopathological re-evaluation.

PubMed

Ling, Helen; O'Sullivan, Sean S; Holton, Janice L; Revesz, Tamas; Massey, Luke A; Williams, David R; Paviour, Dominic C; Lees, Andrew J

2010-07-01

The pathological findings of corticobasal degeneration are associated with several distinct clinical syndromes, and the corticobasal syndrome has been linked with a number of diverse pathologies. We have reviewed all the archival cases in the Queen Square Brain Bank for Neurological Disorders over a 20-year period with either a clinical diagnosis of corticobasal syndrome or pathological diagnosis of corticobasal degeneration in an attempt to identify the main diagnostic pitfalls. Of 19 pathologically confirmed corticobasal degeneration cases, only five had been diagnosed correctly in life (sensitivity=26.3%) and four of these had received an alternative earlier diagnosis. All five of these had a unilateral presentation, clumsy useless limb, limb apraxia and myoclonus, four had cortical sensory impairment and focal limb dystonia and three had an alien limb. Eight cases of corticobasal degeneration had been clinically diagnosed as progressive supranuclear palsy, all of whom had vertical supranuclear palsy and seven had falls within the first 2 years. On the other hand, of 21 cases with a clinical diagnosis of corticobasal syndrome, only five had corticobasal degeneration pathology, giving a positive predictive value of 23.8%; six others had progressive supranuclear palsy pathology, five had Alzheimer's disease and the remaining five had other non-tau pathologies. Corticobasal degeneration can present very commonly with a clinical picture closely resembling classical progressive supranuclear palsy or Richardson's syndrome, and we propose the term corticobasal degeneration-Richardson's syndrome for this subgroup. Cases of corticobasal degeneration-Richardson's syndrome have delayed onset of vertical supranuclear gaze palsy (>3 years after onset of first symptom) and the infrequent occurrence of predominant downgaze abnormalities, both of which can be helpful pointers to their underlying corticobasal degeneration pathology. Fourty-two per cent of corticobasal degeneration cases presented clinically with a progressive supranuclear palsy phenotype and 29% of cases with corticobasal syndrome had underlying progressive supranuclear palsy pathology. In contrast, in the Queen Square Brain Bank archival collection, corticobasal syndrome is a rare clinical presentation of progressive supranuclear palsy occurring in only 6 of the 179 pathologically diagnosed progressive supranuclear palsy cases (3%). Despite these diagnostic difficulties we conclude that corticobasal degeneration is a discrete clinicopathological entity but with a broader clinical spectrum than was originally proposed.

Which ante mortem clinical features predict progressive supranuclear palsy pathology?

PubMed

Respondek, Gesine; Kurz, Carolin; Arzberger, Thomas; Compta, Yaroslau; Englund, Elisabet; Ferguson, Leslie W; Gelpi, Ellen; Giese, Armin; Irwin, David J; Meissner, Wassilios G; Nilsson, Christer; Pantelyat, Alexander; Rajput, Alex; van Swieten, John C; Troakes, Claire; Josephs, Keith A; Lang, Anthony E; Mollenhauer, Brit; Müller, Ulrich; Whitwell, Jennifer L; Antonini, Angelo; Bhatia, Kailash P; Bordelon, Yvette; Corvol, Jean-Christophe; Colosimo, Carlo; Dodel, Richard; Grossman, Murray; Kassubek, Jan; Krismer, Florian; Levin, Johannes; Lorenzl, Stefan; Morris, Huw; Nestor, Peter; Oertel, Wolfgang H; Rabinovici, Gil D; Rowe, James B; van Eimeren, Thilo; Wenning, Gregor K; Boxer, Adam; Golbe, Lawrence I; Litvan, Irene; Stamelou, Maria; Höglinger, Günter U

2017-07-01

Progressive supranuclear palsy (PSP) is a neuropathologically defined disease presenting with a broad spectrum of clinical phenotypes. To identify clinical features and investigations that predict or exclude PSP pathology during life, aiming at an optimization of the clinical diagnostic criteria for PSP. We performed a systematic review of the literature published since 1996 to identify clinical features and investigations that may predict or exclude PSP pathology. We then extracted standardized data from clinical charts of patients with pathologically diagnosed PSP and relevant disease controls and calculated the sensitivity, specificity, and positive predictive value of key clinical features for PSP in this cohort. Of 4166 articles identified by the database inquiry, 269 met predefined standards. The literature review identified clinical features predictive of PSP, including features of the following 4 functional domains: ocular motor dysfunction, postural instability, akinesia, and cognitive dysfunction. No biomarker or genetic feature was found reliably validated to predict definite PSP. High-quality original natural history data were available from 206 patients with pathologically diagnosed PSP and from 231 pathologically diagnosed disease controls (54 corticobasal degeneration, 51 multiple system atrophy with predominant parkinsonism, 53 Parkinson's disease, 73 behavioral variant frontotemporal dementia). We identified clinical features that predicted PSP pathology, including phenotypes other than Richardson's syndrome, with varying sensitivity and specificity. Our results highlight the clinical variability of PSP and the high prevalence of phenotypes other than Richardson's syndrome. The features of variant phenotypes with high specificity and sensitivity should serve to optimize clinical diagnosis of PSP. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.

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

Mitchell, Hugh D.; Eisfeld, Amie J.; Sims, Amy

Respiratory infections stemming from influenza viruses and the Severe Acute Respiratory Syndrome corona virus (SARS-CoV) represent a serious public health threat as emerging pandemics. Despite efforts to identify the critical interactions of these viruses with host machinery, the key regulatory events that lead to disease pathology remain poorly targeted with therapeutics. Here we implement an integrated network interrogation approach, in which proteome and transcriptome datasets from infection of both viruses in human lung epithelial cells are utilized to predict regulatory genes involved in the host response. We take advantage of a novel “crowd-based” approach to identify and combine ranking metricsmore » that isolate genes/proteins likely related to the pathogenicity of SARS-CoV and influenza virus. Subsequently, a multivariate regression model is used to compare predicted lung epithelial regulatory influences with data derived from other respiratory virus infection models. We predicted a small set of regulatory factors with conserved behavior for consideration as important components of viral pathogenesis that might also serve as therapeutic targets for intervention. Our results demonstrate the utility of integrating diverse ‘omic datasets to predict and prioritize regulatory features conserved across multiple pathogen infection models.« less

Evolution of the Pathology Residency Curriculum

PubMed Central

Powell, Suzanne Z.; Black-Schaffer, W. Stephen

2016-01-01

The required medical knowledge and skill set for the pathologist of 2020 are different than in 2005. Pathology residency training curriculum must accordingly change to fulfill the needs of these ever-changing requirements. In order to make rational curricular adjustments, it is important for us to know the current trajectory of resident training in pathology—where we have been, what our actual current training curriculum is now—to understand how that might change in anticipation of meeting the needs of a changing patient and provider population and to fit within the evolving future biomedical and socioeconomic health-care setting. In 2013, there were 143 Accreditation Council for Graduate Medical Education-accredited pathology residency training programs in the United States, with approximately 2400 residents. There is diversity among residency training programs not only with respect to the number of residents but also in training venue(s). To characterize this diversity among pathology residency training programs, a curriculum survey was conducted of pathology residency program directors in 2013 and compared with a similar survey taken almost 9 years previously in 2005 to identify trends in pathology residency curriculum. Clinical pathology has not changed significantly in the number of rotations over 9 years; however, anatomic pathology has changed dramatically, with an increase in the number of surgical pathology rotations coupled with a decline in stand-alone autopsy rotations. With ever-expanding medical knowledge that the graduating pathology resident must know, it is necessary to (1) reflect upon what are the critical need subjects, (2) identify areas that have become of lesser importance, and then (3) prioritize training accordingly. PMID:28725779

[A comparison of characteristics of pathologic hobbies in schizophrenic patients of different age].

PubMed

Sergeev, I I; Deych, R V; Malinochka, S A

2016-01-01

To analyze age-related pathologic hobbies in patients with schizophrenia spectrum disorders. Forty-three inpatients, aged from 4 to 16 years, and 31 patients, aged from 18 to 65 years, were studied. Clinical/psychopathological analysis, psychological experiment and clinical statistics were used. Pathological hobbies substantially differed depending on the age (3-6, 7-15 and 18-65 years). In preschool age, hobbies were immature and infantile, arose autochthonously, their course was relatively stable and they had limited maladaptive effects. In junior school/teenager age, hobbies were more distinct and were associated with more diverse and mature realization patterns. Their origin was more depended on environmental factors, the course was persistent or attack-like with more pronounced and steady maladaptive effects. In some cases, there was a trend to pathological hobby progression. Abnormal hobbies in patients of mature age were the most diverse in their subjects and forms of realization as well as in their clinical variants and dynamic types. In the group of mature patients with schizophrenic spectrum disorders, there was a significantly higher percentage of psychotic forms of pathological hobbies.

The missing link: does tunnelling nanotube-based supercellularity provide a new understanding of chronic and lifestyle diseases?

PubMed

Rustom, Amin

2016-06-01

Tunnelling nanotubes (TNTs) are increasingly recognized as central players in a multitude of cellular mechanisms and diseases. Although their existence and functions in animal organisms are still elusive, emerging evidence suggests that they are involved in developmental processes, tissue regeneration, viral infections or pathogen transfer, stem cell differentiation, immune responses as well as initiation and progression of neurodegenerative disorders and cancer (see Sisakhtnezhad & Khosravi 2015 Eur. J. Cell Biol. 94, 429-443. (doi:10.1016/j.ejcb.2015.06.010)). A broader field of vision, including their striking functional and structural resemblance with nanotube-mediated phenomena found throughout the phylogenetic tree, from plants down to bacteria, points to a universal, conserved and tightly regulated mechanism of cellular assemblies. Based on our initial definition of TNTs as open-ended channels mediating membrane continuity between connected cells (Rustom et al. 2004 Science 303, 1007-1010. (doi:10.1126/science.1093133)), it is suggested that animal tissues represent supercellular assemblies that-besides opening discrete communication pathways-balance diverse stress factors caused by pathological changes or fluctuating physiological and environmental conditions, such as oxidative stress or nutrient shortage. By combining current knowledge about nanotube formation, intercellular transfer and communication phenomena as well as associated molecular pathways, a model evolves, predicting that the linkage between reactive oxygen species, TNT-based supercellularity and the intercellular shuttling of materials will have significant impact on diverse body functions, such as cell survival, redox/metabolic homeostasis and mitochondrial heteroplasmy. It implies that TNTs are intimately linked to the physiological and pathological state of animal cells and represent a central joint element of diverse diseases, such as neurodegenerative disorders, diabetes or cancer. © 2016 The Authors.

The validity and accuracy of MRI arthrogram in the assessment of painful articular disorders of the hip.

PubMed

Rajeev, Aysha; Tuinebreijer, Wim; Mohamed, Abdalla; Newby, Mike

2018-01-01

The assessment of a patient with chronic hip pain can be challenging. The differential diagnosis of intra-articular pathology causing hip pain can be diverse. These includes conditions such as osteoarthritis, fracture, and avascular necrosis, synovitis, loose bodies, labral tears, articular pathology and, femoro-acetabular impingement. Magnetic resonance imaging (MRI) arthrography of the hip has been widely used now for diagnosis of articular pathology of the hip. A retrospective analysis of 113 patients who had MRI arthrogram and who underwent hip arthroscopy was included in the study. The MRI arthrogram was performed using gadolinium injection and reported by a single radiologist. The findings were then compared to that found on arthroscopy. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy and 95% confidence interval were calculated for each pathology. Labral tear-sensitivity 84% (74.3-90.5), specificity 64% (40.7-82.8), PPV 91% (82.1-95.8), NPV 48% (29.5-67.5), accuracy 80%. Delamination -sensitivity 7% (0.8-22.1), specificity 98% (91.6-99.7), PPV 50% (6.8-93.2), NPV 74% (65.1-82.2) and accuracy 39%. Chondral changes-sensitivity 25% (13.3-38.9), specificity 83% (71.3-91.1), PPV 52% (30.6-73.2), NPV 59% (48.0-69.2) and accuracy 58%. Femoro-acetabular impingement (CAM deformity)-sensitivity 34% (19.6-51.4), specificity 83% (72.2-90.4), PPV 50% (29.9-70.1), NPV 71% (60.6-80.5) and accuracy 66%. Synovitis-sensitivity 11% (2.3-28.2), specificity 99% (93.6-100), PPV 75% (19.4-99.4), NPV 77% (68.1-84.6) and accuracy 77%. Our study conclusions are MRI arthrogram is a useful investigation tool in detecting labral tears, it is also helpful in the diagnosis of femoro-acetabular impingement. However, when it comes to the diagnosis of chondral changes, defects and cartilage delamination, the sensitivity and accuracy are low.

[Diagnostic molecular pathology of lymphatic and myeloid neoplasms].

PubMed

Klapper, W; Kreipe, H

2015-03-01

Molecular pathology has been an integral part of the diagnostics of tumors of the hematopoietic system substantially longer than for solid neoplasms. In contrast to solid tumors, the primary objective of molecular pathology in hematopoietic neoplasms is not the prediction of drug efficacy but the diagnosis itself by excluding reactive proliferation and by using molecular features for tumor classification. In the case of malignant lymphomas, the most commonly applied molecular tests are those for gene rearrangements for immunoglobulin heavy chains and T-cell receptors. However, this article puts the focus on new and diagnostically relevant assays in hematopathology. Among these are mutations of MYD88 codon 265 in lymphoplasmacytic lymphomas, B-raf V600E in hairy cell leukemia and Stat3 exon 21 in indolent T-cell lymphomas. In myeloproliferative neoplasms, MPL W515, calreticulin exon 9 and the BCR-ABL and JAK2 V617F junctions are the most frequently analyzed differentiation series. In myelodysplastic and myeloproliferative neoplasms, SRSF2, SETBP1 and CSF3R mutations provide important differential diagnostic information. Genes mutated in myelodysplastic syndromes (MDS) are particularly diverse but their analysis significantly improves the differential diagnostics between reactive conditions and MDS. The most frequent changes in MDS include mutations of TET2 and various genes encoding splicing factors.

Resilient Adolescent Adjustment among Girls: Buffers of Childhood Peer Rejection and Attention-Deficit/Hyperactivity Disorder

PubMed Central

Mikami, Amori Yee; Hinshaw, Stephen P.

2010-01-01

Examined a risk-resilience model of peer rejection and attention-deficit/hyperactivity disorder (ADHD) in a 5-year longitudinal study of 209 ethnically and socioeconomically diverse girls aged 6–13 at baseline and 11–18 at follow-up. Risk factors were childhood ADHD diagnosis and peer rejection; hypothesized protective factors were childhood measures of self-perceived scholastic competence, engagement in goal-directed play when alone, and popularity with adults. Adolescent criterion measures were multi-informant composites of externalizing and internalizing behavior plus indicators of academic achievement, eating pathology, and substance use. ADHD and peer rejection predicted risk for all criterion measures except for substance use, which was predicted by ADHD only. ADHD and peer rejection predicted lower adolescent academic achievement controlling for childhood achievement, but they did not predict adolescent externalizing and internalizing behavior after controlling for baseline levels of these constructs. Regarding buffers, self-perceived scholastic competence in childhood (with control of academic achievement) predicted resilient adolescent functioning. Contrary to hypothesis, goal-directed play in childhood was associated with poor adolescent outcomes. Buffers were not found to have differential effectiveness among girls with ADHD relative to comparison girls. PMID:17051436

Pathological Location of Cranial Nerves in Petroclival Lesions: How to Avoid Their Injury during Anterior Petrosal Approach.

PubMed

Borghei-Razavi, Hamid; Tomio, Ryosuke; Fereshtehnejad, Seyed-Mohammad; Shibao, Shunsuke; Schick, Uta; Toda, Masahiro; Yoshida, Kazunari; Kawase, Takeshi

2016-02-01

Objectives  Numerous surgical approaches have been developed to access the petroclival region. The Kawase approach, through the middle fossa, is a well-described option for addressing cranial base lesions of the petroclival region. Our aim was to gather data about the variation of cranial nerve locations in diverse petroclival pathologies and clarify the most common pathologic variations confirmed during the anterior petrosal approach. Method  A retrospective analysis was made of both videos and operative and histologic records of 40 petroclival tumors from January 2009 to September 2013 in which the Kawase approach was used. The anatomical variations of cranial nerves IV-VI related to the tumor were divided into several location categories: superior lateral (SL), inferior lateral (IL), superior medial (SM), inferior medial (IM), and encased (E). These data were then analyzed taking into consideration pathologic subgroups of meningioma, epidermoid, and schwannoma. Results  In 41% of meningiomas, the trigeminal nerve is encased by the tumor. In 38% of the meningiomas, the trigeminal nerve is in the SL part of the tumor, and it is in 20% of the IL portion of the tumor. In 38% of the meningiomas, the trochlear nerve is encased by the tumor. The abducens nerve is not always visible (35%). The pathologic nerve pattern differs from that of meningiomas for epidermoid and trigeminal schwannomas. Conclusion  The pattern of cranial nerves IV-VI is linked to the type of petroclival tumor. In a meningioma, tumor origin (cavernous, upper clival, tentorial, and petrous apex) is the most important predictor of the location of cranial nerves IV-VI. Classification of four subtypes of petroclival meningiomas using magnetic resonance imaging is very useful to predict the location of deviated cranial nerves IV-VI intraoperatively.

Pathological narcissism and the obstruction of love.

PubMed

Kealy, David; Ogrodniczuk, John S

2014-03-01

Pathological narcissism is a form of maladaptive self-regulation that impedes the capacity to love. Although narcissism is often construed as excessive self-love, individuals with pathological narcissism are impaired in being able to love themselves as well as others. With the subject of impaired love in mind, we review selected conceptualizations from an enormous and diverse psychodynamic literature on narcissism. Major theoretical approaches illustrate a number of psychodynamics associated with narcissistic self-regulatory problems. This paper provides a concise overview of major conceptual themes regarding pathological narcissism and impaired capacity to love.

Sex Differences in Workplace Satisfaction and Engagement of Academic Pathologists: Opportunities to Enhance Faculty Diversity.

PubMed

Howell, Lydia Pleotis; Lyons, Mary Lipscomb; Thor, Ann; Dandar, Valerie

2015-07-01

There is attrition of women across professorial ranks in academic pathology. Women are underrepresented as leaders; 15.4% of academic pathology departments are chaired by women, according to the Association of American Medical Colleges (AAMC). To identify areas for targeted interventions that can advance academic and leadership development of women faculty by examining (1) sex differences in career satisfaction in US medical school pathology departments participating in the AAMC's Faculty Forward Engagement Survey, and (2) findings from a survey of the Association of Pathology Chairs (APC). The AAMC Faculty Forward Engagement Survey data are from 14 US medical schools participating in the 2011-2012 survey. Pathologists' response rate was 66% (461 of 697). To investigate sex differences, t tests and χ(2) analyses were used. The APC survey, administered to academic department chairs, had a 55% response rate (104 of 189). According to the Faculty Forward Engagement Survey, women report more time in patient care and less time in research. Women consider formal mentorship, feedback, and career advancement more important than men do and are less satisfied with communication and governance. The APC survey shows that 20% to 40% of nonchair department leaders are women. More than half of chairs report satisfaction with the sex diversity of their departmental leaders. Opportunities exist for department chairs and professional organizations to create targeted interventions to support career satisfaction, recruitment, retention, and career and leadership development for women in academic pathology. Although chairs report satisfaction with diversity within department leadership, responses of women faculty indicate there is work to be done to grow more women leaders.

Comprehensive Computational Pathological Image Analysis Predicts Lung Cancer Prognosis.

PubMed

Luo, Xin; Zang, Xiao; Yang, Lin; Huang, Junzhou; Liang, Faming; Rodriguez-Canales, Jaime; Wistuba, Ignacio I; Gazdar, Adi; Xie, Yang; Xiao, Guanghua

2017-03-01

Pathological examination of histopathological slides is a routine clinical procedure for lung cancer diagnosis and prognosis. Although the classification of lung cancer has been updated to become more specific, only a small subset of the total morphological features are taken into consideration. The vast majority of the detailed morphological features of tumor tissues, particularly tumor cells' surrounding microenvironment, are not fully analyzed. The heterogeneity of tumor cells and close interactions between tumor cells and their microenvironments are closely related to tumor development and progression. The goal of this study is to develop morphological feature-based prediction models for the prognosis of patients with lung cancer. We developed objective and quantitative computational approaches to analyze the morphological features of pathological images for patients with NSCLC. Tissue pathological images were analyzed for 523 patients with adenocarcinoma (ADC) and 511 patients with squamous cell carcinoma (SCC) from The Cancer Genome Atlas lung cancer cohorts. The features extracted from the pathological images were used to develop statistical models that predict patients' survival outcomes in ADC and SCC, respectively. We extracted 943 morphological features from pathological images of hematoxylin and eosin-stained tissue and identified morphological features that are significantly associated with prognosis in ADC and SCC, respectively. Statistical models based on these extracted features stratified NSCLC patients into high-risk and low-risk groups. The models were developed from training sets and validated in independent testing sets: a predicted high-risk group versus a predicted low-risk group (for patients with ADC: hazard ratio = 2.34, 95% confidence interval: 1.12-4.91, p = 0.024; for patients with SCC: hazard ratio = 2.22, 95% confidence interval: 1.15-4.27, p = 0.017) after adjustment for age, sex, smoking status, and pathologic tumor stage. The results suggest that the quantitative morphological features of tumor pathological images predict prognosis in patients with lung cancer. Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Heterogeneity of interpersonal problems among depressed young adults: Associations with substance abuse and pathological personality traits

PubMed Central

Dawood, Sindes; Thomas, Katherine M.; Wright, Aidan G.C.; Hopwood, Christopher J.

2013-01-01

This study extended previous theory and research on interpersonal heterogeneity in depression by identifying groups of depressed young adults who differ in their type and degree of interpersonal problems, and by examining patterns of pathological personality traits and alcohol abuse among these groups. We examined the interpersonal problems, personality traits, and alcohol-related problems of 172 college students with at least moderate levels of self-reported depression on the Patient Health Questionnaire (Spitzer, Kroenke, & Williams, 1999). Scores from the Inventory of Interpersonal Problems – Short Circumplex (Soldz, Budman, Demby, & Merry, 1995) were subjected to latent profile analysis, which classified individuals into five distinct groups defined by the types of interpersonal problems they experience (dominant, warm, submissive, cold, and undifferentiated). As hypothesized, groups did not differ in depression severity, but did show predicted patterns of differences on normative and maladaptive personality traits, as well as alcohol-related problems. The presence of clinically meaningful interpersonal heterogeneity in depression may have important implications for designing more individualized treatments and prevention efforts for depression that target diverse associated interpersonal problems. PMID:23560433

Pre-treatment neutrophil to lymphocyte ratio as a predictive marker for pathological response to preoperative chemoradiotherapy in pancreatic cancer

PubMed Central

HASEGAWA, SHINICHIRO; EGUCHI, HIDETOSHI; TOMOKUNI, AKIRA; TOMIMARU, YOSHITO; ASAOKA, TADAFUMI; WADA, HIROSHI; HAMA, NAOKI; KAWAMOTO, KOICHI; KOBAYASHI, SHOGO; MARUBASHI, SHIGERU; KONNNO, MASAMITSU; ISHII, HIDESHI; MORI, MASAKI; DOKI, YUICHIRO; NAGANO, HIROAKI

2016-01-01

An elevated neutrophil to lymphocyte ratio (NLR) has been reported to be associated with the pathological response to neoadjuvant therapies in numerous types of cancer. The aim of the current study was to clarify the association between pre-treatment NLR and the pathological response to preoperative chemoradiotherapy in pancreatic cancer patients. This retrospective analysis included data from 56 consecutive patients whose tumors were completely surgically resected. All patients received preoperative therapy, consisting of gemcitabine-based chemotherapy (alone or in combination with S-1) combined with 40 or 50.4 Gy irradiation, prior to surgery. Predictive factors, including NLR, platelet to lymphocyte ratio (PLR), modified Glasgow prognostic score and prognostic nutrition index, were measured prior to treatment. A comparison was made between those who responded well pathologically (good response group, Evans classification IIb/III) and those with a poor response (Evans I/IIa). NLR was determined to be significantly higher in the poor response group. Multivariate analysis identified an elevated NLR as an independent risk factor for the poor pathological response [odds ratio (OR), 5.35; P=0.0257]. The pre-treatment NLR (≥2.2/<2.2) was found to be a statistically significant predictive indicator of pathological response (P=0.00699). The results demonstrate that pre-treatment NLR may be a useful predictive marker for the pathological response to preoperative therapy in pancreatic cancer patients. PMID:26893780

Circumferential resection margin positivity after preoperative chemoradiotherapy based on magnetic resonance imaging for locally advanced rectal cancer: implication of boost radiotherapy to the involved mesorectal fascia.

PubMed

Kim, Kyung Hwan; Park, Min Jung; Lim, Joon Seok; Kim, Nam Kyu; Min, Byung Soh; Ahn, Joong Bae; Kim, Tae Il; Kim, Ho Geun; Koom, Woong Sub

2016-04-01

To identify patients who are at a higher risk of pathologic circumferential resection margin involvement using preoperative magnetic resonance imaging. Between October 2008 and November 2012, 165 patients with locally advanced rectal cancer (cT4 or cT3 with <2 mm distance from tumour to mesorectal fascia) who received preoperative chemoradiotherapy were analysed. The morphologic patterns on post-chemoradiotherapy magnetic resonance imaging were categorized into five patterns from Pattern A (most-likely negative pathologic circumferential resection margin) to Pattern E (most-likely positive pathologic circumferential resection margin). In addition, the location of mesorectal fascia involvement was classified as lateral, posterior and anterior. The diagnostic accuracy of the morphologic criteria was calculated using receiver operating characteristic curve analysis. Pathologic circumferential resection margin involvement was identified in 17 patients (10.3%). The diagnostic accuracy of predicting pathologic circumferential resection margin involvement was 0.73 using the five-scale magnetic resonance imaging pattern. The sensitivity, specificity, positive predictive value and negative predictive value for predicting pathologic circumferential resection margin involvement were 76.5, 65.5, 20.3 and 96.0%, respectively, when cut-off was set between Patterns C and D. On multivariate logistic regression, the magnetic resonance imaging patterns D and E (P= 0.005) and posterior or lateral mesorectal fascia involvement (P= 0.017) were independently associated with increased probability of pathologic circumferential resection margin involvement. The rate of pathologic circumferential resection margin involvement was 30.0% when the patient had Pattern D or E with posterior or lateral mesorectal fascia involvement. Patients who are at a higher risk of pathologic circumferential resection margin involvement can be identified using preoperative magnetic resonance imaging although the predictability is moderate. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Internet images of the speech pathology profession.

PubMed

Byrne, Nicole

2017-06-05

Objective The Internet provides the general public with information about speech pathology services, including client groups and service delivery models, as well as the professionals providing the services. Although this information assists the general public and other professionals to both access and understand speech pathology services, it also potentially provides information about speech pathology as a prospective career, including the types of people who are speech pathologists (i.e. demographics). The aim of the present study was to collect baseline data on how the speech pathology profession was presented via images on the Internet. Methods A pilot prospective observational study using content analysis methodology was conducted to analyse publicly available Internet images related to the speech pathology profession. The terms 'Speech Pathology' and 'speech pathologist' to represent both the profession and the professional were used, resulting in the identification of 200 images. These images were considered across a range of areas, including who was in the image (e.g. professional, client, significant other), the technology used and the types of intervention. Results The majority of images showed both a client and a professional (i.e. speech pathologist). While the professional was predominantly presented as female, the gender of the client was more evenly distributed. The clients were more likely to be preschool or school aged, however male speech pathologists were presented as providing therapy to selected age groups (i.e. school aged and younger adults). Images were predominantly of individual therapy and the few group images that were presented were all paediatric. Conclusion Current images of speech pathology continue to portray narrow professional demographics and client groups (e.g. paediatrics). Promoting images of wider scope to fully represent the depth and breadth of speech pathology professional practice may assist in attracting a more diverse group of people into the profession in the future. What is known about the topic? To date, research has not considered the promotional profile of allied health professionals on the Internet. There has been a lack of consideration of whether the way in which the professions are promoted may affect clients accessing allied health services or people entering careers. What does this paper add? This paper raises awareness of the lack of promotion of a diverse workforce in speech pathology and considers how this may affect changing the professional demographics in the future. It also provides a starting point for documentation in the form of a baseline for tracking future changes. It allows consideration of the fact that when designing health promotional and educational materials, it is crucial that diversity is displayed in the professional role, the client role and the setting in order to provide information and education to the general public about the health services provided. What are the implications for practitioners? The presentation of narrow demographics of both the professional and client may potentially affect people considering speech pathology as a future career. The appearance of narrow client demographics and diagnosis groups may also deter people from accessing services. For example, if the demonstrated images do not show older people accessing speech pathology services, then this may suggest that services are only for children. The results from the present case example are transferrable to other health professions with similar professional demographic profiles (e.g. occupational therapy). Consideration of the need to display a diverse client profile is relevant to all health and medical services, and demonstrates steps towards inclusiveness and increasing engagement of clients who may be currently less likely to access health services (including people who are Aboriginal or from a culturally and linguistically diverse background).

Predictive and Prognostic Molecular Biomarkers for Response to Neoadjuvant Chemoradiation in Rectal Cancer.

PubMed

Dayde, Delphine; Tanaka, Ichidai; Jain, Rekha; Tai, Mei Chee; Taguchi, Ayumu

2017-03-07

The standard of care in locally advanced rectal cancer is neoadjuvant chemoradiation (nCRT) followed by radical surgery. Response to nCRT varies among patients and pathological complete response is associated with better outcome. However, there is a lack of effective methods to select rectal cancer patients who would or would not have a benefit from nCRT. The utility of clinicopathological and radiological features are limited due to lack of adequate sensitivity and specificity. Molecular biomarkers have the potential to predict response to nCRT at an early time point, but none have currently reached the clinic. Integration of diverse types of biomarkers including clinicopathological and imaging features, identification of mechanistic link to tumor biology, and rigorous validation using samples which represent disease heterogeneity, will allow to develop a sensitive and cost-effective molecular biomarker panel for precision medicine in rectal cancer. Here, we aim to review the recent advance in tissue- and blood-based molecular biomarker research and illustrate their potential in predicting nCRT response in rectal cancer.

The Effects of Pathological Gaming on Aggressive Behavior

PubMed Central

Valkenburg, Patti M.; Peter, Jochen

2010-01-01

Studies have shown that pathological involvement with computer or video games is related to excessive gaming binges and aggressive behavior. Our aims for this study were to longitudinally examine if pathological gaming leads to increasingly excessive gaming habits, and how pathological gaming may cause an increase in physical aggression. For this purpose, we conducted a two-wave panel study among 851 Dutch adolescents (49% female) of which 540 played games (30% female). Our analyses indicated that higher levels of pathological gaming predicted an increase in time spent playing games 6 months later. Time spent playing violent games specifically, and not just games per se, increased physical aggression. Furthermore, higher levels of pathological gaming, regardless of violent content, predicted an increase in physical aggression among boys. That this effect only applies to boys does not diminish its importance, because adolescent boys are generally the heaviest players of violent games and most susceptible to pathological involvement. PMID:20549320

The effects of pathological gaming on aggressive behavior.

PubMed

Lemmens, Jeroen S; Valkenburg, Patti M; Peter, Jochen

2011-01-01

Studies have shown that pathological involvement with computer or video games is related to excessive gaming binges and aggressive behavior. Our aims for this study were to longitudinally examine if pathological gaming leads to increasingly excessive gaming habits, and how pathological gaming may cause an increase in physical aggression. For this purpose, we conducted a two-wave panel study among 851 Dutch adolescents (49% female) of which 540 played games (30% female). Our analyses indicated that higher levels of pathological gaming predicted an increase in time spent playing games 6 months later. Time spent playing violent games specifically, and not just games per se, increased physical aggression. Furthermore, higher levels of pathological gaming, regardless of violent content, predicted an increase in physical aggression among boys. That this effect only applies to boys does not diminish its importance, because adolescent boys are generally the heaviest players of violent games and most susceptible to pathological involvement.

Accuracy of Physical Examination, Ultrasonography, and Mammography in Predicting Residual Pathologic Tumor Size in Patients Treated With Neoadjuvant Chemotherapy

PubMed Central

Chagpar, Anees B.; Middleton, Lavinia P.; Sahin, Aysegul A.; Dempsey, Peter; Buzdar, Aman U.; Mirza, Attiqa N.; Ames, Fredrick C.; Babiera, Gildy V.; Feig, Barry W.; Hunt, Kelly K.; Kuerer, Henry M.; Meric-Bernstam, Funda; Ross, Merrick I.; Singletary, S Eva

2006-01-01

Objective: To assess the accuracy of physical examination, ultrasonography, and mammography in predicting residual size of breast tumors following neoadjuvant chemotherapy. Background: Neoadjuvant chemotherapy is an accepted part of the management of stage II and III breast cancer. Accurate prediction of residual pathologic tumor size after neoadjuvant chemotherapy is critical in guiding surgical therapy. Although physical examination, ultrasonography, and mammography have all been used to predict residual tumor size, there have been conflicting reports about the accuracy of these methods in the neoadjuvant setting. Methods: We reviewed the records of 189 patients who participated in 1 of 2 protocols using doxorubicin-containing neoadjuvant chemotherapy, and who had assessment by physical examination, ultrasonography, and/or mammography no more than 60 days before their surgical resection. Size correlations were performed using Spearman rho analysis. Clinical and pathologic measurements were also compared categorically using the weighted kappa statistic. Results: Size estimates by physical examination, ultrasonography, and mammography were only moderately correlated with residual pathologic tumor size after neoadjuvant chemotherapy (correlation coefficients: 0.42, 0.42, and 0.41, respectively), with an accuracy of ±1 cm in 66% of patients by physical examination, 75% by ultrasonography, and 70% by mammography. Kappa values (0.24–0.35) indicated poor agreement between clinical and pathologic measurements. Conclusion: Physical examination, ultrasonography, and mammography were only moderately useful for predicting residual pathologic tumor size after neoadjuvant chemotherapy. PMID:16432360

Automated classification of brain tumor type in whole-slide digital pathology images using local representative tiles.

PubMed

Barker, Jocelyn; Hoogi, Assaf; Depeursinge, Adrien; Rubin, Daniel L

2016-05-01

Computerized analysis of digital pathology images offers the potential of improving clinical care (e.g. automated diagnosis) and catalyzing research (e.g. discovering disease subtypes). There are two key challenges thwarting computerized analysis of digital pathology images: first, whole slide pathology images are massive, making computerized analysis inefficient, and second, diverse tissue regions in whole slide images that are not directly relevant to the disease may mislead computerized diagnosis algorithms. We propose a method to overcome both of these challenges that utilizes a coarse-to-fine analysis of the localized characteristics in pathology images. An initial surveying stage analyzes the diversity of coarse regions in the whole slide image. This includes extraction of spatially localized features of shape, color and texture from tiled regions covering the slide. Dimensionality reduction of the features assesses the image diversity in the tiled regions and clustering creates representative groups. A second stage provides a detailed analysis of a single representative tile from each group. An Elastic Net classifier produces a diagnostic decision value for each representative tile. A weighted voting scheme aggregates the decision values from these tiles to obtain a diagnosis at the whole slide level. We evaluated our method by automatically classifying 302 brain cancer cases into two possible diagnoses (glioblastoma multiforme (N = 182) versus lower grade glioma (N = 120)) with an accuracy of 93.1% (p < 0.001). We also evaluated our method in the dataset provided for the 2014 MICCAI Pathology Classification Challenge, in which our method, trained and tested using 5-fold cross validation, produced a classification accuracy of 100% (p < 0.001). Our method showed high stability and robustness to parameter variation, with accuracy varying between 95.5% and 100% when evaluated for a wide range of parameters. Our approach may be useful to automatically differentiate between the two cancer subtypes. Copyright © 2015 Elsevier B.V. All rights reserved.

The joint impact of cognitive performance in adolescence and familial cognitive aptitude on risk for major psychiatric disorders: a delineation of four potential pathways to illness.

PubMed

Kendler, K S; Ohlsson, H; Keefe, R S E; Sundquist, K; Sundquist, J

2018-04-01

How do joint measures of premorbid cognitive ability and familial cognitive aptitude (FCA) reflect risk for a diversity of psychiatric and substance use disorders? To address this question, we examined, using Cox models, the predictive effects of school achievement (SA) measured at age 16 and FCA-assessed from SA in siblings and cousins, and educational attainment in parents-on risk for 12 major psychiatric syndromes in 1 140 608 Swedes born 1972-1990. Four developmental patterns emerged. In the first, risk was predicted jointly by low levels of SA and high levels of FCA-that is a level of SA lower than would be predicted from the FCA. This pattern was strongest in autism spectrum disorders and schizophrenia, and weakest in bipolar illness. In these disorders, a pathologic process seems to have caused cognitive functioning to fall substantially short of familial potential. In the second pattern, seen in the internalizing conditions of major depression and anxiety disorders, risk was associated with low SA but was unrelated to FCA. Externalizing disorders-drug abuse and alcohol use disorders-demonstrated the third pattern, in which risk was predicted jointly by low SA and low FCA. The fourth pattern, seen in eating disorders, was directly opposite of that observed in externalizing disorders with risk associated with high SA and high FCA. When measured together, adolescent cognitive ability and FCA identified four developmental patterns leading to diverse psychiatric disorders. The value of cognitive assessments in psychiatric research can be substantially increased by also evaluating familial cognitive potential.

Student diversity and implications for clinical competency development amongst domestic and international speech-language pathology students.

PubMed

Attrill, Stacie; Lincoln, Michelle; McAllister, Sue

2012-06-01

International students graduating from speech-language pathology university courses must achieve the same minimum competency standards as domestic students. This study aimed to collect descriptive information about the number, origin, and placement performance of international students as well as perceptions of the performance of international students on placement. University Clinical Education Coordinators (CECs), who manage clinical placements in eight undergraduate and six graduate entry programs across the 10 participating universities in Australia and New Zealand completed a survey about 3455 international and domestic speech-language pathology students. Survey responses were analysed quantitatively and qualitatively with non-parametric statistics and thematic analysis. Results indicated that international students came from a variety of countries, but with a regional focus on the countries of Central and Southern Asia. Although domestic students were noted to experience significantly less placement failure, fewer supplementary placements, and reduced additional placement support than international students, the effect size of these relationships was consistently small and therefore weak. CECs rated international students as more frequently experiencing difficulties with communication competencies on placement. However, CECs qualitative comments revealed that culturally and linguistically diverse (CALD) students may experience more difficulties with speech-language pathology competency development than international students. Students' CALD status should be included in future investigations of factors influencing speech-language pathology competency development.

A single microfocus (5% or less) of Gleason 6 prostate cancer at biopsy--can we predict adverse pathological outcomes?

PubMed

Thong, Alan E; Shikanov, Sergey; Katz, Mark H; Gofrit, Ofer N; Eggener, Scott; Zagaja, Gregory P; Shalhav, Arieh L; Zorn, Kevin C

2008-12-01

Patients with Gleason score 6 microfocal prostate cancer, defined as 5% or less in 1 biopsy core, are often considered to have favorable disease. Few studies have addressed clinical parameters that predict pathological upgrading or up staging at radical prostatectomy. From a prospective database of 1,271 consecutive robot assisted laparoscopic prostatectomies performed from 2003 to 2008 patients with Gleason score 6 microfocal prostate cancer were identified. Adverse pathological outcome was defined as any upgrading and/or up staging on prostatectomy pathological findings. Multivariate logistic regression was used to evaluate the ability of patient age, clinical stage, the total number of biopsy cores, preoperative prostate specific antigen, prostate volume and pathological prostate specific antigen density to predict adverse pathological outcomes. A total of 192 patients with a median age of 59 years (range 42 to 73) were identified with Gleason score 6 prostate cancer involving 5% or less of 1 biopsy core, including 177 (92%) with clinical T1c disease. Mean +/- SD preoperative prostate specific antigen was 6.0 +/- 3.9 ng/ml (range 0.8 to 35). Overall 42 patients (22%) had adverse pathological outcomes, including upgrading in 35 (18%) and up staging in 16 (8%). Multivariate logistic regression revealed that age more than 65 years and pathological prostate specific antigen density greater than 0.20 ng/ml/gm were predictive of an increased risk of adverse pathological results (p = 0.0081 and 0.0169, respectively). While a microfocus of Gleason score 6 prostate cancer on biopsy is commonly considered low risk disease, there was a greater than 1/5 risk of pathological upgrading and/or up staging. Patients with Gleason score 6 microfocal prostate cancer should be counseled that they may harbor more aggressive disease, especially when pretreatment clinical risk factors are present, such as advanced age or high clinical prostate specific antigen density.

Teaching Interprofessional Practice: An Exploratory Course Assignment in Social Work and Speech Language Pathology

ERIC Educational Resources Information Center

Edwards, Claire M.; Newell, Jason M.; Rich, Danielle Waldrep; Hitchcock, Laurel I.

2015-01-01

The professions of social work (SWK) and speech language pathology (SLP) often involve the provision of services to a diverse group of client populations in a variety of settings; this is particularly true when meeting the complex needs of children and their families. It is widely accepted that collaborative treatment approaches utilizing…

Relationship status predicts lower restrictive eating pathology for bisexual and gay men across 10-year follow-up.

PubMed

Brown, Tiffany A; Keel, Pamela K

2015-09-01

Cross-sectional studies support that bisexual and gay (BG) men are at increased risk for eating pathology, and romantic relationships may buffer against risk; however, no studies have examined this association longitudinally. The current study examined how romantic relationships impact the trajectory of eating pathology in BG versus heterosexual men. BG (n = 51) and heterosexual (n = 522) men completed surveys of health and eating behaviors at baseline and 10-year follow-up. For BG men, being single at baseline prospectively predicted an increase in Drive for Thinness scores over 10-year follow-up. Additionally, for BG men in relationships at baseline, lower relationship satisfaction predicted an increase in Drive for Thinness scores over time. Conversely, these relationship variables did not predict trajectory of eating pathology for heterosexual men. Implications for theoretical models of risk, including objectification theory and sexual minority stress theory, and prevention, including peer-led cognitive dissonance based interventions, are discussed. © 2015 Wiley Periodicals, Inc.

Relationship Status Predicts Lower Restrictive Eating Pathology for Bisexual and Gay Men across 10-year Follow-up

PubMed Central

Brown, Tiffany A.; Keel, Pamela K.

2015-01-01

Objective Cross-sectional studies support that bisexual and gay (BG) men are at increased risk for eating pathology, and romantic relationships may buffer against risk; however, no studies have examined this association longitudinally. The current study examined how romantic relationships impact the trajectory of eating pathology in BG versus heterosexual men. Method BG (n=51) and heterosexual (n=522) men completed surveys of health and eating behaviors at baseline and 10-year follow-up. Results For BG men, being single at baseline prospectively predicted an increase in Drive for Thinness scores over 10-year follow-up. Additionally, for BG men in relationships at baseline, lower relationship satisfaction predicted an increase in Drive for Thinness scores over time. Conversely, these relationship variables did not predict trajectory of eating pathology for heterosexual men. Discussion Implications for theoretical models of risk, including objectification theory and sexual minority stress theory, and prevention, including peer-led cognitive dissonance based interventions, are discussed. PMID:26172055

Image analysis and machine learning in digital pathology: Challenges and opportunities.

PubMed

Madabhushi, Anant; Lee, George

2016-10-01

With the rise in whole slide scanner technology, large numbers of tissue slides are being scanned and represented and archived digitally. While digital pathology has substantial implications for telepathology, second opinions, and education there are also huge research opportunities in image computing with this new source of "big data". It is well known that there is fundamental prognostic data embedded in pathology images. The ability to mine "sub-visual" image features from digital pathology slide images, features that may not be visually discernible by a pathologist, offers the opportunity for better quantitative modeling of disease appearance and hence possibly improved prediction of disease aggressiveness and patient outcome. However the compelling opportunities in precision medicine offered by big digital pathology data come with their own set of computational challenges. Image analysis and computer assisted detection and diagnosis tools previously developed in the context of radiographic images are woefully inadequate to deal with the data density in high resolution digitized whole slide images. Additionally there has been recent substantial interest in combining and fusing radiologic imaging and proteomics and genomics based measurements with features extracted from digital pathology images for better prognostic prediction of disease aggressiveness and patient outcome. Again there is a paucity of powerful tools for combining disease specific features that manifest across multiple different length scales. The purpose of this review is to discuss developments in computational image analysis tools for predictive modeling of digital pathology images from a detection, segmentation, feature extraction, and tissue classification perspective. We discuss the emergence of new handcrafted feature approaches for improved predictive modeling of tissue appearance and also review the emergence of deep learning schemes for both object detection and tissue classification. We also briefly review some of the state of the art in fusion of radiology and pathology images and also combining digital pathology derived image measurements with molecular "omics" features for better predictive modeling. The review ends with a brief discussion of some of the technical and computational challenges to be overcome and reflects on future opportunities for the quantitation of histopathology. Copyright © 2016 Elsevier B.V. All rights reserved.

Prediction of pelvic pathology in subfertile women with combined Chlamydia antibody and CA-125 tests.

PubMed

Penninx, Josien; Brandes, Monique; de Bruin, Jan Peter; Schneeberger, Peter M; Hamilton, Carl J C M

2009-12-01

Chlamydia antibody test (CAT) has been proposed to predict tubal disease. A correlation between CA-125 and the extent of endometriosis has been found by others. In this study we explored whether a combination of the two tests adds to the predictive value of the individual tests for predicting tubal disease or endometriosis. We also used the combination of tests as a new index test to screen for severe pelvic pathology. This retrospective study compares the findings of 240 laparoscopies with the serological test results. Findings were classified according to the existing ASRM scoring systems for adnexal adhesions, distal tubal occlusion and endometriosis. Severe pelvic pathology was defined as the presence of ASRM classes III and IV tubal disease or ASRM classes III and IV endometriosis. The predictive value was calculated for both tests separately and for the combined test. The combined test was positive if at least one test result was abnormal (CAT positive and/or CA-125 > or =35 IU/ml). 67/240 women had tubal disease, 81/240 had some degree of endometriosis. The odds ratios (ORs) of the CAT and the combined test to diagnose severe tubal disease were 6.6 (2.6-17.0) and 7.3 (2.9-19.3), respectively. The ORs of the CA-125 and the combined test to diagnose severe endometriosis were 15.6 (6.2-40.2) and 3.0 (1.2-8.0), respectively. Severe pelvic pathology was present in 65/240 women (27%). The ORs for severe pelvic pathology of the CAT, CA-125 and the combined test were 2.5 (1.4-5.3), 4.9 (1.9-9.6) and 6.6 (3.3-13.4), respectively. If the combined test was normal 15 out 131 women (11%) were shown to have severe pelvic pathology. The combined test adds hardly anything to the predictive value of CAT alone to diagnose severe tubal disease. The combined test is better than the CAT to predict severe pelvic pathology, but is not significantly better than the CA-125. If both the CAT and CA-125 are normal one could consider not performing a laparoscopy.

The current state of resident training in genomic pathology: a comprehensive analysis utilizing the Resident In-Service Exam (RISE)

PubMed Central

Haspel, Richard L.; Rinder, Henry M.; Frank, Karen M.; Wagner, Jay; Ali, Asma M.; Fisher, Patrick B.; Parks, Eric R.

2014-01-01

Objectives To determine the current state of pathology resident training in genomic and molecular pathology. Methods The Training Residents in Genomics (TRIG) Working Group developed survey and knowledge questions for the 2013 Pathology Resident In-Service Examination (RISE). Sixteen demographic questions related to amount of training, current and predicted future use, and perceived ability in molecular pathology vs. genomic medicine were included along with five genomic pathology and 19 molecular pathology knowledge questions. Results A total of 2,506 pathology residents took the 2013 RISE with approximately 600 individuals per post-graduate year (PGY). For genomic medicine, 42% of PGY-4 respondents stated they had no training compared to 7% for molecular pathology (p<0.001). PGY-4 resident perceived ability in genomic medicine, comfort in discussing results, and predicted future use as a practicing pathologist were less than reported for molecular pathology (p<0.001). There was a greater increase by PGY in knowledge question scores for molecular than for genomic pathology. Conclusions The RISE is a powerful tool in assessing the state of resident training in genomic pathology and current results suggest a significant deficit. The results also provide a baseline to assess future initiatives to improve genomics education for pathology residents such as those developed by the TRIG Working Group. PMID:25239410

NOS2-deficient mice with hypoxic necrotizing lung lesions predict outcomes of tuberculosis chemotherapy in humans.

PubMed

Gengenbacher, Martin; Duque-Correa, Maria A; Kaiser, Peggy; Schuerer, Stefanie; Lazar, Doris; Zedler, Ulrike; Reece, Stephen T; Nayyar, Amit; Cole, Stewart T; Makarov, Vadim; Barry Iii, Clifton E; Dartois, Véronique; Kaufmann, Stefan H E

2017-08-18

During active TB in humans a spectrum of pulmonary granulomas with central necrosis and hypoxia exists. BALB/c mice, predominantly used in TB drug development, do not reproduce this complex pathology thereby inaccurately predicting clinical outcome. We found that Nos2 -/- mice incapable of NO-production in immune cells as microbial defence uniformly develop hypoxic necrotizing lung lesions, widely observed in human TB. To study the impact of hypoxic necrosis on the efficacy of antimycobacterials and drug candidates, we subjected Nos2 -/- mice with TB to monotherapy before or after establishment of human-like pathology. Isoniazid induced a drug-tolerant persister population only when necrotic lesions were present. Rifapentine was more potent than rifampin prior to development of human-like pathology and equally potent thereafter, in agreement with recent clinical trials. Pretomanid, delamanid and the pre-clinical candidate BTZ043 were bactericidal independent of pulmonary pathology. Linezolid was bacteriostatic in TB-infected Nos2 -/- mice but significantly improved lung pathology. Hypoxic necrotizing lesions rendered moxifloxacin less active. In conclusion, Nos2 -/- mice are a predictive TB drug development tool owing to their consistent development of human-like pathology.

Effect of biodiversity changes in disease risk: exploring disease emergence in a plant-virus system.

PubMed

Pagán, Israel; González-Jara, Pablo; Moreno-Letelier, Alejandra; Rodelo-Urrego, Manuel; Fraile, Aurora; Piñero, Daniel; García-Arenal, Fernando

2012-01-01

The effect of biodiversity on the ability of parasites to infect their host and cause disease (i.e. disease risk) is a major question in pathology, which is central to understand the emergence of infectious diseases, and to develop strategies for their management. Two hypotheses, which can be considered as extremes of a continuum, relate biodiversity to disease risk: One states that biodiversity is positively correlated with disease risk (Amplification Effect), and the second predicts a negative correlation between biodiversity and disease risk (Dilution Effect). Which of them applies better to different host-parasite systems is still a source of debate, due to limited experimental or empirical data. This is especially the case for viral diseases of plants. To address this subject, we have monitored for three years the prevalence of several viruses, and virus-associated symptoms, in populations of wild pepper (chiltepin) under different levels of human management. For each population, we also measured the habitat species diversity, host plant genetic diversity and host plant density. Results indicate that disease and infection risk increased with the level of human management, which was associated with decreased species diversity and host genetic diversity, and with increased host plant density. Importantly, species diversity of the habitat was the primary predictor of disease risk for wild chiltepin populations. This changed in managed populations where host genetic diversity was the primary predictor. Host density was generally a poorer predictor of disease and infection risk. These results support the dilution effect hypothesis, and underline the relevance of different ecological factors in determining disease/infection risk in host plant populations under different levels of anthropic influence. These results are relevant for managing plant diseases and for establishing conservation policies for endangered plant species.

The Delphi Predictions of Pathology Chairmen: A Six-Year Retrospective View.

ERIC Educational Resources Information Center

Hill, Rolla B.; Goodale, Fairfield

1981-01-01

A retrospective review is reported of progress in academic pathology since 1974, when the Association of Pathology Chairmen undertook a Delphi study of pathology chairmen's expectations and desires for the future. The Delphi study was useful in alerting academic pathologists to opportunities and in coalescing activities toward achievement of…

The Virtual Mouse Brain: A Computational Neuroinformatics Platform to Study Whole Mouse Brain Dynamics.

PubMed

Melozzi, Francesca; Woodman, Marmaduke M; Jirsa, Viktor K; Bernard, Christophe

2017-01-01

Connectome-based modeling of large-scale brain network dynamics enables causal in silico interrogation of the brain's structure-function relationship, necessitating the close integration of diverse neuroinformatics fields. Here we extend the open-source simulation software The Virtual Brain (TVB) to whole mouse brain network modeling based on individual diffusion magnetic resonance imaging (dMRI)-based or tracer-based detailed mouse connectomes. We provide practical examples on how to use The Virtual Mouse Brain (TVMB) to simulate brain activity, such as seizure propagation and the switching behavior of the resting state dynamics in health and disease. TVMB enables theoretically driven experimental planning and ways to test predictions in the numerous strains of mice available to study brain function in normal and pathological conditions.

Mitochondrial Dynamics in Diabetic Cardiomyopathy

PubMed Central

Galloway, Chad A.

2015-01-01

Abstract Significance: Cardiac function is energetically demanding, reliant on efficient well-coupled mitochondria to generate adenosine triphosphate and fulfill the cardiac demand. Predictably then, mitochondrial dysfunction is associated with cardiac pathologies, often related to metabolic disease, most commonly diabetes. Diabetic cardiomyopathy (DCM), characterized by decreased left ventricular function, arises independently of coronary artery disease and atherosclerosis. Dysregulation of Ca2+ handling, metabolic changes, and oxidative stress are observed in DCM, abnormalities reflected in alterations in mitochondrial energetics. Cardiac tissue from DCM patients also presents with altered mitochondrial morphology, suggesting a possible role of mitochondrial dynamics in its pathological progression. Recent Advances: Abnormal mitochondrial morphology is associated with pathologies across diverse tissues, suggesting that this highly regulated process is essential for proper cell maintenance and physiological homeostasis. Highly structured cardiac myofibers were hypothesized to limit alterations in mitochondrial morphology; however, recent work has identified morphological changes in cardiac tissue, specifically in DCM. Critical Issues: Mitochondrial dysfunction has been reported independently from observations of altered mitochondrial morphology in DCM. The temporal relationship and causative nature between functional and morphological changes of mitochondria in the establishment/progression of DCM is unclear. Future Directions: Altered mitochondrial energetics and morphology are not only causal for but also consequential to reactive oxygen species production, hence exacerbating oxidative damage through reciprocal amplification, which is integral to the progression of DCM. Therefore, targeting mitochondria for DCM will require better mechanistic characterization of morphological distortion and bioenergetic dysfunction. Antioxid. Redox Signal. 22, 1545–1562. PMID:25738230

Anatomic features of enhancing renal masses predict malignant and high-grade pathology: a preoperative nomogram using the RENAL Nephrometry score.

PubMed

Kutikov, Alexander; Smaldone, Marc C; Egleston, Brian L; Manley, Brandon J; Canter, Daniel J; Simhan, Jay; Boorjian, Stephen A; Viterbo, Rosalia; Chen, David Y T; Greenberg, Richard E; Uzzo, Robert G

2011-08-01

Counseling patients with enhancing renal mass currently occurs in the context of significant uncertainty regarding tumor pathology. We evaluated whether radiographic features of renal masses could predict tumor pathology and developed a comprehensive nomogram to quantitate the likelihood of malignancy and high-grade pathology based on these features. We retrospectively queried Fox Chase Cancer Center's prospectively maintained database for consecutive renal masses where a Nephrometry score was available. All patients in the cohort underwent either partial or radical nephrectomy. The individual components of Nephrometry were compared with histology and grade of resected tumors. We used multiple logistic regression to develop nomograms predicting the malignancy of tumors and likelihood of high-grade disease among malignant tumors. Nephrometry score was available for 525 of 1750 renal masses. Nephrometry score correlated with both tumor grade (p < 0.0001) and histology (p < 0.0001), such that small endophytic nonhilar tumors were more likely to represent benign pathology. Conversely, large interpolar and hilar tumors more often represented high-grade cancers. The resulting nomogram from these data offers a useful tool for the preoperative prediction of tumor histology (area under the curve [AUC]: 0.76) and grade (AUC: 0.73). The model was subjected to out-of-sample cross-validation; however, lack of external validation is a limitation of the study. The current study is the first to objectify the relationship between tumor anatomy and pathology. Using the Nephrometry score, we developed a tool to quantitate the preoperative likelihood of malignant and high-grade pathology of an enhancing renal mass. Copyright © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Vital Signs: How Early Can Resident Evaluation Predict Acquisition of Competency in Surgical Pathology?

PubMed Central

Ducatman, Barbara S.; Williams, H. James; Hobbs, Gerald; Gyure, Kymberly A.

2009-01-01

Objectives To determine whether a longitudinal, case-based evaluation system can predict acquisition of competency in surgical pathology and how trainees at risk can be identified early. Design Data were collected for trainee performance on surgical pathology cases (how well their diagnosis agreed with the faculty diagnosis) and compared with training outcomes. Negative training outcomes included failure to complete the residency, failure to pass the anatomic pathology component of the American Board of Pathology examination, and/or failure to obtain or hold a position immediately following training. Findings Thirty-three trainees recorded diagnoses for 54 326 surgical pathology cases, with outcome data available for 15 residents. Mean case-based performance was significantly higher for those with positive outcomes, and outcome status could be predicted as early as postgraduate year-1 (P  =  .0001). Performance on the first postgraduate year-1 rotation was significantly associated with the outcome (P  =  .02). Although trainees with unsuccessful outcomes improved their performance more rapidly, they started below residents with successful outcomes and did not make up the difference during training. There was no significant difference in Step 1 or 2 United States Medical Licensing Examination (USMLE) scores when compared with performance or final outcomes (P  =  .43 and P  =  .68, respectively) and the resident in-service examination (RISE) had limited predictive ability. Discussion Differences between successful- and unsuccessful-outcome residents were most evident in early residency, ideal for designing interventions or counseling residents to consider another specialty. Conclusion Our longitudinal case-based system successfully identified trainees at risk for failure to acquire critical competencies for surgical pathology early in the program. PMID:21975705

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.

Forest management and the diversity of wood-inhabiting fungi

Treesearch

Daniel L. Lindner Czederpiltz; Glen R. Stanosz; Harold H. Burdsall

1999-01-01

Since the summer of 1996, a project has been underway at the University of Wisconsin-Madison,Dept. of Plant Pathology, to determine how different forest management regimes can affect the diversity of fungi found in northern hardwood forests. This report is an introduction to this project's goals, objectives and methods. A particular group of fungi, the wood-...

Clinical and pathological responses of pigs from two genetically diverse commercial lines to porcine respiratory and reproductive syndrome virus infection

USDA-ARS?s Scientific Manuscript database

The response to infection from porcine reproductive and respiratory syndrome virus (PRRSV) for two genetically diverse commercial pig lines was investigated. Seventy two pigs from each line, aged 6 weeks, were challenged with PRRSV VR-2385, and 66 littermates served as control. The clinical response...

The risk factors of laryngeal pathology in Korean adults using a decision tree model.

PubMed

Byeon, Haewon

2015-01-01

The purpose of this study was to identify risk factors affecting laryngeal pathology in the Korean population and to evaluate the derived prediction model. Cross-sectional study. Data were drawn from the 2008 Korea National Health and Nutritional Examination Survey. The subjects were 3135 persons (1508 male and 2114 female) aged 19 years and older living in the community. The independent variables were age, sex, occupation, smoking, alcohol drinking, and self-reported voice problems. A decision tree analysis was done to identify risk factors for predicting a model of laryngeal pathology. The significant risk factors of laryngeal pathology were age, gender, occupation, smoking, and self-reported voice problem in decision tree model. Four significant paths were identified in the decision tree model for the prediction of laryngeal pathology. Those identified as high risk groups for laryngeal pathology included those who self-reported a voice problem, those who were males in their 50s who did not recognize a voice problem, those who were not economically active males in their 40s, and male workers aged 19 and over and under 50 or 60 and over who currently smoked. The results of this study suggest that individual risk factors, such as age, sex, occupation, health behavior, and self-reported voice problem, affect the onset of laryngeal pathology in a complex manner. Based on the results of this study, early management of the high-risk groups is needed for the prevention of laryngeal pathology. Copyright © 2015 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Pathological gambling in Estonia: relationships with personality, self-esteem, emotional States and cognitive ability.

PubMed

Kaare, Pille-Riin; Mõttus, René; Konstabel, Kenn

2009-09-01

Due to changes in gambling accessibility during the last decade gambling has become more widespread in Estonia and the prevalence of pathological gambling has sharply increased. The present study attempts to identify psychological characteristics of Estonian pathological gamblers. It has been shown that a wide range of social, economic, and individual factors (e.g. personality traits and emotional states) predict the likelihood of becoming a pathological gambler. In the present study, pathological gamblers' (N = 33) personality traits, self-esteem, self-reported emotional states and cognitive ability were compared to the respective characteristics in a non-gambling control group (N = 42) matched for age, gender and educational level. It was found that compared to controls, pathological gamblers had higher scores on Neuroticism (especially on its immoderation facet) and lower scores on Conscientiousness (especially on its dutifulness and cautiousness facets) and on self-esteem scale. They reported more negative emotional states during the previous month (especially depression and anxiety). Finally, pathological gamblers had lower general cognitive ability. In a logistic regression model, the likelihood of being a pathological gambler was best predicted by high immoderation score and low cognitive ability.

Impulsivity, self-regulation,and pathological video gaming among youth: testing a mediation model.

PubMed

Liau, Albert K; Neo, Eng Chuan; Gentile, Douglas A; Choo, Hyekyung; Sim, Timothy; Li, Dongdong; Khoo, Angeline

2015-03-01

Given the potential negative mental health consequences of pathological video gaming, understanding its etiology may lead to useful treatment developments. The purpose of the study was to examine the influence of impulsive and regulatory processes on pathological video gaming. Study 1 involved 2154 students from 6 primary and 4 secondary schools in Singapore. Study 2 involved 191 students from 2 secondary schools. The results of study 1 and study 2 supported the hypothesis that self-regulation is a mediator between impulsivity and pathological video gaming. Specifically, higher levels of impulsivity was related to lower levels of self-regulation, which in turn was related to higher levels of pathological video gaming. The use of impulsivity and self-regulation in predicting pathological video gaming supports the dual-system model of incorporating both impulsive and reflective systems in the prediction of self-control outcomes. The study highlights the development of self-regulatory resources as a possible avenue for future prevention and treatment research. © 2011 APJPH.

Digital pathology in nephrology clinical trials, research, and pathology practice.

PubMed

Barisoni, Laura; Hodgin, Jeffrey B

2017-11-01

In this review, we will discuss (i) how the recent advancements in digital technology and computational engineering are currently applied to nephropathology in the setting of clinical research, trials, and practice; (ii) the benefits of the new digital environment; (iii) how recognizing its challenges provides opportunities for transformation; and (iv) nephropathology in the upcoming era of kidney precision and predictive medicine. Recent studies highlighted how new standardized protocols facilitate the harmonization of digital pathology database infrastructure and morphologic, morphometric, and computer-aided quantitative analyses. Digital pathology enables robust protocols for clinical trials and research, with the potential to identify previously underused or unrecognized clinically useful parameters. The integration of digital pathology with molecular signatures is leading the way to establishing clinically relevant morpho-omic taxonomies of renal diseases. The introduction of digital pathology in clinical research and trials, and the progressive implementation of the modern software ecosystem, opens opportunities for the development of new predictive diagnostic paradigms and computer-aided algorithms, transforming the practice of renal disease into a modern computational science.

Metabolomics of human brain aging and age-related neurodegenerative diseases.

PubMed

Jové, Mariona; Portero-Otín, Manuel; Naudí, Alba; Ferrer, Isidre; Pamplona, Reinald

2014-07-01

Neurons in the mature human central nervous system (CNS) perform a wide range of motor, sensory, regulatory, behavioral, and cognitive functions. Such diverse functional output requires a great diversity of CNS neuronal and non-neuronal populations. Metabolomics encompasses the study of the complete set of metabolites/low-molecular-weight intermediates (metabolome), which are context-dependent and vary according to the physiology, developmental state, or pathologic state of the cell, tissue, organ, or organism. Therefore, the use of metabolomics can help to unravel the diversity-and to disclose the specificity-of metabolic traits and their alterations in the brain and in fluids such as cerebrospinal fluid and plasma, thus helping to uncover potential biomarkers of aging and neurodegenerative diseases. Here, we review the current applications of metabolomics in studies of CNS aging and certain age-related neurodegenerative diseases such as Alzheimer disease, Parkinson disease, and amyotrophic lateral sclerosis. Neurometabolomics will increase knowledge of the physiologic and pathologic functions of neural cells and will place the concept of selective neuronal vulnerability in a metabolic context.

MiRNA Expression Analysis of Pretreatment Biopsies Predicts the Pathological Response of Esophageal Squamous Cell Carcinomas to Neoadjuvant Chemoradiotherapy.

PubMed

Wen, Jing; Luo, Kongjia; Liu, Hui; Liu, Shiliang; Lin, Guangrong; Hu, Yi; Zhang, Xu; Wang, Geng; Chen, Yuping; Chen, Zhijian; Li, Yi; Lin, Ting; Xie, Xiuying; Liu, Mengzhong; Wang, Huiyun; Yang, Hong; Fu, Jianhua

2016-05-01

To identify miRNA markers useful for esophageal squamous cell carcinoma (ESCC) neoadjuvant chemoradiotherapy (neo-CRT) response prediction. Neo-CRT followed by surgery improves ESCC patients' survival compared with surgery alone. However, CRT outcomes are heterogeneous, and no current methods can predict CRT responses. Differentially expressed miRNAs between ESCC pathological responders and nonresponders after neo-CRT were identified by miRNA profiling and verified by real-time quantitative polymerase chain reaction (qPCR) of 27 ESCCs in the training set. Several class prediction algorithms were used to build the response-classifying models with the qPCR data. Predictive powers of the models were further assessed with a second set of 79 ESCCs. Ten miRNAs with greater than a 1.5-fold change between pathological responders and nonresponders were identified and verified, respectively. A support vector machine (SVM) prediction model, composed of 4 miRNAs (miR-145-5p, miR-152, miR-193b-3p, and miR-376a-3p), were developed. It provided overall accuracies of 100% and 87.3% for discriminating pathological responders and nonresponders in the training and external validation sets, respectively. In multivariate analysis, the subgroup determined by the SVM model was the only independent factor significantly associated with neo-CRT response in the external validation sets. Combined qPCR of the 4 miRNAs provides the possibility of ESCC neo-CRT response prediction, which may facilitate individualized ESCC treatment. Further prospective validation in larger independent cohorts is necessary to fully assess its predictive power.

Financial and Health Literacy Predict Incident Alzheimer's Disease Dementia and Pathology.

PubMed

Yu, Lei; Wilson, Robert S; Schneider, Julie A; Bennett, David A; Boyle, Patricia A

2017-01-01

Domain specific literacy is a multidimensional construct that requires multiple resources including cognitive and non-cognitive factors. We test the hypothesis that domain specific literacy is associated with Alzheimer's disease (AD) dementia and AD pathology after controlling for cognition. Participants were community-based older persons who completed a baseline literacy assessment, underwent annual clinical evaluations for up to 8 years, and agreed to organ donation after death. Financial and health literacy was measured using 32 questions and cognition was measured using 19 tests. Annual diagnosis of AD dementia followed standard criteria. AD pathology was examined postmortem by quantifying plaques and tangles. Cox models examined the association of literacy with incident AD dementia. Performance of model prediction for incident AD dementia was assessed using indices for integrated discrimination improvement and continuous net reclassification improvement. Linear regression models examined the independent association of literacy with AD pathology in autopsied participants. All 805 participants were free of dementia at baseline and 102 (12.7%) developed AD dementia during the follow-up. Lower literacy was associated with higher risk for incident AD dementia (p < 0.001), and the association persisted after controlling for cognition (hazard ratio = 1.50, p = 0.004). The model including the literacy measure had better predictive performance than the one with demographics and cognition only. Lower literacy also was associated with higher burden of AD pathology after controlling for cognition (β= 0.07, p = 0.035). Literacy predicts incident AD dementia and AD pathology in community-dwelling older persons, and the association is independent of traditional measures of cognition.

Financial and health literacy predict incident AD dementia and AD pathology

PubMed Central

Yu, Lei; Wilson, Robert S.; Schneider, Julie A.; Bennett, David A.; Boyle, Patricia A.

2017-01-01

Background Domain specific literacy is a multidimensional construct that requires multiple resources including cognitive and non-cognitive factors. Objective We test the hypothesis that domain specific literacy is associated with AD dementia and AD pathology after controlling for cognition. Methods Participants were community based older persons who completed a baseline literacy assessment, underwent annual clinical evaluations for up to 8 years and agreed to organ donation after death. Financial and health literacy was measured using 32 questions and cognition was measured using 19 tests. Annual diagnosis of AD dementia followed standard criteria. AD pathology was examined post-mortem by quantifying plaques and tangles. Cox models examined the association of literacy with incident AD dementia. Performance of model prediction for incident AD dementia was assessed using indices for integrated discrimination improvement and continuous net reclassification improvement. Linear regression models examined the independent association of literacy with AD pathology in autopsied participants. Results All 805 participants were free of dementia at baseline and 102 (12.7%) developed AD dementia during the follow-up. Lower literacy was associated with higher risk for incident AD dementia (p<0.001), and the association persisted after controlling for cognition (Hazard Ratio=1.50, p=0.004). The model including the literacy measure had better predictive performance than the one with demographics and cognition only. Lower literacy also was associated with higher burden of AD pathology after controlling for cognition (β=0.07, p=0.035). Conclusion Literacy predicts incident AD dementia and AD pathology in community-dwelling older persons, and the association is independent of traditional measures of cognition. PMID:28157101

Carbohydrate antigens in nipple aspirate fluid predict the presence of atypia and cancer in women requiring diagnostic breast biopsy.

PubMed

Deutscher, Susan L; Dickerson, Marie; Gui, Gerald; Newton, Jessica; Holm, Jeffrey E; Vogeltanz-Holm, Nancy; Kliethermes, Beth; Hewett, John E; Kumar, Senthil R; Quinn, Thomas P; Sauter, Edward R

2010-10-01

The goal of this prospective study was to determine (a) concentrations of the carbohydrate biomarkers Thomsen Friedenreich (TF) antigen and its precursor, Tn antigen, in nipple discharge (ND) collected from women requiring biopsy because of a suspicious breast lesion; and (b) if concentration levels predicted pathologic diagnosis. Adult women requiring biopsy to exclude breast cancer were enrolled and ND obtained. The samples from 124 women were analyzed using an anti-TF and anti-Tn monoclonal antibodies in direct immunoassay. The highest median concentration in ND for TF and Tn was in women with ductal carcinoma in situ (DCIS). TF was higher in women with 1) cancer (DCIS or invasive) vs. either no cancer (atypia or benign pathology, p = .048), or benign pathology (p = .018); and 2) abnormal (atypia or cancer) versus benign pathology (p = .016); and was more predictive of atypia or cancer in post- compared to premenopausal women. Tn was not predictive of disease. High TF concentration and age were independent predictors of disease, correctly classifying either cancer or abnormal vs. benign pathology 83% of the time in postmenopausal women. TF concentrations in ND were higher in women with precancer and cancer compared to women with benign disease, and TF was an independent predictor of breast atypia and cancer. TF may prove useful in early breast cancer detection.

A Novel Risk Stratification to Predict Local-Regional Failures in Urothelial Carcinoma of the Bladder After Radical Cystectomy

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

Baumann, Brian C.; Guzzo, Thomas J.; He Jiwei

2013-01-01

Purpose: Local-regional failures (LF) following radical cystectomy (RC) plus pelvic lymph node dissection (PLND) with or without chemotherapy for invasive urothelial bladder carcinoma are more common than previously reported. Adjuvant radiation therapy (RT) could reduce LF but currently has no defined role because of previously reported morbidity. Modern techniques with improved normal tissue sparing have rekindled interest in RT. We assessed the risk of LF and determined those factors that predict recurrence to facilitate patient selection for future adjuvant RT trials. Methods and Materials: From 1990-2008, 442 patients with urothelial bladder carcinoma at University of Pennsylvania were prospectively followed aftermore » RC plus PLND with or without chemotherapy with routine pelvic computed tomography (CT) or magnetic resonance imaging (MRI). One hundred thirty (29%) patients received chemotherapy. LF was any pelvic failure detected before or within 3 months of distant failure. Competing risk analyses identified factors predicting increased LF risk. Results: On univariate analysis, pathologic stage {>=}pT3, <10 nodes removed, positive margins, positive nodes, hydronephrosis, lymphovascular invasion, and mixed histology significantly predicted LF; node density was marginally predictive, but use of chemotherapy, number of positive nodes, type of surgical diversion, age, gender, race, smoking history, and body mass index were not. On multivariate analysis, only stage {>=}pT3 and <10 nodes removed were significant independent LF predictors with hazard ratios of 3.17 and 2.37, respectively (P<.01). Analysis identified 3 patient subgroups with significantly different LF risks: low-risk ({<=}pT2), intermediate-risk ({>=}pT3 and {>=}10 nodes removed), and high-risk ({>=}pT3 and <10 nodes) with 5-year LF rates of 8%, 23%, and 42%, respectively (P<.01). Conclusions: This series using routine CT and MRI surveillance to detect LF confirms that such failures are relatively common in cases of locally advanced disease and provides a rubric based on pathological stage and number of nodes removed that stratifies patients into 3 groups with significantly different LF risks to simplify patient selection for future adjuvant radiation therapy trials.« less

Next-Generation Pathology.

PubMed

Caie, Peter D; Harrison, David J

2016-01-01

The field of pathology is rapidly transforming from a semiquantitative and empirical science toward a big data discipline. Large data sets from across multiple omics fields may now be extracted from a patient's tissue sample. Tissue is, however, complex, heterogeneous, and prone to artifact. A reductionist view of tissue and disease progression, which does not take this complexity into account, may lead to single biomarkers failing in clinical trials. The integration of standardized multi-omics big data and the retention of valuable information on spatial heterogeneity are imperative to model complex disease mechanisms. Mathematical modeling through systems pathology approaches is the ideal medium to distill the significant information from these large, multi-parametric, and hierarchical data sets. Systems pathology may also predict the dynamical response of disease progression or response to therapy regimens from a static tissue sample. Next-generation pathology will incorporate big data with systems medicine in order to personalize clinical practice for both prognostic and predictive patient care.

Oral treponeme major surface protein: Sequence diversity and distributions within periodontal niches.

PubMed

You, M; Chan, Y; Lacap-Bugler, D C; Huo, Y-B; Gao, W; Leung, W K; Watt, R M

2017-12-01

Treponema denticola and other species (phylotypes) of oral spirochetes are widely considered to play important etiological roles in periodontitis and other oral infections. The major surface protein (Msp) of T. denticola is directly implicated in several pathological mechanisms. Here, we have analyzed msp sequence diversity across 68 strains of oral phylogroup 1 and 2 treponemes; including reference strains of T. denticola, Treponema putidum, Treponema medium, 'Treponema vincentii', and 'Treponema sinensis'. All encoded Msp proteins contained highly conserved, taxon-specific signal peptides, and shared a predicted 'three-domain' structure. A clone-based strategy employing 'msp-specific' polymerase chain reaction primers was used to analyze msp gene sequence diversity present in subgingival plaque samples collected from a group of individuals with chronic periodontitis (n=10), vs periodontitis-free controls (n=10). We obtained 626 clinical msp gene sequences, which were assigned to 21 distinct 'clinical msp genotypes' (95% sequence identity cut-off). The most frequently detected clinical msp genotype corresponded to T. denticola ATCC 35405 T , but this was not correlated to disease status. UniFrac and libshuff analysis revealed that individuals with periodontitis and periodontitis-free controls harbored significantly different communities of treponeme clinical msp genotypes (P<.001). Patients with periodontitis had higher levels of clinical msp genotype diversity than periodontitis-free controls (Mann-Whitney U-test, P<.05). The relative proportions of 'T. vincentii' clinical msp genotypes were significantly higher in the control group than in the periodontitis group (P=.018). In conclusion, our data clearly show that both healthy and diseased individuals commonly harbor a wide diversity of Treponema clinical msp genotypes within their subgingival niches. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Pathological Dissociation as Measured by the Child Dissociative Checklist

ERIC Educational Resources Information Center

Wherry, Jeffrey N.; Neil, Debra A.; Taylor, Tamara N.

2009-01-01

The component structure of the Child Dissociative Checklist was examined among abused children. A factor described as pathological dissociation emerged that was predicted by participants being male. There also were differences in pathological dissociation between groups of sexually abused and physically abused children. Replication of this factor…

Pathologic response after preoperative therapy predicts prognosis of Chinese colorectal cancer patients with liver metastases.

PubMed

Wang, Yun; Yuan, Yun-Fei; Lin, Hao-Cheng; Li, Bin-Kui; Wang, Feng-Hua; Wang, Zhi-Qiang; Ding, Pei-Rong; Chen, Gong; Wu, Xiao-Jun; Lu, Zhen-Hai; Pan, Zhi-Zhong; Wan, De-Sen; Sun, Peng; Yan, Shu-Mei; Xu, Rui-Hua; Li, Yu-Hong

2017-10-02

Pathologic response is evaluated according to the extent of tumor regression and is used to estimate the efficacy of preoperative treatment. Several studies have reported the association between the pathologic response and clinical outcomes of colorectal cancer patients with liver metastases who underwent hepatectomy. However, to date, no data from Chinese patients have been reported. In this study, we aimed to evaluate the association between the pathologic response to pre-hepatectomy chemotherapy and prognosis in a cohort of Chinese patients. In this retrospective study, we analyzed the data of 380 liver metastases in 159 patients. The pathologic response was evaluated according to the tumor regression grade (TRG). The prognostic role of pathologic response in recurrence-free survival (RFS) and overall survival (OS) was assessed using Kaplan-Meier curves with the log-rank test and multivariate Cox models. Factors that had potential influence on pathologic response were also analyzed using multivariate logistic regression and Kruskal-Wallis/Mann-Whitney U tests. Patients whose tumors achieved pathologic response after preoperative chemotherapy had significant longer RFS and OS than patients whose tumor had no pathologic response to chemotherapy (median RFS: 9.9 vs. 6.5 months, P = 0.009; median OS: 40.7 vs. 28.1 months, P = 0.040). Multivariate logistic regression and Kruskal-Wallis/Mann-Whitney U tests showed that metastases with small diameter, metastases from the left-side primary tumors, and metastases from patients receiving long-duration chemotherapy had higher pathologic response rates than their control metastases (all P < 0.05). A decrease in the serum carcinoembryonic antigen (CEA) level after preoperative chemotherapy predicted an increased pathologic response rate (P < 0.05). Although the application of targeted therapy did not significantly influence TRG scores of all cases of metastases, the addition of cetuximab to chemotherapy resulted in a higher pathologic response rate when combined with irinotecan-based regimens rather than with oxaliplatin-based regimens. We found that the evaluation of pathologic response may predict the prognosis of Chinese colorectal cancer patients with liver metastases after preoperative chemotherapy. Small tumor diameter, long-duration chemotherapy, left primary tumor, and decreased serum CEA level after chemotherapy are associated with increased pathologic response rates.

MYC Amplification as a Predictive Factor of Complete Pathologic Response to Docetaxel-based Neoadjuvant Chemotherapy for Breast Cancer.

PubMed

Pereira, Cynthia Brito Lins; Leal, Mariana Ferreira; Abdelhay, Eliana Saul Furquim Werneck; Demachki, Sâmia; Assumpção, Paulo Pimentel; de Souza, Mirian Carvalho; Moreira-Nunes, Caroline Aquino; Tanaka, Adriana Michiko da Silva; Smith, Marília Cardoso; Burbano, Rommel Rodríguez

2017-06-01

Neoadjuvant chemotherapy is a standard treatment for stage II and III breast cancer. The identification of biomarkers that may help in the prediction of response to neoadjuvant therapies is necessary for a more precise definition of the best drug or drug combination to induce a better response. We assessed the role of Ki67, hormone receptors expression, HER2, MYC genes and their protein status, and KRAS codon 12 mutations as predictor factors of pathologic response to anthracycline-cyclophosphamide (AC) followed by taxane docetaxel (T) neoadjuvant chemotherapy (AC+T regimen) in 51 patients with invasive ductal breast cancer. After neoadjuvant chemotherapy, 82.4% of patients showed pathologic partial response, with only 9.8% showing pathologic complete response. In multivariate analysis, MYC immunoreactivity and high MYC gain defined as MYC/nucleus ≥ 5 were significant predictor factors for pathologic partial response. Using the receiver operating characteristic curve analysis, the ratio of 2.5 MYC/CEP8 (sensitivity of 80% and specificity of 89.1%) or 7 MYC/nuclei copies (sensitivity of 80% and specificity of 73.9%) as the best cutoff in predicting a pathologic complete response was identified. Thus, MYC may have a role in chemosensitivity to AC and/or docetaxel drugs. Additionally, MYC amplification may be a predictor factor of pathologic response to the AC+T regimen in patients with breast cancer. Moreover, patients with an increased number of MYC copies showed pathologic complete response to this neoadjuvant treatment more frequently. The analysis of MYC amplification may help in the identification of patients that may have a better response to AC+T treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

Feasibility of using negative ultrasonography results of axillary lymph nodes to predict sentinel lymph node metastasis in breast cancer patients.

PubMed

Chen, Xue; He, Yingjian; Wang, Jiwei; Huo, Ling; Fan, Zhaoqing; Li, Jinfeng; Xie, Yuntao; Wang, Tianfeng; Ouyang, Tao

2018-06-14

Knowledge of the pathology of axillary lymph nodes (ALN) in breast cancer patients is critical for determining their treatment. Ultrasound is the best noninvasive evaluation for the ALN status. However, the correlation between negative ultrasound results and the sentinel lymph nodes (SLN) pathology remains unknown. To test the hypothesis that negative ultrasound results of ALN predict the negative pathology results of SLN in breast cancer patients, we assessed the association between ALN ultrasonography-negative results and the SLN pathology in 3115 patients with breast cancer recruited between October 2010 and April 2016 from a single cancer center, prospective database. Of these patients who met the inclusion criteria, 2317 (74.4%) had no SLN pathological metastasis. In the univariate analysis, other 798 patient with positive SLN tended to be under age 40 and premenopausal, having large tumor sizes (>2 cm), higher histological grade of primary tumor, positive hormone receptors, and negative HER-2 status (P < .05 for all). In the multivariate analysis, menstrual status, tumor size, ER status and histological types of primary tumor remained to be independent predictors for SLN pathological metastasis. The area under curve (AUC) was 0.658 (95% CI = 0.637-0.679), P > .05. In conclusion, only a 74.4% consistency between ALN ultrasonography-negative results and negative pathological SLN results, although menstrual status, tumor size, histologic subtypes of primary tumor and ER status were found to be statistically independent predictors of positive SLN among patients negative for ALN ultrasonography. Therefore, the present study suggests that negative ultrasound results of ALN do not adequately predict the negative pathology results of SLN in breast cancer patients. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Homeostatic and pathogenic extramedullary hematopoiesis

PubMed Central

Kim, Chang H

2010-01-01

Extramedullary hematopoiesis (EH) is defined as hematopoiesis occurring in organs outside of the bone marrow; it occurs in diverse conditions, including fetal development, normal immune responses, and pathological circumstances. During fetal development, before formation of mature marrow, EH occurs in the yolk sac, fetal liver, and spleen. EH also occurs during active immune responses to pathogens. Most frequently, this response occurs in the spleen and liver for the production of antigen-presenting cells and phagocytes. EH also occurs when the marrow becomes inhabitable for stem and progenitor cells in certain pathological conditions, including myelofibrosis, where marrow cells are replaced with collagenous connective tissue fibers. Thus, EH occurs either actively or passively in response to diverse changes in the hematopoietic environment. This article reviews the key features and regulators of the major types of EH. PMID:22282679

A new pathological scoring system by the Japanese classification to predict renal outcome in diabetic nephropathy.

PubMed

Hoshino, Junichi; Furuichi, Kengo; Yamanouchi, Masayuki; Mise, Koki; Sekine, Akinari; Kawada, Masahiro; Sumida, Keiichi; Hiramatsu, Rikako; Hasegawa, Eiko; Hayami, Noriko; Suwabe, Tatsuya; Sawa, Naoki; Hara, Shigeko; Fujii, Takeshi; Ohashi, Kenichi; Kitagawa, Kiyoki; Toyama, Tadashi; Shimizu, Miho; Takaichi, Kenmei; Ubara, Yoshifumi; Wada, Takashi

2018-01-01

The impact of the newly proposed pathological classification by the Japan Renal Pathology Society (JRPS) on renal outcome is unclear. So we evaluated that impact and created a new pathological scoring to predict outcome using this classification. A multicenter cohort of 493 biopsy-proven Japanese patients with diabetic nephropathy (DN) were analyzed. The association between each pathological factor-Tervaert' and JRPS classifications-and renal outcome (dialysis initiation or 50% eGFR decline) was estimated by adjusted Cox regression. The overall pathological risk score (J-score) was calculated, whereupon its predictive ability for 10-year risk of renal outcome was evaluated. The J-scores of diffuse lesion classes 2 or 3, GBM doubling class 3, presence of mesangiolysis, polar vasculosis, and arteriolar hyalinosis were, respectively, 1, 2, 4, 1, and 2. The scores of IFTA classes 1, 2, and 3 were, respectively, 3, 4, and 4, and those of interstitial inflammation classes 1, 2, and 3 were 5, 5, and 4 (J-score range, 0-19). Renal survival curves, when dividing into four J-score grades (0-5, 6-10, 11-15, and 16-19), were significantly different from each other (p<0.01, log-rank test). After adjusting clinical factors, the J-score was a significant predictor of renal outcome. Ability to predict 10-year renal outcome was improved when the J-score was added to the basic model: c-statistics from 0.661 to 0.685; category-free net reclassification improvement, 0.154 (-0.040, 0.349, p = 0.12); and integrated discrimination improvement, 0.015 (0.003, 0.028, p = 0.02). Mesangiolysis, polar vasculosis, and doubling of GBM-features of the JRPS system-were significantly associated with renal outcome. Prediction of DN patients' renal outcome was better with the J-score than without it.

Targeting EphA2-Sam and Its Interactome: Design and Evaluation of Helical Peptides Enriched in Charged Residues.

PubMed

Mercurio, Flavia A; Marasco, Daniela; Di Natale, Concetta; Pirone, Luciano; Costantini, Susan; Pedone, Emilia M; Leone, Marilisa

2016-11-17

The EphA2 receptor controls diverse physiological and pathological conditions and its levels are often upregulated in cancer. Targeting receptor overexpression, through modulation of endocytosis and consequent degradation, appears to be an appealing strategy for attacking tumor malignancy. In this scenario, the Sam domain of EphA2 plays a pivotal role because it is the site where protein regulators of endocytosis and stability are recruited by means of heterotypic Sam-Sam interactions. Because EphA2-Sam heterotypic complexes are largely based on electrostatic contacts, we have investigated the possibility of attacking these interactions with helical peptides enriched in charged residues. Several peptide sequences with high predicted helical propensities were designed, and detailed conformational analyses were conducted by diverse techniques including NMR, CD, and molecular dynamics (MD) simulations. Interaction studies were also performed by NMR, surface plasmon resonance (SPR), and microscale thermophoresis (MST) and led to the identification of two peptides capable of binding to the first Sam domain of Odin. These molecules represent early candidates for the generation of efficient Sam domain binders and antagonists of Sam-Sam interactions involving EphA2. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Bile acid malabsorption after continent urinary diversion with an ileal reservoir.

PubMed

Olofsson, G; Fjälling, M; Kilander, A; Ung, K A; Jonsson, O

1998-09-01

We determine the effect of urinary diversion with a Kock ileal reservoir on bile acid absorption and bowel habits. We asked 96 patients with a Kock ileal urinary reservoir to record bowel habits and abdominal symptoms for 1 week. Data on 75 patients were further analyzed. Bile acid absorption was determined in 29 healthy control subjects, in 17 before and 6 months after continent urinary diversion, and in 21, 2 to 14 years postoperatively. Bile acid absorption was considered pathological when retention of less than 10% of an oral capsule containing selenium-75 labeled tauroselcholic acid (SeHCAT) was noted after 1 week. Mean number of defecations plus or minus standard deviation was 9.4 +/- 6.1 (75 cases). Of the patients 13% had 15 or more stools per week and 15% complained of always having loose stools. Mean value for the SeHCAT test was 32 +/- 19% preoperatively and 17 +/- 16% 6 months postoperatively (p = 0.0023). The corresponding value for healthy controls was 39 +/- 18%. Significant relationships were found between the results of the SeHCAT test postoperatively, and the number of stools per week and consistency of the feces. All patients with more than 10 defecations per week had a pathological SeHCAT test. Most patients with an ileal urinary reservoir have fairly normal bowel habits. Bile acid absorption is significantly reduced postoperatively and approximately a third of the patients have a pathological SeHCAT test. Preoperative investigation of bowel habits is recommended and a SeHCAT test should be performed in patients with frequent, loose defecations. Other types of diversion should be offered when preoperative retention is below 10 to 20% especially in patients with impaired anal control.

Predictive value of magnetic resonance imaging determined tumor contact length for extracapsular extension of prostate cancer.

PubMed

Baco, Eduard; Rud, Erik; Vlatkovic, Ljiljana; Svindland, Aud; Eggesbø, Heidi B; Hung, Andrew J; Matsugasumi, Toru; Bernhard, Jean-Christophe; Gill, Inderbir S; Ukimura, Osamu

2015-02-01

Tumor contact length is defined as the amount of prostate cancer in contact with the prostatic capsule. We evaluated the ability of magnetic resonance imaging determined tumor contact length to predict microscopic extracapsular extension compared to existing predictors of extracapsular extension. We retrospectively analyzed the records of 111 consecutive patients with magnetic resonance imaging/ultrasound fusion targeted, biopsy proven prostate cancer who underwent radical prostatectomy from January 2010 to July 2013. Median patient age was 64 years and median prostate specific antigen was 8.9 ng/ml. Clinical stage was cT1 in 93 cases (84%) and cT2 in 18 (16%). Postoperative pathological analysis confirmed pT2 in 71 patients (64%) and pT3 in 40 (36%). We evaluated 1) in the radical prostatectomy specimen the correlation of microscopic extracapsular extension with pathological cancer volume, pathological tumor contact length and Gleason score, 2) the correlation between microscopic extracapsular extension and magnetic resonance imaging tumor contact length, and 3) the ability of preoperative variables to predict microscopic extracapsular extension. Logistic regression analysis revealed that pathological tumor contact length correlated better with microscopic extracapsular extension than the predictive power of pathological cancer volume (0.821 vs 0.685). The Spearman correlation between pathological and magnetic resonance imaging tumor contact length was r = 0.839 (p <0.0001). ROC AUC analysis revealed that magnetic resonance imaging tumor contact length outperformed cancer core involvement on targeted biopsy and the Partin tables to predict microscopic extracapsular extension (0.88 vs 0.70 and 0.63, respectively). At a magnetic resonance imaging tumor contact length threshold of 20 mm the accuracy for diagnosing microscopic extracapsular extension was superior to that of conventional magnetic resonance imaging criteria (82% vs 67%, p = 0.015). We developed a predicted probability plot curve of extracapsular extension according to magnetic resonance imaging tumor contact length. Magnetic resonance imaging determined tumor contact length could be a promising quantitative predictor of microscopic extracapsular extension. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Robotic laparoscopic radical prostatectomy for biopsy Gleason 8 to 10: prediction of favorable pathologic outcome with preoperative parameters.

PubMed

Shikanov, Sergey A; Thong, Alan; Gofrit, Ofer N; Zagaja, Gregory P; Steinberg, Gary D; Shalhav, Arieh L; Zorn, Kevin C

2008-07-01

We sought to evaluate the pathologic results and postoperative outcomes for men undergoing robot-assisted laparoscopic radical prostatectomy (RLRP) for biopsy Gleason score (GS) 8 to 10 disease. Stratification of these patients according to preoperative variables was also performed in an attempt to predict organ-confined cancer. A prospective RLRP database identified all patients with preoperative biopsy GS 8 to 10. Variables, including prostate-specific antigen (PSA), percent positive biopsy cores (%PBC), maximal percentage of cancer in biopsy core (%MCB), clinical stage, pathologic stage, pathologic GS, surgical margins status, lymph node status, time to biochemical recurrence, and recurrence rate, were evaluated. Preoperative variables were treated as continuous and categorical using PSA, %PBC and %MCB cutoffs of 10 ng/mL, 50%, and 30%, respectively. Between February 2003 and September 2007, a total of 1225 RLRPs were performed at the University of Chicago Medical Center. Seventy-two (5.9%) patients had preoperative biopsy GS 8 to 10. Two patients received neoadjuvant hormonal therapy and were excluded. Among 70 patients evaluated, 33 (47%) had organconfined (pT(2)N0) disease. Forty (60.6%) patients had pathologic downgrading to GS

CD147 expression predicts biochemical recurrence after prostatectomy independent of histologic and pathologic features.

PubMed

Bauman, Tyler M; Ewald, Jonathan A; Huang, Wei; Ricke, William A

2015-07-25

CD147 is an MMP-inducing protein often implicated in cancer progression. The purpose of this study was to investigate the expression of CD147 in prostate cancer (PCa) progression and the prognostic ability of CD147 in predicting biochemical recurrence after prostatectomy. Plasma membrane-localized CD147 protein expression was quantified in patient samples using immunohistochemistry and multispectral imaging, and expression was compared to clinico-pathological features (pathologic stage, Gleason score, tumor volume, preoperative PSA, lymph node status, surgical margins, biochemical recurrence status). CD147 specificity and expression were confirmed with immunoblotting of prostate cell lines, and CD147 mRNA expression was evaluated in public expression microarray datasets of patient prostate tumors. Expression of CD147 protein was significantly decreased in localized tumors (pT2; p = 0.02) and aggressive PCa (≥pT3; p = 0.004), and metastases (p = 0.001) compared to benign prostatic tissue. Decreased CD147 was associated with advanced pathologic stage (p = 0.009) and high Gleason score (p = 0.02), and low CD147 expression predicted biochemical recurrence (HR 0.55; 95 % CI 0.31-0.97; p = 0.04) independent of clinico-pathologic features. Immunoblot bands were detected at 44 kDa and 66 kDa, representing non-glycosylated and glycosylated forms of CD147 protein, and CD147 expression was lower in tumorigenic T10 cells than non-tumorigenic BPH-1 cells (p = 0.02). Decreased CD147 mRNA expression was associated with increased Gleason score and pathologic stage in patient tumors but is not associated with recurrence status. Membrane-associated CD147 expression is significantly decreased in PCa compared to non-malignant prostate tissue and is associated with tumor progression, and low CD147 expression predicts biochemical recurrence after prostatectomy independent of pathologic stage, Gleason score, lymph node status, surgical margins, and tumor volume in multivariable analysis.

The Ecology of Early Childhood Risk: A Canonical Correlation Analysis of Children’s Adjustment, Family, and Community Context in a High-Risk Sample

PubMed Central

Aiyer, Sophie M.; Wilson, Melvin N.; Shaw, Daniel S.; Dishion, Thomas J.

2013-01-01

The ecology of the emergence of psycho-pathology in early childhood is often approached by the analysis of a limited number of contextual risk factors. In the present study, we provide a comprehensive analysis of ecological risk by conducting a canonical correlation analysis of 13 risk factors at child age 2 and seven narrow-band scales of internalizing and externalizing problem behaviors at child age 4, using a sample of 364 geographically and ethnically diverse, disadvantaged primary caregivers, alternative caregivers, and preschool-age children. Participants were recruited from Special Supplemental Nutrition Program for Women, Infants, and Children sites and were screened for family risk. Canonical correlation analysis revealed that (1) a first latent combination of family and individual risks of caregivers predicted combinations of child emotional and behavioral problems, and that (2) a second latent combination of contextual and structural risks predicted child somatic complaints. Specifically, (1) the combination of chaotic home, conflict with child, parental depression, and parenting hassles predicted a co-occurrence of internalizing and externalizing behaviors, and (2) the combination of father absence, perceived discrimination, neighborhood danger, and fewer children living in the home predicted child somatic complaints. The research findings are discussed in terms of the development of psychopathology, as well as the potential prevention needs of families in high-risk contexts. PMID:23700232

Pure Lymphoepithelioma-Like Carcinoma Originating from the Urinary Bladder

PubMed Central

Nagai, Takashi; Naiki, Taku; Kawai, Noriyasu; Iida, Keitaro; Etani, Toshiki; Ando, Ryosuke; Hamamoto, Shuzo; Sugiyama, Yosuke; Okada, Atsushi; Mizuno, Kentaro; Umemoto, Yukihiro; Yasui, Takahiro

2016-01-01

Lymphoepithelioma-like carcinoma of the urinary bladder (LELCB) is a rare variant of infiltrating urothelial carcinoma. We report a case of LELCB in a 43-year-old man. Ultrasonography and cystoscopy revealed two bladder tumors, one on the left side of the trigone and the other on the right side of the trigone. Transurethral resection of the bladder tumors was performed and pathological analysis revealed undifferentiated carcinoma. We therefore performed radical cystectomy and urinary diversion. Immunohistochemically the tumor cells were positive for cytokeratin, but negative for Epstein-Barr virus-encoded small RNA in situ hybridization as found for previous cases of LELCB. The final pathological diagnosis was a lymphoepithelioma-like variant of urothelial carcinoma with perivesical soft tissue invasion. For adjuvant systemic chemotherapy, three courses of cisplatin were administered. The patient subsequently became free of cancer 72 months postoperatively. Based on the literature, pure or predominant LELCB types show favorable prognoses due to their sensitivity to chemotherapy or radiotherapy. An analysis of the apparent diffusion coefficient (ADC) values of bladder tumors examined in our institution revealed that the ADC value measured for this LELCB was relatively low compared to conventional urothelial carcinomas. This suggests that measuring the ADC value of a lymphoepithelioma-like carcinoma prior to operation may be helpful in predicting LELCB. PMID:27099604

Pediatric Emergency Care Applied Research Network head injuryprediction rules: on the basis of cost and effectiveness

PubMed

Gökharman, Fatma Dilek; Aydın, Sonay; Fatihoğlu, Erdem; Koşar, Pınar Nercis

2017-12-19

Background/aim: Head injuries are commonly seen in the pediatric population. Noncontrast enhanced cranial CT is the method of choice to detect possible traumatic brain injury (TBI). Concerns about ionizing radiation exposure make the evaluation more challenging. The aim of this study was to evaluate the effectiveness of the Pediatric Emergency Care Applied Research Network (PECARN) rules in predicting clinically important TBI and to determine the amount of medical resource waste and unnecessary radiation exposure.Materials and methods: This retrospective study included 1041 pediatric patients presented to the emergency department. The patients were divided into subgroups of "appropriate for cranial CT", "not appropriate for cranial CT" and "cranial CT/observation of patient; both are appropriate". To determine the effectiveness of the PECARN rules, data were analyzed according to the presence of pathological findings Results: "Appropriate for cranial CT" results can predict pathology presence 118,056-fold compared to the "not appropriate for cranial CT" results. With "cranial CT/observation of patient; both are appropriate" results, pathology presence was predicted 11,457-fold compared to "not appropriate for cranial CT" results.Conclusion: PECARN rules can predict pathology presence successfully in pediatric TBI. Using PECARN can decrease resource waste and exposure to ionizing radiation.

Application of neural networks to prediction of fish diversity and salmonid production in the Lake Ontario basin

USGS Publications Warehouse

McKenna, James E.

2005-01-01

Diversity and fish productivity are important measures of the health and status of aquatic systems. Being able to predict the values of these indices as a function of environmental variables would be valuable to management. Diversity and productivity have been related to environmental conditions by multiple linear regression and discriminant analysis, but such methods have several shortcomings. In an effort to predict fish species diversity and estimate salmonid production for streams in the eastern basin of Lake Ontario, I constructed neural networks and trained them on a data set containing abiotic information and either fish diversity or juvenile salmonid abundance. Twenty percent of the original data were retained as a test data set and used in the training. The ability to extend these neural networks to conditions throughout the streams was tested with data not involved in the network training. The resulting neural networks were able to predict the number of salmonids with more than 84% accuracy and diversity with more than 73% accuracy, which was far superior to the performance of multiple regression. The networks also identified the environmental variables with the greatest predictive power, namely, those describing water movement, stream size, and water chemistry. Thirteen input variables were used to predict diversity and 17 to predict salmonid abundance.

Prediction of the intensity and diversity of day-to-day activities among people with schizophrenia using parameters obtained during acute hospitalization.

PubMed

Lipskaya-Velikovsky, Lena; Jarus, Tal; Kotler, Moshe

2017-06-01

Participation in day-to-day activities of people with schizophrenia is restricted, causing concern to them, their families, service providers and the communities at large. Participation is a significant component of health and recovery; however, factors predicting participation are still not well established. This study examines whether the parameters obtained during acute hospitalization can predict the intensity and diversity of participation in day-to-day activities six months after discharge. In-patients with chronic schizophrenia (N = 104) were enrolled into the study and assessed for cognitive functioning, functional capacity in instrumental activities of daily living (IADL), and symptoms. Six months after discharge, the intensity and diversity of participation in day-to-day activities were evaluated (N = 70). Multiple correlations were found between parameters obtained during hospitalization and participation diversity, but not participation intensity. The model that is better suited to the prediction of participation diversity contains cognitive ability of construction, negative symptoms and number of previous hospitalizations. The total explained variance is 37.8% (F 3,66  =   14.99, p < 0.001). This study provides evidence for ecological validity of the in-patient evaluation process for the prediction of participation diversity in day-to-day activities six months after discharge. Participation diversity is best predicted through a set of factors reflecting personal and environmental indicators. Implications for rehabilitation Results of in-patient evaluations can predict the diversity of participation in day-to-day activities six months after discharge. Higher prediction of participation diversity is obtained using a holistic evaluation model that includes assessments for cognitive abilities, negative symptoms severity and number of hospitalizations.

Fostering group identification and creativity in diverse groups: the role of individuation and self-verification.

PubMed

Swann, William B; Kwan, Virginia S Y; Polzer, Jeffrey T; Milton, Laurie P

2003-11-01

A longitudinal study examined the interplay of identity negotiation processes and diversity in small groups of master's of business administration (MBA) students. When perceivers formed relatively positive impressions of other group members, higher diversity predicted more individuation of targets. When perceivers formed relatively neutral impressions of other group members, however, higher diversity predicted less individuation of targets. Individuation at the outset of the semester predicted self-verification effects several weeks later, and self-verification, in turn, predicted group identification and creative task performance. The authors conclude that contrary to self-categorization theory, fostering individuation and self-verification in diverse groups may maximize group identification and productivity.

Prediction of pathologic staging with magnetic resonance imaging after preoperative chemoradiotherapy in rectal cancer: pooled analysis of KROG 10-01 and 11-02.

PubMed

Lee, Jong Hoon; Jang, Hong Seok; Kim, Jun-Gi; Lee, Myung Ah; Kim, Dae Yong; Kim, Tae Hyun; Oh, Jae Hwan; Park, Sung Chan; Kim, Sun Young; Baek, Ji Yeon; Park, Hee Chul; Kim, Hee Cheol; Nam, Taek-Keun; Chie, Eui Kyu; Jung, Ji-Han; Oh, Seong Taek

2014-10-01

The reported overall accuracy of MRI in predicting the pathologic stage of nonirradiated rectal cancer is high. However, the role of MRI in restaging rectal tumors after neoadjuvant CRT is contentious. Thus, we evaluate the accuracy of restaging magnetic resonance imaging (MRI) for rectal cancer patients who receive preoperative chemoradiotherapy (CRT). We analyzed 150 patients with locally advanced rectal cancer (T3-4N0-2) who had received preoperative CRT. Pre-CRT MRI was performed for local tumor and nodal staging. All patients underwent restaging MRI followed by total mesorectal excision after the end of radiotherapy. The primary endpoint of the present study was to estimate the accuracy of post-CRT MRI as compared with pathologic staging. Pathologic T classification matched the post-CRT MRI findings in 97 (64.7%) of 150 patients. 36 (24.0%) of 150 patients were overstaged in T classification, and the concordance degree was moderate (k=0.33, p<0.01). Pathologic N classification matched the post-CRI MRI findings in 85 (56.6%) of 150 patients. 54 (36.0%) of 150 patients were overstaged in N classification. 26 patients achieved downstaging (ycT0-2N0) on restaging MRI after CRT. 23 (88.5%) of 26 patients who had been downstaged on MRI after CRT were confirmed on the pathological staging, and the concordance degree was good (k=0.72, p<0.01). Restaging MRI has low accuracy for the prediction of the pathologic T and N classifications in rectal cancer patients who received preoperative CRT. The diagnostic accuracy of restaging MRI is relatively high in rectal cancer patients who achieved clinical downstaging after CRT. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Personalizing Biomaterials for Precision Nanomedicine Considering the Local Tissue Microenvironment.

PubMed

Oliva, Nuria; Unterman, Shimon; Zhang, Yi; Conde, João; Song, Hyun Seok; Artzi, Natalie

2015-08-05

New advances in (nano)biomaterial design coupled with the detailed study of tissue-biomaterial interactions can open a new chapter in personalized medicine, where biomaterials are chosen and designed to match specific tissue types and disease states. The notion of a "one size fits all" biomaterial no longer exists, as growing evidence points to the value of customizing material design to enhance (pre)clinical performance. The complex microenvironment in vivo at different tissue sites exhibits diverse cell types, tissue chemistry, tissue morphology, and mechanical stresses that are further altered by local pathology. This complex and dynamic environment may alter the implanted material's properties and in turn affect its in vivo performance. It is crucial, therefore, to carefully study tissue context and optimize biomaterials considering the implantation conditions. This practice would enable attaining predictable material performance and enhance clinical outcomes. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Physiological significance of polyploidization in mammalian cells.

PubMed

Pandit, Shusil K; Westendorp, Bart; de Bruin, Alain

2013-11-01

Programmed polyploidization occurs in all mammalian species during development and aging in selected tissues, but the biological properties of polyploid cells remain obscure. Spontaneous polyploidization arises during stress and has been observed in a variety of pathological conditions, such as cancer and degenerative diseases. A major challenge in the field is to test the predicted functions of polyploidization in vivo. However, recent genetic mouse models with diminished polyploidization phenotypes represent novel, powerful tools to unravel the biological function of polyploidization. Contrary to a longstanding hypothesis, polyploidization appears to not be required for differentiation and has no obvious impact on proliferation. Instead, polyploidization leads to increased cell size and genetic diversity, which could promote better adaptation to chronic injury or stress. We discuss here the consequences of reducing polyploidization in mice and review which stress responses and molecular signals trigger polyploidization during development and disease. Copyright © 2013 Elsevier Ltd. All rights reserved.

Utilizing population variation, vaccination, and systems biology to study human immunology

PubMed Central

Tsang, John S.

2016-01-01

The move toward precision medicine has highlighted the importance of understanding biological variability within and across individuals in the human population. In particular, given the prevalent involvement of the immune system in diverse pathologies, an important question is how much and what information about the state of the immune system is required to enable accurate prediction of future health and response to medical interventions. Towards addressing this question, recent studies using vaccination as a model perturbation and systems-biology approaches are beginning to provide a glimpse of how natural population variation together with multiplexed, high-throughput measurement and computational analysis can be used to uncover predictors of immune response quality in humans. Here I discuss recent developments in this emerging field, with emphasis on baseline correlates of vaccination responses, sources of immune-state variability, as well as relevant features of study design, data generation, and computational analysis. PMID:26187853

Describing the silent human virome with an emphasis on giant viruses.

PubMed

Popgeorgiev, Nikolay; Temmam, Sarah; Raoult, Didier; Desnues, Christelle

2013-01-01

Viruses are the most abundant obligate intracellular entities in our body. Until recently, they were only considered to be pathogens that caused a broad array of pathologies, ranging from mild disease to deaths in the most severe cases. However, recent advances in unbiased mass sequencing techniques as well as increasing epidemiological evidence have indicated that the human body is home to diverse viral species under non-pathological conditions. Despite these studies, the description of the presumably healthy viral flora, i.e. the normal human virome, is still in its infancy regarding viral composition and dynamics. This review summarizes our current knowledge of the human virome under non-pathological conditions.

Understanding the Influence of Mental Health Diagnosis and Gender on Placement Decisions for Justice-Involved Youth.

PubMed

Kempker, Samantha M; Schmidt, Adam T; Espinosa, Erin M

2017-07-01

Justice-involved youth have high rates of psychiatric diagnoses, and these youth are often placed out-of-home, although evidence identifies several negative implications of juvenile confinement, especially for youth with psychopathology. Furthermore, youth in the justice system may be processed differently based on gender. As males and females tend to manifest symptoms differently, the psychopathology of youth may act to moderate the relationship between gender and placement in the juvenile justice system. The present study used a large, diverse sample (n = 9 851, 19.8 % female) to examine whether youth placed in various types of out-of-home facilities differed in terms of externalizing, internalizing, substance use, or comorbid disorders, and to determine the predictive value of mental health diagnoses in placement decisions. The moderation effect of psychopathology and substance use on the relationship between gender and placement also was explored. The results indicated that each type of disorder differed across placements, with internalizing being most prevalent in non-secure, and externalizing, comorbid, and substance use being most prevalent in secure settings. Mental health diagnoses improved the prediction of placement in each out-of-home placement beyond legal and demographic factors such that externalizing and substance use disorders decreased the likelihood of placement in non-secure settings, and internalizing, externalizing, and substance use disorders increased the likelihood of placement in secure and state-secure facilities. The relationship between internalizing pathology and placement in more secure facilities was moderated by externalizing pathology. The relationship between gender and placement was significantly moderated by mental health such that females with mental health diagnoses receive less secure placements. Implications for policymakers and practitioners are discussed, as well as implications for reforming juvenile justice within a developmental approach.

Individual Factors Predicting Mental Health Court Diversion Outcome

ERIC Educational Resources Information Center

Verhaaff, Ashley; Scott, Hannah

2015-01-01

Objective: This study examined which individual factors predict mental health court diversion outcome among a sample of persons with mental illness participating in a postcharge diversion program. Method: The study employed secondary analysis of existing program records for 419 persons with mental illness in a court diversion program. Results:…

Exploring the development of cultural awareness amongst post-graduate speech-language pathology students.

PubMed

Howells, Simone; Barton, Georgina; Westerveld, Marleen

2016-06-01

Speech-language pathology programs globally need to prepare graduates to work with culturally and linguistically diverse populations. This study explored the knowledge, perceptions and experiences related to development of cultural awareness of graduate-entry Master of Speech Pathology students at an Australian university. Sixty students across both year-levels completed a cultural awareness survey at the beginning of the semester. To explore how clinical placement influenced students' knowledge and perceptions, year-2 students completed written reflections pre- and post-placement (n = 7) and participated in focus groups post-placement (n = 6). Survey results showed student interest in working with culturally and linguistically diverse populations was high (over 80%) and confidence was moderate (over 50%). More than 80% of students reported awareness of their own cultural identities, stereotypes and prejudices. Content analysis of focus group and written reflection data identified key concepts comprising of: (1) context-university, and clinical placement site; (2) competencies-professional and individual; and (3) cultural implications-clients' and students' cultural backgrounds. Findings suggest clinical placement may positively influence cultural awareness development and students' own cultural backgrounds may influence this more. Further exploration of how students move along a continuum of cultural development is warranted.

The Emerging Role of Inflammasomes as Central Mediators in Inflammatory Bladder Pathology

PubMed Central

Inouye, Brian M.; Hughes, Francis M.; Sexton, Stephanie J.; Purves, J. Todd

2018-01-01

Irritative voiding symptoms (e.g. increased frequency and urgency) occur in many common pathologic conditions such as urinary tract infections and bladder outlet obstruction, and these conditions are well-established to have underlying inflammation that directly triggers these symptoms. However, it remains unclear as to how such diverse stimuli individually generate a common inflammatory process. Jürg Tschopp provided substantial insight into this conundrum when, working with extracts from THP-1 cells, he reported the existence of the inflammasome. He described it as a structure that senses multiple diverse signals from intracellular/extracellular sources and pathogens and triggers inflammation by the maturation and release of the pro-inflammatory cytokines interleukin-1β and interleukin-18. Recently, many of these sensors were found in the bladder and the nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3, has been shown to be a central mediator of inflammation in several urological diseases. In this review, we introduce the nucleotide-binding domain, leucine-rich-containing family, pyrin domaincontaining-3 inflammasome, highlight its emerging role in several common urologic conditions, and speculate on the potential involvement of other inflammasomes in bladder pathology. PMID:29593464

The comparison of pathology in ferrets infected by H9N2 avian influenza viruses with different genomic features.

PubMed

Gao, Rongbao; Bai, Tian; Li, Xiaodan; Xiong, Ying; Huang, Yiwei; Pan, Ming; Zhang, Ye; Bo, Hong; Zou, Shumei; Shu, Yuelong

2016-01-15

H9N2 avian influenza virus circulates widely in poultry and has been responsible for sporadic human infections in several regions. Few studies have been conducted on the pathogenicity of H9N2 AIV isolates that have different genomic features. We compared the pathology induced by a novel reassortant H9N2 virus and two currently circulating H9N2 viruses that have different genomic features in ferrets. The results showed that the three viruses can induce infections with various amounts of viral shedding in ferrets. The novel H9N2 induced respiratory infection, but no pathological lesions were observed in lung tissues. The other two viruses induced mild to intermediate pathological lesions in lung tissues, although the clinical signs presented mildly in ferrets. The pathological lesions presented a diversity consistent with viral replication in ferrets. Copyright © 2015 Elsevier Inc. All rights reserved.

Helicobacter pylori-induced gastric pathology: insights from in vivo and ex vivo models

PubMed Central

Williams, Jonathan M.

2017-01-01

ABSTRACT Gastric colonization with Helicobacter pylori induces diverse human pathological conditions, including superficial gastritis, peptic ulcer disease, mucosa-associated lymphoid tissue (MALT) lymphoma, and gastric adenocarcinoma and its precursors. The treatment of these conditions often relies on the eradication of H. pylori, an intervention that is increasingly difficult to achieve and that does not prevent disease progression in some contexts. There is, therefore, a pressing need to develop new experimental models of H. pylori-associated gastric pathology to support novel drug development in this field. Here, we review the current status of in vivo and ex vivo models of gastric H. pylori colonization, and of Helicobacter-induced gastric pathology, focusing on models of gastric pathology induced by H. pylori, Helicobacter felis and Helicobacter suis in rodents and large animals. We also discuss the more recent development of gastric organoid cultures from murine and human gastric tissue, as well as from human pluripotent stem cells, and the outcomes of H. pylori infection in these systems. PMID:28151409

Plant diversity predicts beta but not alpha diversity of soil microbes across grasslands worldwide

USGS Publications Warehouse

Prober, Suzanne M.; Leff, Jonathan W.; Bates, Scott T.; Borer, Elizabeth T.; Firn, Jennifer; Harpole, W. Stanley; Lind, Eric M.; Seabloom, Eric W.; Adler, Peter B.; Bakker, Jonathan D.; Cleland, Elsa E.; DeCrappeo, Nicole; DeLorenze, Elizabeth; Hagenah, Nicole; Hautier, Yann; Hofmockel, Kirsten S.; Kirkman, Kevin P.; Knops, Johannes M. H.; La Pierre, Kimberly J.; MacDougall, Andrew S.; McCulley, Rebecca L.; Mitchell, Charles E.; Risch, Anita C.; Schuetz, Martin; Stevens, Carly J.; Williams, Ryan J.; Fierer, Noah

2015-01-01

Aboveground–belowground interactions exert critical controls on the composition and function of terrestrial ecosystems, yet the fundamental relationships between plant diversity and soil microbial diversity remain elusive. Theory predicts predominantly positive associations but tests within single sites have shown variable relationships, and associations between plant and microbial diversity across broad spatial scales remain largely unexplored. We compared the diversity of plant, bacterial, archaeal and fungal communities in one hundred and forty-five 1 m2 plots across 25 temperate grassland sites from four continents. Across sites, the plant alpha diversity patterns were poorly related to those observed for any soil microbial group. However, plant beta diversity (compositional dissimilarity between sites) was significantly correlated with the beta diversity of bacterial and fungal communities, even after controlling for environmental factors. Thus, across a global range of temperate grasslands, plant diversity can predict patterns in the composition of soil microbial communities, but not patterns in alpha diversity.

10-Minute Delayed Recall from the Modified Mini-Mental State Test Predicts Alzheimer’s Disease Pathology

PubMed Central

Lyness, Scott A.; Lee, Ae Young; Zarow, Chris; Teng, Evelyn L.; Chui, Helena C.

2014-01-01

We compared the sensitivity and specificity of two delayed recall scores from the Modified Mini-Mental State (3MS) test with consensus clinical diagnosis to differentiate cognitive impairment due to Alzheimer’s disease (AD) versus non-AD pathologies. At a memory disorders clinic, 117 cognitively impaired patients were administered a baseline 3MS test and received a contemporaneous consensus clinical diagnosis. Their brains were examined after death about 5 years later. Using logistic regression with forward selection to predict pathologically defined AD versus non-AD, 10-min delayed recall entered first (p = 0.001), followed by clinical diagnosis (p = 0.02); 1-min delayed recall did not enter. 10-min delayed recall scores ≤4 (score range = 0–9) were 87% sensitive and 47% specific in predicting AD pathology; consensus clinical diagnosis was 82% sensitive and 45% specific. For the 57 patients whose initial Mini-Mental State Examination scores were ≥19 (the median), 3MS 10-min delayed recall scores ≤4 showed some loss of sensitivity (80%) but a substantial gain in specificity (77%). In conclusion, 10-min delayed recall score on the brief 3MS test distinguished between AD versus non-AD pathology about 5 years before death at least as well as consensus clinical diagnosis that requires much more comprehensive information and complex deliberation. PMID:24240637

10-minute delayed recall from the modified mini-mental state test predicts Alzheimer's disease pathology.

PubMed

Lyness, Scott A; Lee, Ae Young; Zarow, Chris; Teng, Evelyn L; Chui, Helena C

2014-01-01

We compared the sensitivity and specificity of two delayed recall scores from the Modified Mini-Mental State (3MS) test with consensus clinical diagnosis to differentiate cognitive impairment due to Alzheimer's disease (AD) versus non-AD pathologies. At a memory disorders clinic, 117 cognitively impaired patients were administered a baseline 3MS test and received a contemporaneous consensus clinical diagnosis. Their brains were examined after death about 5 years later. Using logistic regression with forward selection to predict pathologically defined AD versus non-AD, 10-min delayed recall entered first (p = 0.001), followed by clinical diagnosis (p = 0.02); 1-min delayed recall did not enter. 10-min delayed recall scores ≤4 (score range = 0-9) were 87% sensitive and 47% specific in predicting AD pathology; consensus clinical diagnosis was 82% sensitive and 45% specific. For the 57 patients whose initial Mini-Mental State Examination scores were ≥19 (the median), 3MS 10-min delayed recall scores ≤4 showed some loss of sensitivity (80%) but a substantial gain in specificity (77%). In conclusion, 10-min delayed recall score on the brief 3MS test distinguished between AD versus non-AD pathology about 5 years before death at least as well as consensus clinical diagnosis that requires much more comprehensive information and complex deliberation.

Measurement of serum CA-125 concentrations does not improve the value of Chlamydia trachomatis antibody in predicting tubal pathology at laparoscopy.

PubMed

Ng, E H; Tang, O S; Ho, P C

2001-04-01

Chlamydia antibody testing (CAT) has been used to predict tubal pathology associated with Chlamydia infection, the leading cause of pelvic inflammatory disease (PID). Tubal pathology not related to C. trachomatis is unlikely to be identified by CAT alone. A correlation between serum CA-125 concentrations and the severity of adnexal inflammation during acute PID was demonstrated. The objectives of this study were to determine the prevalence of C. trachomatis infection in an Asian infertile population and to assess the role of a combination of serum CA-125 and CAT in the prediction of tubal pathology as shown by laparoscopy. A total of 110 consecutive women attending an infertility clinic for work-up were recruited. Blood was taken for CAT and CA-125 on the day of hospital admission and an endocervical swab was taken for culture of C. trachomatis prior to laparoscopy. Two (1.8%) women had C. trachomatis found in the endocervix and 28 (25.5%) women had CAT of > or = 1:32. Serum CA-125 concentrations were > 35 IU/ml in 11 (10%) women. The discriminative capacity of CAT in the diagnosis of tubal pathology including both proximal and distal obstruction was not improved by measuring serum CA-125, regardless of the threshold values of serum CA-125 concentration.

Energy gradients and the geographic distribution of local ant diversity.

PubMed

Kaspari, Michael; Ward, Philip S; Yuan, May

2004-08-01

Geographical diversity gradients, even among local communities, can ultimately arise from geographical differences in speciation and extinction rates. We evaluated three models--energy-speciation, energy-abundance, and area--that predict how geographic trends in net diversification rates generate trends in diversity. We sampled 96 litter ant communities from four provinces: Australia, Madagascar, North America, and South America. The energy-speciation hypothesis best predicted ant species richness by accurately predicting the slope of the temperature diversity curve, and accounting for most of the variation in diversity. The communities showed a strong latitudinal gradient in species richness as well as inter-province differences in diversity. The former vanished in the temperature-diversity residuals, suggesting that the latitudinal gradient arises primarily from higher diversification rates in the tropics. However, inter-province differences in diversity persisted in those residuals--South American communities remained more diverse than those in North America and Australia even after the effects of temperature were removed.

Development of a new outcome prediction model for Chinese patients with penile squamous cell carcinoma based on preoperative serum C-reactive protein, body mass index, and standard pathological risk factors: the TNCB score group system.

PubMed

Li, Zai-Shang; Chen, Peng; Yao, Kai; Wang, Bin; Li, Jing; Mi, Qi-Wu; Chen, Xiao-Feng; Zhao, Qi; Li, Yong-Hong; Chen, Jie-Ping; Deng, Chuang-Zhong; Ye, Yun-Lin; Zhong, Ming-Zhu; Liu, Zhuo-Wei; Qin, Zi-Ke; Lin, Xiang-Tian; Liang, Wei-Cong; Han, Hui; Zhou, Fang-Jian

2016-04-12

To determine the predictive value and feasibility of the new outcome prediction model for Chinese patients with penile squamous cell carcinoma. The 3-year disease-specific survival (DSS) survival (DSS) was 92.3% in patients with < 8.70 mg/L CRP and 54.9% in those with elevated CRP (P < 0.001). The 3-year DSS was 86.5% in patients with a BMI < 22.6 Kg/m2 and 69.9% in those with a higher BMI (P = 0.025). In a multivariate analysis, pathological T stage (P < 0.001), pathological N stage (P = 0.002), BMI (P = 0.002), and CRP (P = 0.004) were independent predictors of DSS. A new scoring model was developed, consisting of BMI, CRP, and tumor T and N classification. In our study, we found that the addition of the above-mentioned parameters significantly increased the predictive accuracy of the system of the American Joint Committee on Cancer (AJCC) anatomic stage group. The accuracy of the new prediction category was verified. A total of 172 Chinese patients with penile squamous cell cancer were analyzed retrospectively between November 2005 and November 2014. Statistical data analysis was conducted using the nonparametric method. Survival analysis was performed with the log-rank test and the Cox proportional hazard model. Based on regression estimates of significant parameters in multivariate analysis, a new BMI-, CRP- and pathologic factors-based scoring model was developed to predict disease--specific outcomes. The predictive accuracy of the model was evaluated using the internal and external validation. The present study demonstrated that the TNCB score group system maybe a precise and easy to use tool for predicting outcomes in Chinese penile squamous cell carcinoma patients.

Reinforcer Pathology: The Behavioral Economics of Abuse Liability Testing.

PubMed

Bickel, W K; Snider, S E; Quisenberry, A J; Stein, J S

2017-02-01

Understanding the abuse liability of novel drugs is critical to understanding the risk these new compounds pose to society. Behavioral economics, the integration of psychology and economics, can be used to predict abuse liability of novel substances. Here, we describe the behavioral economic concept of reinforcer pathology and how it may predict the use of novel drugs in existing drug-users and initiation of use in the drug-naive. © 2016 American Society for Clinical Pharmacology and Therapeutics.

Improving the prediction of pathologic outcomes in patients undergoing radical prostatectomy: the value of prostate cancer antigen 3 (PCA3), prostate health index (phi) and sarcosine.

PubMed

Ferro, Matteo; Lucarelli, Giuseppe; Bruzzese, Dario; Perdonà, Sisto; Mazzarella, Claudia; Perruolo, Giuseppe; Marino, Ada; Cosimato, Vincenzo; Giorgio, Emilia; Tagliamonte, Virginia; Bottero, Danilo; De Cobelli, Ottavio; Terracciano, Daniela

2015-02-01

Several efforts have been made to find biomarkers that could help clinicians to preoperatively determine prostate cancer (PCa) pathological characteristics and choose the best therapeutic approach, avoiding over-treatment. On this effort, prostate cancer antigen 3 (PCA3), prostate health index (phi) and sarcosine have been presented as promising tools. We evaluated the ability of these biomarkers to predict the pathologic PCa characteristics within a prospectively collected contemporary cohort of patients who underwent radical prostatectomy (RP) for clinically localized PCa at a single high-volume Institution. The prognostic performance of PCA3, phi and sarcosine were evaluated in 78 patients undergoing RP for biopsy-proven PCa. Receiver operating characteristic (ROC) curve analyses tested the accuracy (area under the curve (AUC)) in predicting PCa pathological characteristics. Decision curve analyses (DCA) were used to assess the clinical benefit of the three biomarkers. We found that PCA3, phi and sarcosine levels were significantly higher in patients with tumor volume (TV)≥0.5 ml, pathologic Gleason sum (GS)≥7 and pT3 disease (all p-values≤0.01). ROC curve analysis showed that phi is an accurate predictor of high-stage (AUC 0.85 [0.77-0.93]), high-grade (AUC 0.83 [0.73-0.93]) and high-volume disease (AUC 0.94 [0.88-0.99]). Sarcosine showed a comparable AUC (0.85 [0.76-0.94]) only for T3 stage prediction, whereas PCA3 score showed lower AUCs, ranging from 0.74 (for GS) to 0.86 (for TV). PCA3, phi and sarcosine are predictors of PCa characteristics at final pathology. Successful clinical translation of these findings would reduce the frequency of surveillance biopsies and may enhance acceptance of active surveillance (AS). Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Development and validation of a preoperative prediction model for colorectal cancer T-staging based on MDCT images and clinical information.

PubMed

Sa, Sha; Li, Jing; Li, Xiaodong; Li, Yongrui; Liu, Xiaoming; Wang, Defeng; Zhang, Huimao; Fu, Yu

2017-08-15

This study aimed to establish and evaluate the efficacy of a prediction model for colorectal cancer T-staging. T-staging was positively correlated with the level of carcinoembryonic antigen (CEA), expression of carbohydrate antigen 19-9 (CA19-9), wall deformity, blurred outer edges, fat infiltration, infiltration into the surrounding tissue, tumor size and wall thickness. Age, location, enhancement rate and enhancement homogeneity were negatively correlated with T-staging. The predictive results of the model were consistent with the pathological gold standard, and the kappa value was 0.805. The total accuracy of staging improved from 51.04% to 86.98% with the proposed model. The clinical, imaging and pathological data of 611 patients with colorectal cancer (419 patients in the training group and 192 patients in the validation group) were collected. A spearman correlation analysis was used to validate the relationship among these factors and pathological T-staging. A prediction model was trained with the random forest algorithm. T staging of the patients in the validation group was predicted by both prediction model and traditional method. The consistency, accuracy, sensitivity, specificity and area under the curve (AUC) were used to compare the efficacy of the two methods. The newly established comprehensive model can improve the predictive efficiency of preoperative colorectal cancer T-staging.

Development of Raman spectral markers to assess metastatic bone in breast cancer

PubMed Central

Ding, Hao; Nyman, Jeffry S.; Sterling, Julie A.; Perrien, Daniel S.; Mahadevan-Jansen, Anita; Bi, Xiaohong

2014-01-01

Abstract. Bone is the most common site for breast cancer metastases. One of the major complications of bone metastasis is pathological bone fracture caused by chronic bone loss and degeneration. Current guidelines for the prediction of pathological fracture mainly rely on radiographs or computed tomography, which are limited in their ability to predict fracture risk. The present study explored the feasibility of using Raman spectroscopy to estimate pathological fracture risk by characterizing the alterations in the compositional properties of metastatic bones. Tibiae with evident bone destruction were investigated using Raman spectroscopy. The carbonation level calculated by the ratio of carbonate/phosphate ν1 significantly increased in the tumor-bearing bone at all the sampling regions at the proximal metaphysis and diaphysis, while tumor-induced elevation in mineralization and crystallinity was more pronounced in the metaphysis. Furthermore, the increased carbonation level is positively correlated to bone lesion size, indicating that this parameter could serve as a unique spectral marker for tumor progression and bone loss. With the promising advances in the development of spatially offset Raman spectroscopy for deep tissue measurement, this spectral marker can potentially be used for future noninvasive evaluation of metastatic bone and prediction of pathological fracture risk. PMID:24933683

Development of Raman spectral markers to assess metastatic bone in breast cancer

NASA Astrophysics Data System (ADS)

Ding, Hao; Nyman, Jeffry S.; Sterling, Julie A.; Perrien, Daniel S.; Mahadevan-Jansen, Anita; Bi, Xiaohong

2014-11-01

Bone is the most common site for breast cancer metastases. One of the major complications of bone metastasis is pathological bone fracture caused by chronic bone loss and degeneration. Current guidelines for the prediction of pathological fracture mainly rely on radiographs or computed tomography, which are limited in their ability to predict fracture risk. The present study explored the feasibility of using Raman spectroscopy to estimate pathological fracture risk by characterizing the alterations in the compositional properties of metastatic bones. Tibiae with evident bone destruction were investigated using Raman spectroscopy. The carbonation level calculated by the ratio of carbonate/phosphate ν1 significantly increased in the tumor-bearing bone at all the sampling regions at the proximal metaphysis and diaphysis, while tumor-induced elevation in mineralization and crystallinity was more pronounced in the metaphysis. Furthermore, the increased carbonation level is positively correlated to bone lesion size, indicating that this parameter could serve as a unique spectral marker for tumor progression and bone loss. With the promising advances in the development of spatially offset Raman spectroscopy for deep tissue measurement, this spectral marker can potentially be used for future noninvasive evaluation of metastatic bone and prediction of pathological fracture risk.

Advances in the Biology and Chemistry of Sialic Acids

PubMed Central

Chen, Xi; Varki, Ajit

2010-01-01

Sialic acids are a subset of nonulosonic acids, which are nine-carbon alpha-keto aldonic acids. Natural existing sialic acid-containing structures are presented in different sialic acid forms, various sialyl linkages, and on diverse underlying glycans. They play important roles in biological, pathological, and immunological processes. Sialobiology has been a challenging and yet attractive research area. Recent advances in chemical and chemoenzymatic synthesis as well as large-scale E. coli cell-based production have provided a large library of sialoside standards and derivatives in amounts sufficient for structure-activity relationship studies. Sialoglycan microarrays provide an efficient platform for quick identification of preferred ligands for sialic acid-binding proteins. Future research on sialic acid will continue to be at the interface of chemistry and biology. Research efforts will not only lead to a better understanding of the biological and pathological importance of sialic acids and their diversity, but could also lead to the development of therapeutics. PMID:20020717

Laboratory Information Systems in Molecular Diagnostics: Why Molecular Diagnostics Data are Different.

PubMed

Lee, Roy E; Henricks, Walter H; Sirintrapun, Sahussapont J

2016-03-01

Molecular diagnostic testing presents new challenges to information management that are yet to be sufficiently addressed by currently available information systems for the molecular laboratory. These challenges relate to unique aspects of molecular genetic testing: molecular test ordering, informed consent issues, diverse specimen types that encompass the full breadth of specimens handled by traditional anatomic and clinical pathology information systems, data structures and data elements specific to molecular testing, varied testing workflows and protocols, diverse instrument outputs, unique needs and requirements of molecular test reporting, and nuances related to the dissemination of molecular pathology test reports. By satisfactorily addressing these needs in molecular test data management, a laboratory information system designed for the unique needs of molecular diagnostics presents a compelling reason to migrate away from the current paper and spreadsheet information management that many molecular laboratories currently use. This paper reviews the issues and challenges of information management in the molecular diagnostics laboratory.

The α‐synuclein gene in multiple system atrophy

PubMed Central

Ozawa, T; Healy, D G; Abou‐Sleiman, P M; Ahmadi, K R; Quinn, N; Lees, A J; Shaw, K; Wullner, U; Berciano, J; Moller, J C; Kamm, C; Burk, K; Josephs, K A; Barone, P; Tolosa, E; Goldstein, D B; Wenning, G; Geser, F; Holton, J L; Gasser, T; Revesz, T; Wood, N W

2006-01-01

Background The formation of α‐synuclein aggregates may be a critical event in the pathogenesis of multiple system atrophy (MSA). However, the role of this gene in the aetiology of MSA is unknown and untested. Method The linkage disequilibrium (LD) structure of the α‐synuclein gene was established and LD patterns were used to identify a set of tagging single nucleotide polymorphisms (SNPs) that represent 95% of the haplotype diversity across the entire gene. The effect of polymorphisms on the pathological expression of MSA in pathologically confirmed cases was also evaluated. Results and conclusion In 253 Gilman probable or definite MSA patients, 457 possible, probable, and definite MSA cases and 1472 controls, a frequency difference for the individual tagging SNPs or tag‐defined haplotypes was not detected. No effect was observed of polymorphisms on the pathological expression of MSA in pathologically confirmed cases. PMID:16543523

Magnetic resonance imaging-detected tumor response for locally advanced rectal cancer predicts survival outcomes: MERCURY experience.

PubMed

Patel, Uday B; Taylor, Fiona; Blomqvist, Lennart; George, Christopher; Evans, Hywel; Tekkis, Paris; Quirke, Philip; Sebag-Montefiore, David; Moran, Brendan; Heald, Richard; Guthrie, Ashley; Bees, Nicola; Swift, Ian; Pennert, Kjell; Brown, Gina

2011-10-01

To assess magnetic resonance imaging (MRI) and pathologic staging after neoadjuvant therapy for rectal cancer in a prospectively enrolled, multicenter study. In a prospective cohort study, 111 patients who had rectal cancer treated by neoadjuvant therapy were assessed for response by MRI and pathology staging by T, N and circumferential resection margin (CRM) status. Tumor regression grade (TRG) was also assessed by MRI. Overall survival (OS) was estimated by using the Kaplan-Meier product-limit method, and Cox proportional hazards models were used to determine associations between staging of good and poor responders on MRI or pathology and survival outcomes after controlling for patient characteristics. On multivariate analysis, the MRI-assessed TRG (mrTRG) hazard ratios (HRs) were independently significant for survival (HR, 4.40; 95% CI, 1.65 to 11.7) and disease-free survival (DFS; HR, 3.28; 95% CI, 1.22 to 8.80). Five-year survival for poor mrTRG was 27% versus 72% (P = .001), and DFS for poor mrTRG was 31% versus 64% (P = .007). Preoperative MRI-predicted CRM independently predicted local recurrence (LR; HR, 4.25; 95% CI, 1.45 to 12.51). Five-year survival for poor post-treatment pathologic T stage (ypT) was 39% versus 76% (P = .001); DFS for the same was 38% versus 84% (P = .001); and LR for the same was 27% versus 6% (P = .018). The 5-year survival for involved pCRM was 30% versus 59% (P = .001); DFS, 28 versus 62% (P = .02); and LR, 56% versus 10% (P = .001). Pathology node status did not predict outcomes. MRI assessment of TRG and CRM are imaging markers that predict survival outcomes for good and poor responders and provide an opportunity for the multidisciplinary team to offer additional treatment options before planning definitive surgery. Postoperative histopathology assessment of ypT and CRM but not post-treatment N status were important postsurgical predictors of outcome.

Feature selection for examining behavior by pathology laboratories.

PubMed

Hawkins, S; Williams, G; Baxter, R

2001-08-01

Australia has a universal health insurance scheme called Medicare, which is managed by Australia's Health Insurance Commission. Medicare payments for pathology services generate voluminous transaction data on patients, doctors and pathology laboratories. The Health Insurance Commission (HIC) currently uses predictive models to monitor compliance with regulatory requirements. The HIC commissioned a project to investigate the generation of new features from the data. Feature generation has not appeared as an important step in the knowledge discovery in databases (KDD) literature. New interesting features for use in predictive modeling are generated. These features were summarized, visualized and used as inputs for clustering and outlier detection methods. Data organization and data transformation methods are described for the efficient access and manipulation of these new features.

The relation between pathological worrying and fatigue in a working population.

PubMed

Andrea, H; Beurskens, A J H M; Kant, Ij; Davey, G C L; Field, A P; van Schayck, C P

2004-10-01

This study aimed to explore cross-sectional and longitudinal associations between pathological worry and fatigue in a working population. In employees with very low or very high fatigue levels, psychometrics of the Penn State Worry Questionnaire (PSWQ; measuring pathological worry) and the Checklist Individual Strength (CIS; measuring fatigue) were examined and their cross-sectional and longitudinal associations were explored. Pathological worry and fatigue can be measured as different constructs. However, pathological worry and fatigue were also associated on a cross-sectional level. Pathological worry predicted fatigue level 10 months later, but this association disappeared after adjustment for the cross-sectional association between pathological worry and fatigue. Although they can be measured as different constructs, pathological worry and fatigue seem to be associated. When studying longitudinal relations between pathological worry and fatigue, their cross-sectional association should be taken into account. Pathological worry might not be a risk factor for fatigue per se, but might act more like a mediating factor.

Predictive factors for intrauterine growth restriction.

PubMed

Albu, A R; Anca, A F; Horhoianu, V V; Horhoianu, I A

2014-06-15

Reduced fetal growth is seen in about 10% of the pregnancies but only a minority has a pathological background and is known as intrauterine growth restriction or fetal growth restriction (IUGR / FGR). Increased fetal and neonatal mortality and morbidity as well as adult pathologic conditions are often associated to IUGR. Risk factors for IUGR are easy to assess but have poor predictive value. For the diagnostic purpose, biochemical serum markers, ultrasound and Doppler study of uterine and spiral arteries, placental volume and vascularization, first trimester growth pattern are object of assessment today. Modern evaluations propose combined algorithms using these strategies, all with the goal of a better prediction of risk pregnancies.

NMR-based Metabolomics Applications in Biological and Environmental Science

EPA Science Inventory

As a complimentary tool to other omics platforms, metabolomics is increasingly being used bybiologists to study the dynamic response of biological systems (cells, tissues, or wholeorganisms) under diverse physiological or pathological conditions. Metabolomics deals with the quali...

Polysaccharide Nanosystems for Future Progress in Cardiovascular Pathologies

PubMed Central

Silva, Amanda Karine Andriola; Letourneur, Didier; Chauvierre, Cédric

2014-01-01

Natural polysaccharides have received a lot of attention in the biomedical field. Indeed, sources of polysaccharides, extracted or produced from plants, bacteria, fungi or algae, are diverse and renewable. Moreover, recent progresses in polysaccharide chemistry and nanotechnologies allow elaborating new dedicated nanosystems. Polysaccharide-based nanosystems may be designed for interacting in several biological processes. In particular, the atherothrombotic pathology is highly concerned by polysaccharide-mediated recognition. Atherothrombotic diseases, regardless of the anatomical localization, remain the main causes of morbidity and mortality in the industrialized world. This review intends to provide an overview on polysaccharide-based nanosystems as drug delivery systems and targeted contrast agents for molecular imaging with an emphasis on the treatment and imaging of cardiovascular pathologies. PMID:24723980

[The autoimmune rheumatic disease and laryngeal pathology].

PubMed

Osipenko, E V; Kotel'nikova, N M

Vocal disorders make up one of the autoimmune pathological conditions characterized by multiple organ system dysfunction. Laryngeal pathology in this condition has an autoimmune nature; it is highly diverse and poorly explored. The objective of the present work based on the analysis of the relevant literature publications was to study clinical manifestations of the autoimmune rheumatic disease affecting the larynx. 'Bamboo nodes' on the vocal folds is a rare manifestation of laryngeal autoimmune diseases. We found out references to 49 cases of this condition in the available literature. All the patients were women presenting with autoimmune diseases. The present review highlights the problems pertaining to etiology of 'bamboo nodes' on the vocal folds and the method for the treatment of this condition.

Progress and Potential

PubMed Central

Haspel, Richard L.; Olsen, Randall J.; Berry, Anna; Hill, Charles E.; Pfeifer, John D.; Schrijver, Iris; Kaul, Karen L.

2014-01-01

Context Genomic medicine is revolutionizing patient care. Physicians in areas as diverse as oncology, obstetrics, and infectious disease have begun using next-generation sequencing assays as standard diagnostic tools. Objective To review the role of pathologists in genomic testing as well as current educational programs and future training needs in genomic pathology. Data Sources Published literature as well as personal experience based on committee membership and genomic pathology curricular design. Conclusion Pathologists, as the directors of the clinical laboratories, must be prepared to integrate genomic testing into their practice. The pathology community has made significant progress in genomics-related education. A continued coordinated and proactive effort will ensure a future vital role for pathologists in the evolving health care system and also the best possible patient care. PMID:24678680

Neo-epitope Peptides as Biomarkers of Disease Progression for Muscular Dystrophies and Other Myopathies

PubMed Central

Arvanitidis, A.; Henriksen, K.; Karsdal, M.A.; Nedergaard, A.

2016-01-01

For several decades, serological biomarkers of neuromuscular diseases as dystrophies, myopathies and myositis have been limited to routine clinical biochemistry panels. Gauging the pathological progression is a prerequisite for proper treatment and therefore identifying accessible, easy to monitor biomarkers that can predict the disease progression would be an important advancement. Most muscle diseases involve accelerated muscle fiber degradation, inflammation, fatty tissue substitution and/or fibrosis. All these pathological traits have been shown to give rise to serological peptide biomarkers in other tissues, underlining the potential application of existing biomarkers of such traits in muscle disorders. A significant quantity of tissue is involved in these pathological mechanisms alongside with qualitative changes in protein turnover in myofibrillar, extra-cellular matrix and immunological cell protein fractions accompanied by alterations in body fluids. We propose that protein and peptides can leak out of the afflicted muscles and can be of use in diagnosis, prediction of pathology trajectory and treatment efficacy. Proteolytic cleavage systems are especially modulated during a range of muscle pathologies, thereby giving rise to peptides that are differentially released during disease manifestation. Therefore, we believe that pathology-specific post-translational modifications like cleavages can give rise to neoepitope peptides that may represent a promising class of peptides for discovery of biomarkers pertaining to neuromuscular diseases. PMID:27854226

Attention problems and pathological gaming: resolving the 'chicken and egg' in a prospective analysis.

PubMed

Ferguson, Christopher J; Ceranoglu, T Atilla

2014-03-01

Pathological gaming (PG) behaviors are behaviors which interfere with other life responsibilities. Continued debate exists regarding whether symptoms of PG behaviors are a unique phenomenon or arise from other mental health problems, including attention problems. Development of attention problems and occurrence of pathological gaming in 144 adolescents were followed during a 1-year prospective analysis. Teens and their parents reported on pathological gaming behaviors, attention problems, and current grade point average, as well as several social variables. Results were analyzed using regression and path analysis. Attention problems tended to precede pathological gaming behaviors, but the inverse was not true. Attention problems but not pathological gaming predicted lower GPA 1 year later. Current results suggest that pathological gaming arises from attention problems, but not the inverse. These results suggest that pathological gaming behaviors are symptomatic of underlying attention related mental health issues, rather than a unique phenomenon.

Evidence for label-retaining tumour-initiating cells in human glioblastoma

PubMed Central

Deleyrolle, Loic P.; Harding, Angus; Cato, Kathleen; Siebzehnrubl, Florian A.; Rahman, Maryam; Azari, Hassan; Olson, Sarah; Gabrielli, Brian; Osborne, Geoffrey; Vescovi, Angelo

2011-01-01

Individual tumour cells display diverse functional behaviours in terms of proliferation rate, cell–cell interactions, metastatic potential and sensitivity to therapy. Moreover, sequencing studies have demonstrated surprising levels of genetic diversity between individual patient tumours of the same type. Tumour heterogeneity presents a significant therapeutic challenge as diverse cell types within a tumour can respond differently to therapies, and inter-patient heterogeneity may prevent the development of general treatments for cancer. One strategy that may help overcome tumour heterogeneity is the identification of tumour sub-populations that drive specific disease pathologies for the development of therapies targeting these clinically relevant sub-populations. Here, we have identified a dye-retaining brain tumour population that displays all the hallmarks of a tumour-initiating sub-population. Using a limiting dilution transplantation assay in immunocompromised mice, label-retaining brain tumour cells display elevated tumour-initiation properties relative to the bulk population. Importantly, tumours generated from these label-retaining cells exhibit all the pathological features of the primary disease. Together, these findings confirm dye-retaining brain tumour cells exhibit tumour-initiation ability and are therefore viable targets for the development of therapeutics targeting this sub-population. PMID:21515906

Erythrocyte plasma membrane-bound ERK1/2 activation promotes ICAM-4-mediated sickle red cell adhesion to endothelium.

PubMed

Zennadi, Rahima; Whalen, Erin J; Soderblom, Erik J; Alexander, Susan C; Thompson, J Will; Dubois, Laura G; Moseley, M Arthur; Telen, Marilyn J

2012-02-02

The core pathology of sickle cell disease (SCD) starts with the erythrocyte (RBC). Aberration in MAPK/ERK1/2 signaling, which can regulate cell adhesion, occurs in diverse pathologies. Because RBCs contain abundant ERK1/2, we predicted that ERK1/2 is functional in sickle (SS) RBCs and promotes adherence, a hallmark of SCD. ERK1/2 remained active in SS but not normal RBCs. β(2)-adrenergic receptor stimulation by epinephrine can enhance ERK1/2 activity only in SS RBCs via PKA- and tyrosine kinase p72(syk)-dependent pathways. ERK signaling is implicated in RBC ICAM-4 phosphorylation, promoting SS RBC adhesion to the endothelium. SS RBC adhesion and phosphorylation of both ERK and ICAM-4 all decreased with continued cell exposure to epinephrine, implying that activation of ICAM-4-mediated SS RBC adhesion is temporally associated with ERK1/2 activation. Furthermore, recombinant ERK2 phosphorylated α- and β-adducins and dematin at the ERK consensus motif. Cytoskeletal protein 4.1 also showed dynamic phosphorylation but not at the ERK consensus motif. These results demonstrate that ERK activation induces phosphorylation of cytoskeletal proteins and the adhesion molecule ICAM-4, promoting SS RBC adhesion to the endothelium. Thus, blocking RBC ERK1/2 activation, such as that promoted by catecholamine stress hormones, could ameliorate SCD pathophysiology.

[Immediate prediction of recovery, based on emotional impact of vertigo].

PubMed

Dal-Lago, Andrés H; Ceballos-Lizarraga, Ricardo; Carmona, Sergio

2014-01-01

This work presents deeper studies of comorbidity between anxiety and vestibular pathology. The aim of this work was to comprehend the reasons why patients do not feel «fully recovered» even though the treating professionals discharge them. We studied the features of personality that can favour the continuity of the condition. The questionnaire for measuring the emotional impact of vertigo makes it possible to determine if the patient has a psychological style with a tendency to develop pathological anxiety levels. Anxiety is a subjective characteristic determinant in difficulties with medical treatment. The questionnaire was applied to 198 patients in Argentina and Mexico in parallel. Each pathology was treated by standard medical procedures. The study focused on determining the correlation between «feeling fully recovered or not at the end of treatment» and the questionnaire scores obtained before the approach. In more than 80% of cases, high scores (>15 points) on the questionnaire were correlated with the difficulty presented by the patients for full recovery from the pathology after medical treatment. The objective assessments (duration and intensity of symptoms, time of onset of the disease, etc.) do not exactly predict possible difficulties during treatment of vertigo. Consequently, we consider the patient's subjective assessment of how the vestibular pathology affects him or her to be determinant. That key information allows us to predict the course of the illness and the probability of a full recovery. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Role of Chemokines and Trafficking of Immune Cells in Parasitic Infections

PubMed Central

McGovern, Kathryn E.; Wilson, Emma H.

2014-01-01

Parasites are diverse eukaryotic pathogens that can have complex life cycles. Their clearance, or control within a mammalian host requires the coordinated effort of the immune system. The cell types recruited to areas of infection can combat the disease, promote parasite replication and survival, or contribute to disease pathology. Location and timing of cell recruitment can be crucial. In this review, we explore the role chemokines play in orchestrating and balancing the immune response to achieve optimal control of parasite replication without promoting pathology. PMID:25383073

Multitrophic functional diversity predicts ecosystem functioning in experimental assemblages of estuarine consumers.

PubMed

Lefcheck, Jonathan S; Duffy, J Emmett

2015-11-01

The use of functional traits to explain how biodiversity affects ecosystem functioning has attracted intense interest, yet few studies have a priori altered functional diversity, especially in multitrophic communities. Here, we manipulated multivariate functional diversity of estuarine grazers and predators within multiple levels of species richness to test how species richness and functional diversity predicted ecosystem functioning in a multitrophic food web. Community functional diversity was a better predictor than species richness for the majority of ecosystem properties, based on generalized linear mixed-effects models. Combining inferences from eight traits into a single multivariate index increased prediction accuracy of these models relative to any individual trait. Structural equation modeling revealed that functional diversity of both grazers and predators was important in driving final biomass within trophic levels, with stronger effects observed for predators. We also show that different species drove different ecosystem responses, with evidence for both sampling effects and complementarity. Our study extends experimental investigations of functional trait diversity to a multilevel food web, and demonstrates that functional diversity can be more accurate and effective than species richness in predicting community biomass in a food web context.

Assessing the interplay of childhood adversities with more recent stressful life events and conditions in predicting panic pathology among adults from the general population.

PubMed

Asselmann, E; Stender, J; Grabe, H J; König, J; Schmidt, C O; Hamm, A O; Pané-Farré, C A

2018-01-01

Although research suggests that (a) childhood adversities and more recent stressful life events/conditions are risk factors for panic pathology and that (b) early life stress increases vulnerability to later psychopathology, it remains unclear whether childhood adversities amplify the association between more recent stressful life events/conditions and panic pathology. Data were derived from a general population sample (Study of Health in Pomerania, SHIP). Lifetime panic pathology was assessed with the Munich Composite International Diagnostic Interview (M-CIDI). Childhood adversities (emotional, physical and sexual abuse; emotional and physical neglect) were assessed with the Childhood Trauma Questionnaire (CTQ). More recent separation/loss events and long-lasting stressful conditions were assessed with the Stralsund Life Event List (SEL). Individuals with lifetime panic pathology (fearful spell, panic attack or panic disorder, N = 286) were compared to controls without any psychopathology (N = 286, matched for sex and age). Conditional logistic regressions revealed that childhood adversities as well as more recent separation/loss events and long-lasting stressful conditions were associated with panic pathology (OR 1.1-2.5). Moreover, more recent separation/loss events - but not long-lasting stressful conditions - interacted statistically with each of the examined childhood adversities except for sexual abuse in predicting panic pathology (OR 1.1-1.3). That is, separation/loss events were associated more strongly with panic pathology among individuals with higher childhood adversities. Data were assessed retrospectively and might be subject to recall biases. Findings suggest that early childhood adversities amplify the risk of developing panic pathology after experiencing separation or loss events. Copyright © 2017. Published by Elsevier B.V.

[Diagnostic accuracy research of needle puncture biopsy during operation for pulmonary single nodules].

PubMed

Chen, Jin-feng; Liu, Yi-nan; Wu, Nan; Feng, Yuan; Wang, Jia; Lü, Chao; Wang, Yu-zhao; Pei, Yu-quan; Yan, Shi; Zheng, Qing-feng; Zhang, Li-jian; Yang, Yue

2012-04-01

To investigate the diagnostic accuracy of needle puncture biopsy and pathological examination of frozen during operation for pulmonary nodules, and whether this diagnostic method can replace tumor resection examination. Totally 50 patients (28 males and 22 females, average age was 59 years) who had the single nodule after imaging examination without any pathological diagnostic from January to October 2010 were selected in this research work. During open operation or video assisted thoracic surgery, needle (14 G model) was used to puncture biopsy for pathological examination of frozen. All the adverse events during puncture biopsy would be recorded. The resection specimens would be accepted paraffin pathological examination. The relationship between puncture frozen pathological and paraffin pathological examination was analyzed. All tumor sizes were ranged from 1.0 cm × 0.6 cm to 5.6 cm × 9.0 cm. The paraffin pathological examination after operation as the golden standard, there were 7 cases of benign tumor and 43 cases of malignant tumor. The diagnostic sensitivity of puncture biopsy was 90.7%, the specificity was 100%, the positive predictive value was 100% and the negative predictive value was 63.6%. There were 11 cases of benign tumor diagnosed by needle puncture biopsy, among which 4 cases were proved as malignant tumor by paraffin pathology, and the false negative rate was 9.3%. The main risk of puncture biopsy was bleeding after puncture immediately, and the rate was 4.0% (2/50). The puncture biopsy during operation had a high specificity for malignant lung tumor, and there was a certain false negative rate for benign tumor. Puncture biopsy and pathological examination of frozen tissue can replace tumor section biopsy in a way.

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.

Improving the pathologic evaluation of lung cancer resection specimens.

PubMed

Osarogiagbon, Raymond U; Hilsenbeck, Holly L; Sales, Elizabeth W; Berry, Allen; Jarrett, Robert W; Giampapa, Christopher S; Finch-Cruz, Clara N; Spencer, David

2015-08-01

Accurate post-operative prognostication and management heavily depend on pathologic nodal stage. Patients with nodal metastasis benefit from post-operative adjuvant chemotherapy, those with mediastinal nodal involvement may also benefit from adjuvant radiation therapy. However, the quality of pathologic nodal staging varies significantly, with major survival implications in large populations of patients. We describe the quality gap in pathologic nodal staging, and provide evidence of its potential reversibility by targeted corrective interventions. One intervention, designed to improve the surgical lymphadenectomy, specimen labeling, and secure transfer between the operating theatre and the pathology laboratory, involves use of pre-labeled specimen collection kits. Another intervention involves application of an improved method of gross dissection of lung resection specimens, to reduce the inadvertent loss of intrapulmonary lymph nodes to histologic examination for metastasis. These corrective interventions are the subject of a regional dissemination and implementation project in diverse healthcare systems in a tri-state region of the United States with some of the highest lung cancer incidence and mortality rates. We discuss the potential of these interventions to significantly improve the accuracy of pathologic nodal staging, risk stratification, and the quality of specimens available for development of stage-independent prognostic markers in lung cancer.

Effectiveness of genomic prediction of maize hybrid performance in different breeding populations and environments.

PubMed

Windhausen, Vanessa S; Atlin, Gary N; Hickey, John M; Crossa, Jose; Jannink, Jean-Luc; Sorrells, Mark E; Raman, Babu; Cairns, Jill E; Tarekegne, Amsal; Semagn, Kassa; Beyene, Yoseph; Grudloyma, Pichet; Technow, Frank; Riedelsheimer, Christian; Melchinger, Albrecht E

2012-11-01

Genomic prediction is expected to considerably increase genetic gains by increasing selection intensity and accelerating the breeding cycle. In this study, marker effects estimated in 255 diverse maize (Zea mays L.) hybrids were used to predict grain yield, anthesis date, and anthesis-silking interval within the diversity panel and testcross progenies of 30 F(2)-derived lines from each of five populations. Although up to 25% of the genetic variance could be explained by cross validation within the diversity panel, the prediction of testcross performance of F(2)-derived lines using marker effects estimated in the diversity panel was on average zero. Hybrids in the diversity panel could be grouped into eight breeding populations differing in mean performance. When performance was predicted separately for each breeding population on the basis of marker effects estimated in the other populations, predictive ability was low (i.e., 0.12 for grain yield). These results suggest that prediction resulted mostly from differences in mean performance of the breeding populations and less from the relationship between the training and validation sets or linkage disequilibrium with causal variants underlying the predicted traits. Potential uses for genomic prediction in maize hybrid breeding are discussed emphasizing the need of (1) a clear definition of the breeding scenario in which genomic prediction should be applied (i.e., prediction among or within populations), (2) a detailed analysis of the population structure before performing cross validation, and (3) larger training sets with strong genetic relationship to the validation set.

CT Accuracy of Extrinsic Tongue Muscle Invasion in Oral Cavity Cancer.

PubMed

Junn, J C; Baugnon, K L; Lacayo, E A; Hudgins, P A; Patel, M R; Magliocca, K R; Corey, A S; El-Deiry, M; Wadsworth, J T; Beitler, J J; Saba, N F; Liu, Y; Aiken, A H

2017-02-01

Extrinsic tongue muscle invasion in oral cavity cancer upstages the primary tumor to a T4a. Despite this American Joint Committee on Cancer staging criterion, no studies have investigated the accuracy or prognostic importance of radiologic extrinsic tongue muscle invasion, the feasibility of standardizing extrinsic tongue muscle invasion reporting, or the degree of agreement across different disciplines: radiology, surgery, and pathology. The purpose of this study was to assess the agreement among radiology, surgery, and pathology for extrinsic tongue muscle invasion and to determine the imaging features most predictive of extrinsic tongue muscle invasion with surgical/pathologic confirmation. Thirty-three patients with untreated primary oral cavity cancer were included. Two head and neck radiologists, 3 otolaryngologists, and 1 pathologist prospectively evaluated extrinsic tongue muscle invasion. Fourteen of 33 patients had radiologic extrinsic tongue muscle invasion; however, only 8 extrinsic tongue muscle invasions were confirmed intraoperatively. Pathologists were unable to determine extrinsic tongue muscle invasion in post-formalin-fixed samples. Radiologic extrinsic tongue muscle invasion had 100% sensitivity, 76% specificity, 57% positive predictive value, and 100% negative predictive value with concurrent surgical-pathologic evaluation of extrinsic tongue muscle invasion as the criterion standard. On further evaluation, the imaging characteristic most consistent with surgical-pathologic evaluation positive for extrinsic tongue muscle invasion was masslike enhancement. Evaluation of extrinsic tongue muscle invasion is a subjective finding for all 3 disciplines. For radiology, masslike enhancement of extrinsic tongue muscle invasion most consistently corresponded to concurrent surgery/pathology evaluation positive for extrinsic tongue muscle invasion. Intraoperative surgical and pathologic evaluation should be encouraged to verify radiologic extrinsic tongue muscle invasion to minimize unnecessary upstaging. Because this process is not routine, imaging can add value by identifying those cases most suspicious for extrinsic tongue muscle invasion, thereby prompting this more detailed evaluation by surgeons and pathologists. © 2017 by American Journal of Neuroradiology.

GLADIATOR: a global approach for elucidating disease modules.

PubMed

Silberberg, Yael; Kupiec, Martin; Sharan, Roded

2017-05-26

Understanding the genetic basis of disease is an important challenge in biology and medicine. The observation that disease-related proteins often interact with one another has motivated numerous network-based approaches for deciphering disease mechanisms. In particular, protein-protein interaction networks were successfully used to illuminate disease modules, i.e., interacting proteins working in concert to drive a disease. The identification of these modules can further our understanding of disease mechanisms. We devised a global method for the prediction of multiple disease modules simultaneously named GLADIATOR (GLobal Approach for DIsease AssociaTed mOdule Reconstruction). GLADIATOR relies on a gold-standard disease phenotypic similarity to obtain a pan-disease view of the underlying modules. To traverse the search space of potential disease modules, we applied a simulated annealing algorithm aimed at maximizing the correlation between module similarity and the gold-standard phenotypic similarity. Importantly, this optimization is employed over hundreds of diseases simultaneously. GLADIATOR's predicted modules highly agree with current knowledge about disease-related proteins. Furthermore, the modules exhibit high coherence with respect to functional annotations and are highly enriched with known curated pathways, outperforming previous methods. Examination of the predicted proteins shared by similar diseases demonstrates the diverse role of these proteins in mediating related processes across similar diseases. Last, we provide a detailed analysis of the suggested molecular mechanism predicted by GLADIATOR for hyperinsulinism, suggesting novel proteins involved in its pathology. GLADIATOR predicts disease modules by integrating knowledge of disease-related proteins and phenotypes across multiple diseases. The predicted modules are functionally coherent and are more in line with current biological knowledge compared to modules obtained using previous disease-centric methods. The source code for GLADIATOR can be downloaded from http://www.cs.tau.ac.il/~roded/GLADIATOR.zip .

Applications of NMR-based metabolomics in biological and environmental research

EPA Science Inventory

As a complimentary tool to other omics platforms, metabolomics is increasingly being used by biologists to study the dynamic response of biological systems (cells, tissues, or whole organisms) under diverse physiological or pathological conditions. Metabolomics deals with the qu...

Multilevel Analysis in Analyzing Speech Data

ERIC Educational Resources Information Center

Guddattu, Vasudeva; Krishna, Y.

2011-01-01

The speech produced by human vocal tract is a complex acoustic signal, with diverse applications in phonetics, speech synthesis, automatic speech recognition, speaker identification, communication aids, speech pathology, speech perception, machine translation, hearing research, rehabilitation and assessment of communication disorders and many…

Pathology smorgasboard: Biocontrol, pathogen movement, and recent fumigation results

USDA-ARS?s Scientific Manuscript database

Research on soilborne pathogens, disease control, and new forest diseases of interest were presented at the Western Forest and Conservation Nursery Association meeting in 2016. Research topics included reduced-rate soil fumigation, Pythium diversity and biocontrol, pathogen movement among nurseries,...

Molecular markers for urothelial bladder cancer prognosis: toward implementation in clinical practice.

PubMed

van Rhijn, Bas W G; Catto, James W; Goebell, Peter J; Knüchel, Ruth; Shariat, Shahrokh F; van der Poel, Henk G; Sanchez-Carbayo, Marta; Thalmann, George N; Schmitz-Dräger, Bernd J; Kiemeney, Lambertus A

2014-10-01

To summarize the current status of clinicopathological and molecular markers for the prediction of recurrence or progression or both in non-muscle-invasive and survival in muscle-invasive urothelial bladder cancer, to address the reproducibility of pathology and molecular markers, and to provide directions toward implementation of molecular markers in future clinical decision making. Immunohistochemistry, gene signatures, and FGFR3-based molecular grading were used as molecular examples focussing on prognostics and issues related to robustness of pathological and molecular assays. The role of molecular markers to predict recurrence is limited, as clinical variables are currently more important. The prediction of progression and survival using molecular markers holds considerable promise. Despite a plethora of prognostic (clinical and molecular) marker studies, reproducibility of pathology and molecular assays has been understudied, and lack of reproducibility is probably the main reason that individual prediction of disease outcome is currently not reliable. Molecular markers are promising to predict progression and survival, but not recurrence. However, none of these are used in the daily clinical routine because of reproducibility issues. Future studies should focus on reproducibility of marker assessment and consistency of study results by incorporating scoring systems to reduce heterogeneity of reporting. This may ultimately lead to incorporation of molecular markers in clinical practice. Copyright © 2014 Elsevier Inc. All rights reserved.

Morphoelastic control of gastro-intestinal organogenesis: Theoretical predictions and numerical insights

NASA Astrophysics Data System (ADS)

Balbi, V.; Kuhl, E.; Ciarletta, P.

2015-05-01

With nine meters in length, the gastrointestinal tract is not only our longest, but also our structurally most diverse organ. During embryonic development, it evolves as a bilayered tube with an inner endodermal lining and an outer mesodermal layer. Its inner surface displays a wide variety of morphological patterns, which are closely correlated to digestive function. However, the evolution of these intestinal patterns remains poorly understood. Here we show that geometric and mechanical factors can explain intestinal pattern formation. Using the nonlinear field theories of mechanics, we model surface morphogenesis as the instability problem of constrained differential growth. To allow for internal and external expansion, we model the gastrointestinal tract with homogeneous Neumann boundary conditions. To establish estimates for the folding pattern at the onset of folding, we perform a linear stability analysis supplemented by the perturbation theory. To predict pattern evolution in the post-buckling regime, we perform a series of nonlinear finite element simulations. Our model explains why longitudinal folds emerge in the esophagus with a thick and stiff outer layer, whereas circumferential folds emerge in the jejunum with a thinner and softer outer layer. In intermediate regions like the feline esophagus, longitudinal and circumferential folds emerge simultaneously. Our model could serve as a valuable tool to explain and predict alterations in esophageal morphology as a result of developmental disorders or certain digestive pathologies including food allergies.

TU-AB-BRA-12: Impact of Image Registration Algorithms On the Prediction of Pathological Response with Radiomic Textures

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

Yip, S; Coroller, T; Niu, N

2015-06-15

Purpose: Tumor regions-of-interest (ROI) can be propagated from the pre-onto the post-treatment PET/CT images using image registration of their CT counterparts, providing an automatic way to compute texture features on longitudinal scans. This exploratory study assessed the impact of image registration algorithms on textures to predict pathological response. Methods: Forty-six esophageal cancer patients (1 tumor/patient) underwent PET/CT scans before and after chemoradiotherapy. Patients were classified into responders and non-responders after the surgery. Physician-defined tumor ROIs on pre-treatment PET were propagated onto the post-treatment PET using rigid and ten deformable registration algorithms. One co-occurrence, two run-length and size zone matrix texturesmore » were computed within all ROIs. The relative difference of each texture at different treatment time-points was used to predict the pathologic responders. Their predictive value was assessed using the area under the receiver-operating-characteristic curve (AUC). Propagated ROIs and texture quantification resulting from different algorithms were compared using overlap volume (OV) and coefficient of variation (CoV), respectively. Results: Tumor volumes were better captured by ROIs propagated by deformable rather than the rigid registration. The OV between rigidly and deformably propagated ROIs were 69%. The deformably propagated ROIs were found to be similar (OV∼80%) except for fast-demons (OV∼60%). Rigidly propagated ROIs with run-length matrix textures failed to significantly differentiate between responders and non-responders (AUC=0.65, p=0.07), while the differentiation was significant with other textures (AUC=0.69–0.72, p<0.03). Among the deformable algorithms, fast-demons was the least predictive (AUC=0.68–0.71, p<0.04). ROIs propagated by all other deformable algorithms with any texture significantly predicted pathologic responders (AUC=0.71–0.78, p<0.01) despite substantial variation in texture quantification (CoV>70%). Conclusion: Propagated ROIs using deformable registration for all textures can lead to accurate prediction of pathologic response, potentially expediting the temporal texture analysis process. However, rigid and fast-demons deformable algorithms are not recommended due to their inferior performance compared to other algorithms. The project was supported in part by a Kaye Scholar Award.« less

Development of a Natural Language Processing Engine to Generate Bladder Cancer Pathology Data for Health Services Research.

PubMed

Schroeck, Florian R; Patterson, Olga V; Alba, Patrick R; Pattison, Erik A; Seigne, John D; DuVall, Scott L; Robertson, Douglas J; Sirovich, Brenda; Goodney, Philip P

2017-12-01

To take the first step toward assembling population-based cohorts of patients with bladder cancer with longitudinal pathology data, we developed and validated a natural language processing (NLP) engine that abstracts pathology data from full-text pathology reports. Using 600 bladder pathology reports randomly selected from the Department of Veterans Affairs, we developed and validated an NLP engine to abstract data on histology, invasion (presence vs absence and depth), grade, the presence of muscularis propria, and the presence of carcinoma in situ. Our gold standard was based on an independent review of reports by 2 urologists, followed by adjudication. We assessed the NLP performance by calculating the accuracy, the positive predictive value, and the sensitivity. We subsequently applied the NLP engine to pathology reports from 10,725 patients with bladder cancer. When comparing the NLP output to the gold standard, NLP achieved the highest accuracy (0.98) for the presence vs the absence of carcinoma in situ. Accuracy for histology, invasion (presence vs absence), grade, and the presence of muscularis propria ranged from 0.83 to 0.96. The most challenging variable was depth of invasion (accuracy 0.68), with an acceptable positive predictive value for lamina propria (0.82) and for muscularis propria (0.87) invasion. The validated engine was capable of abstracting pathologic characteristics for 99% of the patients with bladder cancer. NLP had high accuracy for 5 of 6 variables and abstracted data for the vast majority of the patients. This now allows for the assembly of population-based cohorts with longitudinal pathology data. Published by Elsevier Inc.

Pathological tremor prediction using surface EMG and acceleration: potential use in “ON-OFF” demand driven deep brain stimulator design

PubMed Central

Basu, Ishita; Graupe, Daniel; Tuninetti, Daniela; Shukla, Pitamber; Slavin, Konstantin V.; Metman, Leo Verhagen; Corcos, Daniel M.

2013-01-01

Objective We present a proof of concept for a novel method of predicting the onset of pathological tremor using non-invasively measured surface electromyogram (sEMG) and acceleration from tremor-affected extremities of patients with Parkinson’s disease (PD) and Essential tremor (ET). Approach The tremor prediction algorithm uses a set of spectral (fourier and wavelet) and non-linear time series (entropy and recurrence rate) parameters extracted from the non-invasively recorded sEMG and acceleration signals. Main results The resulting algorithm is shown to successfully predict tremor onset for all 91 trials recorded in 4 PD patients and for all 91 trials recorded in 4 ET patients. The predictor achieves a 100% sensitivity for all trials considered, along with an overall accuracy of 85.7% for all ET trials and 80.2% for all PD trials. By using a Pearson’s chi-square test, the prediction results are shown to significantly differ from a random prediction outcome. Significance The tremor prediction algorithm can be potentially used for designing the next generation of non-invasive closed-loop predictive ON-OFF controllers for deep brain stimulation (DBS), used for suppressing pathological tremor in such patients. Such a system is based on alternating ON and OFF DBS periods, an incoming tremor being predicted during the time intervals when DBS is OFF, so as to turn DBS back ON. The prediction should be a few seconds before tremor re-appears so that the patient is tremor-free for the entire DBS ON-OFF cycle as well as the tremor-free DBS OFF interval should be maximized in order to minimize the current injected in the brain and battery usage. PMID:23658233

Pathological tremor prediction using surface electromyogram and acceleration: potential use in ‘ON-OFF’ demand driven deep brain stimulator design

NASA Astrophysics Data System (ADS)

Basu, Ishita; Graupe, Daniel; Tuninetti, Daniela; Shukla, Pitamber; Slavin, Konstantin V.; Verhagen Metman, Leo; Corcos, Daniel M.

2013-06-01

Objective. We present a proof of concept for a novel method of predicting the onset of pathological tremor using non-invasively measured surface electromyogram (sEMG) and acceleration from tremor-affected extremities of patients with Parkinson’s disease (PD) and essential tremor (ET). Approach. The tremor prediction algorithm uses a set of spectral (Fourier and wavelet) and nonlinear time series (entropy and recurrence rate) parameters extracted from the non-invasively recorded sEMG and acceleration signals. Main results. The resulting algorithm is shown to successfully predict tremor onset for all 91 trials recorded in 4 PD patients and for all 91 trials recorded in 4 ET patients. The predictor achieves a 100% sensitivity for all trials considered, along with an overall accuracy of 85.7% for all ET trials and 80.2% for all PD trials. By using a Pearson’s chi-square test, the prediction results are shown to significantly differ from a random prediction outcome. Significance. The tremor prediction algorithm can be potentially used for designing the next generation of non-invasive closed-loop predictive ON-OFF controllers for deep brain stimulation (DBS), used for suppressing pathological tremor in such patients. Such a system is based on alternating ON and OFF DBS periods, an incoming tremor being predicted during the time intervals when DBS is OFF, so as to turn DBS back ON. The prediction should be a few seconds before tremor re-appears so that the patient is tremor-free for the entire DBS ON-OFF cycle and the tremor-free DBS OFF interval should be maximized in order to minimize the current injected in the brain and battery usage.

Diagnostic criteria for vascular cognitive disorders: a VASCOG statement.

PubMed

Sachdev, Perminder; Kalaria, Raj; O'Brien, John; Skoog, Ingmar; Alladi, Suvarna; Black, Sandra E; Blacker, Deborah; Blazer, Dan G; Chen, Christopher; Chui, Helena; Ganguli, Mary; Jellinger, Kurt; Jeste, Dilip V; Pasquier, Florence; Paulsen, Jane; Prins, Niels; Rockwood, Kenneth; Roman, Gustavo; Scheltens, Philip

2014-01-01

Several sets of diagnostic criteria have been published for vascular dementia since the 1960s. The continuing ambiguity in vascular dementia definition warrants a critical reexamination. Participants at a special symposium of the International Society for Vascular Behavioral and Cognitive Disorders (VASCOG) in 2009 critiqued the current criteria. They drafted a proposal for a new set of criteria, later reviewed through multiple drafts by the group, including additional experts and the members of the Neurocognitive Disorders Work Group of the fifth revision of Diagnostic and Statistical Manual (DSM-5) Task Force. Cognitive disorders of vascular etiology are a heterogeneous group of disorders with diverse pathologies and clinical manifestations, discussed broadly under the rubric of vascular cognitive disorders (VCD). The continuum of vascular cognitive impairment is recognized by the categories of Mild Vascular Cognitive Disorder, and Vascular Dementia or Major Vascular Cognitive Disorder. Diagnostic thresholds are defined. Clinical and neuroimaging criteria are proposed for establishing vascular etiology. Subtypes of VCD are described, and the frequent cooccurrence of Alzheimer disease pathology emphasized. The proposed criteria for VCD provide a coherent approach to the diagnosis of this diverse group of disorders, with a view to stimulating clinical and pathologic validation studies. These criteria can be harmonized with the DSM-5 criteria such that an international consensus on the criteria for VCD may be achieved.

Lipidomics of human brain aging and Alzheimer's disease pathology.

PubMed

Naudí, Alba; Cabré, Rosanna; Jové, Mariona; Ayala, Victoria; Gonzalo, Hugo; Portero-Otín, Manuel; Ferrer, Isidre; Pamplona, Reinald

2015-01-01

Lipids stimulated and favored the evolution of the brain. Adult human brain contains a large amount of lipids, and the largest diversity of lipid classes and lipid molecular species. Lipidomics is defined as "the full characterization of lipid molecular species and of their biological roles with respect to expression of proteins involved in lipid metabolism and function, including gene regulation." Therefore, the study of brain lipidomics can help to unravel the diversity and to disclose the specificity of these lipid traits and its alterations in neural (neurons and glial) cells, groups of neural cells, brain, and fluids such as cerebrospinal fluid and plasma, thus helping to uncover potential biomarkers of human brain aging and Alzheimer disease. This review will discuss the lipid composition of the adult human brain. We first consider a brief approach to lipid definition, classification, and tools for analysis from the new point of view that has emerged with lipidomics, and then turn to the lipid profiles in human brain and how lipids affect brain function. Finally, we focus on the current status of lipidomics findings in human brain aging and Alzheimer's disease pathology. Neurolipidomics will increase knowledge about physiological and pathological functions of brain cells and will place the concept of selective neuronal vulnerability in a lipid context. © 2015 Elsevier Inc. All rights reserved.

Helicobacter pylori-induced gastric pathology: insights from in vivo and ex vivo models.

PubMed

Burkitt, Michael D; Duckworth, Carrie A; Williams, Jonathan M; Pritchard, D Mark

2017-02-01

Gastric colonization with Helicobacter pylori induces diverse human pathological conditions, including superficial gastritis, peptic ulcer disease, mucosa-associated lymphoid tissue (MALT) lymphoma, and gastric adenocarcinoma and its precursors. The treatment of these conditions often relies on the eradication of H. pylori, an intervention that is increasingly difficult to achieve and that does not prevent disease progression in some contexts. There is, therefore, a pressing need to develop new experimental models of H. pylori-associated gastric pathology to support novel drug development in this field. Here, we review the current status of in vivo and ex vivo models of gastric H. pylori colonization, and of Helicobacter-induced gastric pathology, focusing on models of gastric pathology induced by H. pylori, Helicobacter felis and Helicobacter suis in rodents and large animals. We also discuss the more recent development of gastric organoid cultures from murine and human gastric tissue, as well as from human pluripotent stem cells, and the outcomes of H. pylori infection in these systems. © 2017. Published by The Company of Biologists Ltd.

Microvessel prediction in H&E Stained Pathology Images using fully convolutional neural networks.

PubMed

Yi, Faliu; Yang, Lin; Wang, Shidan; Guo, Lei; Huang, Chenglong; Xie, Yang; Xiao, Guanghua

2018-02-27

Pathological angiogenesis has been identified in many malignancies as a potential prognostic factor and target for therapy. In most cases, angiogenic analysis is based on the measurement of microvessel density (MVD) detected by immunostaining of CD31 or CD34. However, most retrievable public data is generally composed of Hematoxylin and Eosin (H&E)-stained pathology images, for which is difficult to get the corresponding immunohistochemistry images. The role of microvessels in H&E stained images has not been widely studied due to their complexity and heterogeneity. Furthermore, identifying microvessels manually for study is a labor-intensive task for pathologists, with high inter- and intra-observer variation. Therefore, it is important to develop automated microvessel-detection algorithms in H&E stained pathology images for clinical association analysis. In this paper, we propose a microvessel prediction method using fully convolutional neural networks. The feasibility of our proposed algorithm is demonstrated through experimental results on H&E stained images. Furthermore, the identified microvessel features were significantly associated with the patient clinical outcomes. This is the first study to develop an algorithm for automated microvessel detection in H&E stained pathology images.

Metabolic theory and elevational diversity of vertebrate ectotherms.

PubMed

McCain, Christy M; Sanders, Nathan J

2010-02-01

The Metabolic Theory of Ecology (MTE) posits that the temperature-dependent kinetics of metabolism shape broad-scale patterns of biodiversity. Here we test whether the MTE accounts for patterns of diversity using 102 elevational diversity gradients of reptiles and amphibians. In particular, we examined the support for the two key predictions of the MTE: that the reciprocal of absolute temperature (1/kT) and diversity are linearly related and that the slope of that relationship is -0.65. We also tested two underlying assumptions of the MTE in cases with appropriate data, namely, that abundance is invariant among samples, and that behavioral thermoregulation influences the MTE predictions. We found that few studies supported the predictions of the MTE for the relationship between environmental temperature and elevational diversity using previous methods on individual gradients and using meta-analysis. The predominant relationship was curvilinear, and the slopes were steeper than predicted. In analyses of individual gradients, only 6% followed the MTE predictions in the strictest application, and 25% in the broadest. We found violations of the assumption of invariant abundances in all five test cases. All four herpetofaunal groups, regardless of behavioral thermoregulatory abilities, demonstrated poor fits to the MTE predictions. Even when arid gradients are removed, ameliorating the potential effects of water limitation, the MTE did not account for herpetofaunal elevational diversity. We conclude that an interplay of factors shapes elevational diversity gradients rather than the simple kinetics of biochemical reactions.

PRospective Imaging of CErvical cancer and neoadjuvant treatment (PRICE) study: role of ultrasound to predict partial response in locally advanced cervical cancer patients undergoing chemoradiation and radical surgery.

PubMed

Testa, A C; Ferrandina, G; Moro, F; Pasciuto, T; Moruzzi, M C; De Blasis, I; Mascilini, F; Foti, E; Autorino, R; Collarino, A; Gui, B; Zannoni, G F; Gambacorta, M A; Valentini, A L; Rufini, V; Scambia, G

2018-05-01

Chemoradiation-based neoadjuvant treatment followed by radical surgery is an alternative therapeutic strategy for locally advanced cervical cancer (LACC), but ultrasound variables used to predict partial response to neoadjuvant treatment are not well defined. Our goal was to analyze prospectively the potential role of transvaginal ultrasound in early prediction of partial pathological response, assessed in terms of residual disease at histology, in a large, single-institution series of LACC patients triaged to neoadjuvant treatment followed by radical surgery. Between October 2010 and June 2014, we screened 108 women with histologically documented LACC Stage IB2-IVA, of whom 88 were included in the final analysis. Tumor volume, three-dimensional (3D) power Doppler indices and contrast parameters were obtained before (baseline examination) and after 2 weeks of treatment. The pathological response was defined as complete (absence of any residual tumor after treatment) or partial (microscopic and/or macroscopic residual tumor at pathological examination). Complete-response and partial-response groups were compared and receiver-operating characteristics (ROC) curves were generated for ultrasound variables that were statistically significant on univariate analysis to evaluate their diagnostic ability to predict partial pathological response. There was a complete pathological response to neoadjuvant therapy in 40 (45.5%) patients and a partial response in 48 (54.5%). At baseline examination, tumor volume did not differ between the two groups. However, after 2 weeks of neoadjuvant treatment, the tumor volume was significantly greater in patients with partial response than it was in those with complete response (P = 0.019). Among the 3D vascular indices, the vascularization index (VI) was significantly lower in the partial-response compared with the complete-response group, both before and after 2 weeks of treatment (P = 0.037 and P = 0.024, respectively). At baseline examination in the contrast analysis, women with partial response had lower tumor peak enhancement (PE) as well as lower tumor wash-in rate (WiR) and longer tumor rise time (RT) compared with complete responders (P = 0.006, P = 0.003, P = 0.038, respectively). There was no difference in terms of contrast parameters after 2 weeks of treatment. ROC-curve analysis of baseline parameters showed that the best cut-offs for predicting partial pathological response were 41.5% for VI (sensitivity, 63.6%; specificity, 66.7%); 16123.5 auxiliary units for tumor PE (sensitivity, 47.9%; specificity, 84.2%); 7.8 s for tumor RT (sensitivity, 68.8%; specificity, 57.9%); and 4902 for tumor WiR (sensitivity, 77.1%; specificity, 60.5%). ROC curves of parameters after 2 weeks of treatment showed that the best cut-off for predicting partial pathological response was 18.1 cm 3 for tumor volume (sensitivity, 70.8%; specificity 60.0%) and 39.5% for VI (sensitivity; 62.5%; specificity, 73.5%). Ultrasound and contrast parameters differ between LACC patients with complete response and those with partial response before and after 2 weeks of neoadjuvant treatment. However, neither ultrasound parameters before treatment nor those after 2 weeks of treatment had cut-off values with acceptable sensitivity and specificity for predicting partial pathological response to neoadjuvant therapy. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

A Tissue Systems Pathology Assay for High-Risk Barrett's Esophagus.

PubMed

Critchley-Thorne, Rebecca J; Duits, Lucas C; Prichard, Jeffrey W; Davison, Jon M; Jobe, Blair A; Campbell, Bruce B; Zhang, Yi; Repa, Kathleen A; Reese, Lia M; Li, Jinhong; Diehl, David L; Jhala, Nirag C; Ginsberg, Gregory; DeMarshall, Maureen; Foxwell, Tyler; Zaidi, Ali H; Lansing Taylor, D; Rustgi, Anil K; Bergman, Jacques J G H M; Falk, Gary W

2016-06-01

Better methods are needed to predict risk of progression for Barrett's esophagus. We aimed to determine whether a tissue systems pathology approach could predict progression in patients with nondysplastic Barrett's esophagus, indefinite for dysplasia, or low-grade dysplasia. We performed a nested case-control study to develop and validate a test that predicts progression of Barrett's esophagus to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC), based upon quantification of epithelial and stromal variables in baseline biopsies. Data were collected from Barrett's esophagus patients at four institutions. Patients who progressed to HGD or EAC in ≥1 year (n = 79) were matched with patients who did not progress (n = 287). Biopsies were assigned randomly to training or validation sets. Immunofluorescence analyses were performed for 14 biomarkers and quantitative biomarker and morphometric features were analyzed. Prognostic features were selected in the training set and combined into classifiers. The top-performing classifier was assessed in the validation set. A 3-tier, 15-feature classifier was selected in the training set and tested in the validation set. The classifier stratified patients into low-, intermediate-, and high-risk classes [HR, 9.42; 95% confidence interval, 4.6-19.24 (high-risk vs. low-risk); P < 0.0001]. It also provided independent prognostic information that outperformed predictions based on pathology analysis, segment length, age, sex, or p53 overexpression. We developed a tissue systems pathology test that better predicts risk of progression in Barrett's esophagus than clinicopathologic variables. The test has the potential to improve upon histologic analysis as an objective method to risk stratify Barrett's esophagus patients. Cancer Epidemiol Biomarkers Prev; 25(6); 958-68. ©2016 AACR. ©2016 American Association for Cancer Research.

Editorial Commentary: Role of Synovial Biomarkers in Patient Outcomes After Knee Arthroscopy.

PubMed

Brand, Jefferson C

2016-03-01

Humans are notably poor at predicting event outcomes. In "Correlation of Synovial Fluid Biomarkers With Cartilage Pathology and Associated Outcomes in Knee Arthroscopy," Cuellar, Cuellar, Kirsch, and Strauss show that some synovial fluid biomarkers (20 were sampled for the investigation) may predict operative findings at the time of arthroscopy and patient-reported outcome measures at follow-up. Further research will clarify the role of synovial biomarkers in knee pathology and, hopefully, narrow the choices to one or two pertinent markers that can be used to improve our ability to predict outcomes from arthroscopic knee surgery. Copyright © 2016 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

ALTERED IRON HOMEOSTATIS AND THE MECHANISM OF BIOLOGIC EFFECT BY PARTICLES

EPA Science Inventory

Several features of the clinical presentation and changes in physiology and pathology following exposure to many diverse ambient air pollution particles are comparable, suggesting a common mechanism for their biological effect. We propose that a mechanism of biological effect com...

Use of registration-based contour propagation in texture analysis for esophageal cancer pathologic response prediction

NASA Astrophysics Data System (ADS)

Yip, Stephen S. F.; Coroller, Thibaud P.; Sanford, Nina N.; Huynh, Elizabeth; Mamon, Harvey; Aerts, Hugo J. W. L.; Berbeco, Ross I.

2016-01-01

Change in PET-based textural features has shown promise in predicting cancer response to treatment. However, contouring tumour volumes on longitudinal scans is time-consuming. This study investigated the usefulness of contour propagation in texture analysis for the purpose of pathologic response prediction in esophageal cancer. Forty-five esophageal cancer patients underwent PET/CT scans before and after chemo-radiotherapy. Patients were classified into responders and non-responders after the surgery. Physician-defined tumour ROIs on pre-treatment PET were propagated onto the post-treatment PET using rigid and ten deformable registration algorithms. PET images were converted into 256 discrete values. Co-occurrence, run-length, and size zone matrix textures were computed within all ROIs. The relative difference of each texture at different treatment time-points was used to predict the pathologic responders. Their predictive value was assessed using the area under the receiver-operating-characteristic curve (AUC). Propagated ROIs from different algorithms were compared using Dice similarity index (DSI). Contours propagated by the fast-demons, fast-free-form and rigid algorithms did not fully capture the high FDG uptake regions of tumours. Fast-demons propagated ROIs had the least agreement with other contours (DSI  =  58%). Moderate to substantial overlap were found in the ROIs propagated by all other algorithms (DSI  =  69%-79%). Rigidly propagated ROIs with co-occurrence texture failed to significantly differentiate between responders and non-responders (AUC  =  0.58, q-value  =  0.33), while the differentiation was significant with other textures (AUC  =  0.71‒0.73, p  <  0.009). Among the deformable algorithms, fast-demons (AUC  =  0.68‒0.70, q-value  <  0.03) and fast-free-form (AUC  =  0.69‒0.74, q-value  <  0.04) were the least predictive. ROIs propagated by all other deformable algorithms with any texture significantly predicted pathologic responders (AUC  =  0.72‒0.78, q-value  <  0.01). Propagated ROIs using deformable registration for all textures can lead to accurate prediction of pathologic response, potentially expediting the temporal texture analysis process. However, fast-demons, fast-free-form, and rigid algorithms should be applied with care due to their inferior performance compared to other algorithms.

Prevalence of alcohol-related pathologies at autopsy: Estonian Forensic Study of Alcohol and Premature Death

PubMed Central

Tuusov, Jana; Lang, Katrin; Väli, Marika; Pärna, Kersti; Tõnisson, Mailis; Ringmets, Inge; McKee, Martin; Helander, Anders; Leon, David A

2014-01-01

Aims Alcohol can induce diverse serious pathologies, yet this complexity may be obscured when alcohol-related deaths are classified according to a single underlying cause. We sought to quantify this issue and its implications for analysing mortality data. Design, Setting and Participants Cross-sectional study included 554 men aged 25–54 in Estonia undergoing forensic autopsy in 2008–09. Measurements Potentially alcohol-related pathologies were identified following macroscopic and histological examination. Alcohol biomarkers levels were determined. For a subset (26%), drinking behaviour was provided by next-of-kin. The Estonian Statistics Office provided underlying cause of death. Findings Most deaths (75%) showed evidence of potentially alcohol-related pathologies, and 32% had pathologies in two or more organs. The liver was most commonly affected [60.5%, 95% confidence interval (CI) = 56.3–64.6] followed by the lungs (18.6%, 95% CI = 15.4–22.1), stomach (17.5%, 95% CI = 14.4–20.9), pancreas (14.1%, 95% CI = 11.3–17.3), heart (4.9%, 95% CI = 3.2–7.0) and oesophagus (1.4%, 95% CI = 0.6–2.8). Only a minority with liver pathology had a second pathology. The number of pathologies correlated with alcohol biomarkers (phosphatidylethanol, gamma-glytamyl transpeptidase in blood, ethylglucuronide, ethylsulphate in urine). Despite the high prevalence of liver pathology, few deaths had alcoholic liver disease specified as the underlying cause. Conclusion The majority of 554 men aged 25–54 undergoing forensic autopsy in Estonia in 2008–09 showed evidence of alcohol-related pathology. However, the recording of deaths by underlying cause failed to capture the scale and nature of alcohol-induced pathologies found. PMID:25066373

Differential induction and spread of tau pathology in young PS19 tau transgenic mice following intracerebral injections of pathological tau from Alzheimer’s disease or corticobasal degeneration brains

PubMed Central

Boluda, Susana; Iba, Michiyo; Zhang, Bin; Raible, Kevin M.; Lee, Virginia M-Y.; Trojanowski, John Q.

2015-01-01

Filamentous tau pathologies are hallmark lesions of several neurodegenerative tauopathies including Alzheimer’s disease (AD) and corticobasal degeneration (CBD) which show cell type-specific and topographically distinct tau inclusions. Growing evidence supports templated transmission of tauopathies through functionally interconnected neuroanatomical pathways suggesting that different self-propagating strains of pathological tau could account for the diverse manifestations of neurodegenerative tauopathies. Here, we describe the rapid and distinct cell type-specific spread of pathological tau following intracerebral injections of CBD or AD brain extracts enriched in pathological tau (designated CBD-Tau and AD-Tau, respectively) in young human mutant P301S tau transgenic (Tg) mice (line PS19) ~6–9 months before they show onset of mutant tau transgene-induced tau pathology. At 1 month post-injection of CBD-Tau, tau inclusions developed predominantly in oligodendrocytes of the fimbria and white matter near the injection sites with infrequent intraneuronal tau aggregates. In contrast, injections of AD-Tau in young PS19 mice induced tau pathology predominantly in neuronal perikarya with little or no oligodendrocyte involvement 1 month post-injection. With longer post-injection survival intervals of up to 6 months, CBD-Tau- and AD-Tau-induced tau pathology spread to different brain regions distant from the injection sites while maintaining the cell type-specific pattern noted above. Finally, CA3 neuron loss was detected 3 months post-injection of AD-Tau but not CBD-Tau. Thus, AD-Tau and CBD-Tau represent specific pathological tau strains that spread differentially and may underlie distinct clinical and pathological features of these two tauopathies. Hence, these strains could become targets to develop disease-modifying therapies for CBD and AD. PMID:25534024

Polygenic risk score analysis of pathologically confirmed Alzheimer disease.

PubMed

Escott-Price, Valentina; Myers, Amanda J; Huentelman, Matt; Hardy, John

2017-08-01

Previous estimates of the utility of polygenic risk score analysis for the prediction of Alzheimer disease have given area under the curve (AUC) estimates of <80%. However, these have been based on the genetic analysis of clinical case-control series. Here, we apply the same analytic approaches to a pathological case-control series and show a predictive AUC of 84%. We suggest that this analysis has clinical utility and that there is limited room for further improvement using genetic data. Ann Neurol 2017;82:311-314. © 2017 American Neurological Association.

Predicting pathological complete response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer: a systematic review.

PubMed

Ryan, J E; Warrier, S K; Lynch, A C; Ramsay, R G; Phillips, W A; Heriot, A G

2016-03-01

Approximately 20% of patients treated with neoadjuvant chemoradiotherapy (nCRT) for locally advanced rectal cancer achieve a pathological complete response (pCR) while the remainder derive the benefit of improved local control and downstaging and a small proportion show a minimal response. The ability to predict which patients will benefit would allow for improved patient stratification directing therapy to those who are likely to achieve a good response, thereby avoiding ineffective treatment in those unlikely to benefit. A systematic review of the English language literature was conducted to identify pathological factors, imaging modalities and molecular factors that predict pCR following chemoradiotherapy. PubMed, MEDLINE and Cochrane Database searches were conducted with the following keywords and MeSH search terms: 'rectal neoplasm', 'response', 'neoadjuvant', 'preoperative chemoradiation', 'tumor response'. After review of title and abstracts, 85 articles addressing the prediction of pCR were selected. Clear methods to predict pCR before chemoradiotherapy have not been defined. Clinical and radiological features of the primary cancer have limited ability to predict response. Molecular profiling holds the greatest potential to predict pCR but adoption of this technology will require greater concordance between cohorts for the biomarkers currently under investigation. At present no robust markers of the prediction of pCR have been identified and the topic remains an area for future research. This review critically evaluates existing literature providing an overview of the methods currently available to predict pCR to nCRT for locally advanced rectal cancer. The review also provides a comprehensive comparison of the accuracy of each modality. Colorectal Disease © 2015 The Association of Coloproctology of Great Britain and Ireland.

The evaluation of different forest structural indices to predict the stand aboveground biomass of even-aged Scotch pine (Pinus sylvestris L.) forests in Kunduz, Northern Turkey.

PubMed

Ercanli, İlker; Kahriman, Aydın

2015-03-01

We assessed the effect of stand structural diversity, including the Shannon, improved Shannon, Simpson, McIntosh, Margelef, and Berger-Parker indices, on stand aboveground biomass (AGB) and developed statistical prediction models for the stand AGB values, including stand structural diversity indices and some stand attributes. The AGB prediction model, including only stand attributes, accounted for 85 % of the total variance in AGB (R (2)) with an Akaike's information criterion (AIC) of 807.2407, Bayesian information criterion (BIC) of 809.5397, Schwarz Bayesian criterion (SBC) of 818.0426, and root mean square error (RMSE) of 38.529 Mg. After inclusion of the stand structural diversity into the model structure, considerable improvement was observed in statistical accuracy, including 97.5 % of the total variance in AGB, with an AIC of 614.1819, BIC of 617.1242, SBC of 633.0853, and RMSE of 15.8153 Mg. The predictive fitting results indicate that some indices describing the stand structural diversity can be employed as significant independent variables to predict the AGB production of the Scotch pine stand. Further, including the stand diversity indices in the AGB prediction model with the stand attributes provided important predictive contributions in estimating the total variance in AGB.

Effectiveness of Genomic Prediction of Maize Hybrid Performance in Different Breeding Populations and Environments

PubMed Central

Windhausen, Vanessa S.; Atlin, Gary N.; Hickey, John M.; Crossa, Jose; Jannink, Jean-Luc; Sorrells, Mark E.; Raman, Babu; Cairns, Jill E.; Tarekegne, Amsal; Semagn, Kassa; Beyene, Yoseph; Grudloyma, Pichet; Technow, Frank; Riedelsheimer, Christian; Melchinger, Albrecht E.

2012-01-01

Genomic prediction is expected to considerably increase genetic gains by increasing selection intensity and accelerating the breeding cycle. In this study, marker effects estimated in 255 diverse maize (Zea mays L.) hybrids were used to predict grain yield, anthesis date, and anthesis-silking interval within the diversity panel and testcross progenies of 30 F2-derived lines from each of five populations. Although up to 25% of the genetic variance could be explained by cross validation within the diversity panel, the prediction of testcross performance of F2-derived lines using marker effects estimated in the diversity panel was on average zero. Hybrids in the diversity panel could be grouped into eight breeding populations differing in mean performance. When performance was predicted separately for each breeding population on the basis of marker effects estimated in the other populations, predictive ability was low (i.e., 0.12 for grain yield). These results suggest that prediction resulted mostly from differences in mean performance of the breeding populations and less from the relationship between the training and validation sets or linkage disequilibrium with causal variants underlying the predicted traits. Potential uses for genomic prediction in maize hybrid breeding are discussed emphasizing the need of (1) a clear definition of the breeding scenario in which genomic prediction should be applied (i.e., prediction among or within populations), (2) a detailed analysis of the population structure before performing cross validation, and (3) larger training sets with strong genetic relationship to the validation set. PMID:23173094

The intermediate disturbance hypothesis should be abandoned.

PubMed

Fox, Jeremy W

2013-02-01

A leading idea about how disturbances and other environmental fluctuations affect species diversity is the intermediate disturbance hypothesis (IDH). The IDH states that diversity of competing species is, or should be expected to be, maximized at intermediate frequencies and/or intensities of disturbance or environmental change. I argue that the IDH has been refuted on both empirical and theoretical grounds, and so should be abandoned. Empirical studies only rarely find the predicted humped diversity-disturbance relationship. Theoretically, the three major mechanisms thought to produce humped diversity-disturbance relationships are logically invalid and do not actually predict what they are thought to predict. Disturbances and other environmental fluctuations can affect diversity, but for different reasons than are commonly recognized. Copyright © 2012 Elsevier Ltd. All rights reserved.

Standardizing the definition of adverse pathology for lower risk men undergoing radical prostatectomy.

PubMed

Kozminski, Michael A; Tomlins, Scott; Cole, Adam; Singhal, Udit; Lu, Louis; Skolarus, Ted A; Palapattu, Ganesh S; Montgomery, Jeffrey S; Weizer, Alon Z; Mehra, Rohit; Hollenbeck, Brent K; Miller, David C; He, Chang; Feng, Felix Y; Morgan, Todd M

2016-09-01

Numerous definitions of adverse pathology at radical prostatectomy (RP) have been proposed and implemented for both research and clinical care, and there is tremendous variation in the specific criteria used to define adverse pathology in these settings. Given the current landscape in which magnetic resonance imaging criteria and biomarker cutoffs are validated for disparate adverse pathology definitions, we sought to identify which of these is most closely tied to biochemical recurrence (BCR) after RP. A total of 2,837 patients who underwent RP at a single institution for localized prostate cancer (PCa) were included. We evaluated the following existing definitions of adverse pathology at RP: (1) Gleason score ≥7, (2) primary Gleason pattern ≥4, (3) Gleason score ≥7 or pathologic stage T3-4, (4) pathologic stage T3-4, (5) primary Gleason pattern ≥4 or pathologic stage T3-4. The primary outcome measure was BCR. Multiple statistical techniques were used to assess BCR prediction. Of the 5 definitions assessed, 1 (primary Gleason pattern ≥4 or pathologic stage T3-4, 540 patients [19% of cohort]) consistently outperformed the other definitions across all statistical measures. Additionally, a total of only 13 (6.6%) and 34 (10.3%) men with very-low-risk and low-risk cancer per National Comprehensive Cancer Network guideline, respectively, met this definition of adverse pathology at the time of RP. Varying definitions of adverse pathology differ in their prognostic performance. The criteria defined by either primary Gleason pattern ≥4 or pT3-4 disease appears to most accurately predict BCR in this subset of patients with lower risk PCa at the time of diagnosis. Additionally, men with very-low-risk or low-risk PCa per National Comprehensive Cancer Network guidelines are relatively unlikely to have adverse pathology at the time of surgical resection. These data may help inform the use of imaging and molecular markers as well as the intensity of surveillance in men with newly diagnosed PCa. Copyright © 2016 Elsevier Inc. All rights reserved.

Species Pool Functional Diversity Plays a Hidden Role in Generating β-Diversity.

PubMed

Patrick, Christopher J; Brown, Bryan L

2018-05-01

Functional trait diversity is used as a way to infer mechanistic processes that drive community assembly. While functional diversity within communities is often viewed as a response variable, here we present and test a framework for how functional diversity among taxa in the regional species pool drives the assembly of communities among habitats. We predicted that species pool functional diversity should work with environmental heterogeneity to drive β-diversity. We tested these predictions by modeling empirical patterns in invertebrate communities from 570 streams in 52 watersheds. Our analysis of the field data provided strong support for the inclusion of both functional diversity and environmental heterogeneity in the models, and our predictions were supported when the community was analyzed all together. However, analyses within individual functional feeding guilds revealed strong context dependency in the relative importance of functional diversity, γ-richness, and environmental heterogeneity to β-diversity. We interpret the results to mean that functional diversity can play an important role in driving β-diversity; however, within guilds the nature of interspecific interactions and species pool size complicate the relationship. Future research should test this conceptual model across different ecosystems and in experimental settings using metacommunity mesocosms to enhance our understanding of the role that functional variation plays in generating spatial biodiversity patterns.

Prediction of Response to Neoadjuvant Chemotherapy and Radiation Therapy with Baseline and Restaging 18F-FDG PET Imaging Biomarkers in Patients with Esophageal Cancer.

PubMed

Beukinga, Roelof J; Hulshoff, Jan Binne; Mul, Véronique E M; Noordzij, Walter; Kats-Ugurlu, Gursah; Slart, Riemer H J A; Plukker, John T M

2018-06-01

Purpose To assess the value of baseline and restaging fluorine 18 ( 18 F) fluorodeoxyglucose (FDG) positron emission tomography (PET) radiomics in predicting pathologic complete response to neoadjuvant chemotherapy and radiation therapy (NCRT) in patients with locally advanced esophageal cancer. Materials and Methods In this retrospective study, 73 patients with histologic analysis-confirmed T1/N1-3/M0 or T2-4a/N0-3/M0 esophageal cancer were treated with NCRT followed by surgery (Chemoradiotherapy for Esophageal Cancer followed by Surgery Study regimen) between October 2014 and August 2017. Clinical variables and radiomic features from baseline and restaging 18 F-FDG PET were selected by univariable logistic regression and least absolute shrinkage and selection operator. The selected variables were used to fit a multivariable logistic regression model, which was internally validated by using bootstrap resampling with 20 000 replicates. The performance of this model was compared with reference prediction models composed of maximum standardized uptake value metrics, clinical variables, and maximum standardized uptake value at baseline NCRT radiomic features. Outcome was defined as complete versus incomplete pathologic response (tumor regression grade 1 vs 2-5 according to the Mandard classification). Results Pathologic response was complete in 16 patients (21.9%) and incomplete in 57 patients (78.1%). A prediction model combining clinical T-stage and restaging NCRT (post-NCRT) joint maximum (quantifying image orderliness) yielded an optimism-corrected area under the receiver operating characteristics curve of 0.81. Post-NCRT joint maximum was replaceable with five other redundant post-NCRT radiomic features that provided equal model performance. All reference prediction models exhibited substantially lower discriminatory accuracy. Conclusion The combination of clinical T-staging and quantitative assessment of post-NCRT 18 F-FDG PET orderliness (joint maximum) provided high discriminatory accuracy in predicting pathologic complete response in patients with esophageal cancer. © RSNA, 2018 Online supplemental material is available for this article.

Serial Magnetic Resonance Imaging in Active Surveillance of Prostate Cancer: Incremental Value.

PubMed

Felker, Ely R; Wu, Jason; Natarajan, Shyam; Margolis, Daniel J; Raman, Steven S; Huang, Jiaoti; Dorey, Fred; Marks, Leonard S

2016-05-01

We assessed whether changes in serial multiparametric magnetic resonance imaging can help predict the pathological progression of prostate cancer in men on active surveillance. A retrospective cohort study was conducted of 49 consecutive men with Gleason 6 prostate cancer who underwent multiparametric magnetic resonance imaging at baseline and again more than 6 months later, each followed by a targeted prostate biopsy, between January 2011 and May 2015. We evaluated whether progression on multiparametric magnetic resonance imaging (an increase in index lesion suspicion score, increase in index lesion volume or decrease in index lesion apparent diffusion coefficient) could predict pathological progression (Gleason 3 + 4 or greater on subsequent biopsy, in systematic or targeted cores). Diagnostic performance of multiparametric magnetic resonance imaging was determined with and without clinical data using a binary logistic regression model. The mean interval between baseline and followup multiparametric magnetic resonance imaging was 28.3 months (range 11 to 43). Pathological progression occurred in 19 patients (39%). The sensitivity, specificity, positive predictive value and negative predictive value of multiparametric magnetic resonance imaging was 37%, 90%, 69% and 70%, respectively. Area under the receiver operating characteristic curve was 0.63. A logistic regression model using clinical information (maximum cancer core length greater than 3 mm on baseline biopsy or a prostate specific antigen density greater than 0.15 ng/ml(2) at followup biopsy) had an AUC of 0.87 for predicting pathological progression. The addition of serial multiparametric magnetic resonance imaging data significantly improved the AUC to 0.91 (p=0.044). Serial multiparametric magnetic resonance imaging adds incremental value to prostate specific antigen density and baseline cancer core length for predicting Gleason 6 upgrading in men on active surveillance. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Pathological response of locally advanced rectal cancer to preoperative chemotherapy without pelvic irradiation.

PubMed

Bensignor, T; Brouquet, A; Dariane, C; Thirot-Bidault, A; Lazure, T; Julié, C; Nordlinger, B; Penna, C; Benoist, S

2015-06-01

Pathological response to chemotherapy without pelvic irradiation is not well defined in rectal cancer. This study aimed to evaluate the objective pathological response to preoperative chemotherapy without pelvic irradiation in middle or low locally advanced rectal cancer (LARC). Between 2008 and 2013, 22 patients with middle or low LARC (T3/4 and/or N+ and circumferential resection margin < 2 mm) and synchronous metastatic disease or a contraindication to pelvic irradiation underwent rectal resection after preoperative chemotherapy. The pathological response of rectal tumour was analysed according to the Rödel tumour regression grading (TRG) system. Predictive factors of objective pathological response (TRG 2-4) were analysed. All patients underwent rectal surgery after a median of six cycles of preoperative chemotherapy. Of these, 20 (91%) had sphincter saving surgery and an R0 resection. Twelve (55%) patients had an objective pathological response (TRG 2-4), including one complete response. Poor response (TRG 0-1) to chemotherapy was noted in 10 (45%) patients. In univariate analyses, none of the factors examined was found to be predictive of an objective pathological response to chemotherapy. At a median follow-up of 37.2 months, none of the 22 patients experienced local recurrence. Of the 19 patients with Stage IV rectal cancer, 15 (79%) had liver surgery with curative intent. Preoperative chemotherapy without pelvic irradiation is associated with objective pathological response and adequate local control in selected patients with LARC. Further prospective controlled studies will address the question of whether it can be used as a valuable alternative to radiochemotherapy in LARC. Colorectal Disease © 2014 The Association of Coloproctology of Great Britain and Ireland.

FIV diversity: FIVPle subtype composition may influence disease outcome in African lions

PubMed Central

Troyer, Jennifer L.; Roelke, Melody E.; Jespersen, Jillian M.; Baggett, Natalie; Buckley-Beason, Valerie; MacNulty, Dan; Craft, Meggan; Packer, Craig; Pecon-Slattery, Jill; O’Brien, Stephen J.

2011-01-01

Feline immunodeficiency virus (FIV) infects domestic cats and at least 20 additional species of non-domestic felids throughout the world. Strains specific to domestic cat (FIVFca) produce AIDS-like disease progression, sequelae and pathology providing an informative model for HIV infection in humans. Less is known about the immunological and pathological influence of FIV in other felid species although multiple distinct strains of FIV circulate in natural populations. As in HIV-1 and HIV-2, multiple diverse cross-species infections may have occurred. In the Serengeti National Park, Tanzania, three divergent subtypes of lion FIV (FIVPle) are endemic, whereby 100% of adult lions are infected with one or more of these strains. Herein, the relative distribution of these subtypes in the population are surveyed and, combined with observed differences in lion mortality due to secondary infections based on FIVPle subtypes, the data suggest that FIVPle subtypes may have different patterns of pathogenicity and transmissibility among wild lion populations. PMID:21723622

Finfish and aquatic invertebrate pathology resources for now and the future✩

PubMed Central

Spitsbergen, Jan M.; Blazer, Vicki S.; Bowser, Paul R.; Cheng, Keith C.; Cooper, Keith R.; Cooper, Timothy K.; Frasca, Salvatore; Groman, David B.; Harper, Claudia M.; (Mac) Law, Jerry M.; Marty, Gary D.; Smolowitz, Roxanna M.; Leger, Judy St.; Wolf, Douglas C.; Wolf, Jeffrey C.

2009-01-01

Utilization of finfish and aquatic invertebrates in biomedical research and as environmental sentinels has grown dramatically in recent decades. Likewise the aquaculture of finfish and invertebrates has expanded rapidly worldwide as populations of some aquatic food species and threatened or endangered aquatic species have plummeted due to overharvesting or habitat degradation. This increasing intensive culture and use of aquatic species has heightened the importance of maintaining a sophisticated understanding of pathology of various organ systems of these diverse species. Yet, except for selected species long cultivated in aquaculture, pathology databases and the workforce of highly trained pathologists lag behind those available for most laboratory animals and domestic mammalian and avian species. Several factors must change to maximize the use, understanding, and protection of important aquatic species: 1) improvements in databases of abnormalities across species; 2) standardization of diagnostic criteria for proliferative and nonproliferative lesions; and 3) more uniform and rigorous training in aquatic morphologic pathology. PMID:18948226

Current Policies and New Directions for Speech-Language Pathology Assistants.

PubMed

Paul-Brown, Diane; Goldberg, Lynette R

2001-01-01

This article provides an overview of current American Speech-Language-Hearing Association (ASHA) policies for the appropriate use and supervision of speech-language pathology assistants with an emphasis on the need to preserve the role of fully qualified speech-language pathologists in the service delivery system. Seven challenging issues surrounding the appropriate use of speech-language pathology assistants are considered. These include registering assistants and approving training programs; membership in ASHA; discrepancies between state requirements and ASHA policies; preparation for serving diverse multicultural, bilingual, and international populations; supervision considerations; funding and reimbursement for assistants; and perspectives on career-ladder/bachelor-level personnel. The formation of a National Leadership Council is proposed to develop a coordinated strategic plan for addressing these controversial and potentially divisive issues related to speech-language pathology assistants. This council would implement strategies for future development in the areas of professional education pertaining to assistant-level supervision, instruction of assistants, communication networks, policy development, research, and the dissemination/promotion of information regarding assistants.

Treatment-Related Predictive and Prognostic Factors in Trimodality Approach in Stage IIIA/N2 Non-Small Cell Lung Cancer.

PubMed

Jeremić, Branislav; Casas, Francesc; Dubinsky, Pavol; Gomez-Caamano, Antonio; Čihorić, Nikola; Videtic, Gregory; Igrutinovic, Ivan

2018-01-01

While there are no established pretreatment predictive and prognostic factors in patients with stage IIIA/pN2 non-small cell lung cancer (NSCLC) indicating a benefit to surgery as a part of trimodality approach, little is known about treatment-related predictive and prognostic factors in this setting. A literature search was conducted to identify possible treatment-related predictive and prognostic factors for patients for whom trimodality approach was reported on. Overall survival was the primary endpoint of this study. Of 30 identified studies, there were two phase II studies, 5 "prospective" studies, and 23 retrospective studies. No study was found which specifically looked at treatment-related predictive factors of improved outcomes in trimodality treatment. Of potential treatment-related prognostic factors, the least frequently analyzed factors among 30 available studies were overall pathologic stage after preoperative treatment and UICC downstaging. Evaluation of treatment response before surgery and by pathologic tumor stage after induction therapy were analyzed in slightly more than 40% of studies and found not to influence survival. More frequently studied factors-resection status, degree of tumor regression, and pathologic nodal stage after induction therapy as well as the most frequently studied factor, the treatment (in almost 75% studies)-showed no discernible impact on survival, due to conflicting results. Currently, it is impossible to identify any treatment-related predictive or prognostic factors for selecting surgery in the treatment of patients with stage IIIA/pN2 NSCLC.

Proteins and carbohydrates in nipple aspirate fluid predict the presence of atypia and cancer in women requiring diagnostic breast biopsy.

PubMed

Qin, Wenyi; Gui, Gerald; Zhang, Ke; Twelves, Dominique; Kliethermes, Beth; Sauter, Edward R

2012-02-01

Herein we present the results of two related investigations. The first study determined if concentrations in breast nipple discharge (ND) of two proteins (urinary plasminogen activator, uPA and its inhibitor, PAI-1) predicted the presence of breast atypia and cancer in pre- and/or postmenopausal women requiring surgery because of a suspicious breast lesion. The second study assessed if these proteins increased the predictive ability of a carbohydrate (Thomsen Friedenreich, TF) which we previously demonstrated predicted the presence of disease in postmenopausal women requiring surgery. In the first study we prospectively enrolled 79 participants from whom we collected ND, measured uPA and PAI-1 and correlated expression with pathologic findings. In the second study we analyzed 35 (uPA and PAI-1 in 24, uPA in an additional 11) ND samples collected from different participants requiring breast surgery, all of whom also had TF results. uPA expression was higher in pre- and PAI-1 in postmenopausal women with 1) cancer (DCIS or invasive) vs. either no cancer (atypia or benign pathology, p = .018 and .025, respectively), or benign pathology (p = .017 and .033, respectively); and 2) abnormal (atypia or cancer) versus benign pathology (p = .018 and .052, respectively). High uPA and PAI-1 concentrations and age were independent predictors of disease in premenopausal women, with an area under the curve (AUC) of 83-87% when comparing diseased vs. benign pathology. uPA, TF, and age correctly classified 35 pre- and postmenopausal women as having disease or not 84-91% of the time, whereas combining uPA+PAI-1+TF correctly classified 24 women 97-100% of the time. uPA and PAI-1 concentrations in ND were higher in women with atypia and cancer compared to women with benign disease. Combining uPA, PAI-1 and TF in the assessment of women requiring diagnostic breast surgery maximized disease prediction. The assessment of these markers may prove useful in early breast cancer detection.

Proteins and carbohydrates in nipple aspirate fluid predict the presence of atypia and cancer in women requiring diagnostic breast biopsy

PubMed Central

2012-01-01

Background Herein we present the results of two related investigations. The first study determined if concentrations in breast nipple discharge (ND) of two proteins (urinary plasminogen activator, uPA and its inhibitor, PAI-1) predicted the presence of breast atypia and cancer in pre- and/or postmenopausal women requiring surgery because of a suspicious breast lesion. The second study assessed if these proteins increased the predictive ability of a carbohydrate (Thomsen Friedenreich, TF) which we previously demonstrated predicted the presence of disease in postmenopausal women requiring surgery. Methods In the first study we prospectively enrolled 79 participants from whom we collected ND, measured uPA and PAI-1 and correlated expression with pathologic findings. In the second study we analyzed 35 (uPA and PAI-1 in 24, uPA in an additional 11) ND samples collected from different participants requiring breast surgery, all of whom also had TF results. Results uPA expression was higher in pre- and PAI-1 in postmenopausal women with 1) cancer (DCIS or invasive) vs. either no cancer (atypia or benign pathology, p = .018 and .025, respectively), or benign pathology (p = .017 and .033, respectively); and 2) abnormal (atypia or cancer) versus benign pathology (p = .018 and .052, respectively). High uPA and PAI-1 concentrations and age were independent predictors of disease in premenopausal women, with an area under the curve (AUC) of 83-87% when comparing diseased vs. benign pathology. uPA, TF, and age correctly classified 35 pre- and postmenopausal women as having disease or not 84-91% of the time, whereas combining uPA+PAI-1+TF correctly classified 24 women 97-100% of the time. Conclusions uPA and PAI-1 concentrations in ND were higher in women with atypia and cancer compared to women with benign disease. Combining uPA, PAI-1 and TF in the assessment of women requiring diagnostic breast surgery maximized disease prediction. The assessment of these markers may prove useful in early breast cancer detection. PMID:22296682

Strategies for teaching pathology to graduate students and allied health professionals.

PubMed

Fenderson, Bruce A

2005-02-01

Pathology is an essential course for many students in the biomedical sciences and allied health professions. These students learn the language of pathology and medicine, develop an appreciation for mechanisms of disease, and understand the close relationship between basic research and clinical medicine. We have developed 3 pathology courses to meet the needs of our undergraduates, graduate students, and allied health professionals. Through experience, we have settled on an approach to teaching pathology that takes into account the diverse educational backgrounds of these students. Educational resources such as assigned reading, online homework, lectures, and review sessions are carefully balanced to adjust course difficulty. Common features of our pathology curricula include a web-based computer laboratory and review sessions on the basis of selected pathology images and open-ended study questions. Lectures, computer-guided homework, and review sessions provide the core educational content for undergraduates. Graduate students, using the same computer program and review material, rely more heavily on assigned reading for core educational content. Our experience adapting a pathology curriculum to the needs of divergent groups of students suggests a general strategy for monitoring course difficulty. We hypothesize that course difficulty is proportional to the information density of specific learning resources (eg, lecture or textbook) multiplied by the weight of those learning resources placed on examinations. This formula allows educators to match the difficulty of a course with the educational needs of students, and provides a useful tool for longitudinal studies of curriculum reform.

A method for normalizing pathology images to improve feature extraction for quantitative pathology.

PubMed

Tam, Allison; Barker, Jocelyn; Rubin, Daniel

2016-01-01

With the advent of digital slide scanning technologies and the potential proliferation of large repositories of digital pathology images, many research studies can leverage these data for biomedical discovery and to develop clinical applications. However, quantitative analysis of digital pathology images is impeded by batch effects generated by varied staining protocols and staining conditions of pathological slides. To overcome this problem, this paper proposes a novel, fully automated stain normalization method to reduce batch effects and thus aid research in digital pathology applications. Their method, intensity centering and histogram equalization (ICHE), normalizes a diverse set of pathology images by first scaling the centroids of the intensity histograms to a common point and then applying a modified version of contrast-limited adaptive histogram equalization. Normalization was performed on two datasets of digitized hematoxylin and eosin (H&E) slides of different tissue slices from the same lung tumor, and one immunohistochemistry dataset of digitized slides created by restaining one of the H&E datasets. The ICHE method was evaluated based on image intensity values, quantitative features, and the effect on downstream applications, such as a computer aided diagnosis. For comparison, three methods from the literature were reimplemented and evaluated using the same criteria. The authors found that ICHE not only improved performance compared with un-normalized images, but in most cases showed improvement compared with previous methods for correcting batch effects in the literature. ICHE may be a useful preprocessing step a digital pathology image processing pipeline.

Island phytophagy: explaining the remarkable diversity of plant-feeding insects

PubMed Central

Joy, Jeffrey B.; Crespi, Bernard J.

2012-01-01

Plant-feeding insects have undergone unparalleled diversification among different plant taxa, yet explanations for variation in their diversity lack a quantitative, predictive framework. Island biogeographic theory has been applied to spatially discrete habitats but not to habitats, such as host plants, separated by genetic distance. We show that relationships between the diversity of gall-inducing flies and their host plants meet several fundamental predictions from island biogeographic theory. First, plant-taxon genetic distinctiveness, an integrator for long-term evolutionary history of plant lineages, is a significant predictor of variance in the diversity of gall-inducing flies among host-plant taxa. Second, range size and structural complexity also explain significant proportions of the variance in diversity of gall-inducing flies among different host-plant taxa. Third, as with other island systems, plant-lineage age does not predict species diversity. Island biogeographic theory, applied to habitats defined by genetic distance, provides a novel, comprehensive framework for analysing and explaining the diversity of plant-feeding insects and other host-specific taxa. PMID:22553094

Island phytophagy: explaining the remarkable diversity of plant-feeding insects.

PubMed

Joy, Jeffrey B; Crespi, Bernard J

2012-08-22

Plant-feeding insects have undergone unparalleled diversification among different plant taxa, yet explanations for variation in their diversity lack a quantitative, predictive framework. Island biogeographic theory has been applied to spatially discrete habitats but not to habitats, such as host plants, separated by genetic distance. We show that relationships between the diversity of gall-inducing flies and their host plants meet several fundamental predictions from island biogeographic theory. First, plant-taxon genetic distinctiveness, an integrator for long-term evolutionary history of plant lineages, is a significant predictor of variance in the diversity of gall-inducing flies among host-plant taxa. Second, range size and structural complexity also explain significant proportions of the variance in diversity of gall-inducing flies among different host-plant taxa. Third, as with other island systems, plant-lineage age does not predict species diversity. Island biogeographic theory, applied to habitats defined by genetic distance, provides a novel, comprehensive framework for analysing and explaining the diversity of plant-feeding insects and other host-specific taxa.

A-kinase anchoring proteins that regulate cardiac remodeling.

PubMed

Carnegie, Graeme K; Burmeister, Brian T

2011-11-01

In response to injury or stress, the adult heart undergoes maladaptive changes, collectively defined as pathological cardiac remodeling. Here, we focus on the role of A-kinase anchoring proteins (AKAPs) in 3 main areas associated with cardiac remodeling and the progression of heart failure: excitation-contraction coupling, sarcomeric regulation, and induction of pathological hypertrophy. AKAPs are a diverse family of scaffold proteins that form multiprotein complexes, integrating cAMP signaling with protein kinases, phosphatases, and other effector proteins. Many AKAPs have been characterized in the heart, where they play a critical role in modulating cardiac function.

A-Kinase Anchoring Proteins That Regulate Cardiac Remodeling

PubMed Central

Carnegie, Graeme K.; Burmeister, Brian T.

2012-01-01

In response to injury or stress, the adult heart undergoes maladaptive changes, collectively defined as pathological cardiac remodeling. Here, we focus on the role of A-kinase anchoring proteins (AKAPs) in 3 main areas associated with cardiac remodeling and the progression of heart failure: excitation–contraction coupling, sarcomeric regulation, and induction of pathological hypertrophy. AKAPs are a diverse family of scaffold proteins that form multi-protein complexes, integrating cAMP signaling with protein kinases, phosphatases, and other effector proteins. Many AKAPs have been characterized in the heart, where they play a critical role in modulating cardiac function. PMID:22075671

The complexity of epigenetic diseases.

PubMed

Brazel, Ailbhe Jane; Vernimmen, Douglas

2016-01-01

Over the past 30 years, a plethora of pathogenic mutations affecting enhancer regions and epigenetic regulators have been identified. Coupled with more recent genome-wide association studies (GWAS) and epigenome-wide association studies (EWAS) implicating major roles for regulatory mutations in disease, it is clear that epigenetic mechanisms represent important biomarkers for disease development and perhaps even therapeutic targets. Here, we discuss the diversity of disease-causing mutations in enhancers and epigenetic regulators, with a particular focus on cancer. © 2015 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Magnetic resonance imaging-ultrasound fusion biopsy for prediction of final prostate pathology.

PubMed

Le, Jesse D; Stephenson, Samuel; Brugger, Michelle; Lu, David Y; Lieu, Patricia; Sonn, Geoffrey A; Natarajan, Shyam; Dorey, Frederick J; Huang, Jiaoti; Margolis, Daniel J A; Reiter, Robert E; Marks, Leonard S

2014-11-01

We explored the impact of magnetic resonance imaging-ultrasound fusion prostate biopsy on the prediction of final surgical pathology. A total of 54 consecutive men undergoing radical prostatectomy at UCLA after fusion biopsy were included in this prospective, institutional review board approved pilot study. Using magnetic resonance imaging-ultrasound fusion, tissue was obtained from a 12-point systematic grid (mapping biopsy) and from regions of interest detected by multiparametric magnetic resonance imaging (targeted biopsy). A single radiologist read all magnetic resonance imaging, and a single pathologist independently rereviewed all biopsy and whole mount pathology, blinded to prior interpretation and matched specimen. Gleason score concordance between biopsy and prostatectomy was the primary end point. Mean patient age was 62 years and median prostate specific antigen was 6.2 ng/ml. Final Gleason score at prostatectomy was 6 (13%), 7 (70%) and 8-9 (17%). A tertiary pattern was detected in 17 (31%) men. Of 45 high suspicion (image grade 4-5) magnetic resonance imaging targets 32 (71%) contained prostate cancer. The per core cancer detection rate was 20% by systematic mapping biopsy and 42% by targeted biopsy. The highest Gleason pattern at prostatectomy was detected by systematic mapping biopsy in 54%, targeted biopsy in 54% and a combination in 81% of cases. Overall 17% of cases were upgraded from fusion biopsy to final pathology and 1 (2%) was downgraded. The combination of targeted biopsy and systematic mapping biopsy was needed to obtain the best predictive accuracy. In this pilot study magnetic resonance imaging-ultrasound fusion biopsy allowed for the prediction of final prostate pathology with greater accuracy than that reported previously using conventional methods (81% vs 40% to 65%). If confirmed, these results will have important clinical implications. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Sequential PET/CT with [18F]-FDG Predicts Pathological Tumor Response to Preoperative Short Course Radiotherapy with Delayed Surgery in Patients with Locally Advanced Rectal Cancer Using Logistic Regression Analysis

PubMed Central

Pecori, Biagio; Lastoria, Secondo; Caracò, Corradina; Celentani, Marco; Tatangelo, Fabiana; Avallone, Antonio; Rega, Daniela; De Palma, Giampaolo; Mormile, Maria; Budillon, Alfredo; Muto, Paolo; Bianco, Francesco; Aloj, Luigi; Petrillo, Antonella; Delrio, Paolo

2017-01-01

Previous studies indicate that FDG PET/CT may predict pathological response in patients undergoing neoadjuvant chemo-radiotherapy for locally advanced rectal cancer (LARC). Aim of the current study is evaluate if pathological response can be similarly predicted in LARC patients after short course radiation therapy alone. Methods: Thirty-three patients with cT2-3, N0-2, M0 rectal adenocarcinoma treated with hypo fractionated short course neoadjuvant RT (5x5 Gy) with delayed surgery (SCRTDS) were prospectively studied. All patients underwent 3 PET/CT studies at baseline, 10 days from RT end (early), and 53 days from RT end (delayed). Maximal standardized uptake value (SUVmax), mean standardized uptake value (SUVmean) and total lesion glycolysis (TLG) of the primary tumor were measured and recorded at each PET/CT study. We use logistic regression analysis to aggregate different measures of metabolic response to predict the pathological response in the course of SCRTDS. Results: We provide straightforward formulas to classify response and estimate the probability of being a major responder (TRG1-2) or a complete responder (TRG1) for each individual. The formulas are based on the level of TLG at the early PET and on the overall proportional reduction of TLG between baseline and delayed PET studies. Conclusions: This study demonstrates that in the course of SCRTDS it is possible to estimate the probabilities of pathological tumor responses on the basis of PET/CT with FDG. Our formulas make it possible to assess the risks associated to LARC borne by a patient in the course of SCRTDS. These risk assessments can be balanced against other health risks associated with further treatments and can therefore be used to make informed therapy adjustments during SCRTDS. PMID:28060889

Sequential PET/CT with [18F]-FDG Predicts Pathological Tumor Response to Preoperative Short Course Radiotherapy with Delayed Surgery in Patients with Locally Advanced Rectal Cancer Using Logistic Regression Analysis.

PubMed

Pecori, Biagio; Lastoria, Secondo; Caracò, Corradina; Celentani, Marco; Tatangelo, Fabiana; Avallone, Antonio; Rega, Daniela; De Palma, Giampaolo; Mormile, Maria; Budillon, Alfredo; Muto, Paolo; Bianco, Francesco; Aloj, Luigi; Petrillo, Antonella; Delrio, Paolo

2017-01-01

Previous studies indicate that FDG PET/CT may predict pathological response in patients undergoing neoadjuvant chemo-radiotherapy for locally advanced rectal cancer (LARC). Aim of the current study is evaluate if pathological response can be similarly predicted in LARC patients after short course radiation therapy alone. Thirty-three patients with cT2-3, N0-2, M0 rectal adenocarcinoma treated with hypo fractionated short course neoadjuvant RT (5x5 Gy) with delayed surgery (SCRTDS) were prospectively studied. All patients underwent 3 PET/CT studies at baseline, 10 days from RT end (early), and 53 days from RT end (delayed). Maximal standardized uptake value (SUVmax), mean standardized uptake value (SUVmean) and total lesion glycolysis (TLG) of the primary tumor were measured and recorded at each PET/CT study. We use logistic regression analysis to aggregate different measures of metabolic response to predict the pathological response in the course of SCRTDS. We provide straightforward formulas to classify response and estimate the probability of being a major responder (TRG1-2) or a complete responder (TRG1) for each individual. The formulas are based on the level of TLG at the early PET and on the overall proportional reduction of TLG between baseline and delayed PET studies. This study demonstrates that in the course of SCRTDS it is possible to estimate the probabilities of pathological tumor responses on the basis of PET/CT with FDG. Our formulas make it possible to assess the risks associated to LARC borne by a patient in the course of SCRTDS. These risk assessments can be balanced against other health risks associated with further treatments and can therefore be used to make informed therapy adjustments during SCRTDS.

Seizures, refractory status epilepticus, and depolarization block as endogenous brain activities

NASA Astrophysics Data System (ADS)

El Houssaini, Kenza; Ivanov, Anton I.; Bernard, Christophe; Jirsa, Viktor K.

2015-01-01

Epilepsy, refractory status epilepticus, and depolarization block are pathological brain activities whose mechanisms are poorly understood. Using a generic mathematical model of seizure activity, we show that these activities coexist under certain conditions spanning the range of possible brain activities. We perform a detailed bifurcation analysis and predict strategies to escape from some of the pathological states. Experimental results using rodent data provide support of the model, highlighting the concept that these pathological activities belong to the endogenous repertoire of brain activities.

Predicting the Creativity of Design Majors Based on the Interaction of Diverse Personality Traits

ERIC Educational Resources Information Center

Chang, Chi-Cheng; Peng, Li-Pei; Lin, Ju-Sen; Liang, Chaoyun

2015-01-01

In this study, design majors were analysed to examine how diverse personality traits interact and influence student creativity. The study participants comprised 476 design majors. The results indicated that openness predicted the originality of creativity, whereas openness, conscientiousness and agreeableness predicted the usefulness of…

Utilizing population variation, vaccination, and systems biology to study human immunology.

PubMed

Tsang, John S

2015-08-01

The move toward precision medicine has highlighted the importance of understanding biological variability within and across individuals in the human population. In particular, given the prevalent involvement of the immune system in diverse pathologies, an important question is how much and what information about the state of the immune system is required to enable accurate prediction of future health and response to medical interventions. Towards addressing this question, recent studies using vaccination as a model perturbation and systems-biology approaches are beginning to provide a glimpse of how natural population variation together with multiplexed, high-throughput measurement and computational analysis can be used to uncover predictors of immune response quality in humans. Here I discuss recent developments in this emerging field, with emphasis on baseline correlates of vaccination responses, sources of immune-state variability, as well as relevant features of study design, data generation, and computational analysis. Copyright © 2015 The Author. Published by Elsevier Ltd.. All rights reserved.

Role of histone deacetylases in gene regulation at nuclear lamina.

PubMed

Milon, Beatrice C; Cheng, Haibo; Tselebrovsky, Mikhail V; Lavrov, Sergei A; Nenasheva, Valentina V; Mikhaleva, Elena A; Shevelyov, Yuri Y; Nurminsky, Dmitry I

2012-01-01

Theoretical models suggest that gene silencing at the nuclear periphery may involve "closing" of chromatin by transcriptional repressors, such as histone deacetylases (HDACs). Here we provide experimental evidence confirming these predictions. Histone acetylation, chromatin compactness, and gene repression in lamina-interacting multigenic chromatin domains were analyzed in Drosophila S2 cells in which B-type lamin, diverse HDACs, and lamina-associated proteins were downregulated by dsRNA. Lamin depletion resulted in decreased compactness of the repressed multigenic domain associated with its detachment from the lamina and enhanced histone acetylation. Our data reveal the major role for HDAC1 in mediating deacetylation, chromatin compaction, and gene silencing in the multigenic domain, and an auxiliary role for HDAC3 that is required for retention of the domain at the lamina. These findings demonstrate the manifold and central involvement of class I HDACs in regulation of lamina-associated genes, illuminating a mechanism by which these enzymes can orchestrate normal and pathological development.

Visualization and Analysis of MiRNA-Targets Interactions Networks.

PubMed

León, Luis E; Calligaris, Sebastián D

2017-01-01

MicroRNAs are a class of small, noncoding RNA molecules of 21-25 nucleotides in length that regulate the gene expression by base-pairing with the target mRNAs, mainly leading to down-regulation or repression of the target genes. MicroRNAs are involved in diverse regulatory pathways in normal and pathological conditions. In this context, it is highly important to identify the targets of specific microRNA in order to understand the mechanism of its regulation and consequently its involvement in disease. However, the microRNA target identification is experimentally laborious and time-consuming. The in silico prediction of microRNA targets is an extremely useful approach because you can identify potential mRNA targets, reduce the number of possibilities and then, validate a few microRNA-mRNA interactions in an in vitro experimental model. In this chapter, we describe, in a simple way, bioinformatics guidelines to use miRWalk database and Cytoscape software for analyzing microRNA-mRNA interactions through their visualization as a network.

Infrared spectroscopic imaging: Label-free biochemical analysis of stroma and tissue fibrosis.

PubMed

Nazeer, Shaiju S; Sreedhar, Hari; Varma, Vishal K; Martinez-Marin, David; Massie, Christine; Walsh, Michael J

2017-11-01

Infrared spectroscopic tissue imaging is a potentially powerful adjunct tool to current histopathology techniques. By coupling the biochemical signature obtained through infrared spectroscopy to the spatial information offered by microscopy, this technique can selectively analyze the chemical composition of different features of unlabeled, unstained tissue sections. In the past, the tissue features that have received the most interest were parenchymal and epithelial cells, chiefly due to their involvement in dysplasia and progression to carcinoma; however, the field has recently turned its focus toward stroma and areas of fibrotic change. These components of tissue present an untapped source of biochemical information that can shed light on many diverse disease processes, and potentially hold useful predictive markers for these same pathologies. Here we review the recent applications of infrared spectroscopic imaging to stromal and fibrotic regions of diseased tissue, and explore the potential of this technique to advance current capabilities for tissue analysis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Integrative Analysis of Disease Signatures Shows Inflammation Disrupts Juvenile Experience-Dependent Cortical Plasticity

PubMed Central

Smith, Milo R.; Burman, Poromendro

2016-01-01

Throughout childhood and adolescence, periods of heightened neuroplasticity are critical for the development of healthy brain function and behavior. Given the high prevalence of neurodevelopmental disorders, such as autism, identifying disruptors of developmental plasticity represents an essential step for developing strategies for prevention and intervention. Applying a novel computational approach that systematically assessed connections between 436 transcriptional signatures of disease and multiple signatures of neuroplasticity, we identified inflammation as a common pathological process central to a diverse set of diseases predicted to dysregulate plasticity signatures. We tested the hypothesis that inflammation disrupts developmental cortical plasticity in vivo using the mouse ocular dominance model of experience-dependent plasticity in primary visual cortex. We found that the administration of systemic lipopolysaccharide suppressed plasticity during juvenile critical period with accompanying transcriptional changes in a particular set of molecular regulators within primary visual cortex. These findings suggest that inflammation may have unrecognized adverse consequences on the postnatal developmental trajectory and indicate that treating inflammation may reduce the burden of neurodevelopmental disorders. PMID:28101530

Artificial Intelligence in Medical Practice: The Question to the Answer?

PubMed

Miller, D Douglas; Brown, Eric W

2018-02-01

Computer science advances and ultra-fast computing speeds find artificial intelligence (AI) broadly benefitting modern society-forecasting weather, recognizing faces, detecting fraud, and deciphering genomics. AI's future role in medical practice remains an unanswered question. Machines (computers) learn to detect patterns not decipherable using biostatistics by processing massive datasets (big data) through layered mathematical models (algorithms). Correcting algorithm mistakes (training) adds to AI predictive model confidence. AI is being successfully applied for image analysis in radiology, pathology, and dermatology, with diagnostic speed exceeding, and accuracy paralleling, medical experts. While diagnostic confidence never reaches 100%, combining machines plus physicians reliably enhances system performance. Cognitive programs are impacting medical practice by applying natural language processing to read the rapidly expanding scientific literature and collate years of diverse electronic medical records. In this and other ways, AI may optimize the care trajectory of chronic disease patients, suggest precision therapies for complex illnesses, reduce medical errors, and improve subject enrollment into clinical trials. Copyright © 2018 Elsevier Inc. All rights reserved.

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

Comparison of the Walz Nomogram and Presence of Secondary Circulating Prostate Cells for Predicting Early Biochemical Failure after Radical Prostatectomy for Prostate Cancer in Chilean Men.

PubMed

Murray, Nigel P; Reyes, Eduardo; Orellana, Nelson; Fuentealba, Cynthia; Jacob, Omar

2015-01-01

To determine the utility of secondary circulating prostate cells for predicting early biochemical failure after radical prostatectomy for prostate cancer and compare the results with the Walz nomagram. A single centre, prospective study of men with prostate cancer treated with radical prostatectomy between 2004 and 2014 was conducted, with registration of clinical-pathological details, total serum PSA pre-surgery, Gleason score, extracapsular extension, positive surgical margins, infiltration of lymph nodes, seminal vesicles and pathological stage. Secondary circulating prostate cells were obtained using differential gel centrifugation and assessed using standard immunocytochemistry with anti-PSA. Biochemical failure was defined as a PSA >0.2ng/ml, predictive values werecalculated using the Walz nomagram and CPC detection. A total of 326 men participated, with a median follow up of 5 years; 64 had biochemical failure within two years. Extracapsular extension, positive surgical margins, pathological stage, Gleason score ≥ 8, infiltration of seminal vesicles and lymph nodes were all associated with higher risk of biochemical failure. The discriminative value for the nomogram and circulating prostate cells was high (AUC >0.80), predictive values were higher for circulating prostate cell detection, with a negative predictive value of 99%, sensitivity of 96% and specificity of 75%. The nomagram had good predictive power to identify men with a high risk of biochemical failure within two years. The presence of circulating prostate cells had the same predictive power, with a higher sensitivity and negative predictive value. The presence of secondary circulating prostate cells identifies a group of men with a high risk of early biochemical failure. Those negative for secondary CPCs have a very low risk of early biochemical failure.

Analysis and Prediction of Myristoylation Sites Using the mRMR Method, the IFS Method and an Extreme Learning Machine Algorithm.

PubMed

Wang, ShaoPeng; Zhang, Yu-Hang; Huang, GuoHua; Chen, Lei; Cai, Yu-Dong

2017-01-01

Myristoylation is an important hydrophobic post-translational modification that is covalently bound to the amino group of Gly residues on the N-terminus of proteins. The many diverse functions of myristoylation on proteins, such as membrane targeting, signal pathway regulation and apoptosis, are largely due to the lipid modification, whereas abnormal or irregular myristoylation on proteins can lead to several pathological changes in the cell. To better understand the function of myristoylated sites and to correctly identify them in protein sequences, this study conducted a novel computational investigation on identifying myristoylation sites in protein sequences. A training dataset with 196 positive and 84 negative peptide segments were obtained. Four types of features derived from the peptide segments following the myristoylation sites were used to specify myristoylatedand non-myristoylated sites. Then, feature selection methods including maximum relevance and minimum redundancy (mRMR), incremental feature selection (IFS), and a machine learning algorithm (extreme learning machine method) were adopted to extract optimal features for the algorithm to identify myristoylation sites in protein sequences, thereby building an optimal prediction model. As a result, 41 key features were extracted and used to build an optimal prediction model. The effectiveness of the optimal prediction model was further validated by its performance on a test dataset. Furthermore, detailed analyses were also performed on the extracted 41 features to gain insight into the mechanism of myristoylation modification. This study provided a new computational method for identifying myristoylation sites in protein sequences. We believe that it can be a useful tool to predict myristoylation sites from protein sequences. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

A Head-to-Head Comparison of the Personality Inventory for DSM-5 (PID-5) With the Personality Diagnostic Questionnaire-4 (PDQ-4) in Predicting the General Level of Personality Pathology Among Community Dwelling Subjects.

PubMed

Fossati, Andrea; Somma, Antonella; Borroni, Serena; Maffei, Cesare; Markon, Kristian E; Krueger, Robert F

2016-02-01

In order to evaluate if measures of DSM-5 Alternative PD Model domains predicted interview-based scores of general personality pathology when compared to self-report measures of DSM-IV Axis II/DSM-5 Section II PD criteria, 300 Italian community adults were administered the Iowa Personality Disorder Screen (IPDS) interview, the Personality Inventory for DSM-5 (PID-5), and the Personality Diagnostic Questionnaire-4+ (PDQ-4+). Multiple regression analyses showed that the five PID-5 domain scales collectively explained an adequate rate of the variance of the IPDS interview total score. This result was slightly lower than the amount of variance in the IPDS total score explained by the 10 PDQ-4+ scales. The PID-5 traits scales performed better than the PDQ-4+, although the difference was marginal. Hierarchical regression analyses revealed that the PID-5 domain and trait scales provided a moderate, but significant increase in the prediction of the general level of personality pathology above and beyond the PDQ-4+ scales.

Vectra DA for the objective measurement of disease activity in patients with rheumatoid arthritis.

PubMed

Segurado, O G; Sasso, E H

2014-01-01

Quantitative and regular assessment of disease activity in rheumatoid arthritis (RA) is required to achieve treatment targets such as remission and to optimize clinical outcomes. To assess inflammation accurately, predict joint damage and monitor treatment response, a measure of disease activity in RA should reflect the pathological processes resulting in irreversible joint damage and functional disability. The Vectra DA blood test is an objective measure of disease activity for patients with RA. Vectra DA provides an accurate, reproducible score on a scale of 1 to 100 based on the concentrations of 12 biomarkers that reflect the pathophysiologic diversity of RA. The analytical validity, clinical validity, and clinical utility of Vectra DA have been evaluated for patients with RA in registries and prospective and retrospective clinical studies. As a biomarker-based instrument for assessing disease activity in RA, the Vectra DA test can help monitor therapeutic response to methotrexate and biologic agents and assess clinically challenging situations, such as when clinical measures are confounded by non-inflammatory pain from fibromyalgia. Vectra DA scores correlate with imaging of joint inflammation and are predictive for radiographic progression, with high Vectra DA scores being associated with more frequent and severe progression and low scores being predictive for non-progression. In summary, the Vectra DA score is an objective measure of RA disease activity that quantifies inflammatory status. By predicting risk for joint damage more effectively than conventional clinical and laboratory measures, it has the potential to complement these measures and optimise clinical decision making.

[Intercultural approach in the care relationship in pediatrics].

PubMed

Doiret, Fabienne

2014-01-01

The intercultural approach in paediatrics requires caregivers to consider care as a specific approach which takes into account the diversity of ages, pathologies or disorders, family environments, education, etc. The professionals integrate these factors in order to adapt their support accordingly and favour the caregiver-patient relationship.

Procalcitonin for prediction of chorioamnionitis in preterm premature rupture of membranes.

PubMed

Thornburg, Loralei L; Queenan, Ruthanne; Brandt-Griffith, Brianne; Pressman, Eva K

2016-01-01

To assess serum procalcitonin (PCT), a marker of monocyte activity, in predicting chorioamnionitis in preterm premature rupture of membranes (PPROM). Prospective cohort study in singleton gestation patients with PPROM between 2 2 + 0 to 3 3 + 6 weeks gestation. Two blood samples were taken - admission and delivery or diagnosis of clinical chorioamnionitis. Maternal serum PCT > 0.1 ng/mL was considered positive. Patients were divided into four groups: clinical evidence of chorioamnionitis confirmed by placental pathology (group C + P); pathological evidence of chorioamnionitis without clinical signs (group P); clinical signs only (group C); and patients without clinical or pathological findings (group N). Groups were compared to gestational age matched controls. Forty eight patients recruited, with 28 eligible for analysis: 10 in C + P group, 10 P group, 3 C group, and 5 N group. None of the control or PPROM patients had positive PCT on admission. At delivery, 3 of 10 group C + P and 4 of 10 group P had positive PCT. Maternal serum PCT sensitivity was 50% and specificity 55.6% for diagnosis of pathological chorioamnionitis. Maternal serum PCT is not detectable in PPROM patients at admission or in uncomplicated pregnant controls and is a poor predictor for clinical or pathological chorioamnionitis.

Gambling, Drinking and Quality of Life: Evidence from Macao and Australia.

PubMed

Loo, Jasmine M Y; Shi, Yongdong; Pu, Xiaohong

2016-06-01

The investigation of the interface between psychological constructs, compulsive consumption of alcohol and pathological gambling is an important avenue for development of future initiatives in social marketing or prevention programs. This cross-cultural study attempts to bridge the gap in literature by providing an evaluation of the predictive ability of psychological variables such as gambling urge, gambling-related erroneous cognitions and comorbid alcohol consumption on pathological gambling behaviour and its impact on overall quality of life indicators. Participants consist of 445 Macao and Australian young adults (Mean age = 23 years). Results indicate that probable pathological gamblers as compared with non-gamblers reported significantly lower quality of life in all domains-physical health, psychological well-being, social relationships and environment. Adults who drank more alcohol and have stronger erroneous cognitions evidenced higher pathological gambling behavior. Our research model fits both cohorts and interestingly, erroneous gambling-related cognitions serve as a full mediator for the predictive relationship between gambling urge and pathological gambling in the Macao sample, but serve as a partial mediator in the Australian sample. Targeting erroneous cognitions in future social marketing or preventive campaigns should demonstrate to be an important strategy in reducing the effects of urge to gamble among at-risk individuals. Further implications for the industry, marketing and governmental strategies are discussed.

Dependent personality features in a complex case of borderline personality disorder.

PubMed

Nirestean, Tudor; Lukacs, Emese; Nirestean, Aurel; Gabos Grecu, Iosif

2016-11-01

Borderline personality disorder is a complex disease model as it encompasses a diversity of pathological personality traits and psychopathological symptoms. It is not surprising, therefore, that it is often manifested by personality disorders across all three clusters and accompanied by other mental (Axis I) disorders. This melange makes both psychological treatment and pharmacotherapy especially challenging, and this paper describes the case of a particularly complex case of a 33-year-old Romanian patient, who has a history of severe deprivation in childhood, mood and substance use disorder in association with borderline pathology. In the course of treatment from many sources and interventions, it has become clear that dependence is a key component of the pathology and has been rewarded with a degree of success in management. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Renal and adrenal tumors: Pathology, radiology, ultrasonography, therapy, immunology

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

Lohr, E.; Leder, L.D.

1987-01-01

Aspects as diverse as radiology, pathology, urology, pediatrics and immunology have been brought together in one book. The most up-do-date methods of tumor diagnosis by CT, NMR, and ultrasound are covered, as are methods of catheter embolization and radiation techniques in case of primarily inoperable tumors. Contents: Pathology of Renal and Adrenal Neoplasms; Ultrasound Diagnosis of Renal and Pararenal Tumors; Computed-Body-Tomography of Renal Carcinoma and Perirenal Masses; Magnetic Resonance Imaging of Renal Mass Lesions; I-125 Embolotherapy of Renal Tumors; Adrenal Mass Lesions in Infants and Children; Computed Tomography of the Adrenal Glands; Scintigraphic Studies of Renal and Adrenal Function; Surgicalmore » Management of Renal Cell Carcinoma; Operative Therapy of Nephroblastoma; Nonoperative Treatment of Renal Cell Carcinoma; Prenatal Wilms' Tumor; Congenital Neuroblastoma; Nonsurgical Management of Wilms' Tumor; Immunologic Aspects of Malignant Renal Disease.« less

Pathological Gleason prediction through gland ring morphometry in immunofluorescent prostate cancer images

NASA Astrophysics Data System (ADS)

Scott, Richard; Khan, Faisal M.; Zeineh, Jack; Donovan, Michael; Fernandez, Gerardo

2016-03-01

The Gleason score is the most common architectural and morphological assessment of prostate cancer severity and prognosis. There have been numerous quantitative techniques developed to approximate and duplicate the Gleason scoring system. Most of these approaches have been developed in standard H and E brightfield microscopy. Immunofluorescence (IF) image analysis of tissue pathology has recently been proven to be extremely valuable and robust in developing prognostic assessments of disease, particularly in prostate cancer. There have been significant advances in the literature in quantitative biomarker expression as well as characterization of glandular architectures in discrete gland rings. In this work we leverage a new method of segmenting gland rings in IF images for predicting the pathological Gleason; both the clinical and the image specific grade, which may not necessarily be the same. We combine these measures with nuclear specific characteristics as assessed by the MST algorithm. Our individual features correlate well univariately with the Gleason grades, and in a multivariate setting have an accuracy of 85% in predicting the Gleason grade. Additionally, these features correlate strongly with clinical progression outcomes (CI of 0.89), significantly outperforming the clinical Gleason grades (CI of 0.78). This work presents the first assessment of morphological gland unit features from IF images for predicting the Gleason grade.

Species richness and traits predict overyielding in stem growth in an early-successional tree diversity experiment.

PubMed

Grossman, Jake J; Cavender-Bares, Jeannine; Hobbie, Sarah E; Reich, Peter B; Montgomery, Rebecca A

2017-10-01

Over the last two decades, empirical work has established that higher biodiversity can lead to greater primary productivity; however, the importance of different aspects of biodiversity in contributing to such relationships is rarely elucidated. We assessed the relative importance of species richness, phylogenetic diversity, functional diversity, and identity of neighbors for stem growth 3 yr after seedling establishment in a tree diversity experiment in eastern Minnesota. Generally, we found that community-weighted means of key functional traits (including mycorrhizal association, leaf nitrogen and calcium, and waterlogging tolerance) as well as species richness were strong, independent predictors of stem biomass growth. More phylogenetically diverse communities did not consistently produce more biomass than expected, and the trait values or diversity of individual functional traits better predicted biomass production than did a multidimensional functional diversity metric. Furthermore, functional traits and species richness best predicted growth at the whole-plot level (12 m 2 ), whereas neighborhood composition best predicted growth at the focal tree level (0.25 m 2 ). The observed effects of biodiversity on growth appear strongly driven by positive complementary effects rather than by species-specific selection effects, suggesting that synergistic species' interactions rather than the influence of a few important species may drive overyielding. © 2017 by the Ecological Society of America.

Discordance between Ureteroscopic Biopsy and Final Pathology for Upper Tract Urothelial Carcinoma.

PubMed

Margolin, Ezra J; Matulay, Justin T; Li, Gen; Meng, Xiaosong; Chao, Brian; Vijay, Varun; Silver, Hayley; Clinton, Timothy N; Krabbe, Laura-Maria; Woldu, Solomon L; Singla, Nirmish; Bagrodia, Aditya; Margulis, Vitaly; Huang, William C; Bjurlin, Marc A; Shah, Ojas; Anderson, Christopher B

2018-06-01

We evaluated the discordance between ureteroscopic biopsy and surgical pathology findings for grading and staging upper tract urothelial carcinoma. We also sought to establish preoperative predictors of aggressive tumors. We retrospectively reviewed the records of 314 patients who underwent ureteroscopic biopsy followed by surgical management of upper tract urothelial carcinoma from 2000 to 2016 at a total of 3 institutions. Our primary outcomes were muscle invasive (pT2 or greater) disease at surgical pathology and upgrading of clinical low grade tumors to pathological high grade. At biopsy 61% of the patients had clinical high grade tumors and 21% had subepithelial connective tissue invasion (cT1+). On final pathology 79% of the patients had pathological high grade tumors and 45% had stage pT2 or greater. On multivariate analysis advanced patient age, clinical high grade and cT1+ were independently associated with pT2 or greater. The combined presence of clinical high grade and cT1+ had 86% positive predictive value for muscle invasion while the combined absence of clinical high grade and cT1+ had 80% negative predictive value. The likelihood of missing invasion on biopsy in patients with muscle invasive disease was increased when biopsy fragments were limited to 1 mm or less. Of clinical low grade cases on biopsy 51% were upgraded at surgery. The presence of positive urine cytology was associated with an increased risk of upgrading but this was not statistically significant. Clinical high grade, cT1+ on biopsy and advanced patient age are independent risk factors for muscle invasive upper tract urothelial carcinoma. There is a significant risk of upgrading in patients with clinical low grade tumors on biopsy, especially when urine cytology is positive. The predictive value of biopsy can likely be improved by more extensive ureteroscopic sampling. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Exploring the free-energy landscape of carbohydrate-protein complexes: development and validation of scoring functions considering the binding-site topology

NASA Astrophysics Data System (ADS)

Eid, Sameh; Saleh, Noureldin; Zalewski, Adam; Vedani, Angelo

2014-12-01

Carbohydrates play a key role in a variety of physiological and pathological processes and, hence, represent a rich source for the development of novel therapeutic agents. Being able to predict binding mode and binding affinity is an essential, yet lacking, aspect of the structure-based design of carbohydrate-based ligands. We assembled a diverse data set comprising 273 carbohydrate-protein crystal structures with known binding affinity and evaluated the prediction accuracy of a large collection of well-established scoring and free-energy functions, as well as combinations thereof. Unfortunately, the tested functions were not capable of reproducing binding affinities in the studied complexes. To simplify the complex free-energy surface of carbohydrate-protein systems, we classified the studied proteins according to the topology and solvent exposure of the carbohydrate-binding site into five distinct categories. A free-energy model based on the proposed classification scheme reproduced binding affinities in the carbohydrate data set with an r 2 of 0.71 and root-mean-squared-error of 1.25 kcal/mol ( N = 236). The improvement in model performance underlines the significance of the differences in the local micro-environments of carbohydrate-binding sites and demonstrates the usefulness of calibrating free-energy functions individually according to binding-site topology and solvent exposure.

Extensive Diversity of Prion Strains Is Defined by Differential Chaperone Interactions and Distinct Amyloidogenic Regions

PubMed Central

Stein, Kevin C.; True, Heather L.

2014-01-01

Amyloidogenic proteins associated with a variety of unrelated diseases are typically capable of forming several distinct self-templating conformers. In prion diseases, these different structures, called prion strains (or variants), confer dramatic variation in disease pathology and transmission. Aggregate stability has been found to be a key determinant of the diverse pathological consequences of different prion strains. Yet, it remains largely unclear what other factors might account for the widespread phenotypic variation seen with aggregation-prone proteins. Here, we examined a set of yeast prion variants of the [RNQ+] prion that differ in their ability to induce the formation of another yeast prion called [PSI+]. Remarkably, we found that the [RNQ+] variants require different, non-contiguous regions of the Rnq1 protein for both prion propagation and [PSI+] induction. This included regions outside of the canonical prion-forming domain of Rnq1. Remarkably, such differences did not result in variation in aggregate stability. Our analysis also revealed a striking difference in the ability of these [RNQ+] variants to interact with the chaperone Sis1. Thus, our work shows that the differential influence of various amyloidogenic regions and interactions with host cofactors are critical determinants of the phenotypic consequences of distinct aggregate structures. This helps reveal the complex interdependent factors that influence how a particular amyloid structure may dictate disease pathology and progression. PMID:24811344

Diagnostic criteria for vascular cognitive disorders: a VASCOG statement

PubMed Central

Sachdev, Perminder; Kalaria, Raj; O’Brien, John; Skoog, Ingmar; Alladi, Suvarna; Black, Sandra E; Blacker, Deborah; Blazer, Dan; Chen, Christopher; Chui, Helena; Ganguli, Mary; Jellinger, Kurt; Jeste, Dilip V.; Pasquier, Florence; Paulsen, Jane; Prins, Niels; Rockwood, Kenneth; Roman, Gustavo; Scheltens, Philip

2014-01-01

Background Several sets of diagnostic criteria have been published for vascular dementia (VaD) since the 1960s. The continuing ambiguity in VaD definition warrants a critical re-examination. Methods Participants at a special symposium of the International Society for Vascular Behavioral and Cognitive Disorders (VASCOG) in 2009 critiqued the current criteria. They drafted a proposal for a new set of criteria, later reviewed through multiple drafts by the group, including additional experts and the members of the Neurocognitive Disorders Work Group of the DSM-5 Task Force. Results Cognitive disorders of vascular etiology are a heterogeneous group of disorders with diverse pathologies and clinical manifestations, discussed broadly under the rubric of vascular cognitive disorders (VCD). The continuum of vascular cognitive impairment is recognized by the categories of Mild Vascular Cognitive Disorder, and Vascular Dementia or Major Vascular Cognitive Disorder. Diagnostic thresholds are defined. Clinical and neuroimaging criteria are proposed for establishing vascular etiology. Subtypes of VCD are described, and the frequent co-occurrence of Alzheimer’s disease pathology emphasized. Conclusions The proposed criteria for VCD provide a coherent approach to the diagnosis of this diverse group of disorders, with a view to stimulating clinical and pathological validation studies. These criteria can be harmonized with the DSM-5 criteria such that an international consensus on the criteria for VCD may be achieved. PMID:24632990

Semi-Automated Digital Image Analysis of Pick’s Disease and TDP-43 Proteinopathy

PubMed Central

Irwin, David J.; Byrne, Matthew D.; McMillan, Corey T.; Cooper, Felicia; Arnold, Steven E.; Lee, Edward B.; Van Deerlin, Vivianna M.; Xie, Sharon X.; Lee, Virginia M.-Y.; Grossman, Murray; Trojanowski, John Q.

2015-01-01

Digital image analysis of histology sections provides reliable, high-throughput methods for neuropathological studies but data is scant in frontotemporal lobar degeneration (FTLD), which has an added challenge of study due to morphologically diverse pathologies. Here, we describe a novel method of semi-automated digital image analysis in FTLD subtypes including: Pick’s disease (PiD, n=11) with tau-positive intracellular inclusions and neuropil threads, and TDP-43 pathology type C (FTLD-TDPC, n=10), defined by TDP-43-positive aggregates predominantly in large dystrophic neurites. To do this, we examined three FTLD-associated cortical regions: mid-frontal gyrus (MFG), superior temporal gyrus (STG) and anterior cingulate gyrus (ACG) by immunohistochemistry. We used a color deconvolution process to isolate signal from the chromogen and applied both object detection and intensity thresholding algorithms to quantify pathological burden. We found object-detection algorithms had good agreement with gold-standard manual quantification of tau- and TDP-43-positive inclusions. Our sampling method was reliable across three separate investigators and we obtained similar results in a pilot analysis using open-source software. Regional comparisons using these algorithms finds differences in regional anatomic disease burden between PiD and FTLD-TDP not detected using traditional ordinal scale data, suggesting digital image analysis is a powerful tool for clinicopathological studies in morphologically diverse FTLD syndromes. PMID:26538548

Semi-Automated Digital Image Analysis of Pick's Disease and TDP-43 Proteinopathy.

PubMed

Irwin, David J; Byrne, Matthew D; McMillan, Corey T; Cooper, Felicia; Arnold, Steven E; Lee, Edward B; Van Deerlin, Vivianna M; Xie, Sharon X; Lee, Virginia M-Y; Grossman, Murray; Trojanowski, John Q

2016-01-01

Digital image analysis of histology sections provides reliable, high-throughput methods for neuropathological studies but data is scant in frontotemporal lobar degeneration (FTLD), which has an added challenge of study due to morphologically diverse pathologies. Here, we describe a novel method of semi-automated digital image analysis in FTLD subtypes including: Pick's disease (PiD, n=11) with tau-positive intracellular inclusions and neuropil threads, and TDP-43 pathology type C (FTLD-TDPC, n=10), defined by TDP-43-positive aggregates predominantly in large dystrophic neurites. To do this, we examined three FTLD-associated cortical regions: mid-frontal gyrus (MFG), superior temporal gyrus (STG) and anterior cingulate gyrus (ACG) by immunohistochemistry. We used a color deconvolution process to isolate signal from the chromogen and applied both object detection and intensity thresholding algorithms to quantify pathological burden. We found object-detection algorithms had good agreement with gold-standard manual quantification of tau- and TDP-43-positive inclusions. Our sampling method was reliable across three separate investigators and we obtained similar results in a pilot analysis using open-source software. Regional comparisons using these algorithms finds differences in regional anatomic disease burden between PiD and FTLD-TDP not detected using traditional ordinal scale data, suggesting digital image analysis is a powerful tool for clinicopathological studies in morphologically diverse FTLD syndromes. © The Author(s) 2015.

Ecosystem Functions across Trophic Levels Are Linked to Functional and Phylogenetic Diversity

PubMed Central

Thompson, Patrick L.; Davies, T. Jonathan; Gonzalez, Andrew

2015-01-01

In experimental systems, it has been shown that biodiversity indices based on traits or phylogeny can outperform species richness as predictors of plant ecosystem function. However, it is unclear whether this pattern extends to the function of food webs in natural ecosystems. Here we tested whether zooplankton functional and phylogenetic diversity explains the functioning of 23 natural pond communities. We used two measures of ecosystem function: (1) zooplankton community biomass and (2) phytoplankton abundance (Chl a). We tested for diversity-ecosystem function relationships within and across trophic levels. We found a strong correlation between zooplankton diversity and ecosystem function, whereas local environmental conditions were less important. Further, the positive diversity-ecosystem function relationships were more pronounced for measures of functional and phylogenetic diversity than for species richness. Zooplankton and phytoplankton biomass were best predicted by different indices, suggesting that the two functions are dependent upon different aspects of diversity. Zooplankton community biomass was best predicted by zooplankton trait-based functional richness, while phytoplankton abundance was best predicted by zooplankton phylogenetic diversity. Our results suggest that the positive relationship between diversity and ecosystem function can extend across trophic levels in natural environments, and that greater insight into variation in ecosystem function can be gained by combining functional and phylogenetic diversity measures. PMID:25693188

Ecosystem functions across trophic levels are linked to functional and phylogenetic diversity.

PubMed

Thompson, Patrick L; Davies, T Jonathan; Gonzalez, Andrew

2015-01-01

In experimental systems, it has been shown that biodiversity indices based on traits or phylogeny can outperform species richness as predictors of plant ecosystem function. However, it is unclear whether this pattern extends to the function of food webs in natural ecosystems. Here we tested whether zooplankton functional and phylogenetic diversity explains the functioning of 23 natural pond communities. We used two measures of ecosystem function: (1) zooplankton community biomass and (2) phytoplankton abundance (Chl a). We tested for diversity-ecosystem function relationships within and across trophic levels. We found a strong correlation between zooplankton diversity and ecosystem function, whereas local environmental conditions were less important. Further, the positive diversity-ecosystem function relationships were more pronounced for measures of functional and phylogenetic diversity than for species richness. Zooplankton and phytoplankton biomass were best predicted by different indices, suggesting that the two functions are dependent upon different aspects of diversity. Zooplankton community biomass was best predicted by zooplankton trait-based functional richness, while phytoplankton abundance was best predicted by zooplankton phylogenetic diversity. Our results suggest that the positive relationship between diversity and ecosystem function can extend across trophic levels in natural environments, and that greater insight into variation in ecosystem function can be gained by combining functional and phylogenetic diversity measures.

Diagnostic effectiveness of quantitative [18F]flutemetamol PET imaging for detection of fibrillar amyloid β using cortical biopsy histopathology as the standard of truth in subjects with idiopathic normal pressure hydrocephalus

PubMed Central

2014-01-01

Introduction PET imaging of amyloid-β (Aβ) in vivo holds promise for aiding in earlier diagnosis and intervention in Alzheimer’s disease (AD) and mild cognitive impairment. AD-like Aβ pathology is a common comorbidity in patients with idiopathic normal pressure hydrocephalus (iNPH). Fifty patients with iNPH needing ventriculo-peritoneal shunting or intracranial pressure monitoring underwent [18F]flutemetamol PET before (N = 28) or after (N = 22) surgery. Cortical uptake of [18F]flutemetamol was assessed visually by blinded reviewers, and also quantitatively via standard uptake value ratio (SUVR) in specific neocortical regions in relation to either cerebellum or pons reference region: the cerebral cortex of (prospective studies) or surrounding (retrospective studies) the biopsy site, the contralateral homolog, and a calculated composite brain measure. Aβ pathology in the biopsy specimen (standard of truth [SoT]) was measured using Bielschowsky silver and thioflavin S plaque scores, percentage area of grey matter positive for monoclonal antibody to Aβ (4G8), and overall pathology impression. We set out to find (1) which pair(s) of PET SUVR and pathology SoT endpoints matched best, (2) whether quantitative measures of [18F]flutemetamol PET were better for predicting the pathology outcome than blinded image examination (BIE), and (3) whether there was a better match between PET image findings in retrospective vs. prospective studies. Results Of the 24 possible endpoint/SoT combinations, the one with composite-cerebellum SUVR and SoT based on overall pathology had the highest Youden index (1.000), receiver operating characteristic area under the curve (1.000), sensitivity (1.000), specificity (1.000), and sum of sensitivity and specificity for the pooled data as well as for the retrospective and prospective studies separately (2.00, for all 3). The BIE sum of sensitivity and specificity, comparable to that for quantitation, was highest using Bielschowsky silver as SoT for all SUVRs (ipsilateral, contralateral, and composite, for both reference regions). The composite SUVR had a 100% positive predictive value (both reference regions) for the overall pathology diagnosis. All SUVRs had a 100% negative predictive value for the Bielschowsky silver result. Conclusion Bielschowsky silver stain and overall pathology judgment showed the strongest associations with imaging results. PMID:24755237

Predicting Problematic Alcohol Use with the DSM-5 Alternative Model of Personality Pathology

PubMed Central

Creswell, Kasey G.; Bachrach, Rachel L.; Wright, Aidan G.C.; Pinto, Anthony; Ansell, Emily

2015-01-01

There is high comorbidity between personality disorders and alcohol use disorders, which appears related to individual differences in underlying personality dimensions of behavioral undercontrol and affective dysregulation. Very little is known about how the DSM-5 Section III trait model of personality pathology relates to alcohol problems, however, or how the strength of the relationship between personality pathology and alcohol problems changes with age and across gender. The current study examined these questions in a sample of 877 participants using the General Assessment of Personality Disorder to assess general personality dysfunction, the Personality Inventory for DSM-5 to measure specific traits, and the Alcohol Use Disorder Identification Test to assess problematic alcohol use. Results demonstrated that general personality pathology (Criterion A) was significantly related to problematic alcohol use after controlling for age and gender effects. Further, two of the five higher-order personality trait domains (Criterion B), Antagonism and Disinhibition, remained significant predictors of problematic alcohol use after accounting for the influence of general personality pathology; however, general personality pathology no longer predicted hazardous alcohol use once Antagonism and Disinhibition were added into the model. Finally, these two specific traits interacted with age, such that Antagonism was a stronger predictor of AUDIT scores among older individuals and Disinhibition was a stronger predictor of alcohol problems among younger individuals. Findings support the general validity of this new personality disorder diagnostic system and suggest important age effects in the relationship between traits and problematic alcohol use. PMID:26389625

Accuracy of contrast-enhanced spectral mammography for estimating residual tumor size after neoadjuvant chemotherapy in patients with breast cancer: a feasibility study.

PubMed

Barra, Filipe Ramos; de Souza, Fernanda Freire; Camelo, Rosimara Eva Ferreira Almeida; Ribeiro, Andrea Campos de Oliveira; Farage, Luciano

2017-01-01

To assess the feasibility of contrast-enhanced spectral mammography (CESM) of the breast for assessing the size of residual tumors after neoadjuvant chemotherapy (NAC). In breast cancer patients who underwent NAC between 2011 and 2013, we evaluated residual tumor measurements obtained with CESM and full-field digital mammography (FFDM). We determined the concordance between the methods, as well as their level of agreement with the pathology. Three radiologists analyzed eight CESM and FFDM measurements separately, considering the size of the residual tumor at its largest diameter and correlating it with that determined in the pathological analysis. Interobserver agreement was also evaluated. The sensitivity, specificity, positive predictive value, and negative predictive value were higher for CESM than for FFDM (83.33%, 100%, 100%, and 66% vs. 50%, 50%, 50%, and 25%, respectively). The CESM measurements showed a strong, consistent correlation with the pathological findings (correlation coefficient = 0.76-0.92; intraclass correlation coefficient = 0.692-0.886). The correlation between the FFDM measurements and the pathological findings was not statistically significant, with questionable consistency (intraclass correlation coefficient = 0.488-0.598). Agreement with the pathological findings was narrower for CESM measurements than for FFDM measurements. Interobserver agreement was higher for CESM than for FFDM (0.94 vs. 0.88). CESM is a feasible means of evaluating residual tumor size after NAC, showing a good correlation and good agreement with pathological findings. For CESM measurements, the interobserver agreement was excellent.

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

Golbus, Jessica R.; Puckelwartz, Megan J.; Dellefave-Castillo, Lisa

Background—Cardiomyopathy is highly heritable but genetically diverse. At present, genetic testing for cardiomyopathy uses targeted sequencing to simultaneously assess the coding regions of more than 50 genes. New genes are routinely added to panels to improve the diagnostic yield. With the anticipated $1000 genome, it is expected that genetic testing will shift towards comprehensive genome sequencing accompanied by targeted gene analysis. Therefore, we assessed the reliability of whole genome sequencing and targeted analysis to identify cardiomyopathy variants in 11 subjects with cardiomyopathy. Methods and Results—Whole genome sequencing with an average of 37× coverage was combined with targeted analysis focused onmore » 204 genes linked to cardiomyopathy. Genetic variants were scored using multiple prediction algorithms combined with frequency data from public databases. This pipeline yielded 1-14 potentially pathogenic variants per individual. Variants were further analyzed using clinical criteria and/or segregation analysis. Three of three previously identified primary mutations were detected by this analysis. In six subjects for whom the primary mutation was previously unknown, we identified mutations that segregated with disease, had clinical correlates, and/or had additional pathological correlation to provide evidence for causality. For two subjects with previously known primary mutations, we identified additional variants that may act as modifiers of disease severity. In total, we identified the likely pathological mutation in 9 of 11 (82%) subjects. We conclude that these pilot data demonstrate that ~30-40× coverage whole genome sequencing combined with targeted analysis is feasible and sensitive to identify rare variants in cardiomyopathy-associated genes.« less

Pathological video-game use among youth ages 8 to 18: a national study.

PubMed

Gentile, Douglas

2009-05-01

Researchers have studied whether some youth are "addicted" to video games, but previous studies have been based on regional convenience samples. Using a national sample, this study gathered information about video-gaming habits and parental involvement in gaming, to determine the percentage of youth who meet clinical-style criteria for pathological gaming. A Harris poll surveyed a randomly selected sample of 1,178 American youth ages 8 to 18. About 8% of video-game players in this sample exhibited pathological patterns of play. Several indicators documented convergent and divergent validity of the results: Pathological gamers spent twice as much time playing as nonpathological gamers and received poorer grades in school; pathological gaming also showed comorbidity with attention problems. Pathological status significantly predicted poorer school performance even after controlling for sex, age, and weekly amount of video-game play. These results confirm that pathological gaming can be measured reliably, that the construct demonstrates validity, and that it is not simply isomorphic with a high amount of play.

A program for automatically predicting supramolecular aggregates and its application to urea and porphin [A programme for the automated geometry prediction of supra-molecular aggregates and its application to the examples of urea and porphin

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

Sachse, Torsten; Martinez, Todd J.; Dietzek, Benjamin

Not only the molecular structure but also the presence or absence of aggregates determines many properties of organic materials. Theoretical investigation of such aggregates requires the prediction of a suitable set of diverse structures. Here, we present the open–source program EnergyScan for the unbiased prediction of geometrically diverse sets of small aggregates. Its bottom–up approach is complementary to existing ones by performing a detailed scan of an aggregate's potential energy surface, from which diverse local energy minima are selected. We crossvalidate this approach by predicting both literature–known and heretofore unreported geometries of the urea dimer. We also predict a diversemore » set of dimers of the less intensely studied case of porphin, which we investigate further using quantum chemistry. For several dimers, we find strong deviations from a reference absorption spectrum, which we explain using computed transition densities. Furthermore, this proof of principle clearly shows that EnergyScan successfully predicts aggregates exhibiting large structural and spectral diversity.« less

A program for automatically predicting supramolecular aggregates and its application to urea and porphin [A programme for the automated geometry prediction of supra-molecular aggregates and its application to the examples of urea and porphin

DOE PAGES

Sachse, Torsten; Martinez, Todd J.; Dietzek, Benjamin; ...

2018-01-03

Not only the molecular structure but also the presence or absence of aggregates determines many properties of organic materials. Theoretical investigation of such aggregates requires the prediction of a suitable set of diverse structures. Here, we present the open–source program EnergyScan for the unbiased prediction of geometrically diverse sets of small aggregates. Its bottom–up approach is complementary to existing ones by performing a detailed scan of an aggregate's potential energy surface, from which diverse local energy minima are selected. We crossvalidate this approach by predicting both literature–known and heretofore unreported geometries of the urea dimer. We also predict a diversemore » set of dimers of the less intensely studied case of porphin, which we investigate further using quantum chemistry. For several dimers, we find strong deviations from a reference absorption spectrum, which we explain using computed transition densities. Furthermore, this proof of principle clearly shows that EnergyScan successfully predicts aggregates exhibiting large structural and spectral diversity.« less

Chapter 15: Preparations of entomopathogens and diseased specimens for more detailed study using microscopy

USDA-ARS?s Scientific Manuscript database

The science of Insect Pathology encompasses a diverse assemblage of pathogens from a large and varied group of hosts. Microscopy techniques and protocols for these organisms are complex and varied and often require modifications and adaptations of standard procedures. The objective of this chapter...

Domain or Not Domain? That Is the Question: Longitudinal Semantic Deterioration in Alzheimer's Disease

ERIC Educational Resources Information Center

Moreno-Martinez, F. Javier; Goni-Imizcoz, Miguel; Spitznagel, Mary Beth

2011-01-01

Category specific semantic impairment (e.g. living versus nonliving things) has been reported in association with various pathologies, including herpes simplex encephalitis and semantic dementia. However, evidence is inconsistent regarding whether this effect exists in diseases progressively impacting diverse cortical regions, such as Alzheimer's…

Hemorrhoids.

PubMed

Sardinha, T Cristina; Corman, Marvin L

2002-12-01

Technologic advances have contributed to numerous diverse approaches to the management of hemorrhoid disease over the past centuries. Better understanding of the pathophysiology and anatomy of the anal canal has also added to the increased success in the treatment of hemorrhoids. This article reviews the clinical and pathological aspects of hemorrhoid disease, emphasizing new therapeutic modalities.

Defining the genus Fusarium in a scientifically robust way that best preserves longstanding use

USDA-ARS?s Scientific Manuscript database

In this talk I will present the argument of a diverse group of scientists advocating a phylogenetic circumscription of the genus Fusarium, that includes virtually all Fusarium species of importance in plant pathology, mycotoxicology, medicine, and basic research. This will free scientists from any o...

The Multiple Roles of Academia in an Inner City Clinic.

ERIC Educational Resources Information Center

Figueroa, Donaldo R.; Silverman, Morton W.

1996-01-01

The Optometric Center of Los Angeles provides students of the Southern California College of Optometry with an urban clinical environment that incorporates diversity, high levels of pathology, and community involvement. Through networking with outside agencies and with foundation help, the center provides a valuable educational setting for…

The Sociolinguistic Model in Speech and Language Pathology.

ERIC Educational Resources Information Center

Wolfram, Walt

A discussion of the role of sociolinguistics in the treatment of communication disorders focuses on issues related to dialect and language variation. It begins with an examination of linguistic diversity and dynamic description of language, reporting on a study of speech and language pathologists' judgments of sentences in African American…

The influence of social anxiety on the body checking behaviors of female college students.

PubMed

White, Emily K; Warren, Cortney S

2014-09-01

Social anxiety and eating pathology frequently co-occur. However, there is limited research examining the relationship between anxiety and body checking, aside from one study in which social physique anxiety partially mediated the relationship between body checking cognitions and body checking behavior (Haase, Mountford, & Waller, 2007). In an independent sample of 567 college women, we tested the fit of Haase and colleagues' foundational model but did not find evidence of mediation. Thus we tested the fit of an expanded path model that included eating pathology and clinical impairment. In the best-fitting path model (CFI=.991; RMSEA=.083) eating pathology and social physique anxiety positively predicted body checking, and body checking positively predicted clinical impairment. Therefore, women who endorse social physique anxiety may be more likely to engage in body checking behaviors and experience impaired psychosocial functioning. Published by Elsevier Ltd.

A 17-gene assay to predict prostate cancer aggressiveness in the context of Gleason grade heterogeneity, tumor multifocality, and biopsy undersampling.

PubMed

Klein, Eric A; Cooperberg, Matthew R; Magi-Galluzzi, Cristina; Simko, Jeffry P; Falzarano, Sara M; Maddala, Tara; Chan, June M; Li, Jianbo; Cowan, Janet E; Tsiatis, Athanasios C; Cherbavaz, Diana B; Pelham, Robert J; Tenggara-Hunter, Imelda; Baehner, Frederick L; Knezevic, Dejan; Febbo, Phillip G; Shak, Steven; Kattan, Michael W; Lee, Mark; Carroll, Peter R

2014-09-01

Prostate tumor heterogeneity and biopsy undersampling pose challenges to accurate, individualized risk assessment for men with localized disease. To identify and validate a biopsy-based gene expression signature that predicts clinical recurrence, prostate cancer (PCa) death, and adverse pathology. Gene expression was quantified by reverse transcription-polymerase chain reaction for three studies-a discovery prostatectomy study (n=441), a biopsy study (n=167), and a prospectively designed, independent clinical validation study (n=395)-testing retrospectively collected needle biopsies from contemporary (1997-2011) patients with low to intermediate clinical risk who were candidates for active surveillance (AS). The main outcome measures defining aggressive PCa were clinical recurrence, PCa death, and adverse pathology at prostatectomy. Cox proportional hazards regression models were used to evaluate the association between gene expression and time to event end points. Results from the prostatectomy and biopsy studies were used to develop and lock a multigene-expression-based signature, called the Genomic Prostate Score (GPS); in the validation study, logistic regression was used to test the association between the GPS and pathologic stage and grade at prostatectomy. Decision-curve analysis and risk profiles were used together with clinical and pathologic characteristics to evaluate clinical utility. Of the 732 candidate genes analyzed, 288 (39%) were found to predict clinical recurrence despite heterogeneity and multifocality, and 198 (27%) were predictive of aggressive disease after adjustment for prostate-specific antigen, Gleason score, and clinical stage. Further analysis identified 17 genes representing multiple biological pathways that were combined into the GPS algorithm. In the validation study, GPS predicted high-grade (odds ratio [OR] per 20 GPS units: 2.3; 95% confidence interval [CI], 1.5-3.7; p<0.001) and high-stage (OR per 20 GPS units: 1.9; 95% CI, 1.3-3.0; p=0.003) at surgical pathology. GPS predicted high-grade and/or high-stage disease after controlling for established clinical factors (p<0.005) such as an OR of 2.1 (95% CI, 1.4-3.2) when adjusting for Cancer of the Prostate Risk Assessment score. A limitation of the validation study was the inclusion of men with low-volume intermediate-risk PCa (Gleason score 3+4), for whom some providers would not consider AS. Genes representing multiple biological pathways discriminate PCa aggressiveness in biopsy tissue despite tumor heterogeneity, multifocality, and limited sampling at time of biopsy. The biopsy-based 17-gene GPS improves prediction of the presence or absence of adverse pathology and may help men with PCa make more informed decisions between AS and immediate treatment. Prostate cancer (PCa) is often present in multiple locations within the prostate and has variable characteristics. We identified genes with expression associated with aggressive PCa to develop a biopsy-based, multigene signature, the Genomic Prostate Score (GPS). GPS was validated for its ability to predict men who have high-grade or high-stage PCa at diagnosis and may help men diagnosed with PCa decide between active surveillance and immediate definitive treatment. Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Genetic diversity and trait genomic prediction in a pea diversity panel.

PubMed

Burstin, Judith; Salloignon, Pauline; Chabert-Martinello, Marianne; Magnin-Robert, Jean-Bernard; Siol, Mathieu; Jacquin, Françoise; Chauveau, Aurélie; Pont, Caroline; Aubert, Grégoire; Delaitre, Catherine; Truntzer, Caroline; Duc, Gérard

2015-02-21

Pea (Pisum sativum L.), a major pulse crop grown for its protein-rich seeds, is an important component of agroecological cropping systems in diverse regions of the world. New breeding challenges imposed by global climate change and new regulations urge pea breeders to undertake more efficient methods of selection and better take advantage of the large genetic diversity present in the Pisum sativum genepool. Diversity studies conducted so far in pea used Simple Sequence Repeat (SSR) and Retrotransposon Based Insertion Polymorphism (RBIP) markers. Recently, SNP marker panels have been developed that will be useful for genetic diversity assessment and marker-assisted selection. A collection of diverse pea accessions, including landraces and cultivars of garden, field or fodder peas as well as wild peas was characterised at the molecular level using newly developed SNP markers, as well as SSR markers and RBIP markers. The three types of markers were used to describe the structure of the collection and revealed different pictures of the genetic diversity among the collection. SSR showed the fastest rate of evolution and RBIP the slowest rate of evolution, pointing to their contrasted mode of evolution. SNP markers were then used to predict phenotypes -the date of flowering (BegFlo), the number of seeds per plant (Nseed) and thousand seed weight (TSW)- that were recorded for the collection. Different statistical methods were tested including the LASSO (Least Absolute Shrinkage ans Selection Operator), PLS (Partial Least Squares), SPLS (Sparse Partial Least Squares), Bayes A, Bayes B and GBLUP (Genomic Best Linear Unbiased Prediction) methods and the structure of the collection was taken into account in the prediction. Despite a limited number of 331 markers used for prediction, TSW was reliably predicted. The development of marker assisted selection has not reached its full potential in pea until now. This paper shows that the high-throughput SNP arrays that are being developed will most probably allow for a more efficient selection in this species.

Predicting carcinogenicity of diverse chemicals using probabilistic neural network modeling approaches

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

Singh, Kunwar P., E-mail: kpsingh_52@yahoo.com; Environmental Chemistry Division, CSIR-Indian Institute of Toxicology Research, Post Box 80, Mahatma Gandhi Marg, Lucknow 226 001; Gupta, Shikha

Robust global models capable of discriminating positive and non-positive carcinogens; and predicting carcinogenic potency of chemicals in rodents were developed. The dataset of 834 structurally diverse chemicals extracted from Carcinogenic Potency Database (CPDB) was used which contained 466 positive and 368 non-positive carcinogens. Twelve non-quantum mechanical molecular descriptors were derived. Structural diversity of the chemicals and nonlinearity in the data were evaluated using Tanimoto similarity index and Brock–Dechert–Scheinkman statistics. Probabilistic neural network (PNN) and generalized regression neural network (GRNN) models were constructed for classification and function optimization problems using the carcinogenicity end point in rat. Validation of the models wasmore » performed using the internal and external procedures employing a wide series of statistical checks. PNN constructed using five descriptors rendered classification accuracy of 92.09% in complete rat data. The PNN model rendered classification accuracies of 91.77%, 80.70% and 92.08% in mouse, hamster and pesticide data, respectively. The GRNN constructed with nine descriptors yielded correlation coefficient of 0.896 between the measured and predicted carcinogenic potency with mean squared error (MSE) of 0.44 in complete rat data. The rat carcinogenicity model (GRNN) applied to the mouse and hamster data yielded correlation coefficient and MSE of 0.758, 0.71 and 0.760, 0.46, respectively. The results suggest for wide applicability of the inter-species models in predicting carcinogenic potency of chemicals. Both the PNN and GRNN (inter-species) models constructed here can be useful tools in predicting the carcinogenicity of new chemicals for regulatory purposes. - Graphical abstract: Figure (a) shows classification accuracies (positive and non-positive carcinogens) in rat, mouse, hamster, and pesticide data yielded by optimal PNN model. Figure (b) shows generalization and predictive abilities of the interspecies GRNN model to predict the carcinogenic potency of diverse chemicals. - Highlights: • Global robust models constructed for carcinogenicity prediction of diverse chemicals. • Tanimoto/BDS test revealed structural diversity of chemicals and nonlinearity in data. • PNN/GRNN successfully predicted carcinogenicity/carcinogenic potency of chemicals. • Developed interspecies PNN/GRNN models for carcinogenicity prediction. • Proposed models can be used as tool to predict carcinogenicity of new chemicals.« less

Development of Web tools to predict axillary lymph node metastasis and pathological response to neoadjuvant chemotherapy in breast cancer patients.

PubMed

Sugimoto, Masahiro; Takada, Masahiro; Toi, Masakazu

2014-12-09

Nomograms are a standard computational tool to predict the likelihood of an outcome using multiple available patient features. We have developed a more powerful data mining methodology, to predict axillary lymph node (AxLN) metastasis and response to neoadjuvant chemotherapy (NAC) in primary breast cancer patients. We developed websites to use these tools. The tools calculate the probability of AxLN metastasis (AxLN model) and pathological complete response to NAC (NAC model). As a calculation algorithm, we employed a decision tree-based prediction model known as the alternative decision tree (ADTree), which is an analog development of if-then type decision trees. An ensemble technique was used to combine multiple ADTree predictions, resulting in higher generalization abilities and robustness against missing values. The AxLN model was developed with training datasets (n=148) and test datasets (n=143), and validated using an independent cohort (n=174), yielding an area under the receiver operating characteristic curve (AUC) of 0.768. The NAC model was developed and validated with n=150 and n=173 datasets from a randomized controlled trial, yielding an AUC of 0.787. AxLN and NAC models require users to input up to 17 and 16 variables, respectively. These include pathological features, including human epidermal growth factor receptor 2 (HER2) status and imaging findings. Each input variable has an option of "unknown," to facilitate prediction for cases with missing values. The websites developed facilitate the use of these tools, and serve as a database for accumulating new datasets.

The prostate health index PHI predicts oncological outcome and biochemical recurrence after radical prostatectomy - analysis in 437 patients

PubMed Central

Maxeiner, Andreas; Kilic, Ergin; Matalon, Julia; Friedersdorff, Frank; Miller, Kurt; Jung, Klaus; Stephan, Carsten; Busch, Jonas

2017-01-01

The purpose of this study was to investigate the Prostate-Health-Index (PHI) for pathological outcome prediction following radical prostatectomy and also for biochemical recurrence prediction in comparison to established parameters such as Gleason-score, pathological tumor stage, resection status (R0/1) and prostate-specific antigen (PSA). Out of a cohort of 460 cases with preoperative PHI-measurements (World Health Organization calibration: Beckman Coulter Access-2-Immunoassay) between 2001 and 2014, 437 patients with complete follow up data were included. From these 437 patients, 87 (19.9%) developed a biochemical recurrence. Patient characteristics were compared by using chi-square test. Predictors were analyzed by multivariate adjusted logistic and Cox regression. The median follow up for a biochemical recurrence was 65 (range 3-161) months. PHI, PSA, [-2]proPSA, PHI- and PSA-density performed as significant variables (p < 0.05) for cancer aggressiveness: Gleason-score <7 or ≥7 (ISUP grade 1 or ≥2) . Concerning pathological tumor stage discrimination and prediction, variables as PHI, PSA, %fPSA, [-2]proPSA, PHI- and PSA-density significantly discriminated between stages

The prostate health index PHI predicts oncological outcome and biochemical recurrence after radical prostatectomy - analysis in 437 patients.

PubMed

Maxeiner, Andreas; Kilic, Ergin; Matalon, Julia; Friedersdorff, Frank; Miller, Kurt; Jung, Klaus; Stephan, Carsten; Busch, Jonas

2017-10-03

The purpose of this study was to investigate the Prostate-Health-Index (PHI) for pathological outcome prediction following radical prostatectomy and also for biochemical recurrence prediction in comparison to established parameters such as Gleason-score, pathological tumor stage, resection status (R0/1) and prostate-specific antigen (PSA). Out of a cohort of 460 cases with preoperative PHI-measurements (World Health Organization calibration: Beckman Coulter Access-2-Immunoassay) between 2001 and 2014, 437 patients with complete follow up data were included. From these 437 patients, 87 (19.9%) developed a biochemical recurrence. Patient characteristics were compared by using chi-square test. Predictors were analyzed by multivariate adjusted logistic and Cox regression. The median follow up for a biochemical recurrence was 65 (range 3-161) months. PHI, PSA, [-2]proPSA, PHI- and PSA-density performed as significant variables (p < 0.05) for cancer aggressiveness: Gleason-score <7 or ≥7 (ISUP grade 1 or ≥2) . Concerning pathological tumor stage discrimination and prediction, variables as PHI, PSA, %fPSA, [-2]proPSA, PHI- and PSA-density significantly discriminated between stages

In situ immune response after neoadjuvant chemotherapy for breast cancer predicts survival.

PubMed

Ladoire, Sylvain; Mignot, Grégoire; Dabakuyo, Sandrine; Arnould, Laurent; Apetoh, Lionel; Rébé, Cedric; Coudert, Bruno; Martin, Francois; Bizollon, Marie Hélène; Vanoli, André; Coutant, Charles; Fumoleau, Pierre; Bonnetain, Franck; Ghiringhelli, François

2011-07-01

Accumulating preclinical evidence suggests that anticancer immune responses contribute to the success of chemotherapy. However, the predictive value of tumour-infiltrating lymphocytes after neoadjuvant chemotherapy for breast cancer remains unknown. We hypothesized that the nature of the immune infiltrate following neoadjuvant chemotherapy would predict patient survival. In a series of 111 consecutive HER2- and a series of 51 non-HER2-overexpressing breast cancer patients treated by neoadjuvant chemotherapy, we studied by immunohistochemistry tumour infiltration by FOXP3 and CD8 T lymphocytes before and after chemotherapy. Kaplan-Meier analysis and Cox modelling were used to assess relapse-free survival (RFS) and overall survival (OS). A predictive scoring system using American Joint Committee on Cancer (AJCC) pathological staging and immunological markers was created. Association of high CD8 and low FOXP3 cell infiltrates after chemotherapy was significantly associated with improved RFS (p = 0.02) and OS (p = 0.002), and outperformed classical predictive factors in multivariate analysis. A combined score associating CD8/FOXP3 ratio and pathological AJCC staging isolated a subgroup of patients with a long-term overall survival of 100%. Importantly, this score also identified patients with a favourable prognosis in an independent cohort of HER2-negative breast cancer patients. These results suggest that immunological CD8 and FOXP3 cell infiltrate after treatment is an independent predictive factor of survival in breast cancer patients treated with neoadjuvant chemotherapy and provides new insights into the role of the immune milieu and cancer. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

A method for normalizing pathology images to improve feature extraction for quantitative pathology

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

Tam, Allison; Barker, Jocelyn; Rubin, Daniel

Purpose: With the advent of digital slide scanning technologies and the potential proliferation of large repositories of digital pathology images, many research studies can leverage these data for biomedical discovery and to develop clinical applications. However, quantitative analysis of digital pathology images is impeded by batch effects generated by varied staining protocols and staining conditions of pathological slides. Methods: To overcome this problem, this paper proposes a novel, fully automated stain normalization method to reduce batch effects and thus aid research in digital pathology applications. Their method, intensity centering and histogram equalization (ICHE), normalizes a diverse set of pathology imagesmore » by first scaling the centroids of the intensity histograms to a common point and then applying a modified version of contrast-limited adaptive histogram equalization. Normalization was performed on two datasets of digitized hematoxylin and eosin (H&E) slides of different tissue slices from the same lung tumor, and one immunohistochemistry dataset of digitized slides created by restaining one of the H&E datasets. Results: The ICHE method was evaluated based on image intensity values, quantitative features, and the effect on downstream applications, such as a computer aided diagnosis. For comparison, three methods from the literature were reimplemented and evaluated using the same criteria. The authors found that ICHE not only improved performance compared with un-normalized images, but in most cases showed improvement compared with previous methods for correcting batch effects in the literature. Conclusions: ICHE may be a useful preprocessing step a digital pathology image processing pipeline.« less

The Preoperative Controlling Nutritional Status Score Predicts Survival After Curative Surgery in Patients with Pathological Stage I Non-small Cell Lung Cancer.

PubMed

Shoji, Fumihiro; Haratake, Naoki; Akamine, Takaki; Takamori, Shinkichi; Katsura, Masakazu; Takada, Kazuki; Toyokawa, Gouji; Okamoto, Tatsuro; Maehara, Yoshihiko

2017-02-01

The prognostic Controlling Nutritional Status (CONUT) score is used to evaluate immuno-nutritional conditions and is a predictive factor of postoperative survival in patients with digestive tract cancer. We retrospectively analyzed clinicopathological features of patients with pathological stage I non-small cell lung cancer (NSCLC) to identify predictors or prognostic factors of postoperative survival and to investigate the role of preoperative CONUT score in predicting survival. We selected 138 consecutive patients with pathological stage I NSCLC treated from August 2005 to August 2010. We measured their preoperative CONUT score in uni- and multivariate Cox regression analyses of postoperative survival. A high CONUT score was positively associated with preoperative serum carcinoembryonic antigen level (p=0.0100) and postoperative recurrence (p=0.0767). In multivariate analysis, the preoperative CONUT score [relative risk (RR)=6.058; 95% confidence interval (CI)=1.068-113.941; p=0.0407), increasing age (RR=7.858; 95% CI=2.034-36.185; p=0.0029), and pleural invasion (RR=36.615; 95% CI=5.900-362.620; p<0.0001) were independent prognostic factors. In Kaplan-Meier analysis of recurrence-free survival (RFS), cancer-specific survival (CS), and overall survival (OS), the group with high CONUT score had a significantly shorter RFS, CS, and OS than did the low-CONUT score group by log-rank test (p=0.0458, p=0.0104 and p=0.0096, respectively). The preoperative CONUT score is both a predictive and prognostic factor in patients with pathological stage I NSCLC. This immuno-nutritional score can indicate patients at high risk of postoperative recurrence and death. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Effect of pathologic revision and Ki67 and ERG immunohistochemistry on predicting radical prostatectomy outcome in men initially on active surveillance.

PubMed

Bokhorst, Leonard P; Roobol, Monique J; Bangma, Chris H; van Leenders, Geert J

2017-07-01

To investigate if pathologic biopsy reevaluation and implementation of immunohistochemical biomarkers could improve prediction of radical prostatectomy outcome in men initially on active surveillance. Biopsy specimens from diagnosis until switching to radical prostatectomy in men initially on active surveillance in the Dutch part of the Prostate cancer Research International Active Surveillance (PRIAS) study were collected and revised by a single pathologist. Original and revised biopsy Gleason score were compared and correlated with radical prostatectomy Gleason score. Biopsy specimens were immunohistochemically stained for Ki67 and ERG. Predictive ability of clinical characteristics and biomarkers on Gleason ≥7 or ≥pT3 on radical prostatectomy was tested using logistic regression and ROC curve analysis. A total of 150 biopsies in 95 men were revised. In 13% of diagnostic or second-to-last biopsies and 20% of the last biopsies on active surveillance revision of Gleason score resulted in change of recommendation (ie, active treatment or active surveillance). Concordance with Gleason score on radical prostatectomy was however similar for both the revised and original Gleason on biopsy. Ki67 and ERG were not statistically significant predictors of Gleason ≥7 or ≥pT3 on radical prostatectomy. Although interobserver differences in pathology reporting on biopsy could result in a change of management strategy in approximately 13-20% of men on active surveillance, both pathological revision and tested biomarkers (Ki67 and ERG) did not improve prediction of outcome on radical prostatectomy. Undersampling of most aggressive tumor remains the main focus in order to increase accurate grading at time of treatment decision making. © 2017 Wiley Periodicals, Inc.

Fluorine-18-fluorodeoxyglucose positron emission tomography as an objective substitute for CT morphologic response criteria in patients undergoing chemotherapy for colorectal liver metastases.

PubMed

Nishioka, Yujiro; Yoshioka, Ryuji; Gonoi, Wataru; Sugawara, Toshitaka; Yoshida, Shuntaro; Hashimoto, Masaji; Shindoh, Junichi

2018-05-01

The computed tomography (CT) morphologic response of colorectal liver metastases (CLM) after chemotherapy is reportedly correlated with pathologic response and survival outcomes of patients undergoing surgery. However, they are rather subjective criteria and not evaluable without adequate quality of contrast-enhanced CT images. This study sought the potential use of fluorine-18-fluorodeoxyglucose (FDG) positron emission tomography (PET) as an objective substitute for predicting pathological viability of CLM after chemotherapy. Predictive ability of tumor viability of ≤10% was compared between FDG-PET/CT and contrast-enhanced CT in 34 patients who underwent curative surgical resection for CLM after chemotherapy. The CT morphology and response were defined according to the reported criteria (Chun YS, JAMA 2009). The mean standard uptake value (SUV-mean) in CLM was significantly lower in patients with group 1 and group 2 CT morphology (median, 2.53 and 3.00, respectively) than in group 3 (median, 3.32). The tumor SUV-mean showed moderate correlation with the tumor pathologic viability (r = 0.660, P < 0.0001). A receiver operating characteristic curve analysis revealed that both the tumor SUV-mean (area under the curve [AUC], 0.916; the cut-off value, 3.00) and the CT morphology (AUC, 0.882) have excellent predictive power for ≤10% of tumor viability, while degree of tumor shrinkage showed lower predictive power (AUC, 0.692). FDG-PET shows significant correlation with pathologic viability of CLM after chemotherapy and may offer additional objective information for estimating tumor viability when the CT morphologic response is not evaluable.

Intratumor partitioning and texture analysis of dynamic contrast-enhanced (DCE)-MRI identifies relevant tumor subregions to predict pathological response of breast cancer to neoadjuvant chemotherapy.

PubMed

Wu, Jia; Gong, Guanghua; Cui, Yi; Li, Ruijiang

2016-11-01

To predict pathological response of breast cancer to neoadjuvant chemotherapy (NAC) based on quantitative, multiregion analysis of dynamic contrast enhancement magnetic resonance imaging (DCE-MRI). In this Institutional Review Board-approved study, 35 patients diagnosed with stage II/III breast cancer were retrospectively investigated using 3T DCE-MR images acquired before and after the first cycle of NAC. First, principal component analysis (PCA) was used to reduce the dimensionality of the DCE-MRI data with high temporal resolution. We then partitioned the whole tumor into multiple subregions using k-means clustering based on the PCA-defined eigenmaps. Within each tumor subregion, we extracted four quantitative Haralick texture features based on the gray-level co-occurrence matrix (GLCM). The change in texture features in each tumor subregion between pre- and during-NAC was used to predict pathological complete response after NAC. Three tumor subregions were identified through clustering, each with distinct enhancement characteristics. In univariate analysis, all imaging predictors except one extracted from the tumor subregion associated with fast washout were statistically significant (P < 0.05) after correcting for multiple testing, with area under the receiver operating characteristic (ROC) curve (AUC) or AUCs between 0.75 and 0.80. In multivariate analysis, the proposed imaging predictors achieved an AUC of 0.79 (P = 0.002) in leave-one-out cross-validation. This improved upon conventional imaging predictors such as tumor volume (AUC = 0.53) and texture features based on whole-tumor analysis (AUC = 0.65). The heterogeneity of the tumor subregion associated with fast washout on DCE-MRI predicted pathological response to NAC in breast cancer. J. Magn. Reson. Imaging 2016;44:1107-1115. © 2016 International Society for Magnetic Resonance in Medicine.

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.

External validation and comparison of two nomograms predicting the probability of Gleason sum upgrading between biopsy and radical prostatectomy pathology in two patient populations: a retrospective cohort study.

PubMed

Utsumi, Takanobu; Oka, Ryo; Endo, Takumi; Yano, Masashi; Kamijima, Shuichi; Kamiya, Naoto; Fujimura, Masaaki; Sekita, Nobuyuki; Mikami, Kazuo; Hiruta, Nobuyuki; Suzuki, Hiroyoshi

2015-11-01

The aim of this study is to validate and compare the predictive accuracy of two nomograms predicting the probability of Gleason sum upgrading between biopsy and radical prostatectomy pathology among representative patients with prostate cancer. We previously developed a nomogram, as did Chun et al. In this validation study, patients originated from two centers: Toho University Sakura Medical Center (n = 214) and Chibaken Saiseikai Narashino Hospital (n = 216). We assessed predictive accuracy using area under the curve values and constructed calibration plots to grasp the tendency for each institution. Both nomograms showed a high predictive accuracy in each institution, although the constructed calibration plots of the two nomograms underestimated the actual probability in Toho University Sakura Medical Center. Clinicians need to use calibration plots for each institution to correctly understand the tendency of each nomogram for their patients, even if each nomogram has a good predictive accuracy. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The predictive value of MRI in detecting thyroid gland invasion in patients with advanced laryngeal or hypopharyngeal carcinoma.

PubMed

Lin, Peiliang; Huang, Xiaoming; Zheng, Chushan; Cai, Qian; Guan, Zhong; Liang, Faya; Zheng, Yiqing

2017-01-01

The aim of this study was to evaluate the predictive value of magnetic resonance imaging (MRI) in detecting thyroid gland invasion (TGI) in patients with advanced laryngeal or hypopharyngeal carcinoma. In a retrospective chart review, 41 patients with advanced laryngeal or hypopharyngeal carcinoma underwent MRI scan before total laryngectomy and ipsilateral or bilateral thyroidectomy during the past 5 years. The MRI findings were compared with the postoperative pathological results. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. Among the 41 patients, 3 had thyroid gland invasion in postoperative pathological results. MRI correctly predicted the absence of TGI in 37 of 38 patients and TGI in all 3 patients. The sensitivity, specificity, PPV, and NPV of MRI were 100.0, 97.4, 75.0, and 100 %, respectively, with the diagnostic accuracy of 97.6 %. In consideration of the high negative predictive value of MRI, it may help surgeons selectively preserve thyroid gland in total laryngectomy and reduce the incidence of hypothyroidism and hypoparathyroidism postoperatively.

The Effect and Relative Importance of Neutral Genetic Diversity for Predicting Parasitism Varies across Parasite Taxa

PubMed Central

Ruiz-López, María José; Monello, Ryan J.; Gompper, Matthew E.; Eggert, Lori S.

2012-01-01

Understanding factors that determine heterogeneity in levels of parasitism across individuals is a major challenge in disease ecology. It is known that genetic makeup plays an important role in infection likelihood, but the mechanism remains unclear as does its relative importance when compared to other factors. We analyzed relationships between genetic diversity and macroparasites in outbred, free-ranging populations of raccoons (Procyon lotor). We measured heterozygosity at 14 microsatellite loci and modeled the effects of both multi-locus and single-locus heterozygosity on parasitism using an information theoretic approach and including non-genetic factors that are known to influence the likelihood of parasitism. The association of genetic diversity and parasitism, as well as the relative importance of genetic diversity, differed by parasitic group. Endoparasite species richness was better predicted by a model that included genetic diversity, with the more heterozygous hosts harboring fewer endoparasite species. Genetic diversity was also important in predicting abundance of replete ticks (Dermacentor variabilis). This association fit a curvilinear trend, with hosts that had either high or low levels of heterozygosity harboring fewer parasites than those with intermediate levels. In contrast, genetic diversity was not important in predicting abundance of non-replete ticks and lice (Trichodectes octomaculatus). No strong single-locus effects were observed for either endoparasites or replete ticks. Our results suggest that in outbred populations multi-locus diversity might be important for coping with parasitism. The differences in the relationships between heterozygosity and parasitism for the different parasites suggest that the role of genetic diversity varies with parasite-mediated selective pressures. PMID:23049796

Spatial-Temporal [{sup 18}F]FDG-PET Features for Predicting Pathologic Response of Esophageal Cancer to Neoadjuvant Chemoradiation Therapy

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

Tan, Shan; Department of Control Science and Engineering, Huazhong University of Science and Technology, Wuhan; Kligerman, Seth

2013-04-01

Purpose: To extract and study comprehensive spatial-temporal {sup 18}F-labeled fluorodeoxyglucose ([{sup 18}F]FDG) positron emission tomography (PET) features for the prediction of pathologic tumor response to neoadjuvant chemoradiation therapy (CRT) in esophageal cancer. Methods and Materials: Twenty patients with esophageal cancer were treated with trimodal therapy (CRT plus surgery) and underwent [{sup 18}F]FDG-PET/CT scans both before (pre-CRT) and after (post-CRT) CRT. The 2 scans were rigidly registered. A tumor volume was semiautomatically delineated using a threshold standardized uptake value (SUV) of ≥2.5, followed by manual editing. Comprehensive features were extracted to characterize SUV intensity distribution, spatial patterns (texture), tumor geometry, andmore » associated changes resulting from CRT. The usefulness of each feature in predicting pathologic tumor response to CRT was evaluated using the area under the receiver operating characteristic curve (AUC) value. Results: The best traditional response measure was decline in maximum SUV (SUV{sub max}; AUC, 0.76). Two new intensity features, decline in mean SUV (SUV{sub mean}) and skewness, and 3 texture features (inertia, correlation, and cluster prominence) were found to be significant predictors with AUC values ≥0.76. According to these features, a tumor was more likely to be a responder when the SUV{sub mean} decline was larger, when there were relatively fewer voxels with higher SUV values pre-CRT, or when [{sup 18}F]FDG uptake post-CRT was relatively homogeneous. All of the most accurate predictive features were extracted from the entire tumor rather than from the most active part of the tumor. For SUV intensity features and tumor size features, changes were more predictive than pre- or post-CRT assessment alone. Conclusion: Spatial-temporal [{sup 18}F]FDG-PET features were found to be useful predictors of pathologic tumor response to neoadjuvant CRT in esophageal cancer.« less

T2-weighted signal intensity-selected volumetry for prediction of pathological complete response after preoperative chemoradiotherapy in locally advanced rectal cancer.

PubMed

Kim, Sungwon; Han, Kyunghwa; Seo, Nieun; Kim, Hye Jin; Kim, Myeong-Jin; Koom, Woong Sub; Ahn, Joong Bae; Lim, Joon Seok

2018-06-01

To evaluate the diagnostic value of signal intensity (SI)-selected volumetry findings in T2-weighted magnetic resonance imaging (MRI) as a potential biomarker for predicting pathological complete response (pCR) to preoperative chemoradiotherapy (CRT) in patients with rectal cancer. Forty consecutive patients with pCR after preoperative CRT were compared with 80 age- and sex-matched non-pCR patients in a case-control study. SI-selected tumor volume was measured on post-CRT T2-weighted MRI, which included voxels of the treated tumor exceeding the SI (obturator internus muscle SI + [ischiorectal fossa fat SI - obturator internus muscle SI] × 0.2). Three blinded readers independently rated five-point pCR confidence scores and compared the diagnostic outcome with SI-selected volumetry findings. The SI-selected volumetry protocol was validated in 30 additional rectal cancer patients. The area under the receiver-operating characteristic curve (AUC) of SI-selected volumetry for pCR prediction was 0.831, with an optimal cutoff value of 649.6 mm 3 (sensitivity 0.850, specificity 0.725). The AUC of the SI-selected tumor volume was significantly greater than the pooled AUC of readers (0.707, p < 0.001). At this cutoff, the validation trial yielded an accuracy of 0.87. SI-selected volumetry in post-CRT T2-weighted MRI can help predict pCR after preoperative CRT in patients with rectal cancer. • Fibrosis and viable tumor MRI signal intensities (SIs) are difficult to distinguish. • T2 SI-selected volumetry yields high diagnostic performance for assessing pathological complete response. • T2 SI-selected volumetry is significantly more accurate than readers and non-SI-selected volumetry. • Post-chemoradiation therapy T2-weighted MRI SI-selected volumetry facilitates prediction of pathological complete response.

Predictability in Pathological Gambling? Applying the Duplication of Purchase Law to the Understanding of Cross-Purchases Between Regular and Pathological Gamblers.

PubMed

Lam, Desmond; Mizerski, Richard

2017-06-01

The objective of this study is to explore the gambling participations and game purchase duplication of light regular, heavy regular and pathological gamblers by applying the Duplication of Purchase Law. Current study uses data collected by the Australian Productivity Commission for eight different types of games. Key behavioral statistics on light regular, heavy regular, and pathological gamblers were computed and compared. The key finding is that pathological gambling, just like regular gambling, follows the Duplication of Purchase Law, which states that the dominant factor of purchase duplication between two brands is their market shares. This means that gambling between any two games at pathological level, like any regular consumer purchases, exhibits "law-like" regularity based on the pathological gamblers' participation rate of each game. Additionally, pathological gamblers tend to gamble more frequently across all games except lotteries and instant as well as make greater cross-purchases compared to heavy regular gamblers. A better understanding of the behavioral traits between regular (particularly heavy regular) and pathological gamblers can be useful to public policy makers and social marketers in order to more accurately identify such gamblers and better manage the negative impacts of gambling.

Phenotypic diversity, population structure and stress protein-based capacitoring in populations of Xeropicta derbentina, a heat-tolerant land snail species.

PubMed

Di Lellis, Maddalena A; Sereda, Sergej; Geißler, Anna; Picot, Adrien; Arnold, Petra; Lang, Stefanie; Troschinski, Sandra; Dieterich, Andreas; Hauffe, Torsten; Capowiez, Yvan; Mazzia, Christophe; Knigge, Thomas; Monsinjon, Tiphaine; Krais, Stefanie; Wilke, Thomas; Triebskorn, Rita; Köhler, Heinz-R

2014-11-01

The shell colour of many pulmonate land snail species is highly diverse. Besides a genetic basis, environmentally triggered epigenetic mechanisms including stress proteins as evolutionary capacitors are thought to influence such phenotypic diversity. In this study, we investigated the relationship of stress protein (Hsp70) levels with temperature stress tolerance, population structure and phenotypic diversity within and among different populations of a xerophilic Mediterranean snail species (Xeropicta derbentina). Hsp70 levels varied considerably among populations, and were significantly associated with shell colour diversity: individuals in populations exhibiting low diversity expressed higher Hsp70 levels both constitutively and under heat stress than those of phenotypically diverse populations. In contrast, population structure (cytochrome c oxidase subunit I gene) did not correlate with phenotypic diversity. However, genetic parameters (both within and among population differences) were able to explain variation in Hsp70 induction at elevated but non-pathologic temperatures. Our observation that (1) population structure had a high explanatory potential for Hsp70 induction and that (2) Hsp70 levels, in turn, correlated with phenotypic diversity while (3) population structure and phenotypic diversity failed to correlate provides empirical evidence for Hsp70 to act as a mediator between genotypic variation and phenotype and thus for chaperone-driven evolutionary capacitance in natural populations.

Colorectal tumors: the histology report.

PubMed

Lanza, Giovanni; Messerini, Luca; Gafà, Roberta; Risio, Mauro

2011-03-01

Epithelial colorectal tumors are common pathologic entities. Their histology report should be comprehensive of a series of pathologic parameters essential for the correct clinical management of the patients. Diagnostic histologic criteria of adenomatous, serrated, inflammatory, and hamartomatous polyps and of polyposis syndromes are discussed. In addition, the pathologic features of early and advanced colorectal cancer are described and a checklist is given. Finally, molecular prognostic and predictive factors currently employed in the treatment of colorectal cancer are discussed. Copyright © 2011 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd.. All rights reserved.

Resource-consumer diversity: testing the effects of leaf litter species diversity on stream macroinvertebrate communities.

Treesearch

John S. Kominoski; Catherine M. Pringle

2009-01-01

1. Understanding relationships between resource and consumer diversity is essential to predicting how changes in resource diversity might affect several trophic levels and overall ecosystem functioning...

Digestive capacity predicts diet diversity in Neotropical frugivorous bats.

PubMed

Saldaña-Vázquez, Romeo A; Ruiz-Sanchez, Eduardo; Herrera-Alsina, Leonel; Schondube, Jorge E

2015-09-01

1. Predicting the diet diversity of animals is important to basic and applied ecology. Knowledge of diet diversity in animals helps us understand niche partitioning, functional diversity and ecosystem services such as pollination, pest control and seed dispersal. 2. There is a negative relationship between the length of the digestive tract and diet diversity in animals; however, the role of digestive physiology in determining diet diversity has been ignored. This is especially important in vertebrates with powered flight because, unlike non-flying vertebrates, they have limitations that may constrain gut size. 3. Here, we evaluate the relationship between digestive capacity and diet diversity in Carollinae and Stenodermatinae frugivorous bats. These bats disperse the seeds of plants that are key to Neotropical forest regeneration. 4. Our results show that digestive capacity is a good predictor of diet diversity in Carollinae and Stenodermatinae frugivorous bats (R(2) = 0·77). 5. Surprisingly, the most phylogenetically closely related species were not similar in their digestive capacity or diet diversity. The lack of a phylogenetic signal for the traits evaluated implies differences in digestive physiology and diet in closely related species. 6. Our results highlight the predictive usefulness of digestive physiology for understanding the feeding ecology of animals. © 2015 The Authors. Journal of Animal Ecology © 2015 British Ecological Society.

AMPK at the Nexus of Energetics and Aging

PubMed Central

Burkewitz, Kristopher; Zhang, Yue; Mair, William B.

2014-01-01

When energy supply is low, organisms respond by slowing aging and increasing resistance to diverse age-related pathologies. Targeting the mechanisms underpinning this response may therefore treat multiple disorders through a single intervention. Here we discuss AMP-activated protein kinase (AMPK) as an integrator and mediator of several pathways and processes linking energetics to longevity. Activated by low energy, AMPK is both pro-longevity and druggable, but its role in some pathologies may not be beneficial. As such, activating AMPK may modulate multiple longevity pathways to promote healthy aging, but unlocking its full potential may require selective targeting towards substrates involved in longevity-assurance. PMID:24726383

Histopathology of lung disease in the connective tissue diseases.

PubMed

Vivero, Marina; Padera, Robert F

2015-05-01

The pathologic correlates of interstitial lung disease (ILD) secondary to connective tissue disease (CTD) comprise a diverse group of histologic patterns. Lung biopsies in patients with CTD-associated ILD tend to demonstrate simultaneous involvement of multiple anatomic compartments of the lung. Certain histologic patterns tend to predominate in each defined CTD, and it is possible in many cases to confirm connective tissue-associated lung disease and guide patient management using surgical lung biopsy. This article will cover the pulmonary pathologies seen in rheumatoid arthritis, systemic sclerosis, myositis, systemic lupus erythematosus, Sjögren syndrome, and mixed CTD. Copyright © 2015 Elsevier Inc. All rights reserved.

Diversity of deep-water cetaceans in relation to temperature: implications for ocean warming.

PubMed

Whitehead, Hal; McGill, Brian; Worm, Boris

2008-11-01

Understanding the effects of natural environmental variation on biodiversity can help predict response to future anthropogenic change. Here we analyse a large, long-term data set of sightings of deep-water cetaceans from the Atlantic, Pacific and Indian Oceans. Seasonal and geographic changes in the diversity of these genera are well predicted by a convex function of sea-surface temperature peaking at c. 21 degrees C. Thus, diversity is highest at intermediate latitudes - an emerging general pattern for the pelagic ocean. When applied to a range of Intergovernmental Panel on Climate Change global change scenarios, the predicted response is a decline of cetacean diversity across the tropics and increases at higher latitudes. This suggests that deep-water oceanic communities that dominate > 60% of the planet's surface may reorganize in response to ocean warming, with low-latitude losses of diversity and resilience.

Prostate Health Index (PHI) Predicts High-stage Pathology in African American Men.

PubMed

Schwen, Zeyad R; Tosoian, Jeffrey J; Sokoll, Lori J; Mangold, Leslie; Humphreys, Elizabeth; Schaeffer, Edward M; Partin, Alan W; Ross, Ashley E

2016-04-01

To evaluate the association between the Prostate Health Index (PHI) and adverse pathology in a cohort of African American (AA) men undergoing radical prostatectomy. Eighty AA men with prostate-specific antigen (PSA) of 2-10 ng/mL underwent measurement of PSA, free PSA (fPSA), and p2PSA prior to radical prostatectomy. PHI was calculated as [(p2PSA/fPSA) × (PSA)(½)]. Biomarker association with pT3 disease was assessed using logistic regression, and covariates were added to a baseline multivariable model including digital rectal examination. Biomarker ability to predict pT3 disease was measured using the area under the receiver operator characteristic curve. Sixteen men (20%) demonstrated pT3 disease on final pathology. Mean age, PSA, and %fPSA were similar in men with and without pT3 disease (all P  >  .05), whereas PHI was significantly greater in men with pT3 disease (mean 57.2 vs 46.6, P  =  .04). Addition of PHI to the baseline multivariable model improved discriminative ability by 12.9% (P  =. .04) and yielded greater diagnostic accuracy than models, including other individual biomarkers. In AA men with PSA of 2-10 ng/mL, PHI was predictive of pT3 prostate cancer and may help to identify men at increased risk of adverse pathology. Additional studies are needed to substantiate these findings and identify appropriate thresholds for clinical use. Copyright © 2016 Elsevier Inc. All rights reserved.

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.

Mechanisms of Autoantibody-Induced Pathology

PubMed Central

Ludwig, Ralf J.; Vanhoorelbeke, Karen; Leypoldt, Frank; Kaya, Ziya; Bieber, Katja; McLachlan, Sandra M.; Komorowski, Lars; Luo, Jie; Cabral-Marques, Otavio; Hammers, Christoph M.; Lindstrom, Jon M.; Lamprecht, Peter; Fischer, Andrea; Riemekasten, Gabriela; Tersteeg, Claudia; Sondermann, Peter; Rapoport, Basil; Wandinger, Klaus-Peter; Probst, Christian; El Beidaq, Asmaa; Schmidt, Enno; Verkman, Alan; Manz, Rudolf A.; Nimmerjahn, Falk

2017-01-01

Autoantibodies are frequently observed in healthy individuals. In a minority of these individuals, they lead to manifestation of autoimmune diseases, such as rheumatoid arthritis or Graves’ disease. Overall, more than 2.5% of the population is affected by autoantibody-driven autoimmune disease. Pathways leading to autoantibody-induced pathology greatly differ among different diseases, and autoantibodies directed against the same antigen, depending on the targeted epitope, can have diverse effects. To foster knowledge in autoantibody-induced pathology and to encourage development of urgently needed novel therapeutic strategies, we here categorized autoantibodies according to their effects. According to our algorithm, autoantibodies can be classified into the following categories: (1) mimic receptor stimulation, (2) blocking of neural transmission, (3) induction of altered signaling, triggering uncontrolled (4) microthrombosis, (5) cell lysis, (6) neutrophil activation, and (7) induction of inflammation. These mechanisms in relation to disease, as well as principles of autoantibody generation and detection, are reviewed herein. PMID:28620373

Pathophysiology of keratinization

PubMed Central

Deo, Priya Nimish; Deshmukh, Revati

2018-01-01

Cytoskeleton of a cell is made up of microfilaments, microtubules and intermediate filaments. Keratins are diverse proteins. These intermediate filaments maintain the structural integrity of the keratinocytes. The word keratin covers these intermediate filament-forming proteins within the keratinocytes. They are expressed in a specific pattern and according to the stage of cellular differentiation. They always occur in pairs. Mutations in the genes which regulate the expression of keratin proteins are associated with a number of disorders which show defects in both skin and mucosa. In addition, there are a number of disorders which are seen because of abnormal keratinization. These keratins and keratin-associated proteins have become important markers in diagnostic pathology. This review article discusses the classification, structure, functions, the stains used for the demonstration of keratin and associated pathology. The review describes the physiology of keratinization, pathology behind abnormal keratin formation and various keratin disorders. PMID:29731562

Mechanisms of CaMKII Activation in the Heart.

PubMed

Erickson, Jeffrey R

2014-01-01

Calcium/calmodulin (Ca(2+)/CaM) dependent protein kinase II (CaMKII) has emerged as a key nodal protein in the regulation of cardiac physiology and pathology. Due to the particularly elegant relationship between the structure and function of the kinase, CaMKII is able to translate a diverse set of signaling events into downstream physiological effects. While CaMKII is typically autoinhibited at basal conditions, prolonged rapid Ca(2+) cycling can activate the kinase and allow post-translational modifications that depend critically on the biochemical environment of the heart. These modifications result in sustained, autonomous CaMKII activation and have been associated with pathological cardiac signaling. Indeed, improved understanding of CaMKII activation mechanisms could potentially lead to new clinical therapies for the treatment or prevention of cardiovascular disease. Here we review the known mechanisms of CaMKII activation and discuss some of the pathological signaling pathways in which they play a role.

[Allergy and autoimmunity: Molecular diagnostics, therapy, and presumable pathogenesis].

PubMed

Arefieva, A S; Smoldovskaya, O V; Tikhonov, A A; Rubina, A Yu

2017-01-01

Allergic and autoimmune diseases represent immunopathological reactions of an organism to antigens. Despite that the allergy is a result of exaggerated immune response to foreign antigens (allergens) and autoimmune diseases are characterized by the pathological response to internal antigens (autoantigens), the underlying mechanisms of these diseases are probably common. Thus, both types of diseases represent variations in the hypersensitivity reaction. A large percentage of both the adult and pediatric population is in need of early diagnostics of these pathologies of the immune system. Considering the diversity of antibodies produced in allergic and autoimmune disease and the difficulties accompanying clinical diagnosing, molecular diagnostics of these pathological processes should be carried out in several stages, including screening and confirmatory studies. In this review, we summarize the available data on the molecular diagnostics and therapy of allergic and autoimmune diseases and discuss the basic similarities and differences in the mechanisms of their development.

Interpretation of coagulation test results using a web-based reporting system.

PubMed

Quesada, Andres E; Jabcuga, Christine E; Nguyen, Alex; Wahed, Amer; Nedelcu, Elena; Nguyen, Andy N D

2014-01-01

Web-based synoptic reporting has been successfully integrated into diverse fields of pathology, improving efficiency and reducing typographic errors. Coagulation is a challenging field for practicing pathologists and pathologists-in-training alike. To develop a Web-based program that can expedite the generation of a individualized interpretive report for a variety of coagulation tests. We developed a Web-based synoptic reporting system composed of 119 coagulation report templates and 38 thromboelastography (TEG) report templates covering a wide range of findings. Our institution implemented this reporting system in July 2011; it is currently used by pathology residents and attending pathologists. Feedback from the users of these reports have been overwhelmingly positive. Surveys note the time saved and reduced errors. Our easily accessible, user-friendly, Web-based synoptic reporting system for coagulation is a valuable asset to our laboratory services. Copyright© by the American Society for Clinical Pathology (ASCP).

Melatonin: a chemical photoperiodic signal with clinical significance in humans.

PubMed

Pang, S F; Pang, C S; Poon, A M; Lee, P P; Liu, Z M; Shiu, S Y

1998-03-01

Secretion of pineal melatonin exhibits a diumal rhythm and a seasonal rhythm in humans. Night-time melatonin is high at 3-5 year-old and decreases with age. Many drugs and pathological conditions also change melatonin levels in the circulation. Melatonin has a mild sedative effect and has been used effectively in synchronizing the sleep-wake cycle of patients with sleep disorders. Immunoenhancing, anti-cancer, anti-aging and anti-oxidant effects of melatonin have been proposed. Recent studies suggest that melatonin receptors are present in central and peripheral tissues. The importance of melatonin receptors on the nervous, reproductive, immune and renal functions is implicated. Studies on the molecular biology, physiology and pathology of melatonin receptors in different tissues are progressing rapidly. The physiological and pathological changes in melatonin secretion, multifarious melatonin actions, and diverse melatonin receptors reported suggest that melatonin is a photoperiodic signal with clinical significance in humans.

Obesity and Cardiometabolic Defects in Heart Failure Pathology.

PubMed

Halade, Ganesh V; Kain, Vasundhara

2017-09-12

Obesity is a major global epidemic that sets the stage for diverse multiple pathologies, including cardiovascular disease. The obesity-related low-grade chronic inflamed milieu is more pronounced in aging and responsive to cardiac dysfunction in heart failure pathology. Metabolic dysregulation of obesity integrates with immune reservoir in spleen and kidney network. Therefore, an integrative systems biology approach is necessary to delay progressive cardiac alternations. The purpose of this comprehensive review is to largely discuss the impact of obesity on the cardiovascular pathobiology in the context of problems and challenges, with major emphasis on the diversified models, and to study cardiac remodeling in obesity. The information in this article is immensely helpful in teaching advanced undergraduate, graduate, and medical students about the advancement and impact of obesity on cardiovascular health. © 2017 American Physiological Society. Compr Physiol 7:1463-1477, 2017. Copyright © 2017 John Wiley & Sons, Inc.

Diagnostic issues in self-mutilation.

PubMed

Favazza, A R; Rosenthal, R J

1993-02-01

Pathological self-mutilation--the deliberate alteration or destruction of body tissue without conscious suicidal intent--was examined both as a symptom of mental disorders and as a distinct syndrome. Data from more than 250 articles and books were reviewed, as well as data obtained by the authors from their extensive clinical experience in treating self-mutilating patients. The diverse behaviors that constitute pathological self-mutilation can be categorized into three basic types: major--infrequent acts that result in significant tissue damage, usually associated with psychoses and acute intoxications; stereotypic--fixed, rhythmic behavior seemingly devoid of symbolism, commonly associated with mental retardation; and superficial or moderate--behavior such as skin cutting, burning, and scratching associated with a variety of mental disorders. The authors propose that a syndrome of repetitive superficial or moderate self-mutilation should be regarded as an axis I impulse disorder. In most cases, the syndrome coexists with character pathology.

Microglia: new roles for the synaptic stripper.

PubMed

Kettenmann, Helmut; Kirchhoff, Frank; Verkhratsky, Alexei

2013-01-09

Any pathologic event in the brain leads to the activation of microglia, the immunocompetent cells of the central nervous system. In recent decades diverse molecular pathways have been identified by which microglial activation is controlled and by which the activated microglia affects neurons. In the normal brain microglia were considered "resting," but it has recently become evident that they constantly scan the brain environment and contact synapses. Activated microglia can remove damaged cells as well as dysfunctional synapses, a process termed "synaptic stripping." Here we summarize evidence that molecular pathways characterized in pathology are also utilized by microglia in the normal and developing brain to influence synaptic development and connectivity, and therefore should become targets of future research. Microglial dysfunction results in behavioral deficits, indicating that microglia are essential for proper brain function. This defines a new role for microglia beyond being a mere pathologic sensor. Copyright © 2013 Elsevier Inc. All rights reserved.

Interaction between personality traits and cerebrospinal fluid biomarkers of Alzheimer's disease pathology modulates cognitive performance.

PubMed

Tautvydaitė, Domilė; Kukreja, Deepti; Antonietti, Jean-Philippe; Henry, Hugues; von Gunten, Armin; Popp, Julius

2017-02-02

During adulthood, personality characteristics may contribute to the individual capacity to compensate the impact of developing cerebral Alzheimer's disease (AD) pathology on cognitive impairment in later life. In this study we aimed to investigate whether and how premorbid personality traits interact with cerebrospinal fluid (CSF) markers of AD pathology to predict cognitive performance in subjects with mild cognitive impairment or mild AD dementia and in participants with normal cognition. One hundred and ten subjects, of whom 66 were patients with mild cognitive impairment or mild AD dementia and 44 were healthy controls, had a comprehensive medical and neuropsychological examination as well as lumbar puncture to measure CSF biomarkers of AD pathology (amyloid beta 1-42 , phosphorylated tau and total-tau). Participants' proxies completed the Revised NEO Personality Inventory, Form R to retrospectively assess subjects' premorbid personality. In hierarchical multivariate regression analyses, including age, gender, education, APOEε4 status and cognitive level, premorbid neuroticism, conscientiousness and agreeableness modulated the effect of CSF biomarkers on cognitive performance. Low premorbid openness independently predicted lower levels of cognitive functioning after controlling for biomarker concentrations. Our findings suggest that specific premorbid personality traits are associated with cerebral AD pathology and modulate its impact on cognitive performance. Considering personality characteristics may help to appraise a person's cognitive reserve and the risk of cognitive decline in later life.

Prediction of Tibial Rotation Pathologies Using Particle Swarm Optimization and K-Means Algorithms.

PubMed

Sari, Murat; Tuna, Can; Akogul, Serkan

2018-03-28

The aim of this article is to investigate pathological subjects from a population through different physical factors. To achieve this, particle swarm optimization (PSO) and K-means (KM) clustering algorithms have been combined (PSO-KM). Datasets provided by the literature were divided into three clusters based on age and weight parameters and each one of right tibial external rotation (RTER), right tibial internal rotation (RTIR), left tibial external rotation (LTER), and left tibial internal rotation (LTIR) values were divided into three types as Type 1, Type 2 and Type 3 (Type 2 is non-pathological (normal) and the other two types are pathological (abnormal)), respectively. The rotation values of every subject in any cluster were noted. Then the algorithm was run and the produced values were also considered. The values of the produced algorithm, the PSO-KM, have been compared with the real values. The hybrid PSO-KM algorithm has been very successful on the optimal clustering of the tibial rotation types through the physical criteria. In this investigation, Type 2 (pathological subjects) is of especially high predictability and the PSO-KM algorithm has been very successful as an operation system for clustering and optimizing the tibial motion data assessments. These research findings are expected to be very useful for health providers, such as physiotherapists, orthopedists, and so on, in which this consequence may help clinicians to appropriately designing proper treatment schedules for patients.

[Clinico-pathologic Characteristics of Adult Patients with Atypical Infectious Mononucleosis].

PubMed

Yu, Ya-Ping; Song, Ping; An, Zhi-Ming; Zhou, Xiao-Gang; Li, Feng; Wang, Li-Ping; Mei, Jian-Gang; Zhai, Yong-Ping

2016-12-01

To investigate the clinicopathologic characteristics of adult patients with atypical infectious mononucleosis(IM). From January 2003 to December 2013, a total of 5 cases of atypical IM misdiagnosed as lymphoma were selected, and the clinico-pathological characteristics and efficacy of treatment were analyzed. Biopsy of lymph node or tonsil was performed to evaluate the possibility of lymphoma. Peripheral blood EBV antibody and EBV-DNA were examined by ELISA and real-time fluorescence quantitative PCR, respectively. All the cases were considered as lymphoma on the basis of morphological features in initial evaluation before relapse. These features included a florid immunoblastic proliferation, distortion of the underlying nodal or tonsillar architecture and the presence of necrosis. The immunophenotypic features, EBV encoded RNA (EBER) in situ hybridization and the gene rearrangement of immunoglobulin or T cell receptor may be helpful for the distinction of atypical IM from lymphoma. IM as EBV-related lymphoproliferative process shows marked clinical and histological diversity. Atypical case of IM may mimic many different type of lymphoma in clinical and pathologic features, and the misdiagnosis should be avoided by using molecular and pathological examination.

Life After Being a Pathology Department Chair

PubMed Central

Lipscomb, Mary F.; Gorstein, Fred; Wilkinson, David; Sanfilippo, Fred

2016-01-01

Although there is a considerable literature on transition of faculty members to the position of department chair, there is a dearth of publications about transitioning from the chair to other activities including retirement. The Association of Pathology Chairs senior fellows (all of whom are former chairs of academic departments of pathology) made this topic a focus of discussion at the Association of Pathology Chairs 2016 Annual Meeting. Of the 33 senior fellows engaged in this discussion, following their time as chairs, a small majority (18) transitioned to other administrative posts within or outside the university, while the others either returned to the active faculty (7) or retired (8). The motivating factors and influences for transitioning from the chair were probed along with the processes used in executing the transition, such as the development of transition plans. The reasons for selecting the specific type of postchair activity were also investigated. There was extraordinary diversity in the type of post-chair activities pursued. To our knowledge, no other medical specialty has examined these issues, which may be potentially relevant for the career planning of active chairs. PMID:28725780

Case mix, outcome and activity for obstetric admissions to adult, general critical care units: a secondary analysis of the ICNARC Case Mix Programme Database

PubMed Central

2005-01-01

Introduction Risk prediction scores usually overestimate mortality in obstetric populations because mortality rates in this group are considerably lower than in others. Studies examining this effect were generally small and did not distinguish between obstetric and nonobstetric pathologies. We evaluated the performance of the Acute Physiology and Chronic Health Evaluation (APACHE) II model in obstetric admissions to critical care units contributing to the ICNARC Case Mix Programme. Methods All obstetric admissions were extracted from the ICNARC Case Mix Programme Database of 219,468 admissions to UK critical care units from 1995 to 2003 inclusive. Cases were divided into direct obstetric pathologies and indirect or coincidental pathologies, and compared with a control cohort of all women aged 16–50 years not included in the obstetric categories. The predictive ability of APACHE II was evaluated in the three groups. A prognostic model was developed for direct obstetric admissions to predict the risk for hospital mortality. A log-linear model was developed to predict the length of stay in the critical care unit. Results A total of 1452 direct obstetric admissions were identified, the most common pathologies being haemorrhage and hypertensive disorders of pregnancy. There were 278 admissions identified as indirect or coincidental and 22,938 in the nonpregnant control cohort. Hospital mortality rates were 2.2%, 6.0% and 19.6% for the direct obstetric group, the indirect or coincidental group, and the control cohort, respectively. Cox regression calibration analysis showed a reasonable fit of the APACHE II model for the nonpregnant control cohort (slope = 1.1, intercept = -0.1). However, the APACHE II model vastly overestimated mortality for obstetric admissions (mortality ratio = 0.25). Risk prediction modelling demonstrated that the Glasgow Coma Scale score was the best discriminator between survival and death in obstetric admissions. Conclusion This study confirms that APACHE II overestimates mortality in obstetric admissions to critical care units. This may be because of the physiological changes in pregnancy or the unique scoring profile of obstetric pathologies such as HELLP syndrome. It may be possible to recalibrate the APACHE II score for obstetric admissions or to devise an alternative score specifically for obstetric admissions.

Imaging correlates of pathology in corticobasal syndrome(Podcast)

PubMed Central

Whitwell, J.L.; Jack, C.R.; Boeve, B.F.; Parisi, J.E.; Ahlskog, J.E.; Drubach, D.A.; Senjem, M.L.; Knopman, D.S.; Petersen, R.C.; Dickson, D.W.; Josephs, K.A.

2010-01-01

Background: Corticobasal syndrome (CBS) can be associated with different underlying pathologies that are difficult to predict based on clinical presentation. The aim of this study was to determine whether patterns of atrophy on imaging could be useful to help predict underlying pathology in CBS. Methods: This was a case-control study of 24 patients with CBS who had undergone MRI during life and came to autopsy. Pathologic diagnoses included frontotemporal lobar degeneration (FTLD) with TDP-43 immunoreactivity in 5 (CBS-TDP), Alzheimer disease (AD) in 6 (CBS-AD), corticobasal degeneration in 7 (CBS-CBD), and progressive supranuclear palsy in 6 (CBS-PSP). Voxel-based morphometry and atlas-based parcellation were used to assess atrophy across the CBS groups and compared to 24 age- and gender-matched controls. Results: All CBS pathologic groups showed gray matter loss in premotor cortices, supplemental motor area, and insula on imaging. However, CBS-TDP and CBS-AD showed more widespread patterns of loss, with frontotemporal loss observed in CBS-TDP and temporoparietal loss observed in CBS-AD. CBS-TDP showed significantly greater loss in prefrontal cortex than the other groups, whereas CBS-AD showed significantly greater loss in parietal lobe than the other groups. The focus of loss was similar in CBS-CBD and CBS-PSP, although more severe in CBS-CBD. Conclusions: Imaging patterns of atrophy in CBS vary according to pathologic diagnosis. Widespread atrophy points toward a pathologic diagnosis of FTLD-TDP or AD, with frontotemporal loss suggesting FTLD-TDP and temporoparietal loss suggesting AD. On the contrary, more focal atrophy predominantly involving the premotor and supplemental motor area suggests CBD or PSP pathology. GLOSSARY AAL = automated anatomic labeling; AD = Alzheimer disease; CBD = corticobasal degeneration; CBS = corticobasal syndrome; CDR-SB = Clinical Dementia Rating sum of boxes; FDR = false discovery rate; FTLD = frontotemporal lobar degeneration; MMSE = Mini-Mental State Examination; PSP = progressive supranuclear palsy; ROI = region of interest; SMA = supplemental motor area; TDP = TDP-43 immunoreactivity; TIV = total intracranial volume; VBM = voxel-based morphometry. PMID:21098403

Value of adding the renal pathological score to the kidney failure risk equation in advanced diabetic nephropathy.

PubMed

Yamanouchi, Masayuki; Hoshino, Junichi; Ubara, Yoshifumi; Takaichi, Kenmei; Kinowaki, Keiichi; Fujii, Takeshi; Ohashi, Kenichi; Mise, Koki; Toyama, Tadashi; Hara, Akinori; Kitagawa, Kiyoki; Shimizu, Miho; Furuichi, Kengo; Wada, Takashi

2018-01-01

There have been a limited number of biopsy-based studies on diabetic nephropathy, and therefore the clinical importance of renal biopsy in patients with diabetes in late-stage chronic kidney disease (CKD) is still debated. We aimed to clarify the renal prognostic value of pathological information to clinical information in patients with diabetes and advanced CKD. We retrospectively assessed 493 type 2 diabetics with biopsy-proven diabetic nephropathy in four centers in Japan. 296 patients with stage 3-5 CKD at the time of biopsy were identified and assigned two risk prediction scores for end-stage renal disease (ESRD): the Kidney Failure Risk Equation (KFRE, a score composed of clinical parameters) and the Diabetic Nephropathy Score (D-score, a score integrated pathological parameters of the Diabetic Nephropathy Classification by the Renal Pathology Society (RPS DN Classification)). They were randomized 2:1 to development and validation cohort. Hazard Ratios (HR) of incident ESRD were reported with 95% confidence interval (CI) of the KFRE, D-score and KFRE+D-score in Cox regression model. Improvement of risk prediction with the addition of D-score to the KFRE was assessed using c-statistics, continuous net reclassification improvement (NRI), and integrated discrimination improvement (IDI). During median follow-up of 1.9 years, 194 patients developed ESRD. The cox regression analysis showed that the KFRE,D-score and KFRE+D-score were significant predictors of ESRD both in the development cohort and in the validation cohort. The c-statistics of the D-score was 0.67. The c-statistics of the KFRE was good, but its predictive value was weaker than that in the miscellaneous CKD cohort originally reported (c-statistics, 0.78 vs. 0.90) and was not significantly improved by adding the D-score (0.78 vs. 0.79, p = 0.83). Only continuous NRI was positive after adding the D-score to the KFRE (0.4%; CI: 0.0-0.8%). We found that the predict values of the KFRE and the D-score were not as good as reported, and combining the D-score with the KFRE did not significantly improve prediction of the risk of ESRD in advanced diabetic nephropathy. To improve prediction of renal prognosis for advanced diabetic nephropathy may require different approaches with combining clinical and pathological parameters that were not measured in the KFRE and the RPS DN Classification.

Regional variations in the diversity and predicted metabolic potential of benthic prokaryotes in coastal northern Zhejiang, East China Sea

PubMed Central

Wang, Kai; Ye, Xiansen; Zhang, Huajun; Chen, Heping; Zhang, Demin; Liu, Lian

2016-01-01

Knowledge about the drivers of benthic prokaryotic diversity and metabolic potential in interconnected coastal sediments at regional scales is limited. We collected surface sediments across six zones covering ~200 km in coastal northern Zhejiang, East China Sea and combined 16 S rRNA gene sequencing, community-level metabolic prediction, and sediment physicochemical measurements to investigate variations in prokaryotic diversity and metabolic gene composition with geographic distance and under local environmental conditions. Geographic distance was the most influential factor in prokaryotic β-diversity compared with major environmental drivers, including temperature, sediment texture, acid-volatile sulfide, and water depth, but a large unexplained variation in community composition suggested the potential effects of unmeasured abiotic/biotic factors and stochastic processes. Moreover, prokaryotic assemblages showed a biogeographic provincialism across the zones. The predicted metabolic gene composition similarly shifted as taxonomic composition did. Acid-volatile sulfide was strongly correlated with variation in metabolic gene composition. The enrichments in the relative abundance of sulfate-reducing bacteria and genes relevant with dissimilatory sulfate reduction were observed and predicted, respectively, in the Yushan area. These results provide insights into the relative importance of geographic distance and environmental condition in driving benthic prokaryotic diversity in coastal areas and predict specific biogeochemically-relevant genes for future studies. PMID:27917954

Exploring International Perspectives in Hearing Health Care

ERIC Educational Resources Information Center

Montgomery, Judy K.

2007-01-01

This article presents an interview with Dr. Dolores E. Battle, a professor of speech-language pathology and senior advisor to the president for equity and campus diversity at Buffalo State College. She is a former president of the American Speech-Language-Hearing Association (in 2005) and a very active member of international organizations of both…

Guide to Experts in Forestry and Natural Resources

Treesearch

Northeastern Research Station

2000-01-01

To help you gain access to what the Forest Service knows, we?ve compiled a list of experts who work for the Northeastern Research Station. They represent a diversity of scientific disciplines and knowledge?from forestry to sociology, from plant pathology to meteorology, from genetic engineering to economics. Together with other scientists, technicians and...

Moving the Lab into the Field: The Making of Pathologized (Non)Citizens in US Science Education

ERIC Educational Resources Information Center

Kirchgasler, Kathryn L.

2018-01-01

This article examines how notions of health and citizenship have become entangled in US science education reforms targeting particular populations. Current science education policy assumes that marginalized groups have been historically ignored, and that new research is required to "make diversity visible" in order to adapt instruction…

Diversifying Theory and Science: Expanding the Boundaries of Empirically Supported Interventions in School Psychology.

ERIC Educational Resources Information Center

Kratochwill, Thomas R.; Stoiber, Karen Callan

2000-01-01

Developmental psychopathology and principles advance in Hughes' target article can be useful to promote development, evaluation, and application of empirically supported interventions (ESIs), but embracing a pathological framework is extremely limited given the diversity in theoretical approaches relevant to school-based ESIs. Argues that in order…

Molecular identification, genetic diversity, population genetics and genomics of Rhizoctonia solani. In:perspective of plant pathology in genomic era

USDA-ARS?s Scientific Manuscript database

The basidiomycetous soilborne fungus Rhizoctonia (sensu lato) is an economically important pathogen of worldwide distribution and it is known to attack at least 188 species of higher plants, including agronomic crops, vegetables, ornamentals, forest trees and turfgrasses. The pathogenic isolates may...

A Conceptual Framework for Responsive Global Engagement in Communication Sciences and Disorders

ERIC Educational Resources Information Center

Hyter, Yvette D.

2014-01-01

The field of speech-language pathology needs a conceptual framework to guide the provision of services in a globalized world. Proposed in this article is a conceptual framework designed to facilitate responsive global engagement for professionals such as speech-language pathologists, who are increasingly serving diverse populations around the…

FIV diversity: FIV Ple subtype composition may influence disease outcome in African lions.

PubMed

Troyer, Jennifer L; Roelke, Melody E; Jespersen, Jillian M; Baggett, Natalie; Buckley-Beason, Valerie; MacNulty, Dan; Craft, Meggan; Packer, Craig; Pecon-Slattery, Jill; O'Brien, Stephen J

2011-10-15

Feline immunodeficiency virus (FIV) infects domestic cats and at least 20 additional species of non-domestic felids throughout the world. Strains specific to domestic cat (FIV(Fca)) produce AIDS-like disease progression, sequelae and pathology providing an informative model for HIV infection in humans. Less is known about the immunological and pathological influence of FIV in other felid species although multiple distinct strains of FIV circulate in natural populations. As in HIV-1 and HIV-2, multiple diverse cross-species infections may have occurred. In the Serengeti National Park, Tanzania, three divergent subtypes of lion FIV (FIV(Ple)) are endemic, whereby 100% of adult lions are infected with one or more of these strains. Herein, the relative distribution of these subtypes in the population are surveyed and, combined with observed differences in lion mortality due to secondary infections based on FIV(Ple) subtypes, the data suggest that FIV(Ple) subtypes may have different patterns of pathogenicity and transmissibility among wild lion populations. Copyright © 2011 Elsevier B.V. All rights reserved.

Bacterial diversity in the feces of dogs with CPV infection.

PubMed

Zheng, Yun; Hao, Xiangqi; Lin, Xi; Zheng, Qingxu; Zhang, Wenyan; Zhou, Pei; Li, Shoujun

2018-04-27

Canine parvovirus (CPV) is a contagious disease in dogs that has high morbidity and mortality. In cases of infection, the pups tend to have a higher mortality and more severe clinical symptoms than the adult dogs because the dehydration is difficult for pups to bear. Following the natural infection, there is a rapid antibody response neutralizing the extracellular virus. As a result, virus titers in tissue and feces become markedly reduced. Hence, it is important to have an effective symptomatic therapy of supporting animals to survive in the early stages of CPV infection. Furthermore, the co-infection with bacteria could increase the severity of lesions and clinical signs as well. In this paper, we obtained the bacterial diversity in feces of CPV infected dogs with the enrichment of five bacteria genera (Shigella, Peptoclostridium, Peptostreptococcus, Streptococcus, Fusobacterium). These microorganisms may partly result in the intestinal pathology of the infection. In summary, the discussion of the bacterial biodiversity in feces of CPV infected dogs provides further insights into the pathology of CPV disease and the targets of developing more effective treatment strategies. Copyright © 2018 Elsevier Ltd. All rights reserved.

Automated Cancer Registry Notifications: Validation of a Medical Text Analytics System for Identifying Patients with Cancer from a State-Wide Pathology Repository

PubMed Central

Nguyen, Anthony N; Moore, Julie; O'Dwyer, John; Philpot, Shoni

2016-01-01

The paper assesses the utility of Medtex on automating Cancer Registry notifications from narrative histology and cytology reports from the Queensland state-wide pathology information system. A corpus of 45.3 million pathology HL7 messages (including 119,581 histology and cytology reports) from a Queensland pathology repository for the year of 2009 was analysed by Medtex for cancer notification. Reports analysed by Medtex were consolidated at a patient level and compared against patients with notifiable cancers from the Queensland Oncology Repository (QOR). A stratified random sample of 1,000 patients was manually reviewed by a cancer clinical coder to analyse agreements and discrepancies. Sensitivity of 96.5% (95% confidence interval: 94.5-97.8%), specificity of 96.5% (95.3-97.4%) and positive predictive value of 83.7% (79.6-86.8%) were achieved for identifying cancer notifiable patients. Medtex achieved high sensitivity and specificity across the breadth of cancers, report types, pathology laboratories and pathologists throughout the State of Queensland. The high sensitivity also resulted in the identification of cancer patients that were not found in the QOR. High sensitivity was at the expense of positive predictive value; however, these cases may be considered as lower priority to Cancer Registries as they can be quickly reviewed. Error analysis revealed that system errors tended to be tumour stream dependent. Medtex is proving to be a promising medical text analytic system. High value cancer information can be generated through intelligent data classification and extraction on large volumes of unstructured pathology reports. PMID:28269893

Accuracy of contrast-enhanced spectral mammography for estimating residual tumor size after neoadjuvant chemotherapy in patients with breast cancer: a feasibility study

PubMed Central

Barra, Filipe Ramos; de Souza, Fernanda Freire; Camelo, Rosimara Eva Ferreira Almeida; Ribeiro, Andrea Campos de Oliveira; Farage, Luciano

2017-01-01

Objective To assess the feasibility of contrast-enhanced spectral mammography (CESM) of the breast for assessing the size of residual tumors after neoadjuvant chemotherapy (NAC). Materials and methods In breast cancer patients who underwent NAC between 2011 and 2013, we evaluated residual tumor measurements obtained with CESM and full-field digital mammography (FFDM). We determined the concordance between the methods, as well as their level of agreement with the pathology. Three radiologists analyzed eight CESM and FFDM measurements separately, considering the size of the residual tumor at its largest diameter and correlating it with that determined in the pathological analysis. Interobserver agreement was also evaluated. Results The sensitivity, specificity, positive predictive value, and negative predictive value were higher for CESM than for FFDM (83.33%, 100%, 100%, and 66% vs. 50%, 50%, 50%, and 25%, respectively). The CESM measurements showed a strong, consistent correlation with the pathological findings (correlation coefficient = 0.76-0.92; intraclass correlation coefficient = 0.692-0.886). The correlation between the FFDM measurements and the pathological findings was not statistically significant, with questionable consistency (intraclass correlation coefficient = 0.488-0.598). Agreement with the pathological findings was narrower for CESM measurements than for FFDM measurements. Interobserver agreement was higher for CESM than for FFDM (0.94 vs. 0.88). Conclusion CESM is a feasible means of evaluating residual tumor size after NAC, showing a good correlation and good agreement with pathological findings. For CESM measurements, the interobserver agreement was excellent. PMID:28894329

Predicting problematic alcohol use with the DSM-5 alternative model of personality pathology.

PubMed

Creswell, Kasey G; Bachrach, Rachel L; Wright, Aidan G C; Pinto, Anthony; Ansell, Emily

2016-01-01

High comorbidity between personality disorders and alcohol use disorders appears related to individual differences in underlying personality dimensions of behavioral undercontrol and affective dysregulation. However, very little is known about how the Diagnostic and Statistical Manual of Mental Disorders (5th edition; DSM-5) Section III trait model of personality pathology relates to alcohol problems or how the strength of the relationship between personality pathology and alcohol problems changes with age and across gender. The current study examined these questions in a sample of 877 participants using the General Assessment of Personality Disorder to assess general personality dysfunction, the Personality Inventory for DSM-5 to measure specific traits, and the Alcohol Use Disorder Identification Test (AUDIT) to assess problematic alcohol use. Results demonstrated that general personality pathology (Criterion A) was significantly related to problematic alcohol use after controlling for age and gender effects. Furthermore, 2 of the 5 higher-order personality trait domains (Criterion B), Antagonism and Disinhibition, remained significant predictors of problematic alcohol use after accounting for the influence of general personality pathology; however, general personality pathology no longer predicted hazardous alcohol use once Antagonism and Disinhibition were added into the model. Finally, these 2 specific traits interacted with age, such that Antagonism was a stronger predictor of AUDIT scores among older individuals and Disinhibition was a stronger predictor of alcohol problems among younger individuals. Findings support the general validity of this new personality disorder diagnostic system and suggest important age effects in the relationship between traits and problematic alcohol use. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Automated Cancer Registry Notifications: Validation of a Medical Text Analytics System for Identifying Patients with Cancer from a State-Wide Pathology Repository.

PubMed

Nguyen, Anthony N; Moore, Julie; O'Dwyer, John; Philpot, Shoni

2016-01-01

The paper assesses the utility of Medtex on automating Cancer Registry notifications from narrative histology and cytology reports from the Queensland state-wide pathology information system. A corpus of 45.3 million pathology HL7 messages (including 119,581 histology and cytology reports) from a Queensland pathology repository for the year of 2009 was analysed by Medtex for cancer notification. Reports analysed by Medtex were consolidated at a patient level and compared against patients with notifiable cancers from the Queensland Oncology Repository (QOR). A stratified random sample of 1,000 patients was manually reviewed by a cancer clinical coder to analyse agreements and discrepancies. Sensitivity of 96.5% (95% confidence interval: 94.5-97.8%), specificity of 96.5% (95.3-97.4%) and positive predictive value of 83.7% (79.6-86.8%) were achieved for identifying cancer notifiable patients. Medtex achieved high sensitivity and specificity across the breadth of cancers, report types, pathology laboratories and pathologists throughout the State of Queensland. The high sensitivity also resulted in the identification of cancer patients that were not found in the QOR. High sensitivity was at the expense of positive predictive value; however, these cases may be considered as lower priority to Cancer Registries as they can be quickly reviewed. Error analysis revealed that system errors tended to be tumour stream dependent. Medtex is proving to be a promising medical text analytic system. High value cancer information can be generated through intelligent data classification and extraction on large volumes of unstructured pathology reports.

Evaluation of endorectal ultrasound (ERUS) and MRI for prediction of circumferential resection margin (CRM) for rectal cancer.

PubMed

Tsai, Catherine; Hague, Cameron; Xiong, Wei; Raval, Manoj; Karimuddin, Ahmer; Brown, Carl; Phang, P Terry

2017-05-01

ERUS and MRI are used for preoperative imaging of rectal cancer. Here, we compare ERUS and MRI for accuracy of CRM prediction at mid- and distal rectal locations. In retrospective review, 20 rectal cancer patients having TME surgery had both ERUS and MRI preoperatively: 8 mid rectum and 12 in distal rectum. Predicted CRM by ERUS and MRI were compared to TME pathology. Overall, predicted CRM was 6.5 ± 3.6 mm by ERUS, 7.7 ± 5.0 mm by MRI, and 6.0 ± 4.6 mm by pathology. Overall, correlation coefficients to pathology were 0.77 (p = 0.0004) for ERUS and 0.64 (p = 0.008) for MRI. In distal rectum, correlation coefficients were 0.71 (p = 0.02) for ERUS and -0.10 (p = 0.79) for MRI. In mid rectum, correlation coefficients were 0.92 (p = 0.01) for ERUS and 0.44 (p = 0.38) for MRI. While MRI is used routinely for preoperative rectal cancer imaging, ERUS can provide additional assessment of CRM for mid or distal rectal lesions. Further investigation is needed to support these preliminary ERUS CRM findings in mid and distal rectum. Copyright © 2017 Elsevier Inc. All rights reserved.

Phylogenetic approaches reveal biodiversity threats under climate change

NASA Astrophysics Data System (ADS)

González-Orozco, Carlos E.; Pollock, Laura J.; Thornhill, Andrew H.; Mishler, Brent D.; Knerr, Nunzio; Laffan, Shawn W.; Miller, Joseph T.; Rosauer, Dan F.; Faith, Daniel P.; Nipperess, David A.; Kujala, Heini; Linke, Simon; Butt, Nathalie; Külheim, Carsten; Crisp, Michael D.; Gruber, Bernd

2016-12-01

Predicting the consequences of climate change for biodiversity is critical to conservation efforts. Extensive range losses have been predicted for thousands of individual species, but less is known about how climate change might impact whole clades and landscape-scale patterns of biodiversity. Here, we show that climate change scenarios imply significant changes in phylogenetic diversity and phylogenetic endemism at a continental scale in Australia using the hyper-diverse clade of eucalypts. We predict that within the next 60 years the vast majority of species distributions (91%) across Australia will shrink in size (on average by 51%) and shift south on the basis of projected suitable climatic space. Geographic areas currently with high phylogenetic diversity and endemism are predicted to change substantially in future climate scenarios. Approximately 90% of the current areas with concentrations of palaeo-endemism (that is, places with old evolutionary diversity) are predicted to disappear or shift their location. These findings show that climate change threatens whole clades of the phylogenetic tree, and that the outlined approach can be used to forecast areas of biodiversity losses and continental-scale impacts of climate change.

Multimodal assessment of emotional reactivity in borderline personality pathology: The moderating role of posttraumatic stress disorder symptoms

PubMed Central

Dixon-Gordon, Katherine L.; Gratz, Kim L.; Tull, Matthew T.

2013-01-01

Emotional reactivity has been theorized to play a central role in borderline personality (BP) pathology. Although growing research provides evidence for subjective emotional reactivity in BP pathology, research on physiological or biological reactivity among people with BP pathology is less conclusive. With regard to biological reactivity in particular, research on cortisol reactivity (a neurobiological marker of emotional reactivity) in response to stressors among individuals with BP pathology has produced contradictory results and highlighted the potential moderating role of PTSD-related pathology. Thus, this study sought to examine the moderating role of PTSD symptoms in the relation between BP pathology and both subjective (self-report) and biological (cortisol) emotional reactivity to a laboratory stressor. Participants were 171 patients in a residential substance use disorder treatment center. Consistent with hypotheses, results revealed a significant main effect of BP pathology on subjective emotional reactivity to the laboratory stressor. Furthermore, results revealed a significant interaction between BP pathology and PTSD symptoms in the prediction of cortisol reactivity, such that BP pathology was associated with heightened cortisol reactivity only among participants with low levels of PTSD symptoms. Similar findings were obtained when examining the interaction between BP pathology and the reexperiencing and avoidance/numbing symptoms of PTSD specifically. Results highlight the moderating role of PTSD symptoms in the BP-reactivity relation. PMID:23375184

The Intestinal Eukaryotic and Bacterial Biome of Spotted Hyenas: The Impact of Social Status and Age on Diversity and Composition.

PubMed

Heitlinger, Emanuel; Ferreira, Susana C M; Thierer, Dagmar; Hofer, Heribert; East, Marion L

2017-01-01

In mammals, two factors likely to affect the diversity and composition of intestinal bacteria (bacterial microbiome) and eukaryotes (eukaryome) are social status and age. In species in which social status determines access to resources, socially dominant animals maintain better immune processes and health status than subordinates. As high species diversity is an index of ecosystem health, the intestinal biome of healthier, socially dominant animals should be more diverse than those of subordinates. Gradual colonization of the juvenile intestine after birth predicts lower intestinal biome diversity in juveniles than adults. We tested these predictions on the effect of: (1) age (juvenile/adult) and (2) social status (low/high) on bacterial microbiome and eukaryome diversity and composition in the spotted hyena ( Crocuta crocuta ), a highly social, female-dominated carnivore in which social status determines access to resources. We comprehensively screened feces from 35 individually known adult females and 7 juveniles in the Serengeti ecosystem for bacteria and eukaryotes, using a set of 48 different amplicons (4 for bacterial 16S, 44 for eukaryote 18S) in a multi-amplicon sequencing approach. We compared sequence abundances to classical coprological egg or oocyst counts. For all parasite taxa detected in more than six samples, the number of sequence reads significantly predicted the number of eggs or oocysts counted, underscoring the value of an amplicon sequencing approach for quantitative measurements of parasite load. In line with our predictions, our results revealed a significantly less diverse microbiome in juveniles than adults and a significantly higher diversity of eukaryotes in high-ranking than low-ranking animals. We propose that free-ranging wildlife can provide an intriguing model system to assess the adaptive value of intestinal biome diversity for both bacteria and eukaryotes.

The Intestinal Eukaryotic and Bacterial Biome of Spotted Hyenas: The Impact of Social Status and Age on Diversity and Composition

PubMed Central

Heitlinger, Emanuel; Ferreira, Susana C. M.; Thierer, Dagmar; Hofer, Heribert; East, Marion L.

2017-01-01

In mammals, two factors likely to affect the diversity and composition of intestinal bacteria (bacterial microbiome) and eukaryotes (eukaryome) are social status and age. In species in which social status determines access to resources, socially dominant animals maintain better immune processes and health status than subordinates. As high species diversity is an index of ecosystem health, the intestinal biome of healthier, socially dominant animals should be more diverse than those of subordinates. Gradual colonization of the juvenile intestine after birth predicts lower intestinal biome diversity in juveniles than adults. We tested these predictions on the effect of: (1) age (juvenile/adult) and (2) social status (low/high) on bacterial microbiome and eukaryome diversity and composition in the spotted hyena (Crocuta crocuta), a highly social, female-dominated carnivore in which social status determines access to resources. We comprehensively screened feces from 35 individually known adult females and 7 juveniles in the Serengeti ecosystem for bacteria and eukaryotes, using a set of 48 different amplicons (4 for bacterial 16S, 44 for eukaryote 18S) in a multi-amplicon sequencing approach. We compared sequence abundances to classical coprological egg or oocyst counts. For all parasite taxa detected in more than six samples, the number of sequence reads significantly predicted the number of eggs or oocysts counted, underscoring the value of an amplicon sequencing approach for quantitative measurements of parasite load. In line with our predictions, our results revealed a significantly less diverse microbiome in juveniles than adults and a significantly higher diversity of eukaryotes in high-ranking than low-ranking animals. We propose that free-ranging wildlife can provide an intriguing model system to assess the adaptive value of intestinal biome diversity for both bacteria and eukaryotes. PMID:28670573

The General Assessment of Personality Disorder (GAPD): factor structure, incremental validity of self-pathology, and relations to DSM-IV personality disorders.

PubMed

Hentschel, Annett G; Livesley, W John

2013-01-01

Recent developments in the classification of personality disorder, especially moves toward more dimensional systems, create the need to assess general personality disorder apart from individual differences in personality pathology. The General Assessment of Personality Disorder (GAPD) is a self-report questionnaire designed to evaluate general personality disorder. The measure evaluates 2 major components of disordered personality: self or identity problems and interpersonal dysfunction. This study explores whether there is a single factor reflecting general personality pathology as proposed by the Diagnostic and Statistical Manual of Mental Disorders (5th ed.), whether self-pathology has incremental validity over interpersonal pathology as measured by GAPD, and whether GAPD scales relate significantly to Diagnostic and Statistical Manual of Mental Disorders (4th ed. [DSM-IV]) personality disorders. Based on responses from a German psychiatric sample of 149 participants, parallel analysis yielded a 1-factor model. Self Pathology scales of the GAPD increased the predictive validity of the Interpersonal Pathology scales of the GAPD. The GAPD scales showed a moderate to high correlation for 9 of 12 DSM-IV personality disorders.

Spanish adaptation of the Gambling Motives Questionnaire (GMQ): Validation in adult pathological gamblers and relationship with anxious-depressive symptomatology and perceived stress.

PubMed

Jauregui, Paula; Estevez, Ana; Onaindia, Jaione

2018-10-01

Gambling has been found to be related to different motives, such as enhancement, social, and behavioral and emotional coping. The most used instrument in this field is the Gambling Motives Questionnaire (GMQ; Stewart & Zack, 2008), which has not been validated in clinical samples. This study aimed to validate a Spanish version of the GMQ in a sample of adult pathological gamblers and to analyze its relationship with pathological gambling, anxiety, depression, and perceived stress. A sample of 164 gamblers was recruited from centers for the treatment of pathological gambling. The three-factor structure (enhancement, social, and coping motives) of the GMQ was validated through exploratory and confirmatory factorial analyses, and its convergent validity was proven. Gambling motives correlated with pathological gambling, anxiety, depression, and perceived stress. Enhancement motives predicted pathological gambling, while controlling for the effect of anxiety, depression, and perceived stress. These results are relevant for clinical evaluation and intervention with adult pathological gamblers. Copyright © 2018 Elsevier Ltd. All rights reserved.

Disturbance, neutral theory, and patterns of beta diversity in soil communities.

PubMed

Maaß, Stefanie; Migliorini, Massimo; Rillig, Matthias C; Caruso, Tancredi

2014-12-01

Beta diversity describes how local communities within an area or region differ in species composition/abundance. There have been attempts to use changes in beta diversity as a biotic indicator of disturbance, but lack of theory and methodological caveats have hampered progress. We here propose that the neutral theory of biodiversity plus the definition of beta diversity as the total variance of a community matrix provide a suitable, novel, starting point for ecological applications. Observed levels of beta diversity (BD) can be compared to neutral predictions with three possible outcomes: Observed BD equals neutral prediction or is larger (divergence) or smaller (convergence) than the neutral prediction. Disturbance might lead to either divergence or convergence, depending on type and strength. We here apply these ideas to datasets collected on oribatid mites (a key, very diverse soil taxon) under several regimes of disturbances. When disturbance is expected to increase the heterogeneity of soil spatial properties or the sampling strategy encompassed a range of diverging environmental conditions, we observed diverging assemblages. On the contrary, we observed patterns consistent with neutrality when disturbance could determine homogenization of soil properties in space or the sampling strategy encompassed fairly homogeneous areas. With our method, spatial and temporal changes in beta diversity can be directly and easily monitored to detect significant changes in community dynamics, although the method itself cannot inform on underlying mechanisms. However, human-driven disturbances and the spatial scales at which they operate are usually known. In this case, our approach allows the formulation of testable predictions in terms of expected changes in beta diversity, thereby offering a promising monitoring tool.

A call for tiger management using "reserves" of genetic diversity.

PubMed

Bay, Rachael A; Ramakrishnan, Uma; Hadly, Elizabeth A

2014-01-01

Tigers (Panthera tigris), like many large carnivores, are threatened by anthropogenic impacts, primarily habitat loss and poaching. Current conservation plans for tigers focus on population expansion, with the goal of doubling census size in the next 10 years. Previous studies have shown that because the demographic decline was recent, tiger populations still retain a large amount of genetic diversity. Although maintaining this diversity is extremely important to avoid deleterious effects of inbreeding, management plans have yet to consider predictive genetic models. We used coalescent simulations based on previously sequenced mitochondrial fragments (n = 125) from 5 of 6 extant subspecies to predict the population growth needed to maintain current genetic diversity over the next 150 years. We found that the level of gene flow between populations has a large effect on the local population growth necessary to maintain genetic diversity, without which tigers may face decreases in fitness. In the absence of gene flow, we demonstrate that maintaining genetic diversity is impossible based on known demographic parameters for the species. Thus, managing for the genetic diversity of the species should be prioritized over the riskier preservation of distinct subspecies. These predictive simulations provide unique management insights, hitherto not possible using existing analytical methods.

Life history trade-off moderates model predictions of diversity loss from climate change.

PubMed

Moor, Helen

2017-01-01

Climate change can trigger species range shifts, local extinctions and changes in diversity. Species interactions and dispersal capacity are important mediators of community responses to climate change. The interaction between multispecies competition and variation in dispersal capacity has recently been shown to exacerbate the effects of climate change on diversity and to increase predictions of extinction risk dramatically. Dispersal capacity, however, is part of a species' overall ecological strategy and are likely to trade off with other aspects of its life history that influence population growth and persistence. In plants, a well-known example is the trade-off between seed mass and seed number. The presence of such a trade-off might buffer the diversity loss predicted by models with random but neutral (i.e. not impacting fitness otherwise) differences in dispersal capacity. Using a trait-based metacommunity model along a warming climatic gradient the effect of three different dispersal scenarios on model predictions of diversity change were compared. Adding random variation in species dispersal capacity caused extinctions by the introduction of strong fitness differences due an inherent property of the dispersal kernel. Simulations including a fitness-equalising trade-off based on empirical relationships between seed mass (here affecting dispersal distance, establishment probability, and seedling biomass) and seed number (fecundity) maintained higher initial species diversity and predicted lower extinction risk and diversity loss during climate change than simulations with variable dispersal capacity. Large seeded species persisted during climate change, but developed lags behind their climate niche that may cause extinction debts. Small seeded species were more extinction-prone during climate change but tracked their niches through dispersal and colonisation, despite competitive resistance from residents. Life history trade-offs involved in coexistence mechanisms may increase community resilience to future climate change and are useful guides for model development.

Risk factors contributing to a poor prognosis of papillary thyroid carcinoma: validity of UICC/AJCC TNM classification and stage grouping.

PubMed

Ito, Yasuhiro; Miyauchi, Akira; Jikuzono, Tomoo; Higashiyama, Takuya; Takamura, Yuuki; Miya, Akihiro; Kobayashi, Kaoru; Matsuzuka, Fumio; Ichihara, Kiyoshi; Kuma, Kanji

2007-04-01

In 2002, the UICC/AJCC TNM classification for papillary thyroid carcinoma was revised. In this study, we examined the validity of this classification system by investigating the predictors of disease-free survival (DFS) and cause-specific survival (CSS) in patients. We examined various clinicopathological features, including the component of the TNM classification, for 1,740 patients who underwent initial and curative surgery for papillary carcinoma between 1987 and 1995. Clinical and pathological T4a, clinical N1b in the TNM classification, and patient age were recognized as independent predictors of not only DFS, but also CSS of patients. Tumor size, male gender, and central node metastasis independently affected DFS only. There were 1,005 pathological N1b patients, but pathological N1b did not independently affect either DFS or CSS. Regarding the stage grouping, clinical stage IVA including clinical N1b more clearly affected DFS and CSS than pathological stage IVA including pathological N1b. Clinical stage grouping was more useful than pathological stage grouping for predicting the prognosis of papillary carcinoma patients possibly because pathological stage overestimates the biological characteristics of many pathological N1b tumors.

A geographical analysis of speech-language pathology services to support multilingual children.

PubMed

Verdon, Sarah; McLeod, Sharynne; McDonald, Simon

2014-06-01

The speech-language pathology workforce strives to provide equitable, quality services to multilingual people. However, the extent to which this is being achieved is unknown. Participants in this study were 2849 members of Speech Pathology Australia and 4386 children in the Birth cohort of the Longitudinal Study of Australian Children (LSAC). Statistical and geospatial analyses were undertaken to identify the linguistic diversity and geographical distribution of Australian speech-language pathology services and Australian children. One fifth of services offered by Speech Pathology Australia members (20.2%) were available in a language other than English. Services were most commonly offered in Australian Sign Language (Auslan) (4.3%), French (3.1%), Italian (2.2%), Greek (1.6%), and Cantonese (1.5%). Among 4-5-year-old children in the nationally representative LSAC, 15.3% regularly spoke and/or understood a language other than English. The most common languages spoken by the children were Arabic (1.5%), Italian (1.2%), Greek (0.9%), Spanish (0.9%), and Vietnamese (0.9%). There was a mismatch between the location of and languages in which multilingual services were offered, and the location of and languages spoken by children. These findings highlight the need for SLPs to be culturally competent in providing equitable services to all clients, regardless of the languages they speak.

High Proliferation Predicts Pathological Complete Response to Neoadjuvant Chemotherapy in Early Breast Cancer

PubMed Central

Lluch, Ana; Ribelles, Nuria; Anton-Torres, Antonio; Sanchez-Rovira, Pedro; Albanell, Joan; Calvo, Lourdes; García-Asenjo, Jose Antonio Lopez; Palacios, Jose; Chacon, Jose Ignacio; Ruiz, Amparo; De la Haba-Rodriguez, Juan; Segui-Palmer, Miguel A.; Cirauqui, Beatriz; Margeli, Mireia; Plazaola, Arrate; Barnadas, Agusti; Casas, Maribel; Caballero, Rosalia; Carrasco, Eva; Rojo, Federico

2016-01-01

Background. In the neoadjuvant setting, changes in the proliferation marker Ki67 are associated with primary endocrine treatment efficacy, but its value as a predictor of response to chemotherapy is still controversial. Patients and Methods. We analyzed 262 patients with centralized basal Ki67 immunohistochemical evaluation derived from 4 GEICAM (Spanish Breast Cancer Group) clinical trials of neoadjuvant chemotherapy for breast cancer. The objective was to identify the optimal threshold for Ki67 using the receiver-operating characteristic curve method to maximize its predictive value for chemotherapy benefit. We also evaluated the predictive role of the defined Ki67 cutoffs for molecular subtypes defined by estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2). Results. A basal Ki67 cutpoint of 50% predicted pathological complete response (pCR). Patients with Ki67 >50% achieved a pCR rate of 40% (36 of 91) versus a pCR rate of 19% in patients with Ki67 ≤50% (33 of 171) (p = .0004). Ki67 predictive value was especially relevant in ER-HER2− and ER-HER2+ patients (pCR rates of 42% and 64%, respectively, in patients with Ki67 >50% versus 15% and 45%, respectively, in patients with Ki67 ≤50%; p = .0337 and .3238, respectively). Both multivariate analyses confirmed the independent predictive value of the Ki67 cutpoint of 50%. Conclusion. Basal Ki67 proliferation index >50% should be considered an independent predictive factor for pCR reached after neoadjuvant chemotherapy, suggesting that cell proliferation is a phenomenon closely related to chemosensitivity. These findings could help to identify a group of patients with a potentially favorable long-term prognosis. Implications for Practice: The use of basal Ki67 status as a predictive factor of chemotherapy benefit could facilitate the identification of a patient subpopulation with high probability of achieving pathological complete response when treated with primary chemotherapy, and thus with a potentially favorable long-term prognosis. PMID:26786263

Early PET/CT scan is more effective than RECIST in predicting outcome of patients with liver metastases from colorectal cancer treated with preoperative chemotherapy plus bevacizumab.

PubMed

Lastoria, Secondo; Piccirillo, Maria Carmela; Caracò, Corradina; Nasti, Guglielmo; Aloj, Luigi; Arrichiello, Cecilia; de Lutio di Castelguidone, Elisabetta; Tatangelo, Fabiana; Ottaiano, Alessandro; Iaffaioli, Rosario Vincenzo; Izzo, Francesco; Romano, Giovanni; Giordano, Pasqualina; Signoriello, Simona; Gallo, Ciro; Perrone, Francesco

2013-12-01

Markers predictive of treatment effect might be useful to improve the treatment of patients with metastatic solid tumors. Particularly, early changes in tumor metabolism measured by PET/CT with (18)F-FDG could predict the efficacy of treatment better than standard dimensional Response Evaluation Criteria In Solid Tumors (RECIST) response. We performed PET/CT evaluation before and after 1 cycle of treatment in patients with resectable liver metastases from colorectal cancer, within a phase 2 trial of preoperative FOLFIRI plus bevacizumab. For each lesion, the maximum standardized uptake value (SUV) and the total lesion glycolysis (TLG) were determined. On the basis of previous studies, a ≤ -50% change from baseline was used as a threshold for significant metabolic response for maximum SUV and, exploratively, for TLG. Standard RECIST response was assessed with CT after 3 mo of treatment. Pathologic response was assessed in patients undergoing resection. The association between metabolic and CT/RECIST and pathologic response was tested with the McNemar test; the ability to predict progression-free survival (PFS) and overall survival (OS) was tested with the Log-rank test and a multivariable Cox model. Thirty-three patients were analyzed. After treatment, there was a notable decrease of all the parameters measured by PET/CT. Early metabolic PET/CT response (either SUV- or TLG-based) had a stronger, independent and statistically significant predictive value for PFS and OS than both CT/RECIST and pathologic response at multivariate analysis, although with different degrees of statistical significance. The predictive value of CT/RECIST response was not significant at multivariate analysis. PET/CT response was significantly predictive of long-term outcomes during preoperative treatment of patients with liver metastases from colorectal cancer, and its predictive ability was higher than that of CT/RECIST response after 3 mo of treatment. Such findings need to be confirmed by larger prospective trials.

Hunter-gatherer dental pathology: Do historic accounts of Aboriginal Australians correspond to the archeological record of dental disease?

PubMed

Littleton, Judith

2018-03-01

Studies of hunter-gatherer oral pathology, particularly in Australia, often focus upon dental wear and caries or assume that historic studies of Aboriginal people reflect the precontact past. Consequently the range of population variation has been underestimated. In this paper dental pathology from human remains from Roonka are compared with a model of dental pathology derived from historic studies. The aim is to identify aspects of dental pathology indicative of regional or intra-population diversity. Adult dentitions (n = 115) dating from the mid to late Holocene were recorded for the following conditions: dental wear, caries, periapical voids, calculus, periodontal disease and antemortem tooth loss. Statistical analysis was used to identify patterns of dental pathology and to identify causal relationships between conditions. Dental wear is marked while dental caries rates are extremely low. Other indications of dental pathology are uncommon (<7% of teeth affected). Temporal heterogeneity is apparent: there are 3 young adults with caries who died in the postcontact period. There is also a small group of middle age to old adults with disproportionate abscessing and pulp exposure who may represent temporal variation or heterogeneity in individual frailty. The results confirm dental wear as the major cause of dental pathology in this group and that, at a general level, historic accounts do correspond with this archeological sample. However, intra-sample heterogeneity is apparent while 2 dental conditions, calculus and periodontal disease, along with the pattern of sex differences deviate from expectation, demonstrating that to identify regional variation attention needs to be paid to the dentoalveolar complex as a whole. © 2017 Wiley Periodicals, Inc.

Effects of complex life cycles on genetic diversity: cyclical parthenogenesis.

PubMed

Rouger, R; Reichel, K; Malrieu, F; Masson, J P; Stoeckel, S

2016-11-01

Neutral patterns of population genetic diversity in species with complex life cycles are difficult to anticipate. Cyclical parthenogenesis (CP), in which organisms undergo several rounds of clonal reproduction followed by a sexual event, is one such life cycle. Many species, including crop pests (aphids), human parasites (trematodes) or models used in evolutionary science (Daphnia), are cyclical parthenogens. It is therefore crucial to understand the impact of such a life cycle on neutral genetic diversity. In this paper, we describe distributions of genetic diversity under conditions of CP with various clonal phase lengths. Using a Markov chain model of CP for a single locus and individual-based simulations for two loci, our analysis first demonstrates that strong departures from full sexuality are observed after only a few generations of clonality. The convergence towards predictions made under conditions of full clonality during the clonal phase depends on the balance between mutations and genetic drift. Second, the sexual event of CP usually resets the genetic diversity at a single locus towards predictions made under full sexuality. However, this single recombination event is insufficient to reshuffle gametic phases towards full-sexuality predictions. Finally, for similar levels of clonality, CP and acyclic partial clonality (wherein a fixed proportion of individuals are clonally produced within each generation) differentially affect the distribution of genetic diversity. Overall, this work provides solid predictions of neutral genetic diversity that may serve as a null model in detecting the action of common evolutionary or demographic processes in cyclical parthenogens (for example, selection or bottlenecks).

The marine diversity spectrum

PubMed Central

Reuman, Daniel C; Gislason, Henrik; Barnes, Carolyn; Mélin, Frédéric; Jennings, Simon

2014-01-01

Distributions of species body sizes within a taxonomic group, for example, mammals, are widely studied and important because they help illuminate the evolutionary processes that produced these distributions. Distributions of the sizes of species within an assemblage delineated by geography instead of taxonomy (all the species in a region regardless of clade) are much less studied but are equally important and will illuminate a different set of ecological and evolutionary processes. We develop and test a mechanistic model of how diversity varies with body mass in marine ecosystems. The model predicts the form of the ‘diversity spectrum’, which quantifies the distribution of species' asymptotic body masses, is a species analogue of the classic size spectrum of individuals, and which we have found to be a new and widely applicable description of diversity patterns. The marine diversity spectrum is predicted to be approximately linear across an asymptotic mass range spanning seven orders of magnitude. Slope −0·5 is predicted for the global marine diversity spectrum for all combined pelagic zones of continental shelf seas, and slopes for large regions are predicted to lie between −0·5 and −0·1. Slopes of −0·5 and −0·1 represent markedly different communities: a slope of −0·5 depicts a 10-fold reduction in diversity for every 100-fold increase in asymptotic mass; a slope of −0·1 depicts a 1·6-fold reduction. Steeper slopes are predicted for larger or colder regions, meaning fewer large species per small species for such regions. Predictions were largely validated by a global empirical analysis. Results explain for the first time a new and widespread phenomenon of biodiversity. Results have implications for estimating numbers of species of small asymptotic mass, where taxonomic inventories are far from complete. Results show that the relationship between diversity and body mass can be explained from the dependence of predation behaviour, dispersal, and life history on body mass, and a neutral assumption about speciation and extinction. PMID:24588547

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

The alumni of today's Pathology Informatics and Clinical Informatics fellowships fill diverse roles in academia, large health systems, and industry. The evolving training tracks and curriculum of Pathology Informatics fellowships have been well documented. However, less attention has been given to the posttraining experiences of graduates from informatics training programs. Here, we examine the career paths of subspecialty fellowship-trained pathology informaticians. Alumni from four Pathology Informatics fellowship training programs were contacted for their voluntary participation in the study. We analyzed various components of training, and the subsequent career paths of Pathology Informatics fellowship alumni using data extracted from alumni provided curriculum vitae. Twenty-three out of twenty-seven alumni contacted contributed to the study. A majority had completed undergraduate study in science, technology, engineering, and math fields and combined track training in anatomic and clinical pathology. Approximately 30% (7/23) completed residency in a program with an in-house Pathology Informatics fellowship. Most completed additional fellowships (15/23) and many also completed advanced degrees (10/23). Common primary posttraining appointments included chief medical informatics officer (3/23), director of Pathology Informatics (10/23), informatics program director (2/23), and various roles in industry (3/23). Many alumni also provide clinical care in addition to their informatics roles (14/23). Pathology Informatics alumni serve on a variety of institutional committees, participate in national informatics organizations, contribute widely to scientific literature, and more than half (13/23) have obtained subspecialty certification in Clinical Informatics to date. Our analysis highlights several interesting phenomena related to the training and career trajectory of Pathology Informatics fellowship alumni. We note the long training track alumni complete in 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.

A General, Synthetic Model for Predicting Biodiversity Gradients from Environmental Geometry.

PubMed

Gross, Kevin; Snyder-Beattie, Andrew

2016-10-01

Latitudinal and elevational biodiversity gradients fascinate ecologists, and have inspired dozens of explanations. The geometry of the abiotic environment is sometimes thought to contribute to these gradients, yet evaluations of geometric explanations are limited by a fragmented understanding of the diversity patterns they predict. This article presents a mathematical model that synthesizes multiple pathways by which environmental geometry can drive diversity gradients. The model characterizes species ranges by their environmental niches and limits on range sizes and places those ranges onto the simplified geometries of a sphere or cone. The model predicts nuanced and realistic species-richness gradients, including latitudinal diversity gradients with tropical plateaus and mid-latitude inflection points and elevational diversity gradients with low-elevation diversity maxima. The model also illustrates the importance of a mid-environment effect that augments species richness at locations with intermediate environments. Model predictions match multiple empirical biodiversity gradients, depend on ecological traits in a testable fashion, and formally synthesize elements of several geometric models. Together, these results suggest that previous assessments of geometric hypotheses should be reconsidered and that environmental geometry may play a deeper role in driving biodiversity gradients than is currently appreciated.

Amygdala functional connectivity, HPA axis genetic variation, and life stress in children and relations to anxiety and emotion regulation

PubMed Central

Pagliaccio, David; Luby, Joan L.; Bogdan, Ryan; Agrawal, Arpana; Gaffrey, Michael S.; Belden, Andrew C.; Botteron, Kelly N.; Harms, Michael P.; Barch, Deanna M.

2015-01-01

Internalizing pathology is related to alterations in amygdala resting state functional connectivity, potentially implicating altered emotional reactivity and/or emotion regulation in the etiological pathway. Importantly, there is accumulating evidence that stress exposure and genetic vulnerability impact amygdala structure/function and risk for internalizing pathology. The present study examined whether early life stress and genetic profile scores (10 single nucleotide polymorphisms within four hypothalamic-pituitary-adrenal axis genes: CRHR1, NR3C2, NR3C1, and FKBP5) predicted individual differences in amygdala functional connectivity in school-age children (9–14 year olds; N=120). Whole-brain regression analyses indicated that increasing genetic ‘risk’ predicted alterations in amygdala connectivity to the caudate and postcentral gyrus. Experience of more stressful and traumatic life events predicted weakened amygdala-anterior cingulate cortex connectivity. Genetic ‘risk’ and stress exposure interacted to predict weakened connectivity between the amygdala and the inferior and middle frontal gyri, caudate, and parahippocampal gyrus in those children with the greatest genetic and environmental risk load. Furthermore, amygdala connectivity longitudinally predicted anxiety symptoms and emotion regulation skills at a later follow-up. Amygdala connectivity mediated effects of life stress on anxiety and of genetic variants on emotion regulation. The current results suggest that considering the unique and interacting effects of biological vulnerability and environmental risk factors may be key to understanding the development of altered amygdala functional connectivity, a potential factor in the risk trajectory for internalizing pathology. PMID:26595470

Amygdala functional connectivity, HPA axis genetic variation, and life stress in children and relations to anxiety and emotion regulation.

PubMed

Pagliaccio, David; Luby, Joan L; Bogdan, Ryan; Agrawal, Arpana; Gaffrey, Michael S; Belden, Andrew C; Botteron, Kelly N; Harms, Michael P; Barch, Deanna M

2015-11-01

Internalizing pathology is related to alterations in amygdala resting state functional connectivity, potentially implicating altered emotional reactivity and/or emotion regulation in the etiological pathway. Importantly, there is accumulating evidence that stress exposure and genetic vulnerability impact amygdala structure/function and risk for internalizing pathology. The present study examined whether early life stress and genetic profile scores (10 single nucleotide polymorphisms within 4 hypothalamic-pituitary-adrenal axis genes: CRHR1, NR3C2, NR3C1, and FKBP5) predicted individual differences in amygdala functional connectivity in school-age children (9- to 14-year-olds; N = 120). Whole-brain regression analyses indicated that increasing genetic "risk" predicted alterations in amygdala connectivity to the caudate and postcentral gyrus. Experience of more stressful and traumatic life events predicted weakened amygdala-anterior cingulate cortex connectivity. Genetic "risk" and stress exposure interacted to predict weakened connectivity between the amygdala and the inferior and middle frontal gyri, caudate, and parahippocampal gyrus in those children with the greatest genetic and environmental risk load. Furthermore, amygdala connectivity longitudinally predicted anxiety symptoms and emotion regulation skills at a later follow-up. Amygdala connectivity mediated effects of life stress on anxiety and of genetic variants on emotion regulation. The current results suggest that considering the unique and interacting effects of biological vulnerability and environmental risk factors may be key to understanding the development of altered amygdala functional connectivity, a potential factor in the risk trajectory for internalizing pathology. (c) 2015 APA, all rights reserved).

Scaffolding protein RanBPM and its interactions in diverse signaling pathways in health and disease.

PubMed

Das, Soumyadip; Haq, Saba; Ramakrishna, Suresh

2018-04-01

Ran-binding protein in the microtubule-organizing center (RanBPM) is an evolutionarily conserved, nucleocytoplasmic scaffolding protein involved in various cellular processes and several signal transduction pathways. RanBPM has a crucial role in mediating disease pathology by interacting with diverse proteins to regulate their functions. Previously, we compiled diverse cellular functions of RanBPM. Since then the functions of RanBPM have increased exponentially. In this article, we have updated the functions of RanBPM through its manifold interactions that have been investigated to date, according to their roles in protein stability, transcriptional activity, cellular development, neurobiology, and the cell cycle. Our review provides a complete guide on RanBPM interactors, the physiological role of RanBPM in cellular functions, and potential applications in disease therapeutics.

Understanding mechanisms and seeking cures for Alzheimer's disease: why we must be "extraordinarily diverse".

PubMed

Thambisetty, Madhav

2017-10-01

After more than a century since Dr. Alois Alzheimer first described the pathological hallmarks accompanying the defining clinical features of the disease, we have yet to deliver any meaningful disease-modifying treatments to our patients. In this article, I present a rationale for the need to be "extraordinarily diverse" in seeking effective ways to treat or prevent this devastating disease. This approach is based on applying a systems-biology perspective at the population level, using a diverse array of "OMICS" methodologies to identify molecular mechanisms associated with well-established AD risk factors including systemic inflammation, obesity, and insulin resistance. We believe that applying this strategy to understand longitudinal changes in human physiology during aging is of paramount importance in identifying meaningful opportunities to intervene effectively in AD.

MRI Predictive Factors for Tumor Response in Rectal Cancer Following Neoadjuvant Chemoradiation Therapy - Implications for Induction Chemotherapy?

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

Yu, Stanley K.T.; Tait, Diana; Chau, Ian

2013-11-01

Purpose: Clinical and magnetic resonance imaging (MRI) characteristics at baseline and following chemoradiation therapy (CRT) most strongly associated with histopathologic response were investigated and survival outcomes evaluated in accordance with imaging and pathological response. Methods and Materials: Responders were defined as mrT3c/d-4 downstaged to ypT0-2 on pathology or low at risk mrT2 downstaged to ypT1 or T0. Multivariate logistic regression of baseline and posttreatment MRI: T, N, extramural venous invasion (EMVI), circumferential resection margin, craniocaudal length <5 cm, and MRI tumor height ≤5 cm were used to identify independent predictor(s) for response. An association between induction chemotherapy and EMVI statusmore » was analyzed. Survival outcomes for pathologic and MRI responders and nonresponders were analyzed. Results: Two hundred eighty-one patients were eligible; 114 (41%) patients were pathology responders. Baseline MRI negative EMVI (odds ratio 2.94, P=.007), tumor height ≤5 cm (OR 1.96, P=.02), and mrEMVI status change (positive to negative) following CRT (OR 3.09, P<.001) were the only predictors for response. There was a strong association detected between induction chemotherapy and ymrEMVI status change after CRT (OR 9.0, P<.003). ymrT0-2 gave a positive predictive value of 80% and OR of 9.1 for ypT0-2. ymrN stage accuracy of ypN stage was 75%. Three-year disease-free survival for pathology and MRI responders were similar at 80% and 79% and significantly better than poor responders. Conclusions: Tumor height and mrEMVI status are more important than baseline size and stage of the tumor as predictors of response to CRT. Both MRI- and pathologic-defined responders have significantly improved survival. “Good response” to CRT in locally advanced rectal cancer with ypT0-2 carries significantly better 3-year overall survival and disease-free survival. Use of induction chemotherapy for improving mrEMVI status and knowledge of MRI predictive factors could be taken into account in the pursuit of individualized neoadjuvant treatments for patients with rectal cancer.« less

Computed tomography of the anterior mediastinum in myasthemia gravis: a radiologic-pathologic correlative study

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

Fon, G.T.; Bein, M.E.; Mancuso, A.A.

1982-01-01

Chest radiographs and computed tomographic (CT) scans of the mediastinum were correlated with pathologic findings of the thymus following thymectomy in 57 patients with myasthenia gravis. Based on the patient's age and the overall morphology of the anterior mediastinum, CT scans were assigned one of four grades in an attempt to predict thymus pathologic findings. Using this grading, 14 of 16 cases of thymoma were suspected or definitely diagnosed. One of the two cases not diagnosed on CT was a microscopic tumor. There were no false-positive diagnoses in 11 cases graded as definitely thymoma. We conclude that thymoma can bemore » sensitively diagnosed in patients older than 40 years of age. However, thymoma cannot be predicted with a high level of confidence in patients younger than 40 because of the difficulty in differentiating normal thymus or hyperplasia from thymoma. Recommendations for the use of CT in the preoperative evaluation of myasthenic patients are presented.« less

The child behavior checklist dysregulation profile predicts adolescent DSM-5 pathological personality traits 4 years later.

PubMed

De Caluwé, Elien; Decuyper, Mieke; De Clercq, Barbara

2013-07-01

Emotional dysregulation in childhood has been associated with various forms of later psychopathology, although no studies have investigated the personality related adolescent outcomes associated with early emotional dysregulation. The present study uses a typological approach to examine how the child behavior checklist-dysregulation profile (CBCL-DP) predicts DSM-5 pathological personality traits (as measured with the personality inventory for the diagnostic and statistical manual of mental disorders 5 or PID-5 by Krueger et al. (Psychol Med 2012)) across a time span of 4 years in a sample of 243 children aged 8-14 years (57.2 % girls). The results showed that children assigned to the CBCL-DP class are at risk for elevated scores on a wide range of DSM-5 personality pathology features, including higher scores on hostility, risk taking, deceitfulness, callousness, grandiosity, irresponsibility, impulsivity and manipulativeness. These results are discussed in the context of identifying early manifestations of persistent regulation problems, because of their enduring impact on a child's personality development.

A two-component rain model for the prediction of attenuation and diversity improvement

NASA Technical Reports Server (NTRS)

Crane, R. K.

1982-01-01

A new model was developed to predict attenuation statistics for a single Earth-satellite or terrestrial propagation path. The model was extended to provide predictions of the joint occurrences of specified or higher attenuation values on two closely spaced Earth-satellite paths. The joint statistics provide the information required to obtain diversity gain or diversity advantage estimates. The new model is meteorologically based. It was tested against available Earth-satellite beacon observations and terrestrial path measurements. The model employs the rain climate region descriptions of the Global rain model. The rms deviation between the predicted and observed attenuation values for the terrestrial path data was 35 percent, a result consistent with the expectations of the Global model when the rain rate distribution for the path is not used in the calculation. Within the United States the rms deviation between measurement and prediction was 36 percent but worldwide it was 79 percent.

Motion compensation via redundant-wavelet multihypothesis.

PubMed

Fowler, James E; Cui, Suxia; Wang, Yonghui

2006-10-01

Multihypothesis motion compensation has been widely used in video coding with previous attention focused on techniques employing predictions that are diverse spatially or temporally. In this paper, the multihypothesis concept is extended into the transform domain by using a redundant wavelet transform to produce multiple predictions that are diverse in transform phase. The corresponding multiple-phase inverse transform implicitly combines the phase-diverse predictions into a single spatial-domain prediction for motion compensation. The performance advantage of this redundant-wavelet-multihypothesis approach is investigated analytically, invoking the fact that the multiple-phase inverse involves a projection that significantly reduces the power of a dense-motion residual modeled as additive noise. The analysis shows that redundant-wavelet multihypothesis is capable of up to a 7-dB reduction in prediction-residual variance over an equivalent single-phase, single-hypothesis approach. Experimental results substantiate the performance advantage for a block-based implementation.

Exploring the structural diversity in inhibitors of α-synuclein amyloidogenic folding, aggregation and neurotoxicity

NASA Astrophysics Data System (ADS)

Das, Sukanya; Pukala, Tara L.; Smid, Scott D.

2018-05-01

Aggregation of α-Synuclein (αS) protein to amyloid fibrils is a neuropathological hallmark of Parkinson’s disease (PD). Growing evidence suggests that extracellular αS aggregation plays a pivotal role in neurodegeneration found in PD in addition to the intracellular αS aggregates in Lewy bodies (LB). Here, we identified and compared a diverse set of molecules capable of mitigating protein aggregation and exogenous toxicity of αSA53T, a more aggregation-prone αS mutant found in familial PD. For the first time, we investigated the αS anti-amyloid activity of semi-synthetic flavonoid 2', 3', 4' trihydroxyflavone or 2-D08, which was compared with natural flavones myricetin and transilitin, as well as such structurally diverse polyphenols as honokiol and punicalagin. Additionally, two novel synthetic compounds with a dibenzyl imidazolidine scaffold, Compound 1 and Compound 2, were also investigated as they exhibited favourable binding with αSA53T. All seven compounds inhibited αSA53T aggregation as demonstrated by Thioflavin T fluorescence assays, with modified fibril morphology observed by transmission electron microscopy. Ion mobility-mass spectrometry (IM-MS) was used to monitor the structural conversion of native αSA53T into amyloidogenic conformations and all seven compounds preserved the native unfolded conformations of αSA53T following 48 hrs incubation. The presence of each test compound in a 1:2 molar ratio was also shown to inhibit the neurotoxicity of preincubated αSA53T using phaeochromocytoma (PC12) cell viability assays. Among the seven tested compounds 2-D08, honokiol and the synthetic Compound 2 demonstrated the highest inhibition of aggregation, coupled with neuroprotection from preincubated αSA53T in vitro. Molecular docking predicted that all compounds bound near the lysine-rich region of the N-terminus of αSA53T, where the flavonoids and honokiol predominantly interacted with Lys 23. Overall, these findings highlight that i) restricted vicinal trihydroxylation in the flavone B-ring is more effective in stabilizing the native αS conformations, thus blocking amyloidogenic aggregation, than dihydroxylation in both A and B-ring, and ii) honokiol, punicalagin and the synthetic imidazolidine Compound 2 also inhibit αS amyloidogenic aggregation by stabilizing its native conformations. This diverse set of molecules acting on a singular pathological target with predicted binding to αSA53T in the folding-prone N-terminal region may contribute towards novel drug-design for PD.

Exploring the Structural Diversity in Inhibitors of α-Synuclein Amyloidogenic Folding, Aggregation, and Neurotoxicity

PubMed Central

Das, Sukanya; Pukala, Tara L.; Smid, Scott D.

2018-01-01

Aggregation of α-Synuclein (αS) protein to amyloid fibrils is a neuropathological hallmark of Parkinson's disease (PD). Growing evidence suggests that extracellular αS aggregation plays a pivotal role in neurodegeneration found in PD in addition to the intracellular αS aggregates in Lewy bodies (LB). Here, we identified and compared a diverse set of molecules capable of mitigating protein aggregation and exogenous toxicity of αSA53T, a more aggregation-prone αS mutant found in familial PD. For the first time, we investigated the αS anti-amyloid activity of semi-synthetic flavonoid 2′, 3′, 4′ trihydroxyflavone or 2-D08, which was compared with natural flavones myricetin and transilitin, as well as such structurally diverse polyphenols as honokiol and punicalagin. Additionally, two novel synthetic compounds with a dibenzyl imidazolidine scaffold, Compound 1 and Compound 2, were also investigated as they exhibited favorable binding with αSA53T. All seven compounds inhibited αSA53T aggregation as demonstrated by Thioflavin T fluorescence assays, with modified fibril morphology observed by transmission electron microscopy. Ion mobility-mass spectrometry (IM-MS) was used to monitor the structural conversion of native αSA53T into amyloidogenic conformations and all seven compounds preserved the native unfolded conformations of αSA53T following 48 h incubation. The presence of each test compound in a 1:2 molar ratio was also shown to inhibit the neurotoxicity of preincubated αSA53T using phaeochromocytoma (PC12) cell viability assays. Among the seven tested compounds 2-D08, honokiol, and the synthetic Compound 2 demonstrated the highest inhibition of aggregation, coupled with neuroprotection from preincubated αSA53T in vitro. Molecular docking predicted that all compounds bound near the lysine-rich region of the N-terminus of αSA53T, where the flavonoids and honokiol predominantly interacted with Lys 23. Overall, these findings highlight that (i) restricted vicinal trihydroxylation in the flavone B-ring is more effective in stabilizing the native αS conformations, thus blocking amyloidogenic aggregation, than dihydroxylation aggregation in both A and B-ring, and (ii) honokiol, punicalagin, and the synthetic imidazolidine Compound 2 also inhibit αS amyloidogenic aggregation by stabilizing its native conformations. This diverse set of molecules acting on a singular pathological target with predicted binding to αSA53T in the folding-prone N-terminal region may contribute toward novel drug-design for PD. PMID:29888220

Dimensions of biodiversity loss: Spatial mismatch in land-use impacts on species, functional and phylogenetic diversity of European bees.

PubMed

De Palma, Adriana; Kuhlmann, Michael; Bugter, Rob; Ferrier, Simon; Hoskins, Andrew J; Potts, Simon G; Roberts, Stuart P M; Schweiger, Oliver; Purvis, Andy

2017-12-01

Agricultural intensification and urbanization are important drivers of biodiversity change in Europe. Different aspects of bee community diversity vary in their sensitivity to these pressures, as well as independently influencing ecosystem service provision (pollination). To obtain a more comprehensive understanding of human impacts on bee diversity across Europe, we assess multiple, complementary indices of diversity. One Thousand four hundred and forty six sites across Europe. We collated data on bee occurrence and abundance from the published literature and supplemented them with the PREDICTS database. Using Rao's Quadratic Entropy, we assessed how species, functional and phylogenetic diversity of 1,446 bee communities respond to land-use characteristics including land-use class, cropland intensity, human population density and distance to roads. We combined these models with statistically downscaled estimates of land use in 2005 to estimate and map-at a scale of approximately 1 km 2 -the losses in diversity relative to semi-natural/natural baseline (the predicted diversity of an uninhabited grid square, consisting only of semi-natural/natural vegetation). We show that-relative to the predicted local diversity in uninhabited semi-natural/natural habitat-half of all EU27 countries have lost over 10% of their average local species diversity and two-thirds of countries have lost over 5% of their average local functional and phylogenetic diversity. All diversity measures were generally lower in pasture and higher-intensity cropland than in semi-natural/natural vegetation, but facets of diversity showed less consistent responses to human population density. These differences have led to marked spatial mismatches in losses: losses in phylogenetic diversity were in some areas almost 20 percentage points (pp.) more severe than losses in species diversity, but in other areas losses were almost 40 pp. less severe. These results highlight the importance of exploring multiple measures of diversity when prioritizing and evaluating conservation actions, as species-diverse assemblages may be phylogenetically and functionally impoverished, potentially threatening pollination service provision.

An environmental stress model correctly predicts unimodal trends in overall species richness and diversity along intertidal elevation gradients

NASA Astrophysics Data System (ADS)

Zwerschke, Nadescha; Bollen, Merle; Molis, Markus; Scrosati, Ricardo A.

2013-12-01

Environmental stress is a major factor structuring communities. An environmental stress model (ESM) predicts that overall species richness and diversity should follow a unimodal trend along the full stress gradient along which assemblages from a regional biota can occur (not to be confused with the intermediate disturbance hypothesis, which makes predictions only for basal species along an intermediate-to-high stress range). Past studies could only provide partial support for ESM predictions because of the limited stress range surveyed or a low sampling resolution. In this study, we measured overall species richness and diversity (considering all seaweeds and invertebrates) along the intertidal elevation gradient on two wave-sheltered rocky shores from Helgoland Island, on the NE Atlantic coast. In intertidal habitats, tides cause a pronounced gradient of increasing stress from low to high elevations. We surveyed up to nine contiguous elevation zones between the lowest intertidal elevation (low stress) and the high intertidal boundary (high stress). Nonlinear regression analyses revealed that overall species richness and diversity followed unimodal trends across elevations on the two studied shores. Therefore, our study suggests that the ESM might constitute a useful tool to predict local richness and diversity as a function of environmental stress. Performing tests on other systems (marine as well as terrestrial) should help to refine the model.

Sex Differences: A Resultant of an Evolutionary Pressure?

PubMed

Della Torre, Sara; Maggi, Adriana

2017-03-07

Spurred by current research policy, we are witnessing a significant growth in the number of studies that observe and describe sexual diversities in human physiology and sex prevalence in a large number of pathologies. Yet we are far from the comprehension of the mechanisms underpinning these differences, which are the result of a long evolutionary history. This Essay is meant to underline female reproductive function as a driver for the positive selection of the specific physiological features that explain male and female differential susceptibility to diseases and metabolic disturbances, in particular. A clear understanding of the causes underlying sexual dimorphisms in the physio-pathology is crucial for precision medicine. Copyright © 2017 Elsevier Inc. All rights reserved.

Soil properties drive a negative correlation between species diversity and genetic diversity in a tropical seasonal rainforest

PubMed Central

Xu, Wumei; Liu, Lu; He, Tianhua; Cao, Min; Sha, Liqing; Hu, Yuehua; Li, Qiaoming; Li, Jie

2016-01-01

A negative species-genetic diversity correlation (SGDC) could be predicted by the niche variation hypothesis, whereby an increase in species diversity within community reduces the genetic diversity of the co-occurring species because of the reduction in average niche breadth; alternatively, competition could reduce effective population size and therefore genetic diversity of the species within community. We tested these predictions within a 20 ha tropical forest dynamics plot (FDP) in the Xishuangbanna tropical seasonal rainforest. We established 15 plots within the FDP and investigated the soil properties, tree diversity, and genetic diversity of a common tree species Beilschmiedia roxburghiana within each plot. We observed a significant negative correlation between tree diversity and the genetic diversity of B. roxburghiana within the communities. Using structural equation modeling, we further determined that the inter-plot environmental characteristics (soil pH and phosphorus availability) directly affected tree diversity and that the tree diversity within the community determined the genetic diversity of B. roxburghiana. Increased soil pH and phosphorus availability might promote the coexistence of more tree species within community and reduce genetic diversity of B. roxburghiana for the reduced average niche breadth; alternatively, competition could reduce effective population size and therefore genetic diversity of B. roxburghiana within community. PMID:26860815

Soil properties drive a negative correlation between species diversity and genetic diversity in a tropical seasonal rainforest.

PubMed

Xu, Wumei; Liu, Lu; He, Tianhua; Cao, Min; Sha, Liqing; Hu, Yuehua; Li, Qiaoming; Li, Jie

2016-02-10

A negative species-genetic diversity correlation (SGDC) could be predicted by the niche variation hypothesis, whereby an increase in species diversity within community reduces the genetic diversity of the co-occurring species because of the reduction in average niche breadth; alternatively, competition could reduce effective population size and therefore genetic diversity of the species within community. We tested these predictions within a 20 ha tropical forest dynamics plot (FDP) in the Xishuangbanna tropical seasonal rainforest. We established 15 plots within the FDP and investigated the soil properties, tree diversity, and genetic diversity of a common tree species Beilschmiedia roxburghiana within each plot. We observed a significant negative correlation between tree diversity and the genetic diversity of B. roxburghiana within the communities. Using structural equation modeling, we further determined that the inter-plot environmental characteristics (soil pH and phosphorus availability) directly affected tree diversity and that the tree diversity within the community determined the genetic diversity of B. roxburghiana. Increased soil pH and phosphorus availability might promote the coexistence of more tree species within community and reduce genetic diversity of B. roxburghiana for the reduced average niche breadth; alternatively, competition could reduce effective population size and therefore genetic diversity of B. roxburghiana within community.

The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project

Treesearch

Lawrence N. Hudson; Joseph Wunderle M.; And Others

2016-01-01

The PREDICTS project—Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)—has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to...

From diagnostics to metagenomics: Applications of DNA-based tools in forest pathology

Treesearch

Amy L. Ross-Davis; Mee-Sook Kim; Jane E. Stewart; John W. Hanna; John D. Shaw; Ned B. Klopfenstein

2013-01-01

Advances in molecular technology provide an accessible set of tools to 1) help forest pathologists detect, identify, and monitor forest pathogens, 2) examine the evolutionary relationships and global distributions of forest pathogens and their hosts, 3) assess the diversity and structure of host and pathogen populations, and 4) evaluate the structure and function of...

Does head CT scan pathology predict outcome after mild traumatic brain injury?

PubMed

Lannsjö, M; Backheden, M; Johansson, U; Af Geijerstam, J L; Borg, J

2013-01-01

More evidence is needed to forward our understanding of the key determinants of poor outcome after mild traumatic brain injury (MTBI). A large, prospective, national cohort of patients was studied to analyse the effect of head CT scan pathology on the outcome. One-thousand two-hundred and sixty-two patients with MTBI (Glasgow Coma Scale score 15) at 39 emergency departments completed a study protocol including acute head CT scan examination and follow-up by the Rivermead Post Concussion Symptoms Questionnaire and the Glasgow Outcome Scale Extended (GOSE) at 3 months after MTBI. Binary logistic regression was used for the assessment of prediction ability. In 751 men (60%) and 511 women (40%), with a mean age of 30 years (median 21, range 6-94), we observed relevant or suspect relevant pathologic findings on acute CT scan in 52 patients (4%). Patients aged below 30 years reported better outcome both with respect to symptoms and GOSE as compared to patients in older age groups. Men reported better outcome than women as regards symptoms (OR 0.64, CI 0.49-0.85 for ≥3 symptoms) and global function (OR 0.60, CI 0.39-0.92 for GOSE 1-6). Pathology on acute CT scan examination had no effect on self-reported symptoms or global function at 3 months after MTBI. Female gender and older age predicted a less favourable outcome. The findings support the view that other factors than brain injury deserve attention to minimize long-term complaints after MTBI. © 2012 The Author(s) European Journal of Neurology © 2012 EFNS.

Targeted Analysis of Whole Genome Sequence Data to Diagnose Genetic Cardiomyopathy

DOE PAGES

Golbus, Jessica R.; Puckelwartz, Megan J.; Dellefave-Castillo, Lisa; ...

2014-09-01

Background—Cardiomyopathy is highly heritable but genetically diverse. At present, genetic testing for cardiomyopathy uses targeted sequencing to simultaneously assess the coding regions of more than 50 genes. New genes are routinely added to panels to improve the diagnostic yield. With the anticipated $1000 genome, it is expected that genetic testing will shift towards comprehensive genome sequencing accompanied by targeted gene analysis. Therefore, we assessed the reliability of whole genome sequencing and targeted analysis to identify cardiomyopathy variants in 11 subjects with cardiomyopathy. Methods and Results—Whole genome sequencing with an average of 37× coverage was combined with targeted analysis focused onmore » 204 genes linked to cardiomyopathy. Genetic variants were scored using multiple prediction algorithms combined with frequency data from public databases. This pipeline yielded 1-14 potentially pathogenic variants per individual. Variants were further analyzed using clinical criteria and/or segregation analysis. Three of three previously identified primary mutations were detected by this analysis. In six subjects for whom the primary mutation was previously unknown, we identified mutations that segregated with disease, had clinical correlates, and/or had additional pathological correlation to provide evidence for causality. For two subjects with previously known primary mutations, we identified additional variants that may act as modifiers of disease severity. In total, we identified the likely pathological mutation in 9 of 11 (82%) subjects. We conclude that these pilot data demonstrate that ~30-40× coverage whole genome sequencing combined with targeted analysis is feasible and sensitive to identify rare variants in cardiomyopathy-associated genes.« less

Can phylogeny predict chemical diversity and potential medicinal activity of plants? A case study of Amaryllidaceae

USDA-ARS?s Scientific Manuscript database

During evolution, plants and other organisms have developed a diversity of chemical defences, leading to the evolution of various groups of specialized metabolites selected for their endogenous biological function. A correlation between phylogeny and biosynthetic pathways could offer a predictive ap...

Comparing Magnetic Resonance Imaging and High-Resolution Dynamic Ultrasonography for Diagnosis of Plantar Plate Pathology: A Case Series.

PubMed

Donegan, Ryan J; Stauffer, Anthony; Heaslet, Michael; Poliskie, Michael

Plantar plate pathology has gained noticeable attention in recent years as an etiology of lesser metatarsophalangeal joint pain. The heightened clinical awareness has led to the need for more effective diagnostic imaging accuracy. Numerous reports have established the accuracy of both magnetic resonance imaging and ultrasonography for the diagnosis of plantar plate pathology. However, no conclusions have been made regarding which is the superior imaging modality. The present study reports a case series directly comparing high-resolution dynamic ultrasonography and magnetic resonance imaging. A multicenter retrospective comparison of magnetic resonance imaging versus high-resolution dynamic ultrasonography to evaluate plantar plate pathology with surgical confirmation was conducted. The sensitivity, specificity, and positive and negative predictive values for magnetic resonance imaging were 60%, 100%, 100%, and 33%, respectively. The overall diagnostic accuracy compared with the intraoperative findings was 66%. The sensitivity, specificity, and positive and negative predictive values for high-resolution dynamic ultrasound imaging were 100%, 100%, 100%, and 100%, respectively. The overall diagnostic accuracy compared with the intraoperative findings was 100%. The p value using Fisher's exact test for magnetic resonance imaging and high-resolution dynamic ultrasonography was p = .45, a difference that was not statistically significant. High-resolution dynamic ultrasonography had greater accuracy than magnetic resonance imaging in diagnosing lesser metatarsophalangeal joint plantar plate pathology, although the difference was not statistically significant. The present case series suggests that high-resolution dynamic ultrasonography can be considered an equally accurate imaging modality for plantar plate pathology at a potential cost savings compared with magnetic resonance imaging. Therefore, high-resolution dynamic ultrasonography warrants further investigation in a prospective study. Copyright © 2016 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

Contrast-Enhanced Spectral Mammography is Comparable to MRI in the Assessment of Residual Breast Cancer Following Neoadjuvant Systemic Therapy.

PubMed

Patel, Bhavika K; Hilal, Talal; Covington, Matthew; Zhang, Nan; Kosiorek, Heidi E; Lobbes, Marc; Northfelt, Donald W; Pockaj, Barbara A

2018-05-01

To evaluate the performance of contrast-enhanced spectral mammography (CESM) compared to MRI in the assessment of tumor response in breast cancer patients undergoing neoadjuvant systemic therapy (NST). The institutional review board approved this study. From September 2014 to June 2017, we identified patients with pathologically confirmed invasive breast cancer who underwent NST. All patients had both CESM and MRI performed pre- and post-NST with pathological assessment after surgical management. Size of residual malignancy on post-NST CESM and MRI was compared with surgical pathology. Lin concordance and Pearson correlation coefficient were used to assess agreement. Bland-Altman plots were used to visualize the differences between tumor size on imaging and pathology. Sixty-five patients were identified. Mean age was 52.7 (range 30-76) years. Type of NST included chemotherapy in 53 (82%) and endocrine therapy in 12 (18%). Mean tumor size after NST was 14.6 (range 0-105) mm for CESM and 14.2 mm (range 0-75 mm) for MRI compared with 19.6 (range 0-100) mm on final surgical pathology. Equivalence tests demonstrated that mean tumor size measured by CESM (p = 0.009) or by MRI (p = 0.01) was equivalent to the mean tumor size measured by pathology within - 1 and 1-cm range. Comparing CESM versus MRI for assessment of complete response, the sensitivity was 95% versus 95%, specificity 66.7% versus 68.9%, positive predictive value 55.9% versus 57.6%, and negative predictive value 96.7% versus 96.9% respectively. CESM was comparable to MRI in assessing residual malignancy after completion of NST.

Barium enema and CT volumetry for predicting pathologic response to preoperative chemoradiotherapy in rectal cancer patients.

PubMed

Murono, Koji; Kawai, Kazushige; Tsuno, Nelson H; Ishihara, Soichiro; Yamaguchi, Hironori; Sunami, Eiji; Kitayama, Joji; Watanabe, Toshiaki

2014-06-01

Preoperative chemoradiotherapy has been widely used for the prevention of local recurrence of locally advanced rectal cancer, and the effect of chemoradiotherapy is known to be associated with overall survival. We aimed to evaluate the association of the pathologic response grade with tumor recurrence rate after chemoradiotherapy, using radiographic analysis and the Response Evaluation Criteria in Solid Tumors as the parameters. This study was conducted at a single tertiary care institution in Japan. This was a retrospective cohort study of patients undergoing preoperative chemoradiotherapy. A total of 101 low rectal cancer patients receiving preoperative chemoradiotherapy from July 2004 to August 2012 were enrolled. The tumor reduction rate was measured with the use of traditional Response Evaluation Criteria in Solid Tumors, barium enema, and CT volumetry, and the correlation between the reduction rate and the pathologic response grade was examined. The tumor reduction rate assessed according to Response Evaluation Criteria in Solid Tumors showed no association with the pathologic response grade (p =0.61). In contrast, the radiographic response rate by both barium enema and CT volumetry strongly correlated with the pathologic response grade (p < 0.0001 and p = 0.001).In terms of local tumor recurrence, those diagnosed as high responders by the pathologic response grade, Response Evaluation Criteria in Solid Tumors, barium enema, and CT volumetry had a lower recurrence rate (p =0.03, p =0.03, p =0.0002, and p =0.001). The difference between high responders and low responders was especially prominent by barium enema and CT volumetry. The study is limited by its retrospective nature. Double-contrast barium enema and CT volumetry were superior to Response Evaluation Criteria in Solid Tumors in evaluating the effect of chemoradiotherapy and predicting the likelihood of tumor recurrence.

In vivo study of the effectiveness of quantitative percussion diagnostics as an indicator of the level of structural pathology of teeth after restoration.

PubMed

Sheets, Cherilyn G; Wu, Jean C; Rashad, Samer; Phelan, Michael; Earthman, James C

2017-02-01

Conventional diagnostic aids based upon imagery and patient symptoms do not indicate whether restorative treatments have eliminated structural pathology. The purpose of this clinical study was to evaluate quantitative percussion diagnostics (QPD), a mechanics-based methodology that tests the structural integrity of teeth noninvasively. The study hypothesis was that QPD would provide knowledge of the structural instability of teeth after restorative work. Eight participants with 60 sites needing restoration were enrolled in an IRB-approved clinical study. Each participant was examined comprehensively, including QPD testing. Each site was disassembled and microscopically video documented, and the results were recorded on a defect assessment sheet. A predictive model was developed for the pathology rating based on normalized fit error (NFE) values using data from the before treatment phase of the study published previously. Each restored site was then tested using QPD. The mean change in NFE values after restoration was evaluated by the pathology rating before treatment. The model was then used to predictively classify the rating after restoration based on the NFE values after treatment. The diagnostic potential of the rating was explored as a marker for risk of pathology after restoration. After restoration, 51 of the 60 sites fell below an NFE of 0.04, representing a greatly stabilized tooth site sample group. Several sites remained in the high-risk category and some increased in pathologic micromovement. Two models were used to determine severity with indicative cutoff points to group sites with similar values. The data support the hypothesis that QPD can indicate a revised level of structural instability of teeth after restoration. Copyright © 2016 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

Genomic selection in sugar beet breeding populations.

PubMed

Würschum, Tobias; Reif, Jochen C; Kraft, Thomas; Janssen, Geert; Zhao, Yusheng

2013-09-18

Genomic selection exploits dense genome-wide marker data to predict breeding values. In this study we used a large sugar beet population of 924 lines representing different germplasm types present in breeding populations: unselected segregating families and diverse lines from more advanced stages of selection. All lines have been intensively phenotyped in multi-location field trials for six agronomically important traits and genotyped with 677 SNP markers. We used ridge regression best linear unbiased prediction in combination with fivefold cross-validation and obtained high prediction accuracies for all except one trait. In addition, we investigated whether a calibration developed based on a training population composed of diverse lines is suited to predict the phenotypic performance within families. Our results show that the prediction accuracy is lower than that obtained within the diverse set of lines, but comparable to that obtained by cross-validation within the respective families. The results presented in this study suggest that a training population derived from intensively phenotyped and genotyped diverse lines from a breeding program does hold potential to build up robust calibration models for genomic selection. Taken together, our results indicate that genomic selection is a valuable tool and can thus complement the genomics toolbox in sugar beet breeding.

Determination of hepatocellular carcinoma grade by needle biopsy is unreliable for liver transplant candidate selection.

PubMed

Court, Colin M; Harlander-Locke, Michael P; Markovic, Daniela; French, Samuel W; Naini, Bita V; Lu, David S; Raman, Steven S; Kaldas, Fady M; Zarrinpar, Ali; Farmer, Douglas G; Finn, Richard S; Sadeghi, Saeed; Tomlinson, James S; Busuttil, Ronald W; Agopian, Vatche G

2017-09-01

The objective of this article is to evaluate the utility of preoperative needle biopsy (PNB) grading of hepatocellular carcinoma (HCC) as a biomarker for liver transplantation (LT) candidate selection. Given the prognostic significance of HCC tumor grade, PNB grading has been proposed as a biomarker for LT candidate selection. Clinicopathologic characteristics of HCC LT recipients (1989-2014) with a PNB were analyzed, and the concordance of PNB grade to explant grade and vascular invasion was assessed to determine whether incorporation of PNB grade to accepted transplant criteria improved candidate selection. Of 965 patients undergoing LT for HCC, 234 (24%) underwent PNB at a median of 280 days prior to transplant. Grade by PNB had poor concordance to final explant pathology (κ = 0.22; P = 0.003), and low sensitivity (29%) and positive predictive value (35%) in identifying poorly differentiated tumors. Vascular invasion was predicted by explant pathologic grade (r s = 0.24; P < 0.001) but not PNB grade (r s = -0.05; P = 0.50). Increasing explant pathology grade (P = 0.02), but not PNB grade (P = 0.65), discriminated post-LT HCC recurrence risk. The incorporation of PNB grade to the established radiologic Milan criteria (MC) did not result in improved prognostication of post-LT recurrence (net reclassification index [NRI] = 0%), whereas grade by explant pathology resulted in significantly improved reclassification of risk (NRI = 19%). Preoperative determination of HCC grade by PNB has low concordance with explant pathologic grade and low sensitivity and positive predictive value in identifying poorly differentiated tumors. PNB grade did not accurately discriminate post-LT HCC recurrence and had no utility in improving prognostication compared with the MC alone. Incorporation of PNB to guide transplant candidate selection appears unjustified. Liver Transplantation 23 1123-1132 2017 AASLD. © 2017 by the American Association for the Study of Liver Diseases.

Accuracy of pre-operative hysteroscopic guided biopsy for predicting final pathology in uterine malignancies.

PubMed

Martinelli, Fabio; Ditto, Antonino; Bogani, Giorgio; Signorelli, Mauro; Chiappa, Valentina; Lorusso, Domenica; Haeusler, Edward; Raspagliesi, Francesco

2017-07-01

To evaluate concordance (C) between pre-operative hysteroscopic-directed sampling and final pathology in uterine cancers. A retrospective cross-sectional evaluation of prospectively collected data of women who underwent hysterectomy for uterine malignancies and a previous hysteroscopic-guided biopsy was performed. Diagnostic concordance between pre-operative (hysteroscopic biopsy) and postoperative (uterine specimen) histology was evaluated. In endometrioid-endometrial cancers cases Kappa (k) statistics was applied to evaluate agreement for grading (G) between the preoperative and final pathology. A total 101 hysterectomies for uterine malignancies were evaluated. There were 23 non-endometrioid cancers: 7 serous (C:5/7, 71.4%); 10 carcinosarcomas (C:7/10, 70%, remaining 3 cases only epithelial component diagnosed); 3 clear cell (C:3/3, 100%); 3 sarcomas (C:3/3, 100%). In 78 cases an endometrioid endometrial cancer was found. In 63 cases there was a histological C (63/78, 80.8%) between hysteroscopic-guided biopsy and final pathology, while in 15 cases (19.2%) only hyperplasia (with/without atypia) was found preoperatively. Overall accuracy to detect endometrial cancer was 80.2%. In 50 out of 63 endometrial cancers (79.4%) grading was concordant. The overall level of agreement between preoperative and postoperative grading was "substantial" according to Kappa (k) statistics (k 0.64; 95% CI: 0.449-0.83; p < 0.001), as well as for G1 (0.679; 95% CI: 0.432-0.926; p < 0.001) and G3 (0.774; 94% CI: 0.534-1; p < 0.001), while for G2 (0.531; 95% CI: 0.286-0.777; p < 0.001) it was moderate. In our series we found an 80% C between pre-operative hysteroscopic-guided biopsy and final pathology, in uterine malignancies. Moreover, hysteroscopic biopsy accurately predicted endometrial cancer in 80% of cases and "substantially" predicted histological grading. Hysteroscopic-guided uterine sampling could be a useful tool to tailor treatment in patients with uterine malignancies.

Detection of AA-type amyloid protein in labial salivary glands.

PubMed

Sacsaquispe, Sonia-Julia; Antúnez-de Mayolo, Eleazar-Antonio; Vicetti, Rodolfo; Delgado, Wilson-Alejandro

2011-03-01

Among the diverse forms of amyloidosis, secondary type is the most frequent one. Diagnosis of amyloid deposition is based on the identification of the fibrillary protein amyloid by means of Congo Red (CR) or crystal violet (CV) stains, but these techniques do not differentiate between the different types of amyloid fibrils. The aim of this study was to identify by immunofluorescence (IF) AA amyloid a pathological fibrillar low-molecular-weight protein formed by cleavage of serum amyloid A (SAA) protein in labial salivary gland (LSG) biopsies from patients with secondary amyloidosis. 98 LSG were studied, 65 were from patients with secondary amyloidosis and 33 from subjects with chronic inflammatory diseases without evidence of this anomaly. All sections were stained with hematoxylin and eosin (H &E), CV, CR and IF using anti-AA antibodies. Positive and negative controls were used for all techniques. CV and CR demonstrated that the amyloid substance was found mainly distributed periductally (93.8%), followed by periacinar and perivascular locations (p <0.001); however, the IF demonstrated that amyloid AA substance predominates in the periacinar area (73.8%), followed by periductal and perivascular locations (p <0.001). IF has a sensitivity of 83%, 100% of specificity, 100% of predictive positive value and 75% of predictive negative value. The results of this study confirm the efficacy of the LSG biopsy as a highly reliable method for diagnosis of secondary amyloidosis.

Thyroid gland involvement in advanced laryngeal cancer: association with clinical and pathologic characteristics.

PubMed

Hilly, Ohad; Raz, Raanan; Vaisbuch, Yona; Strenov, Yulia; Segal, Karl; Koren, Rumelia; Shvero, Jacob

2012-11-01

Indications for thyroidectomy during laryngectomy are controversial. We examined whether clinicopathologic features can predict thyroid gland involvement, and the prognostic effect of thyroid gland involvement in patients undergoing total laryngectomy. The study set out to review preoperative assessment, operation findings, pathologic findings, and follow-up data. Thyroid gland involvement was found in 11 of 53 patients (21%) undergoing total laryngectomy and thyroidectomy. Preoperative work-up failed to predict thyroid gland involvement. Thyroid gland involvement was associated with salvage procedures (p = .025), paratracheal metastases (p = .003), and poor overall survival (hazard ratio = 2.74, p = .008). Thyroid gland involvement in patients undergoing total laryngectomy is frequent and is associated with poor prognosis. Preoperative assessment failed to predict thyroid gland involvement. We believe that thyroidectomy should be considered in cases with paratracheal lymphatic spread irrespective of tumor location within the larynx. Copyright © 2011 Wiley Periodicals, Inc.

Analysis of the genetic diversity of ovine herpesvirus 2 in samples from livestock with malignant catarrhal fever.

PubMed

Russell, George C; Scholes, Sandra F; Twomey, David F; Courtenay, Ann E; Grant, Dawn M; Lamond, Bruce; Norris, David; Willoughby, Kim; Haig, David M; Stewart, James P

2014-08-06

In order to define better virus isolates from animals with malignant catarrhal fever (MCF), segments of three genes of ovine herpesvirus-2 were amplified from diagnostic samples representing MCF cases with a range of clinical presentations in cattle, including head and eye, alimentary and neurological. The variation within each gene segment was estimated by DNA sequencing, which confirmed that the newly-annotated Ov9.5 gene was significantly more polymorphic than either of the other loci tested (segments of ORF50 and ORF75), with alleles that differed at over 60% of nucleotide positions. Despite this, the nine Ov9.5 alleles characterised had identical predicted splicing patterns and could be translated into Ov9.5 polypeptides with at least 49% amino acid identity. This multi-locus approach has potential for use in epidemiological studies and in charactering chains of infection. However there was no association between specific variants of OvHV-2 and the clinical/pathological presentation of MCF in the cattle analysed. Copyright © 2014 Elsevier B.V. All rights reserved.

A Peptide Targeting Inflammatory CNS Lesions in the EAE Rat Model of Multiple Sclerosis.

PubMed

Boiziau, Claudine; Nikolski, Macha; Mordelet, Elodie; Aussudre, Justine; Vargas-Sanchez, Karina; Petry, Klaus G

2018-06-01

Multiple sclerosis is characterized by inflammatory lesions dispersed throughout the central nervous system (CNS) leading to severe neurological handicap. Demyelination, axonal damage, and blood brain barrier alterations are hallmarks of this pathology, whose precise processes are not fully understood. In the experimental autoimmune encephalomyelitis (EAE) rat model that mimics many features of human multiple sclerosis, the phage display strategy was applied to select peptide ligands targeting inflammatory sites in CNS. Due to the large diversity of sequences after phage display selection, a bioinformatics procedure called "PepTeam" designed to identify peptides mimicking naturally occurring proteins was used, with the goal to predict peptides that were not background noise. We identified a circular peptide CLSTASNSC called "Ph48" as an efficient binder of inflammatory regions of EAE CNS sections including small inflammatory lesions of both white and gray matter. Tested on human brain endothelial cells hCMEC/D3, Ph48 was able to bind efficiently when these cells were activated with IL1β to mimic inflammatory conditions. The peptide is therefore a candidate for further analyses of the molecular alterations in inflammatory lesions.

Chronic gastritis in China: a national multi-center survey

PubMed Central

2014-01-01

Background Chronic gastritis is one of the most common findings at upper endoscopy in the general population, and chronic atrophic gastritis is epidemiologically associated with the occurrence of gastric cancer. However, the current status of diagnosis and treatment of chronic gastritis in China is unclear. Methods A multi-center national study was performed; all patients who underwent diagnostic upper endoscopy for evaluation of gastrointestinal symptoms from 33 centers were enrolled. Data including sex, age, symptoms and endoscopic findings were prospectively recorded. Results Totally 8892 patients were included. At endoscopy, 4389, 3760 and 1573 patients were diagnosed to have superficial gastritis, erosive gastritis, and atrophic gastritis, respectively. After pathologic examination, it is found that atrophic gastritis, intestinal metaplasia and dysplasia were prevalent, which accounted for 25.8%, 23.6% and 7.3% of this patient population. Endoscopic features were useful for predicting pathologic atrophy (PLR = 4.78), but it was not useful for predicting erosive gastritis. Mucosal-protective agents and PPI were most commonly used medications for chronic gastritis. Conclusions The present study suggests non-atrophic gastritis is the most common endoscopic finding in Chinese patients with upper GI symptoms. Precancerous lesions, including atrophy, intestinal metaplasia and dysplasia are prevalent in Chinese patients with chronic gastritis, and endoscopic features are useful for predicting pathologic atrophy. PMID:24502423

Chronic gastritis in China: a national multi-center survey.

PubMed

Du, Yiqi; Bai, Yu; Xie, Pei; Fang, Jingyuan; Wang, Xiaozhong; Hou, Xiaohua; Tian, Dean; Wang, Chengdang; Liu, Yandi; Sha, Weihong; Wang, Bangmao; Li, Yanqing; Zhang, Guoliang; Li, Yan; Shi, Ruihua; Xu, Jianming; Li, Youming; Huang, Minghe; Han, Shengxi; Liu, Jie; Ren, Xu; Xie, Pengyan; Wang, Zhangliu; Cui, Lihong; Sheng, Jianqiu; Luo, Hesheng; Wang, Zhaohui; Zhao, Xiaoyan; Dai, Ning; Nie, Yuqiang; Zou, Yiyou; Xia, Bing; Fan, Zhining; Chen, Zhitan; Lin, Sanren; Li, Zhao-Shen

2014-02-07

Chronic gastritis is one of the most common findings at upper endoscopy in the general population, and chronic atrophic gastritis is epidemiologically associated with the occurrence of gastric cancer. However, the current status of diagnosis and treatment of chronic gastritis in China is unclear. A multi-center national study was performed; all patients who underwent diagnostic upper endoscopy for evaluation of gastrointestinal symptoms from 33 centers were enrolled. Data including sex, age, symptoms and endoscopic findings were prospectively recorded. Totally 8892 patients were included. At endoscopy, 4389, 3760 and 1573 patients were diagnosed to have superficial gastritis, erosive gastritis, and atrophic gastritis, respectively. After pathologic examination, it is found that atrophic gastritis, intestinal metaplasia and dysplasia were prevalent, which accounted for 25.8%, 23.6% and 7.3% of this patient population. Endoscopic features were useful for predicting pathologic atrophy (PLR = 4.78), but it was not useful for predicting erosive gastritis. Mucosal-protective agents and PPI were most commonly used medications for chronic gastritis. The present study suggests non-atrophic gastritis is the most common endoscopic finding in Chinese patients with upper GI symptoms. Precancerous lesions, including atrophy, intestinal metaplasia and dysplasia are prevalent in Chinese patients with chronic gastritis, and endoscopic features are useful for predicting pathologic atrophy.

Proteopathic tau seeding predicts tauopathy in vivo

PubMed Central

Holmes, Brandon B.; Furman, Jennifer L.; Mahan, Thomas E.; Yamasaki, Tritia R.; Mirbaha, Hilda; Eades, William C.; Belaygorod, Larisa; Cairns, Nigel J.; Holtzman, David M.; Diamond, Marc I.

2014-01-01

Transcellular propagation of protein aggregates, or proteopathic seeds, may drive the progression of neurodegenerative diseases in a prion-like manner. In tauopathies such as Alzheimer’s disease, this model predicts that tau seeds propagate pathology through the brain via cell–cell transfer in neural networks. The critical role of tau seeding activity is untested, however. It is unknown whether seeding anticipates and correlates with subsequent development of pathology as predicted for a causal agent. One major limitation has been the lack of a robust assay to measure proteopathic seeding activity in biological specimens. We engineered an ultrasensitive, specific, and facile FRET-based flow cytometry biosensor assay based on expression of tau or synuclein fusions to CFP and YFP, and confirmed its sensitivity and specificity to tau (∼300 fM) and synuclein (∼300 pM) fibrils. This assay readily discriminates Alzheimer’s disease vs. Huntington's disease and aged control brains. We then carried out a detailed time-course study in P301S tauopathy mice, comparing seeding activity versus histological markers of tau pathology, including MC1, AT8, PG5, and Thioflavin S. We detected robust seeding activity at 1.5 mo, >1 mo before the earliest histopathological stain. Proteopathic tau seeding is thus an early and robust marker of tauopathy, suggesting a proximal role for tau seeds in neurodegeneration. PMID:25261551

The predictive value of magnetic resonance imaging of retinoblastoma for the likelihood of high-risk pathologic features.

PubMed

Hiasat, Jamila G; Saleh, Alaa; Al-Hussaini, Maysa; Al Nawaiseh, Ibrahim; Mehyar, Mustafa; Qandeel, Monther; Mohammad, Mona; Deebajah, Rasha; Sultan, Iyad; Jaradat, Imad; Mansour, Asem; Yousef, Yacoub A

2018-06-01

To evaluate the predictive value of magnetic resonance imaging in retinoblastoma for the likelihood of high-risk pathologic features. A retrospective study of 64 eyes enucleated from 60 retinoblastoma patients. Contrast-enhanced magnetic resonance imaging was performed before enucleation. Main outcome measures included demographics, laterality, accuracy, sensitivity, and specificity of magnetic resonance imaging in detecting high-risk pathologic features. Optic nerve invasion and choroidal invasion were seen microscopically in 34 (53%) and 28 (44%) eyes, respectively, while they were detected in magnetic resonance imaging in 22 (34%) and 15 (23%) eyes, respectively. The accuracy of magnetic resonance imaging in detecting prelaminar invasion was 77% (sensitivity 89%, specificity 98%), 56% for laminar invasion (sensitivity 27%, specificity 94%), 84% for postlaminar invasion (sensitivity 42%, specificity 98%), and 100% for optic cut edge invasion (sensitivity100%, specificity 100%). The accuracy of magnetic resonance imaging in detecting focal choroidal invasion was 48% (sensitivity 33%, specificity 97%), and 84% for massive choroidal invasion (sensitivity 53%, specificity 98%), and the accuracy in detecting extrascleral extension was 96% (sensitivity 67%, specificity 98%). Magnetic resonance imaging should not be the only method to stratify patients at high risk from those who are not, eventhough it can predict with high accuracy extensive postlaminar optic nerve invasion, massive choroidal invasion, and extrascleral tumor extension.

The role of sex, attachment and autonomy-connectedness in personality functioning.

PubMed

Bachrach, Nathan; Croon, Marcel A; Bekker, Marrie H J

2015-11-01

Previous studies have found significant relationships among sex, attachment and autonomy-connectedness and DSM-IV personality characteristics. In the present study, we aimed to add to the current knowledge about attachment-related aspects of personality pathology, by examining the relationships of these same variables with dimensions of pathological personality structure as conceptualized by Kernberg. The study was performed among 106 ambulatory patients from a Dutch mental healthcare institute. A path model based upon neo-analytical object relation theory and attachment theory was tested. We expected significant associations among sex, attachment, autonomy and aspects of personality functioning. Both insecure attachment styles as well as the autonomy-connectedness components of sensitivity to others (SO) and capacity of managing new situations predicted general personality dysfunctioning significantly. More specifically, reality testing was negatively predicted by the autonomy component of capacity of managing new situations, and aggression was significantly predicted by sex as well as both insecure attachment styles. We advise scientists as well as clinicians to be alert on sex differences in autonomy-connectedness and aspects of personality dysfunctioning. Taking sex-specific variations in attachment and autonomy into account next to a more explicit focus on insecure attachment styles and autonomy problems may enhance, the current relatively low, treatment effectiveness for personality pathology. Copyright © 2015 John Wiley & Sons, Ltd.

Pathological Gambling and Associated Drug and Alcohol Abuse, Emotion Regulation, and Anxious-Depressive Symptomatology.

PubMed

Jauregui, Paula; Estévez, Ana; Urbiola, Irache

2016-06-01

Background and aims Pathological gambling is associated with comorbid disorders, such as anxiety, depression, and drug and alcohol abuse. Difficulties of emotion regulation may be one of the factors related to the presence of addictive disorders, along with comorbid symptomatology in pathological gamblers. Therefore, the aim of this study was to evaluate the difficulties of emotion regulation, drug and alcohol abuse, and anxious and depressive symptomatology in pathological gamblers, and the mediating role of difficulties of emotion regulation between anxiety and pathological gambling. Methods The study sample included 167 male pathological gamblers (mean age = 39.29 years) and 107 non-gamblers (mean age = 33.43 years). Pathological gambling (SOGS), difficulties of emotion regulation (DERS), drug and alcohol abuse (MUTICAGE CAD-4), and anxious and depressive symptomatology (SA-45) were measured. Student's t, Pearson's r, stepwise multiple linear regression and multiple mediation analyses were conducted. The study was approved by an Investigational Review Board. Results Relative to non-gamblers, pathological gamblers exhibited greater difficulties of emotion regulation, as well as more anxiety, depression, and drug abuse. Moreover, pathological gambling correlated with emotion regulation difficulties, anxiety, depression, and drug abuse. Besides, emotion regulation difficulties correlated with and predicted pathological gambling, drug and alcohol abuse, and anxious and depressive symptomatology. Finally, emotion regulation difficulties mediated the relationship between anxiety and pathological gambling controlling the effect of age, both when controlling and not controlling for the effect of other abuses. Discussion and conclusions These results suggest that difficulties of emotion regulation may provide new keys to understanding and treating pathological gambling and comorbid disorders.

The characteristic ultrasound features of specific types of ovarian pathology (Review)

PubMed Central

SAYASNEH, AHMAD; EKECHI, CHRISTINE; FERRARA, LAURA; KAIJSER, JEROEN; STALDER, CATRIONA; SUR, SHYAMALY; TIMMERMAN, DIRK; BOURNE, TOM

2015-01-01

Characterizing ovarian masses enables patients with malignancy to be appropriately triaged for treatment by subspecialist gynecological oncologists, which has been shown to optimize care and improve survival. Furthermore, correctly classifying benign masses facilitates the selection of patients with ovarian pathology that may either not require intervention, or be suitable for minimal access surgery if intervention is required. However, predicting whether a mass is benign or malignant is not the only clinically relevant information that we need to know before deciding on appropriate treatment. Knowing the specific histology of a mass is becoming of increasing importance as management options become more tailored to the individual patient. For example predicting a mucinous borderline tumor gives the opportunity for fertility sparing surgery, and will highlight the need for further gastrointestinal assessment. For benign disease, predicting the presence of an endometrioma and possible deeply infiltrating endometriosis is important when considering both who should perform and the extent of surgery. An examiner’s subjective assessment of the morphological and vascular features of a mass using ultrasonography has been shown to be highly effective for predicting whether a mass is benign or malignant. Many masses also have features that enable a reliable diagnosis of the specific pathology of a particular mass to be made. In this narrative review we aim to describe the typical morphological features seen on ultrasound of different adnexal masses and illustrate these by showing representative ultrasound images. PMID:25406094

Evidence-based pathology in its second decade: toward probabilistic cognitive computing.

PubMed

Marchevsky, Alberto M; Walts, Ann E; Wick, Mark R

2017-03-01

Evidence-based pathology advocates using a combination of best available data ("evidence") from the literature and personal experience for the diagnosis, estimation of prognosis, and assessment of other variables that impact individual patient care. Evidence-based pathology relies on systematic reviews of the literature, evaluation of the quality of evidence as categorized by evidence levels and statistical tools such as meta-analyses, estimates of probabilities and odds, and others. However, it is well known that previously "statistically significant" information usually does not accurately forecast the future for individual patients. There is great interest in "cognitive computing" in which "data mining" is combined with "predictive analytics" designed to forecast future events and estimate the strength of those predictions. This study demonstrates the use of IBM Watson Analytics software to evaluate and predict the prognosis of 101 patients with typical and atypical pulmonary carcinoid tumors in which Ki-67 indices have been determined. The results obtained with this system are compared with those previously reported using "routine" statistical software and the help of a professional statistician. IBM Watson Analytics interactively provides statistical results that are comparable to those obtained with routine statistical tools but much more rapidly, with considerably less effort and with interactive graphics that are intuitively easy to apply. It also enables analysis of natural language variables and yields detailed survival predictions for patient subgroups selected by the user. Potential applications of this tool and basic concepts of cognitive computing are discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

Phylogenetic structure of soil bacterial communities predicts ecosystem functioning.

PubMed

Pérez-Valera, Eduardo; Goberna, Marta; Verdú, Miguel

2015-05-01

Quantifying diversity with phylogeny-informed metrics helps understand the effects of diversity on ecosystem functioning (EF). The sign of these effects remains controversial because phylogenetic diversity and taxonomic identity may interactively influence EF. Positive relationships, traditionally attributed to complementarity effects, seem unimportant in natural soil bacterial communities. Negative relationships could be attributed to fitness differences leading to the overrepresentation of few productive clades, a mechanism recently invoked to assemble soil bacteria communities. We tested in two ecosystems contrasting in terms of environmental heterogeneity whether two metrics of phylogenetic community structure, a simpler measure of phylogenetic diversity (NRI) and a more complex metric incorporating taxonomic identity (PCPS), correctly predict microbially mediated EF. We show that the relationship between phylogenetic diversity and EF depends on the taxonomic identity of the main coexisting lineages. Phylogenetic diversity was negatively related to EF in soils where a marked fertility gradient exists and a single and productive clade (Proteobacteria) outcompete other clades in the most fertile plots. However, phylogenetic diversity was unrelated to EF in soils where the fertility gradient is less marked and Proteobacteria coexist with other abundant lineages. Including the taxonomic identity of bacterial lineages in metrics of phylogenetic community structure allows the prediction of EF in both ecosystems. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Radiographic signs of pathology determining removal of an impacted mandibular third molar assessed in a panoramic image or CBCT

PubMed Central

Schropp, Lars; Spin-Neto, Rubens; Wenzel, Ann

2017-01-01

Objectives: To (1) compare pathological findings related to the mandibular third molar in panoramic images (PAN) and CBCT; (2) estimate the frequency of removals if pathological findings were indicative; and (3) assess factors in PAN associated with resorption and marginal bone loss at the second molar as observed in CBCT. Methods: 379 mandibular third molars were examined with PAN and CBCT. Four observers registered resorption and marginal bone loss at the second molar and increased periodontal space at the third molar in both imaging modalities. Agreement between PAN and CBCT, frequency of removals based on pathological findings in either of the two modalities and interobserver reproducibility was calculated. Logistic regression analyses assessed factors in PAN, which could predict marginal bone loss and resorption observed in CBCT. Results: Agreement between PAN and CBCT: resorption 54–74%; marginal bone loss 66–85%; and increased periodontal space 92–97%. Removals based on CBCT and PAN: 58–71% and 36–65%. Interobserver percentage accordance and kappa values ranged from 57 to 98% and 0.10–0.91 for PAN and 61–97% and 0.22–0.78 for CBCT, respectively. Mesioangulated/horizontally positioned third molars were associated with marginal bone loss [odds ratio (OR) = 7.0–31.3; p < 0.001] and resorption (OR = 2.9–35.6; p < 0.001) in CBCT. Overprojection between the third and the second molars in PAN predicted resorption observed in CBCT (OR = 5.6–21.2; p < 0.001). Conclusions: Pathology associated with the third molar is more often observed in CBCT than in PAN. More third molars would be removed if pathological findings are based on CBCT. Mesioangulated/horizontally positioned third molars overprojecting the cervical/root part of the second molar in PAN are strongly associated with pathology observed in CBCT. PMID:27681861

Radiographic signs of pathology determining removal of an impacted mandibular third molar assessed in a panoramic image or CBCT.

PubMed

Matzen, Louise H; Schropp, Lars; Spin-Neto, Rubens; Wenzel, Ann

2017-01-01

To (1) compare pathological findings related to the mandibular third molar in panoramic images (PAN) and CBCT; (2) estimate the frequency of removals if pathological findings were indicative; and (3) assess factors in PAN associated with resorption and marginal bone loss at the second molar as observed in CBCT. 379 mandibular third molars were examined with PAN and CBCT. Four observers registered resorption and marginal bone loss at the second molar and increased periodontal space at the third molar in both imaging modalities. Agreement between PAN and CBCT, frequency of removals based on pathological findings in either of the two modalities and interobserver reproducibility was calculated. Logistic regression analyses assessed factors in PAN, which could predict marginal bone loss and resorption observed in CBCT. Agreement between PAN and CBCT: resorption 54-74%; marginal bone loss 66-85%; and increased periodontal space 92-97%. Removals based on CBCT and PAN: 58-71% and 36-65%. Interobserver percentage accordance and kappa values ranged from 57 to 98% and 0.10-0.91 for PAN and 61-97% and 0.22-0.78 for CBCT, respectively. Mesioangulated/horizontally positioned third molars were associated with marginal bone loss [odds ratio (OR) = 7.0-31.3; p < 0.001] and resorption (OR = 2.9-35.6; p < 0.001) in CBCT. Overprojection between the third and the second molars in PAN predicted resorption observed in CBCT (OR = 5.6-21.2; p < 0.001). Pathology associated with the third molar is more often observed in CBCT than in PAN. More third molars would be removed if pathological findings are based on CBCT. Mesioangulated/horizontally positioned third molars overprojecting the cervical/root part of the second molar in PAN are strongly associated with pathology observed in CBCT.

Diagnostic value of the 2011 International Federation for Cervical Pathology and Colposcopy Terminology in predicting cervical lesions.

PubMed

Fan, Aiping; Wang, Chen; Zhang, Liqin; Yan, Ye; Han, Cha; Xue, Fengxia

2018-02-06

To evaluate the diagnostic accuracy of the 2011 International Federation for Cervical Pathology and Colposcopy (IFCPC) colposcopic terminology. The clinicopathological data of 2262 patients who underwent colposcopy from September 2012 to September 2016 were reviewed. The colposcopic findings, colposcopic impression, and cervical histopathology of the patients were analyzed. Correlations between variables were evaluated using cervical histopathology as the gold standard. Colposcopic diagnosis matched biopsy histopathology in 1482 patients (65.5%), and the weighted kappa strength of agreement was 0.480 (P<0.01). Colposcopic diagnoses more often underestimated (22.1%) than overestimated (12.3%) cervical pathology. There was no significant difference between the colposcopic diagnosis and cervical pathology agreement among the various grades of lesions (P=0.282). The sensitivity, specificity for detecting high-grade lesions/carcinoma was 71.6% and 98.0%, respectively. Multivariate analysis showed that major changes were independent factors in predicting high-grade lesion/carcinoma, whereas transformation zone, lesion size, and non-stained were not statistically related to high-grade lesion/carcinoma. The 2011 IFCPC terminology can improve the diagnostic accuracy for all lesion severities. The categorization of major changes and minor changes is appropriate. However, colposcopic diagnosis remains unsatisfactory. Poor reproducibility of type 2 transformation zone and the significance of leukoplakia require further study.

Effects of complex life cycles on genetic diversity: cyclical parthenogenesis

PubMed Central

Rouger, R; Reichel, K; Malrieu, F; Masson, J P; Stoeckel, S

2016-01-01

Neutral patterns of population genetic diversity in species with complex life cycles are difficult to anticipate. Cyclical parthenogenesis (CP), in which organisms undergo several rounds of clonal reproduction followed by a sexual event, is one such life cycle. Many species, including crop pests (aphids), human parasites (trematodes) or models used in evolutionary science (Daphnia), are cyclical parthenogens. It is therefore crucial to understand the impact of such a life cycle on neutral genetic diversity. In this paper, we describe distributions of genetic diversity under conditions of CP with various clonal phase lengths. Using a Markov chain model of CP for a single locus and individual-based simulations for two loci, our analysis first demonstrates that strong departures from full sexuality are observed after only a few generations of clonality. The convergence towards predictions made under conditions of full clonality during the clonal phase depends on the balance between mutations and genetic drift. Second, the sexual event of CP usually resets the genetic diversity at a single locus towards predictions made under full sexuality. However, this single recombination event is insufficient to reshuffle gametic phases towards full-sexuality predictions. Finally, for similar levels of clonality, CP and acyclic partial clonality (wherein a fixed proportion of individuals are clonally produced within each generation) differentially affect the distribution of genetic diversity. Overall, this work provides solid predictions of neutral genetic diversity that may serve as a null model in detecting the action of common evolutionary or demographic processes in cyclical parthenogens (for example, selection or bottlenecks). PMID:27436524

Climate-driven range shifts explain the distribution of extant gene pools and predict future loss of unique lineages in a marine brown alga.

PubMed

Assis, J; Serrão, E A; Claro, B; Perrin, C; Pearson, G A

2014-06-01

The climate-driven dynamics of species ranges is a critical research question in evolutionary ecology. We ask whether present intraspecific diversity is determined by the imprint of past climate. This is an ongoing debate requiring interdisciplinary examination of population genetic pools and persistence patterns across global ranges. Previously, contrasting inferences and predictions have resulted from distinct genomic coverage and/or geographical information. We aim to describe and explain the causes of geographical contrasts in genetic diversity and their consequences for the future baseline of the global genetic pool, by comparing present geographical distribution of genetic diversity and differentiation with predictive species distribution modelling (SDM) during past extremes, present time and future climate scenarios for a brown alga, Fucus vesiculosus. SDM showed that both atmospheric and oceanic variables shape the global distribution of intertidal species, revealing regions of persistence, extinction and expansion during glacial and postglacial periods. These explained the distribution and structure of present genetic diversity, consisting of differentiated genetic pools with maximal diversity in areas of long-term persistence. Most of the present species range comprises postglacial expansion zones and, in contrast to highly dispersive marine organisms, expansions involved only local fronts, leaving distinct genetic pools at rear edges. Besides unravelling a complex phylogeographical history and showing congruence between genetic diversity and persistent distribution zones, supporting the hypothesis of niche conservatism, range shifts and loss of unique genetic diversity at the rear edge were predicted for future climate scenarios, impoverishing the global gene pool. © 2014 John Wiley & Sons Ltd.

Increased pathologic upstaging with rising time to treatment initiation for head and neck cancer: A mechanism for increased mortality.

PubMed

Xiao, Roy; Ward, Matthew C; Yang, Kailin; Adelstein, David J; Koyfman, Shlomo A; Prendes, Brandon L; Burkey, Brian B

2018-04-01

Time to treatment initiation (TTI) is increasing and is associated with worsening survival. In the current study, the authors sought to identify a mechanism for this relationship by assessing the effect of TTI on clinical-to-pathologic upstaging in patients with head and neck squamous cell carcinoma (HNSCC). Using the National Cancer Data Base, the authors analyzed patients receiving definitive surgery for SCC of the oral cavity, oropharynx, larynx, and hypopharynx from 2005 through 2014. The primary outcome was T, N, or stage group upstaging, defined as higher pathologic stage than clinical stage. TTI was defined as the time between diagnosis and surgery. Multivariable logistic and Cox proportional hazards regression modeled upstaging and survival, respectively. Cohorts of 60,194 patients, 51,380 patients, and 52,980 patients, respectively, with complete T, N, and stage group data were included. N upstaging was most common (18.6%), followed by stage group (17.4%) and T (12.1%) upstaging; all types were predicted by TTI. Compared with a TTI of 1 to 6 days, TTIs as short as 7 to 13 days (odds ratio, 1.20; P = .038) or ≥ 70 days (odds ratio, 2.04; P < .001) were found to predict T upstaging, a finding that is consistent for N and stage group upstaging. Using restricted cubic splines, relative odds of T and stage group upstaging escalated to 2.25 and 1.93, respectively, at a TTI of 365 days. In survival analyses, T (hazard ratio [HR], 1.53), N (HR, 1.88), and stage group (HR, 1.69) upstaging all predicted mortality (P < .001), whereas TTI only predicted mortality after 70 days (HR, 1.11; P = .023). Tumor progression, measured by clinical-to-pathologic upstaging, increases mortality for patients with HNSCC experiencing treatment delays. Cancer 2018;124:1400-14. © 2018 American Cancer Society. © 2018 American Cancer Society.

Anatomical and/or pathological predictors for the “incorrect” classification of red dot markers on wrist radiographs taken following trauma

PubMed Central

Kranz, R

2015-01-01

Objective: To establish the prevalence of red dot markers in a sample of wrist radiographs and to identify any anatomical and/or pathological characteristics that predict “incorrect” red dot classification. Methods: Accident and emergency (A&E) wrist cases from a digital imaging and communications in medicine/digital teaching library were examined for red dot prevalence and for the presence of several anatomical and pathological features. Binary logistic regression analyses were run to establish if any of these features were predictors of incorrect red dot classification. Results: 398 cases were analysed. Red dot was “incorrectly” classified in 8.5% of cases; 6.3% were “false negatives” (“FNs”)and 2.3% false positives (FPs) (one decimal place). Old fractures [odds ratio (OR), 5.070 (1.256–20.471)] and reported degenerative change [OR, 9.870 (2.300–42.359)] were found to predict FPs. Frykman V [OR, 9.500 (1.954–46.179)], Frykman VI [OR, 6.333 (1.205–33.283)] and non-Frykman positive abnormalities [OR, 4.597 (1.264–16.711)] predict “FNs”. Old fractures and Frykman VI were predictive of error at 90% confidence interval (CI); the rest at 95% CI. Conclusion: The five predictors of incorrect red dot classification may inform the image interpretation training of radiographers and other professionals to reduce diagnostic error. Verification with larger samples would reinforce these findings. Advances in knowledge: All healthcare providers strive to eradicate diagnostic error. By examining specific anatomical and pathological predictors on radiographs for such error, as well as extrinsic factors that may affect reporting accuracy, image interpretation training can focus on these “problem” areas and influence which radiographic abnormality detection schemes are appropriate to implement in A&E departments. PMID:25496373

Predicting Acceptance of Diversity in Pre-Kindergarten Classrooms

ERIC Educational Resources Information Center

Sanders, Kay; Downer, Jason

2012-01-01

This study examined classroom-level contributors to an acceptance of diversity in publicly supported pre-kindergarten classrooms across 11 states. Classroom composition, process quality, and teacher characteristics were examined as predictors of diversity-promoting practices as measured by the ECERS-R, acceptance of diversity construct. Findings…

Examining the Relationships among Coaching Staff Diversity, Perceptions of Diversity, Value Congruence, and Life Satisfaction

ERIC Educational Resources Information Center

Cunningham, George B.

2009-01-01

The purpose of this study was to examine relationships among coaching staff diversity, perceptions of diversity, value congruence, and life satisfaction. Data were collected from 71 coaching staffs (N = 196 coaches). Observed path analysis was used to examine the study predictions. Results indicate that actual staff diversity was positively…

Impact of marital status in patients undergoing radical cystectomy for bladder cancer.

PubMed

Pruthi, Raj S; Lentz, Aaron C; Sand, Matthew; Kouba, Erik; Wallen, Eric M

2009-08-01

Married (vs. unmarried) individuals have improved health status and longer life expectancies in a variety of benign and malignant disease states, including prostate, breast, head/neck, and lung cancers. We sought to evaluate a cohort of patients undergoing cystectomy for bladder cancer to evaluate the impact of marital status on demographic, peri-operative, and pathological outcomes in order to better understand the factors which may contribute to the survival differences observed. Two-hundred and two patients underwent radical cystectomy and urinary diversion for bladder cancer. Patients were categorized based on marital status as either married or unmarried (widowed, divorced, never married). Correlations were made to demographic factors (age, race, gender, BMI, tobacco use, alcohol use), perioperative factors (pre-op renal function (creatinine), hematocrit, EBL, hospital stay, choice of diversion), and pathological outcomes (organ-confined status, LN positivity). Of the 202 patients, 74% were married. Married individuals (vs. unmarried) were more often male (84 vs. 62%) and had a higher BMI (28.1 vs. 25.9). Married persons had a significantly lower pre-op creatinine (1.1 vs. 1.4) and higher hematocrit (39 vs. 34). Hospital stay was shorter in married patients by a mean of 1.6 days. Regarding operative pathology, married patients had a higher rate of organ-confined disease (59 vs. 47%) (P = 0.05, 0.08 on multivariate) and trended towards a lower rate of LN positivity (15 vs. 21%; P = 0.10, 0.12 multivariate). In patients undergoing cystectomy for bladder cancer, married individuals appear to have improved pre-operative laboratory variables, shorter hospitalization, and improved pathological outcomes versus unmarried patients in our case series. These findings may support the evidence (observed in other tumor types and other disease states) that married persons present earlier than unmarried individuals, and this may help explain the improved survival outcomes that have been observed in married patients with bladder cancer.

Sources of Variability in Children’s Language Growth

PubMed Central

Huttenlocher, Janellen; Waterfall, Heidi; Vasilyeva, Marina; Vevea, Jack; Hedges, Larry V.

2010-01-01

The present longitudinal study examines the role of caregiver speech in language development, especially syntactic development, using 47 parent-child pairs of diverse SES background from 14 to 46 months. We assess the diversity (variety) of words and syntactic structures produced by caregivers and children. We use lagged correlations to examine language growth and its relation to caregiver speech. Results show substantial individual differences among children, and indicate that diversity of earlier caregiver speech significantly predicts corresponding diversity in later child speech. For vocabulary, earlier child speech also predicts later caregiver speech, suggesting mutual influence. However, for syntax, earlier child speech does not significantly predict later caregiver speech, suggesting a causal flow from caregiver to child. Finally, demographic factors, notably SES, are related to language growth, and are, at least partially, mediated by differences in caregiver speech, showing the pervasive influence of caregiver speech on language growth. PMID:20832781

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.

Endoscopic ultrasound evaluation in the surgical treatment of duodenal and peri-ampullary adenomas.

PubMed

Azih, Lilian C; Broussard, Brett L; Phadnis, Milind A; Heslin, Martin J; Eloubeidi, Mohamad A; Varadarajulu, Shayam; Arnoletti, Juan Pablo

2013-01-28

To investigate endoscopic ultrasound (EUS) for predicting depth of mucosal invasion and to analyze outcomes following endoscopic and transduodenal resection. Records of 111 patients seen at our institution from November 1999 to July 2011 with the post-operative pathological diagnosis of benign ampullary and duodenal adenomas were reviewed. Records of patients who underwent preoperative EUS for diagnostic purposes were identified. The accuracy of EUS in predicting the absence of muscular invasion was assessed by comparing EUS reports to the final surgical pathological results. In addition, the incidence of the post-operative complications over a period of 30 d and the subsequent long-term outcome (recurrence) over a period of 30 mo associated with endoscopic and transduodenal surgical resection was recorded, compared and analyzed. Among 111 patients with benign ampullary and duodenal adenomas, 47 underwent preoperative EUS for 29 peri-ampullary lesions and 18 duodenal lesions. In addition, computed tomography was performed in 18 patients, endoscopic retrograde cholangio-pancreatography in 10 patients and esophagogastroduodenoscopy in 22 patients. There were 43 patients with sporadic adenomas and 4 patients with familial adenomatous polyposis (FAP)/other polyposis syndromes. In 38 (81%, P < 0.05) patients, EUS reliably identified absence of submucosal and muscularis invasion. In 4 cases, EUS underestimated submucosal invasion that was proven by pathology. In the other 5 patients, EUS predicted muscularis invasion which could not be demonstrated in the resected specimen. EUS predicted tumor muscularis invasion with a specificity of 88% and negative predictive value of 90% (P < 0.05). Types of resection performed included endoscopic resection in 22 cases, partial duodenectomy in 9 cases, transduodenal ampullectomy with sphincteroplasty in 10 cases and pancreaticoduodenectomy in 6 cases. The main post-operative final pathological results included villous adenoma (n = 5), adenoma (n = 8), tubulovillous adenoma (n = 10), tubular adenoma (n = 20) and hyperplastic polyp (n = 2). Among the 47 patients who underwent resection, 8 (17%, 5 of which corresponded to surgical resection) developed post-procedural complications which included retroperitoneal hematoma, intra-abdominal abscess, wound infection, delayed gastric emptying and prolonged ileus. After median follow-up of 20 mo there were 6 local recurrences (13%, median follow-up = 20 mo) 4 of which were in patients with FAP. EUS accurately predicts the depth of mucosal invasion in suspected benign ampullary and duodenal adenomas. These patients can safely undergo endoscopic or local resection.

Predicting College Students' Intergroup Friendships across Race/Ethnicity, Religion, Sexual Orientation, and Social Class

ERIC Educational Resources Information Center

Goldstein, Susan B.

2013-01-01

This study seeks to expand the literature on predicting friendship diversity beyond race/ethnicity to include religion, social class, and sexual orientation. Survey packets elicited information regarding up to four close friendships developed during college. Additional measures assessed pre-college friendship diversity, participation in college…

Diverse Physiological Roles of Calcitonin Gene-Related Peptide in Migraine Pathology: Modulation of Neuronal-Glial-Immune Cells to Promote Peripheral and Central Sensitization

PubMed Central

Durham, Paul L.

2018-01-01

The neuropeptide calcitonin gene-related peptide (CGRP) is implicated in the underlying pathology of migraine by promoting the development of a sensitized state of primary and secondary nociceptive neurons. The ability of CGRP to initiate and maintain peripheral and central sensitization is mediated by modulation of neuronal, glial, and immune cells in the trigeminal nociceptive signaling pathway. There is accumulating evidence to support a key role of CGRP in promoting cross excitation within the trigeminal ganglion that may help to explain the high co-morbidity of migraine with rhinosinusitis and temporomandibular joint disorder. In addition, there is emerging evidence that CGRP facilitates and sustains a hyperresponsive neuronal state in migraineurs mediated by reported risk factors such as stress and anxiety. In this review, the significant role of CGRP as a modulator of the trigeminal system will be discussed to provide a better understanding of the underlying pathology associated with the migraine phenotype. PMID:27334137

A review of multi-threat medical countermeasures against chemical warfare and terrorism.

PubMed

Cowan, Fred M; Broomfield, Clarence A; Stojiljkovic, Milos P; Smith, William J

2004-11-01

The Multi-Threat Medical Countermeasure (MTMC) hypothesis has been proposed with the aim of developing a single countermeasure drug with efficacy against different pathologies caused by multiple classes of chemical warfare agents. Although sites and mechanisms of action and the pathologies caused by different chemical insults vary, common biochemical signaling pathways, molecular mediators, and cellular processes provide targets for MTMC drugs. This article will review the MTMC hypothesis for blister and nerve agents and will expand the scope of the concept to include other chemicals as well as briefly consider biological agents. The article will also consider how common biochemical signaling pathways, molecular mediators, and cellular processes that contribute to clinical pathologies and syndromes may relate to the toxicity of threat agents. Discovery of MTMC provides the opportunity for the integration of diverse researchers and clinicians, and for the exploitation of cutting-edge technologies and drug discovery. The broad-spectrum nature of MTMC can augment military and civil defense to combat chemical warfare and chemical terrorism.

Next-Generation Sequencing for Infectious Disease Diagnosis and Management: A Report of the Association for Molecular Pathology.

PubMed

Lefterova, Martina I; Suarez, Carlos J; Banaei, Niaz; Pinsky, Benjamin A

2015-11-01

Next-generation sequencing (NGS) technologies are increasingly being used for diagnosis and monitoring of infectious diseases. Herein, we review the application of NGS in clinical microbiology, focusing on genotypic resistance testing, direct detection of unknown disease-associated pathogens in clinical specimens, investigation of microbial population diversity in the human host, and strain typing. We have organized the review into three main sections: i) applications in clinical virology, ii) applications in clinical bacteriology, mycobacteriology, and mycology, and iii) validation, quality control, and maintenance of proficiency. Although NGS holds enormous promise for clinical infectious disease testing, many challenges remain, including automation, standardizing technical protocols and bioinformatics pipelines, improving reference databases, establishing proficiency testing and quality control measures, and reducing cost and turnaround time, all of which would be necessary for widespread adoption of NGS in clinical microbiology laboratories. Copyright © 2015 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

Disentangling the Impact of Diversity Courses: Examining the Influence of Diversity Course Content on Students' Civic Engagement

ERIC Educational Resources Information Center

Castellanos, Michelle; Cole, Darnell

2015-01-01

Utilizing Bennett's genres of multicultural education, the authors examine whether diversity course content clusters influence students' civic engagement. Diversity course content clusters were predicted to influence White students and students of color differently, given principles identified by social development, cognitive development, and…

Predicting Acceptance of Diversity in Pre-Kindergarten Classrooms. Research Brief

ERIC Educational Resources Information Center

Sanders, Kay; Downer, Jason T.

2013-01-01

Given the increasing ethnic and language diversity within the United States, this study examined practices that acknowledge and promote diversity in pre-Kindergarten classrooms. Findings indicate that acceptance of diversity is a component of positive environments for young children, particularly in classrooms with high poverty levels where there…

Neuropsychological Testing Predicts Cerebrospinal Fluid Aβ in Mild Cognitive Impairment (MCI)

PubMed Central

Kandel, Benjamin M.; Avants, Brian B.; Gee, James C.; Arnold, Steven E.; Wolk, David A.

2015-01-01

Background Psychometric tests predict conversion of Mild Cognitive Impairment (MCI) to probable Alzheimer's Disease (AD). Because the definition of clinical AD relies on those same psychometric tests, the ability of these tests to identify underlying AD pathology remains unclear. Objective To determine the degree to which psychometric testing predicts molecular evidence of AD amyloid pathology, as indicated by CSF Aβ1–42, in patients with MCI, as compared to neuroimaging biomarkers. Methods We identified 408 MCI subjects with CSF Aβ levels, psychometric test data, FDG-PET scans, and acceptable volumetric MR scans from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). We used psychometric tests and imaging biomarkers in univariate and multivariate models to predict Aβ status. Results The 30-minute delayed recall score of the Rey Auditory Verbal Learning Test (AVLT) was the best predictor of Aβ status among the psychometric tests, achieving an AUC of 0.67±0.02 and odds ratio of 2.5±0.4. FDG-PET was the best imaging-based biomarker (AUC 0.67±0.03, OR 3.2±1.2), followed by hippocampal volume (AUC 0.64±0.02,,OR 2.4±0.3). A multivariate analysis based on the psychometric tests improved on the univariate predictors, achieving an AUC of 0.68±0.03 (OR 3.38±1.2). Adding imaging biomarkers to the multivariate analysis did not improve the AUC. Conclusion Psychometric tests perform as well as imaging biomarkers to predict presence of molecular markers of AD pathology in MCI patients and should be considered in the determination of the likelihood that MCI is due to AD. PMID:25881908

Predictive model for inflammation grades of chronic hepatitis B: Large-scale analysis of clinical parameters and gene expressions.

PubMed

Zhou, Weichen; Ma, Yanyun; Zhang, Jun; Hu, Jingyi; Zhang, Menghan; Wang, Yi; Li, Yi; Wu, Lijun; Pan, Yida; Zhang, Yitong; Zhang, Xiaonan; Zhang, Xinxin; Zhang, Zhanqing; Zhang, Jiming; Li, Hai; Lu, Lungen; Jin, Li; Wang, Jiucun; Yuan, Zhenghong; Liu, Jie

2017-11-01

Liver biopsy is the gold standard to assess pathological features (eg inflammation grades) for hepatitis B virus-infected patients although it is invasive and traumatic; meanwhile, several gene profiles of chronic hepatitis B (CHB) have been separately described in relatively small hepatitis B virus (HBV)-infected samples. We aimed to analyse correlations among inflammation grades, gene expressions and clinical parameters (serum alanine amino transaminase, aspartate amino transaminase and HBV-DNA) in large-scale CHB samples and to predict inflammation grades by using clinical parameters and/or gene expressions. We analysed gene expressions with three clinical parameters in 122 CHB samples by an improved regression model. Principal component analysis and machine-learning methods including Random Forest, K-nearest neighbour and support vector machine were used for analysis and further diagnosis models. Six normal samples were conducted to validate the predictive model. Significant genes related to clinical parameters were found enriching in the immune system, interferon-stimulated, regulation of cytokine production, anti-apoptosis, and etc. A panel of these genes with clinical parameters can effectively predict binary classifications of inflammation grade (area under the ROC curve [AUC]: 0.88, 95% confidence interval [CI]: 0.77-0.93), validated by normal samples. A panel with only clinical parameters was also valuable (AUC: 0.78, 95% CI: 0.65-0.86), indicating that liquid biopsy method for detecting the pathology of CHB is possible. This is the first study to systematically elucidate the relationships among gene expressions, clinical parameters and pathological inflammation grades in CHB, and to build models predicting inflammation grades by gene expressions and/or clinical parameters as well. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

PREOPERATIVE MRI IMPROVES PREDICTION OF EXTENSIVE OCCULT AXILLARY LYMPH NODE METASTASES IN BREAST CANCER PATIENTS WITH A POSITIVE SENTINEL LYMPH NODE BIOPSY

PubMed Central

Loiselle, Christopher; Eby, Peter R.; Kim, Janice N.; Calhoun, Kristine E.; Allison, Kimberly H.; Gadi, Vijayakrishna K.; Peacock, Sue; Storer, Barry; Mankoff, David A.; Partridge, Savannah C.; Lehman, Constance D.

2014-01-01

Rationale and Objectives To test the ability of quantitative measures from preoperative Dynamic Contrast Enhanced MRI (DCE-MRI) to predict, independently and/or with the Katz pathologic nomogram, which breast cancer patients with a positive sentinel lymph node biopsy will have ≥ 4 positive axillary lymph nodes upon completion axillary dissection. Methods and Materials A retrospective review was conducted to identify clinically node-negative invasive breast cancer patients who underwent preoperative DCE-MRI, followed by sentinel node biopsy with positive findings and complete axillary dissection (6/2005 – 1/2010). Clinical/pathologic factors, primary lesion size and quantitative DCE-MRI kinetics were collected from clinical records and prospective databases. DCE-MRI parameters with univariate significance (p < 0.05) to predict ≥ 4 positive axillary nodes were modeled with stepwise regression and compared to the Katz nomogram alone and to a combined MRI-Katz nomogram model. Results Ninety-eight patients with 99 positive sentinel biopsies met study criteria. Stepwise regression identified DCE-MRI total persistent enhancement and volume adjusted peak enhancement as significant predictors of ≥4 metastatic nodes. Receiver operating characteristic (ROC) curves demonstrated an area under the curve (AUC) of 0.78 for the Katz nomogram, 0.79 for the DCE-MRI multivariate model, and 0.87 for the combined MRI-Katz model. The combined model was significantly more predictive than the Katz nomogram alone (p = 0.003). Conclusion Integration of DCE-MRI primary lesion kinetics significantly improved the Katz pathologic nomogram accuracy to predict presence of metastases in ≥ 4 nodes. DCE-MRI may help identify sentinel node positive patients requiring further localregional therapy. PMID:24331270

Impact of different variables on the outcome of patients with clinically confined prostate carcinoma: prediction of pathologic stage and biochemical failure using an artificial neural network.

PubMed

Ziada, A M; Lisle, T C; Snow, P B; Levine, R F; Miller, G; Crawford, E D

2001-04-15

The advent of advanced computing techniques has provided the opportunity to analyze clinical data using artificial intelligence techniques. This study was designed to determine whether a neural network could be developed using preoperative prognostic indicators to predict the pathologic stage and time of biochemical failure for patients who undergo radical prostatectomy. The preoperative information included TNM stage, prostate size, prostate specific antigen (PSA) level, biopsy results (Gleason score and percentage of positive biopsy), as well as patient age. All 309 patients underwent radical prostatectomy at the University of Colorado Health Sciences Center. The data from all patients were used to train a multilayer perceptron artificial neural network. The failure rate was defined as a rise in the PSA level > 0.2 ng/mL. The biochemical failure rate in the data base used was 14.2%. Univariate and multivariate analyses were performed to validate the results. The neural network statistics for the validation set showed a sensitivity and specificity of 79% and 81%, respectively, for the prediction of pathologic stage with an overall accuracy of 80% compared with an overall accuracy of 67% using the multivariate regression analysis. The sensitivity and specificity for the prediction of failure were 67% and 85%, respectively, demonstrating a high confidence in predicting failure. The overall accuracy rates for the artificial neural network and the multivariate analysis were similar. Neural networks can offer a convenient vehicle for clinicians to assess the preoperative risk of disease progression for patients who are about to undergo radical prostatectomy. Continued investigation of this approach with larger data sets seems warranted. Copyright 2001 American Cancer Society.

ROLE OF IMAGING TESTS FOR PREOPERATIVE LOCATION OF PATHOLOGIC PARATHYROID TISSUE IN PATIENTS WITH PRIMARY HYPERPARATHYROIDISM.

PubMed

Coelho, Maria Caroline Alves; de Oliveira E Silva de Morais, Nathalie Anne; Beuren, Andrea Cristiani; Lopes, Cristiane Bertolino; Santos, Camila Vicente; Cantoni, Joyce; Neto, Leonardo Vieira; Lima, Maurício Barbosa

2016-09-01

Primary hyperparathyroidism (PHPT) can be cured by parathyroidectomy, and the preoperative location of enlarged pathologic parathyroid glands is determined by imaging studies, especially cervical ultrasonography and scintigraphy scanning. The aim of this retrospective study was to evaluate the use of preoperative cervical ultrasonography and/or parathyroid scintigraphy in locating pathologic parathyroid tissue in a group of patients with PHPT followed in the same endocrine center. We examined the records of 61 patients who had undergone parathyroidectomy for PHPT following (99m)Tc-sestamibi scintigraphy scan and/or cervical ultrasonography. Scintigraphic and ultrasonographic findings were compared to histopathologic results of the surgical specimens. Ultrasonography detected enlarged parathyroid glands in 87% (48/55) of patients with PHPT and (99m)Tc-sestamibi scintigraphy in 79% (37/47) of the cases. Ultrasonography was able to correctly predict the surgical findings in 75% (41/55) of patients and scintigraphy in 72% (34/47). Of 7 patients who had negative ultrasonography, scintigraphy correctly predicted the surgical results in 2 (29%). Of 10 patients who had negative scintigraphy, ultrasonography correctly predicted the surgical results in 4 (40%). When we analyzed only patients with solitary eutopic parathyroid adenomas, the predictive positive values of ultrasonography and scintigraphy were 90% and 86%, respectively. Cervical ultrasonography had a higher likelihood of a correct positive test and a greater predictive positive value for solitary adenoma compared to (99m)Tc-sestamibi and should be used as the first diagnostic tool for preoperative localization of affected parathyroid glands in PHPT. Ca = calcium IEDE = Instituto Estadual de Diabetes e Endocrinologia Luiz Capriglione PHPT = primary hyperparathyroidism PTH = parathyroid hormone.

Predicting neo-adjuvant chemotherapy response and progression-free survival of locally advanced breast cancer using textural features of intratumoral heterogeneity on F-18 FDG PET/CT and diffusion-weighted MR imaging.

PubMed

Yoon, Hai-Jeon; Kim, Yemi; Chung, Jin; Kim, Bom Sahn

2018-03-30

Predicting response to neo-adjuvant chemotherapy (NAC) and survival in locally advanced breast cancer (LABC) is important. This study investigated the prognostic value of tumor heterogeneity evaluated with textural analysis through F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) and diffusion-weighted imaging (DWI). We enrolled 83 patients with LABC who had completed NAC and curative surgery. Tumor texture indices from pretreatment FDG PET and DWI were extracted from histogram analysis and 7 different parent matrices: co-occurrence matrix, the voxel-alignment matrix, neighborhood intensity difference matrix, intensity size-zone matrix (ISZM), normalized gray-level co-occurrence matrix (NGLCM), neighboring gray-level dependence matrix (NGLDM), and texture spectrum matrix. The predictive values of textural features were tested regarding both pathologic NAC response and progression-free survival. Among 83 patients, 46 were pathologic responders, while 37 were nonresponders. The PET texture indices from 7 parent matrices, DWI texture indices from histogram, and 1 parent matrix (NGLCM) showed significant differences according to NAC response. On multivariable analysis, number nonuniformity of PET extracted from the NGLDM was an independent predictor of pathologic response (P = .009). During a median follow-up period of 17.3 months, 14 patients experienced recurrence. High-intensity zone emphasis (HIZE) and high-intensity short-zone emphasis (HISZE) from PET extracted from ISZM were significant textural predictors (P = .011 and P = .033). On Cox regression analysis, only HIZE was a significant predictor of recurrence (P = .027), while HISZE showed borderline significance (P = .107). Tumor texture indices are useful for NAC response prediction in LABC. Moreover, PET texture indices can help to predict disease recurrence. © 2018 Wiley Periodicals, Inc.

Sequential stages and distribution patterns of aging-related tau astrogliopathy (ARTAG) in the human brain.

PubMed

Kovacs, Gabor G; Xie, Sharon X; Robinson, John L; Lee, Edward B; Smith, Douglas H; Schuck, Theresa; Lee, Virginia M-Y; Trojanowski, John Q

2018-06-11

Aging-related tau astrogliopathy (ARTAG) describes tau pathology in astrocytes in different locations and anatomical regions. In the present study we addressed the question of whether sequential distribution patterns can be recognized for ARTAG or astroglial tau pathologies in both primary FTLD-tauopathies and non-FTLD-tauopathy cases. By evaluating 687 postmortem brains with diverse disorders we identified ARTAG in 455. We evaluated frequencies and hierarchical clustering of anatomical involvement and used conditional probability and logistic regression to model the sequential distribution of ARTAG and astroglial tau pathologies across different brain regions. For subpial and white matter ARTAG we recognize three and two patterns, respectively, each with three stages initiated or ending in the amygdala. Subependymal ARTAG does not show a clear sequential pattern. For grey matter (GM) ARTAG we recognize four stages including a striatal pathway of spreading towards the cortex and/or amygdala, and the brainstem, and an amygdala pathway, which precedes the involvement of the striatum and/or cortex and proceeds towards the brainstem. GM ARTAG and astrocytic plaque pathology in corticobasal degeneration follows a predominantly frontal-parietal cortical to temporal-occipital cortical, to subcortical, to brainstem pathway (four stages). GM ARTAG and tufted astrocyte pathology in progressive supranuclear palsy shows a striatum to frontal-parietal cortical to temporal to occipital, to amygdala, and to brainstem sequence (four stages). In Pick's disease cases with astroglial tau pathology an overlapping pattern with PSP can be appreciated. We conclude that tau-astrogliopathy type-specific sequential patterns cannot be simplified as neuron-based staging systems. The proposed cytopathological and hierarchical stages provide a conceptual approach to identify the initial steps of the pathogenesis of tau pathologies in ARTAG and primary FTLD-tauopathies.

[Clinical and pathological features of Alport syndrome in children].

PubMed

Zhu, Chun-Hua; Huang, Song-Ming; Wu, Hong-Mei; Bao, Hua-Ying; Chen, Ying; Han, Yuan; Zhao, Fei; Zhang, Ai-Hua; Zhang, Wei-Zhen

2010-03-01

To study the clinical and pathological features of Alport syndrome in children. The clinical and histopathological data of 10 hospitalized children with Alport syndrome from February 2007 to February 2009 were retrospectively reviewed. There were 7 males and 3 females, with the age ranging from 2 years to 6 years and 7 months (mean 3 years and 2 months). Five of 10 cases had positive family history. X-linked dominant inheritance Alport syndrome was diagnosed in 8 cases, and autosomal recessive inheritance Alport syndrome in 2 cases. Recurrent gross hematuria was found in 5 cases, hematuria and proteinuria in 3 cases, massive proteinuria in 1 case, and nephritic syndrome in 1 case. Under the light microscope, 8 cases presented with mesangial proliferation glomerulonephritis, and 2 cases with focal segmental glomerulosclerosis. Immunofluorescence assay showed that all cases had IgM deposition in glomerulus. Only 1 case showed typical glomerular basement membrane (GBM) pathological changes. All cases showed abnormal alpha-chain distribution in renal collagen IV. The children with Alport syndrome have diverse clinical manifestations. Characteristic histopathological presentations could not be found under a light microscope, mesangial proliferation glomerulonephritis is the dominant pathological change, and IgM deposition in glomerulus is common. The GBM pathological change in children is not common. Immunofluorescence assay of alpha-chain in collagen IV is needed for the diagnosis of Alport syndrome.

Performance of wavelet analysis and neural networks for pathological voices identification

NASA Astrophysics Data System (ADS)

Salhi, Lotfi; Talbi, Mourad; Abid, Sabeur; Cherif, Adnane

2011-09-01

Within the medical environment, diverse techniques exist to assess the state of the voice of the patient. The inspection technique is inconvenient for a number of reasons, such as its high cost, the duration of the inspection, and above all, the fact that it is an invasive technique. This study focuses on a robust, rapid and accurate system for automatic identification of pathological voices. This system employs non-invasive, non-expensive and fully automated method based on hybrid approach: wavelet transform analysis and neural network classifier. First, we present the results obtained in our previous study while using classic feature parameters. These results allow visual identification of pathological voices. Second, quantified parameters drifting from the wavelet analysis are proposed to characterise the speech sample. On the other hand, a system of multilayer neural networks (MNNs) has been developed which carries out the automatic detection of pathological voices. The developed method was evaluated using voice database composed of recorded voice samples (continuous speech) from normophonic or dysphonic speakers. The dysphonic speakers were patients of a National Hospital 'RABTA' of Tunis Tunisia and a University Hospital in Brussels, Belgium. Experimental results indicate a success rate ranging between 75% and 98.61% for discrimination of normal and pathological voices using the proposed parameters and neural network classifier. We also compared the average classification rate based on the MNN, Gaussian mixture model and support vector machines.

IL-1 as a target in inflammation.

PubMed

Ito, Yuki; Kaneko, Naoe; Iwasaki, Tomoyuki; Morikawa, Shinnosuke; Kaneko, Kentaro; Masumoto, Junya

2015-03-16

Inflammation is a protective response to eliminate cytotoxic agents and pathogens. Various factors are thought to be involved in the pathological changes in tissues caused by inflammation. Interleukin 1, an inflammatory cytokine, is thought to have diverse physiological functions and to play an important role in inflammatory disease. In this review, we discuss interleukin-1 as a target of inflammatory disease.

IL-1 as a target in inflammation.

PubMed

Ito, Yuki; Kaneko, Naoe; Iwasaki, Tomoyuki; Morikawa, Shinnosuke; Kaneko, Kentaro; Masumoto, Junya

2015-01-01

Inflammation is a protective response to eliminate cytotoxic agents and pathogens. Various factors are thought to be involved in the pathological changes in tissues caused by inflammation. Interleukin 1, an inflammatory cytokine, is thought to have diverse physiological functions and to play an important role in inflammatory disease. In this review, we discuss interleukin-1 as a target of inflammatory disease.

International educational opportunities for dermatology residents.

PubMed

Chacon, Anna H

2015-05-01

International resident opportunities in dermatology allow residents to become immersed in different systems of medical care and expose physicians to different dermatologic conditions, cultures, and traditions that are prevalent in each country. Due to the prevalence of some dermatologic conditions in only certain regions, international opportunities expose residents to a variety of skin pathology and disease as well as a rich and diverse experience abroad.

Synchrotron-based X-ray fluorescence microscopy enables multiscale spatial visualization of ions involved in fungal lignocellulose deconstruction

Treesearch

Grant T. Kirker; Samuel Zelinka; Sophie-Charlotte Gleber; David Vine; Lydia Finney; Si Chen; Young Pyo Hong; Omar Uyarte; Stefan Vogt; Jody Jellison; Barry Goodell; Joseph E. Jakes

2017-01-01

The role of ions in the fungal decay process of lignocellulose biomaterials, and more broadly fungal metabolism, has implications for diverse research disciplines ranging from plant pathology and forest ecology, to carbon sequestration. Despite the importance of ions in fungal decay mechanisms, the spatial distribution and quantification of ions in lignocellulosic cell...

Life history trade-off moderates model predictions of diversity loss from climate change

PubMed Central

2017-01-01

Climate change can trigger species range shifts, local extinctions and changes in diversity. Species interactions and dispersal capacity are important mediators of community responses to climate change. The interaction between multispecies competition and variation in dispersal capacity has recently been shown to exacerbate the effects of climate change on diversity and to increase predictions of extinction risk dramatically. Dispersal capacity, however, is part of a species’ overall ecological strategy and are likely to trade off with other aspects of its life history that influence population growth and persistence. In plants, a well-known example is the trade-off between seed mass and seed number. The presence of such a trade-off might buffer the diversity loss predicted by models with random but neutral (i.e. not impacting fitness otherwise) differences in dispersal capacity. Using a trait-based metacommunity model along a warming climatic gradient the effect of three different dispersal scenarios on model predictions of diversity change were compared. Adding random variation in species dispersal capacity caused extinctions by the introduction of strong fitness differences due an inherent property of the dispersal kernel. Simulations including a fitness-equalising trade-off based on empirical relationships between seed mass (here affecting dispersal distance, establishment probability, and seedling biomass) and seed number (fecundity) maintained higher initial species diversity and predicted lower extinction risk and diversity loss during climate change than simulations with variable dispersal capacity. Large seeded species persisted during climate change, but developed lags behind their climate niche that may cause extinction debts. Small seeded species were more extinction-prone during climate change but tracked their niches through dispersal and colonisation, despite competitive resistance from residents. Life history trade-offs involved in coexistence mechanisms may increase community resilience to future climate change and are useful guides for model development. PMID:28520770

Symbiotic flagellate protists as cryptic drivers of adaptation and invasiveness of the subterranean termite Reticulitermes grassei Clément.

PubMed

Duarte, Sónia; Nobre, Tânia; Borges, Paulo A V; Nunes, Lina

2018-06-01

Changes in flagellate protist communities of subterranean termite Reticulitermes grassei across different locations were evaluated following four predictions: (i) Rural endemic (Portugal mainland) termite populations will exhibit high diversity of symbionts; (ii) invasive urban populations (Horta city, Faial island, Azores), on the contrary, will exhibit lower diversity of symbionts, showing high similarity of symbiont assemblages through environmental filtering; (iii) recent historical colonization of isolated regions-as the case of islands-will imply a loss of symbiont diversity; and (iv) island isolation will trigger a change in colony breeding structure toward a less aggressive behavior. Symbiont flagellate protist communities were morphologically identified, and species richness and relative abundances, as well as biodiversity indices, were used to compare symbiotic communities in colonies from urban and rural environments and between island invasive and mainland endemic populations. To evaluate prediction on the impact of isolation (iv), aggression tests were performed among termites comprising island invasive and mainland endemic populations. A core group of flagellates and secondary facultative symbionts was identified. Termites from rural environments showed, in the majority of observed colonies, more diverse and abundant protist communities, probably confirming prediction (i). Corroborating prediction (ii), the two least diverse communities belong to termites captured inside urban areas. The Azorean invasive termite colonies had more diverse protist communities than expected and prediction (iii) which was not verified within this study. Termites from mainland populations showed a high level of aggressiveness between neighboring colonies, in contrast to the invasive colonies from Horta city, which were not aggressive to neighbors according to prediction (iv). The symbiotic flagellate community of R. grassei showed the ability to change in a way that might be consistent with adaptation to available conditions, possibly contributing to optimization of the colonization of new habitats and spreading of its distribution area, highlighting R. grassei potential as an invasive species.

EEG Oscillatory States: Universality, Uniqueness and Specificity across Healthy-Normal, Altered and Pathological Brain Conditions

PubMed Central

Fingelkurts, Alexander A.; Fingelkurts, Andrew A.

2014-01-01

For the first time the dynamic repertoires and oscillatory types of local EEG states in 13 diverse conditions (examined over 9 studies) that covered healthy-normal, altered and pathological brain states were quantified within the same methodological and conceptual framework. EEG oscillatory states were assessed by the probability-classification analysis of short-term EEG spectral patterns. The results demonstrated that brain activity consists of a limited repertoire of local EEG states in any of the examined conditions. The size of the state repertoires was associated with changes in cognition and vigilance or neuropsychopathologic conditions. Additionally universal, optional and unique EEG states across 13 diverse conditions were observed. It was demonstrated also that EEG oscillations which constituted EEG states were characteristic for different groups of conditions in accordance to oscillations’ functional significance. The results suggested that (a) there is a limit in the number of local states available to the cortex and many ways in which these local states can rearrange themselves and still produce the same global state and (b) EEG individuality is determined by varying proportions of universal, optional and unique oscillatory states. The results enriched our understanding about dynamic microstructure of EEG-signal. PMID:24505292

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

PubMed

Quesada, Jorge; Amato, Robert

2012-01-01

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

A Trickster in Disguise: Hyaluronan’s Ambivalent Roles in the Matrix

PubMed Central

Bohaumilitzky, Lena; Huber, Ann-Kathrin; Stork, Eva Maria; Wengert, Simon; Woelfl, Franziska; Boehm, Heike

2017-01-01

Hyaluronan (HA) is a simple but diverse glycosaminoglycan. It plays a major role in aging, cellular senescence, cancer, and tissue homeostasis. In which way HA affects the surrounding tissues greatly depends on the molecular weight of HA. Whereas high molecular weight HA is associated with homeostasis and protective effects, HA fragments tend to be linked to the pathologic state. Furthermore, the interaction of HA with its binding partners, the hyaladherins, such as CD44, is essential for sustaining tissue integrity and is likewise related to cancer. The naked mole rat, a rodent species, possesses a special form of very high molecular weight (vHMW) HA, which is associated with the extraordinary cancer resistance and longevity of those animals. This review addresses HA and its diverse facets: from HA synthesis to degradation, from oligomeric HA to vHMW-HA and from its beneficial properties to the involvement in pathologies. We further discuss the functions of HA in the naked mole rat and compare them to human conditions. Though intensively researched, this simple polymer bears some secrets that may hold the key for a better understanding of cellular processes and the development of diseases, such as cancer. PMID:29062810

Partial biochemical characterization of a metalloproteinase from the bloodstream forms of Trypanosoma brucei brucei parasites.

PubMed

de Sousa, Karina Pires; Atouguia, Jorge; Silva, Marcelo Sousa

2010-05-01

Metalloproteinases (MMP) belong to the family of cation dependent endopeptidases that degrade matrices at physiological pH and to cleave extracellular matrix proteins. They play an important role in diverse physiological and pathological processes; not only there diverse types of MMP differ in structure and functionally, but also their enzymatic activity is regulated at multiple levels. Trying to shed some light over the processes that govern the pathology of African Trypanosomiasis, the aim of the present study was to examine the proteolytic activity of the crude trypanosome protein extract obtained from the bloodstream forms of Trypanosoma brucei brucei parasites. We hereby report the partial biochemical characterization of a neutral Trypanosoma brucei-metalloproteinase that displays marked proteolytic activities on gelatin and casein, with a molecular mass of approximately 40 kDa, whose activity is strongly dependent of pH and temperature. Furthermore, we show that this activity can be inhibited by classical MMP inhibitors such as EDTA, EGTA, phenantroline, and also by tetracycline and derivatives. This study has a relevant role in the search for new therapeutical targets, for the use of metalloproteinases inhibitors as treatment strategies, or as enhancement to trypanocidal drugs used in the treatment of the disease.

Cotransin induces accumulation of a cytotoxic clusterin variant that cotranslationally rerouted to the cytosol

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

Choi, Ilho; Kim, Jiyeon; Park, Joong-Yeol

2013-05-01

Although clusterin (CLU) was originally identified as a secreted glycoprotein that plays cytoprotective role, several intracellular CLU variants have been recently identified in the diverse pathological conditions. The mechanistic basis of these variants is now believed to be alternative splicing and retrotranslocation. Here, we uncovered, an unglycosylated and signal sequence-unprocessed, CLU variant in the cytosol. This variant proved to be a product that cotranslationally rerouted to the cytosol during translocation. Cytosolic CLU was prone to aggregation at peri-nuclear region of cells and induced cell death. Signal sequence is shown to be an important determinant for cytosolic CLU generation and aggregation.more » These results provide not only a new mechanistic insight into the cytosolic CLU generation but also an idea for therapeutic mislocalization of CLU as a strategy for cancer treatment. - Highlights: ► Intracellular CLU variants have been recently identified in the diverse pathological conditions. ► Translocation of clusterin is less efficient than that of Prl. ► We identified a new cytotoxic clusterin variant whose signal sequence was unprocessed. ► This variant proved to be a product that cotranslationally rerouted to cytosol.« less

Prevalence and diversity of avian Haemosporida infecting songbirds in southwest Michigan.

PubMed

Smith, Jamie D; Gill, Sharon A; Baker, Kathleen M; Vonhof, Maarten J

2018-02-01

Avian blood parasites from the genera Plasmodium, Haemoproteus, and Leucocytozoon (Haemosporida) affect hosts in numerous ways. They influence species interactions, host behavior, reproductive success, and cause pathology and mortality in birds. The Great Lakes region of North America has extensive aquatic and wetland habitat and supports a diverse vector community. Here we describe the community of bird-infecting Haemosporida in southwest Michigan and their host associations by measuring parasite prevalence, diversity, and host breadth across a diverse community of avian hosts. Over 700 songbirds of 55 species were screened for Haemosporida infection across southwest Michigan, including 11 species that were targeted for larger sample sizes. In total, 71 parasite lineages infected over 40% of birds. Of these, 42 were novel, yet richness estimates suggest that approximately half of the actual parasite diversity in the host community was observed despite intensive sampling of multiple host species. Parasite prevalence varied among parasite genera (7-24%) and target host species (0-85%), and parasite diversity was consistently high across most target species. Host breadth varied widely across the most prevalent parasite lineages, and we detected around 60% of host species richness for these parasite lineages. We report many new lineages and novel host-parasite associations, but substantial parasite diversity remains undiscovered in the Midwest.

Disturbance Regimes Predictably Alter Diversity in an Ecologically Complex Bacterial System

PubMed Central

Scholz, Monika; Hutchison, Alan L.; Dinner, Aaron R.; Gilbert, Jack A.; Coleman, Maureen L.

2016-01-01

ABSTRACT Diversity is often associated with the functional stability of ecological communities from microbes to macroorganisms. Understanding how diversity responds to environmental perturbations and the consequences of this relationship for ecosystem function are thus central challenges in microbial ecology. Unimodal diversity-disturbance relationships, in which maximum diversity occurs at intermediate levels of disturbance, have been predicted for ecosystems where life history tradeoffs separate organisms along a disturbance gradient. However, empirical support for such peaked relationships in macrosystems is mixed, and few studies have explored these relationships in microbial systems. Here we use complex microbial microcosm communities to systematically determine diversity-disturbance relationships over a range of disturbance regimes. We observed a reproducible switch between community states, which gave rise to transient diversity maxima when community states were forced to mix. Communities showed reduced compositional stability when diversity was highest. To further explore these dynamics, we formulated a simple model that reveals specific regimes under which diversity maxima are stable. Together, our results show how both unimodal and non-unimodal diversity-disturbance relationships can be observed as a system switches between two distinct microbial community states; this process likely occurs across a wide range of spatially and temporally heterogeneous microbial ecosystems. PMID:27999158

An incidental enterocolic lymphocytic phlebitis pattern is seen commonly in the rectal stump of patients with diversion colitis superimposed on inflammatory bowel disease.

PubMed

Chetty, R; Hafezi, S; Montgomery, E

2009-05-01

Enterocolic lymphocytic phlebitis (ELP) is an uncommon cause of bowel pathology and most frequently results in ischaemia. It is characterised by an artery-sparing, venulocentric lymphoid infiltrate that causes a phlebitis and vascular compromise. Rare cases of ELP have been encountered with lymphocytic colitis in the absence of ischaemic bowel change. The present study examined the occurrence of ELP in the setting of diversion colitis and inflammatory bowel disease, as well as in random colectomy specimens. The study cohort comprised the following: 26 completion proctectomy specimens for ulcerative colitis with superimposed diversion colitis in the rectal stump; 3 colectomy specimens for Crohn disease with diversion colitis; 6 colectomy specimens for adenocarcinoma and/or diverticular disease with diversion colitis; 34 resection specimens with ulcerative colitis only; 19 with Crohn disease only; and 100 random colon resection specimens for adenocarcinoma, adenoma, diverticular disease and ischaemia. ELP was present in 18 of the 26 ulcerative colitis cases with diversion colitis, 3/3 Crohn disease cases with diversion colitis, 1/6 cases of diverticular disease with diversion colitis, 6/34 cases of ulcerative colitis without diversion, 2/19 Crohn disease cases without diversion colitis, and only 1 of 100 colectomy cases without inflammatory bowel disease or diversion colitis. ELP occurs most frequently in cases that have been diverted for inflammatory bowel disease. Fewer cases of ELP were noted in cases of inflammatory bowel disease in the absence of diversion colitis. It is postulated that altered bowel flora and immune dysregulation may be pivotal in the causation of this association.

Enhancement of hepatitis virus immunoassay outcome predictions in imbalanced routine pathology data by data balancing and feature selection before the application of support vector machines.

PubMed

Richardson, Alice M; Lidbury, Brett A

2017-08-14

Data mining techniques such as support vector machines (SVMs) have been successfully used to predict outcomes for complex problems, including for human health. Much health data is imbalanced, with many more controls than positive cases. The impact of three balancing methods and one feature selection method is explored, to assess the ability of SVMs to classify imbalanced diagnostic pathology data associated with the laboratory diagnosis of hepatitis B (HBV) and hepatitis C (HCV) infections. Random forests (RFs) for predictor variable selection, and data reshaping to overcome a large imbalance of negative to positive test results in relation to HBV and HCV immunoassay results, are examined. The methodology is illustrated using data from ACT Pathology (Canberra, Australia), consisting of laboratory test records from 18,625 individuals who underwent hepatitis virus testing over the decade from 1997 to 2007. Overall, the prediction of HCV test results by immunoassay was more accurate than for HBV immunoassay results associated with identical routine pathology predictor variable data. HBV and HCV negative results were vastly in excess of positive results, so three approaches to handling the negative/positive data imbalance were compared. Generating datasets by the Synthetic Minority Oversampling Technique (SMOTE) resulted in significantly more accurate prediction than single downsizing or multiple downsizing (MDS) of the dataset. For downsized data sets, applying a RF for predictor variable selection had a small effect on the performance, which varied depending on the virus. For SMOTE, a RF had a negative effect on performance. An analysis of variance of the performance across settings supports these findings. Finally, age and assay results for alanine aminotransferase (ALT), sodium for HBV and urea for HCV were found to have a significant impact upon laboratory diagnosis of HBV or HCV infection using an optimised SVM model. Laboratories looking to include machine learning via SVM as part of their decision support need to be aware that the balancing method, predictor variable selection and the virus type interact to affect the laboratory diagnosis of hepatitis virus infection with routine pathology laboratory variables in different ways depending on which combination is being studied. This awareness should lead to careful use of existing machine learning methods, thus improving the quality of laboratory diagnosis.

Ecological and evolutionary drivers of the elevational gradient of diversity.

PubMed

Laiolo, Paola; Pato, Joaquina; Obeso, José Ramón

2018-05-02

Ecological, evolutionary, spatial and neutral theories make distinct predictions and provide distinct explanations for the mechanisms that control the relationship between diversity and the environment. Here, we test predictions of the elevational diversity gradient focusing on Iberian bumblebees, grasshoppers and birds. Processes mediated by local abundance and regional diversity concur in explaining local diversity patterns along elevation. Effects expressed through variation in abundance were similar among taxa and point to the overriding role of a physical factor, temperature. This determines how energy is distributed among individuals and ultimately how the resulting pattern of abundance affects species incidence. Effects expressed through variation in regional species pools depended instead on taxon-specific evolutionary history, and lead to diverging responses under similar environmental pressures. Local filters and regional variation also explain functional diversity gradients, in line with results from species richness that indicate an (local) ecological and (regional) historical unfolding of diversity-elevation relationships. © 2018 John Wiley & Sons Ltd/CNRS.

Pathological worry, anxiety disorders and the impact of co-occurrence with depressive and other anxiety disorders.

PubMed

Starcevic, Vladan; Berle, David; Milicevic, Denise; Hannan, Anthony; Lamplugh, Claire; Eslick, Guy D

2007-01-01

The Penn State Worry Questionnaire (PSWQ) was administered to 123 outpatients with principal diagnoses of generalized anxiety disorder (GAD), social anxiety disorder (SAD), panic disorder with agoraphobia, and panic disorder without agoraphobia (PD) to examine the specificity of pathological worry for GAD. The mean PSWQ scores in patients with GAD and SAD were significantly higher than the mean PSWQ scores in patients with PD, while not differing significantly in the subgroups without any co-occurring depressive or anxiety disorders. Patients with any co-occurring depressive or anxiety disorder scored significantly higher on the PSWQ. In a logistic regression analysis, high PSWQ scores independently predicted only GAD and SAD diagnoses. The study suggests that pathological worry is specific not only for GAD, and indicates that a significant relationship exists between pathological worry, GAD and SAD, and that depressive and anxiety disorders co-occurrence increases levels of pathological worry in patients with anxiety disorders.

A Tissue Systems Pathology Test Detects Abnormalities Associated with Prevalent High-Grade Dysplasia and Esophageal Cancer in Barrett's Esophagus.

PubMed

Critchley-Thorne, Rebecca J; Davison, Jon M; Prichard, Jeffrey W; Reese, Lia M; Zhang, Yi; Repa, Kathleen; Li, Jinhong; Diehl, David L; Jhala, Nirag C; Ginsberg, Gregory G; DeMarshall, Maureen; Foxwell, Tyler; Jobe, Blair A; Zaidi, Ali H; Duits, Lucas C; Bergman, Jacques J G H M; Rustgi, Anil; Falk, Gary W

2017-02-01

There is a need for improved tools to detect high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC) in patients with Barrett's esophagus. In previous work, we demonstrated that a 3-tier classifier predicted risk of incident progression in Barrett's esophagus. Our aim was to determine whether this risk classifier could detect a field effect in nondysplastic (ND), indefinite for dysplasia (IND), or low-grade dysplasia (LGD) biopsies from Barrett's esophagus patients with prevalent HGD/EAC. We performed a multi-institutional case-control study to evaluate a previously developed risk classifier that is based upon quantitative image features derived from 9 biomarkers and morphology, and predicts risk for HGD/EAC in Barrett's esophagus patients. The risk classifier was evaluated in ND, IND, and LGD biopsies from Barrett's esophagus patients diagnosed with HGD/EAC on repeat endoscopy (prevalent cases, n = 30, median time to HGD/EAC diagnosis 140.5 days) and nonprogressors (controls, n = 145, median HGD/EAC-free surveillance time 2,015 days). The risk classifier stratified prevalent cases and non-progressor patients into low-, intermediate-, and high-risk classes [OR, 46.0; 95% confidence interval, 14.86-169 (high-risk vs. low-risk); P < 0.0001]. The classifier also provided independent prognostic information that outperformed the subspecialist and generalist diagnosis. A tissue systems pathology test better predicts prevalent HGD/EAC in Barrett's esophagus patients than pathologic variables. The results indicate that molecular and cellular changes associated with malignant transformation in Barrett's esophagus may be detectable as a field effect using the test. A tissue systems pathology test may provide an objective method to facilitate earlier identification of Barrett's esophagus patients requiring therapeutic intervention. Cancer Epidemiol Biomarkers Prev; 26(2); 240-8. ©2016 AACR. ©2016 American Association for Cancer Research.

Diagnostic uncertainty in a severely demented male patient: a case report

PubMed Central

Maiovis, Pantelis; Gavopoulou, Evgenia; Eleftheriou, Marina; Tsokanari, Ioanna; Tsolaki, Magda

2008-01-01

Introduction Current trends in dementia research focus on early and accurate diagnosis. In clinical practice however, this is not always possible, as multiple underlying pathologies produce mixed dementia syndromes. Furthermore, patients with severe dementia are often underestimated. Case presentation We present a case of a 71 year old Caucasian male with severe Alzheimer's Disease, bedridden and fully dependent in activities of everyday living, whose general cognitive function is almost intact. We emphasize on the diverse underlying pathologies contributing to this intriguing clinical presentation and to diagnostic uncertainty. Conclusion Understanding the complexity of the dementia process in every patient using a multidimensional approach, contributes to more rational management strategies and finally to high quality care for patients and caregivers. PMID:18928571

Planar cell polarity pathway in vertebrate epidermal development, homeostasis and repair

PubMed Central

Dworkin, Sebastian; Jane, Stephen M

2011-01-01

The planar cell polarity (PCP) pathway plays a critical role in diverse developmental processes that require coordinated cellular movement, including neural tube closure and renal tubulogenesis. Recent studies have demonstrated that this pathway also has emerging relevance to the epidermis, as PCP signaling underpins many aspects of skin biology and pathology, including epidermal development, hair orientation, stem cell division and cancer. Coordinated cellular movement required for epidermal repair in mammals is also regulated by PCP signaling, and in this context, a new PCP gene encoding the developmental transcription factor Grainyhead-like 3 (Grhl3) is critical. This review focuses on the role that PCP signaling plays in the skin across a variety of epidermal functions and highlights perturbations that induce epidermal pathologies. PMID:22041517

Antioxidants and the Integrity of Ocular Tissues

PubMed Central

Cabrera, Marcela P.; Chihuailaf, Ricardo H.

2011-01-01

Oxygen-derived free radicals are normally generated in many pathways. These radicals can interact with various cellular components and induce cell injury. When free radicals exceed the antioxidant capacity, cell injury causes diverse pathologic changes in the organs. The imbalance between the generation of free radicals and antioxidant defence is known as oxidative stress. The eye can suffer the effect of oxidative damage due to the etiopathogenesis of some pathological changes related to oxidative stress. This paper reviews the role of oxidative stress in the onset and progression of damage in different eye structures, the involvement of the antioxidant network in protecting and maintaining the homeostasis of this organ, and the potential assessment methodologies used in research and in some cases in clinical practice. PMID:21789267

Pathological Gambling and Associated Drug and Alcohol Abuse, Emotion Regulation, and Anxious-Depressive Symptomatology

PubMed Central

Jauregui, Paula; Estévez, Ana; Urbiola, Irache

2016-01-01

Background and aims Pathological gambling is associated with comorbid disorders, such as anxiety, depression, and drug and alcohol abuse. Difficulties of emotion regulation may be one of the factors related to the presence of addictive disorders, along with comorbid symptomatology in pathological gamblers. Therefore, the aim of this study was to evaluate the difficulties of emotion regulation, drug and alcohol abuse, and anxious and depressive symptomatology in pathological gamblers, and the mediating role of difficulties of emotion regulation between anxiety and pathological gambling. Methods The study sample included 167 male pathological gamblers (mean age = 39.29 years) and 107 non-gamblers (mean age = 33.43 years). Pathological gambling (SOGS), difficulties of emotion regulation (DERS), drug and alcohol abuse (MUTICAGE CAD-4), and anxious and depressive symptomatology (SA-45) were measured. Student’s t, Pearson’s r, stepwise multiple linear regression and multiple mediation analyses were conducted. The study was approved by an Investigational Review Board. Results Relative to non-gamblers, pathological gamblers exhibited greater difficulties of emotion regulation, as well as more anxiety, depression, and drug abuse. Moreover, pathological gambling correlated with emotion regulation difficulties, anxiety, depression, and drug abuse. Besides, emotion regulation difficulties correlated with and predicted pathological gambling, drug and alcohol abuse, and anxious and depressive symptomatology. Finally, emotion regulation difficulties mediated the relationship between anxiety and pathological gambling controlling the effect of age, both when controlling and not controlling for the effect of other abuses. Discussion and conclusions These results suggest that difficulties of emotion regulation may provide new keys to understanding and treating pathological gambling and comorbid disorders. PMID:27348555

Mapping Plant Diversity and Composition Across North Carolina Piedmont Forest Landscapes Using Lidar-Hyperspectral Remote Sensing

NASA Astrophysics Data System (ADS)

Hakkenberg, Christopher R.

Forest modification, from local stress to global change, has given rise to efforts to model, map, and monitor critical properties of forest communities like structure, composition, and diversity. Predictive models based on data from spatially-nested field plots and LiDAR-hyperspectral remote sensing systems are one particularly effective means towards the otherwise prohibitively resource-intensive task of consistently characterizing forest community dynamics at landscape scales. However, to date, most predictive models fail to account for actual (rather than idealized) species and community distributions, are unsuccessful in predicting understory components in structurally and taxonomically heterogeneous forests, and may suffer from diminished predictive accuracy due to incongruity in scale and precision between field plot samples, remotely-sensed data, and target biota of varying size and density. This three-part study addresses these and other concerns in the modeling and mapping of emergent properties of forest communities by shifting the scope of prediction from the individual or taxon to the whole stand or community. It is, after all, at the stand scale where emergent properties like functional processes, biodiversity, and habitat aggregate and manifest. In the first study, I explore the relationship between forest structure (a proxy for successional demographics and resource competition) and tree species diversity in the North Carolina Piedmont, highlighting the empirical basis and potential for utilizing forest structure from LiDAR in predictive models of tree species diversity. I then extend these conclusions to map landscape pattern in multi-scale vascular plant diversity as well as turnover in community-continua at varying compositional resolutions in a North Carolina Piedmont landscape using remotely-sensed LiDAR-hyperspectral estimates of topography, canopy structure, and foliar biochemistry. Recognizing that the distinction between correlation and causation mirrors that between knowledge and understanding, all three studies distinguish between prediction of pattern and inference of process. Thus, in addition to advancing mapping methodologies relevant to a range of forest ecosystem management and monitoring applications, all three studies are noteworthy for assessing the ecological relationship between environmental predictors and emergent landscape patterns in plant composition and diversity in North Carolina Piedmont forests.

A Jungle in There: Bacteria in Belly Buttons are Highly Diverse, but Predictable

PubMed Central

Hulcr, Jiri; Latimer, Andrew M.; Henley, Jessica B.; Rountree, Nina R.; Fierer, Noah; Lucky, Andrea; Lowman, Margaret D.; Dunn, Robert R.

2012-01-01

The belly button is one of the habitats closest to us, and yet it remains relatively unexplored. We analyzed bacteria and arachaea from the belly buttons of humans from two different populations sampled within a nation-wide citizen science project. We examined bacterial and archaeal phylotypes present and their diversity using multiplex pyrosequencing of 16S rDNA libraries. We then tested the oligarchy hypothesis borrowed from tropical macroecology, namely that the frequency of phylotypes in one sample of humans predicts its frequency in another independent sample. We also tested the predictions that frequent phylotypes (the oligarchs) tend to be common when present, and tend to be more phylogenetically clustered than rare phylotypes. Once rarefied to four hundred reads per sample, bacterial communities from belly buttons proved to be at least as diverse as communities known from other skin studies (on average 67 bacterial phylotypes per belly button). However, the belly button communities were strongly dominated by a few taxa: only 6 phylotypes occurred on >80% humans. While these frequent bacterial phylotypes (the archaea were all rare) are a tiny part of the total diversity of bacteria in human navels (<0.3% of phylotypes), they constitute a major portion of individual reads (∼1/3), and are predictable among independent samples of humans, in terms of both the occurrence and evolutionary relatedness (more closely related than randomly drawn equal sets of phylotypes). Thus, the hypothesis that “oligarchs” dominate diverse assemblages appears to be supported by human-associated bacteria. Although it remains difficult to predict which species of bacteria might be found on a particular human, predicting which species are most frequent (or rare) seems more straightforward, at least for those species living in belly buttons. PMID:23144827

Efficacy of extracting indices from large-scale acoustic recordings to monitor biodiversity.

PubMed

Buxton, Rachel; McKenna, Megan F; Clapp, Mary; Meyer, Erik; Stabenau, Erik; Angeloni, Lisa M; Crooks, Kevin; Wittemyer, George

2018-04-20

Passive acoustic monitoring has the potential to be a powerful approach for assessing biodiversity across large spatial and temporal scales. However, extracting meaningful information from recordings can be prohibitively time consuming. Acoustic indices offer a relatively rapid method for processing acoustic data and are increasingly used to characterize biological communities. We examine the ability of acoustic indices to predict the diversity and abundance of biological sounds within recordings. First we reviewed the acoustic index literature and found that over 60 indices have been applied to a range of objectives with varying success. We then implemented a subset of the most successful indices on acoustic data collected at 43 sites in temperate terrestrial and tropical marine habitats across the continental U.S., developing a predictive model of the diversity of animal sounds observed in recordings. For terrestrial recordings, random forest models using a suite of acoustic indices as covariates predicted Shannon diversity, richness, and total number of biological sounds with high accuracy (R 2 > = 0.94, mean squared error MSE < = 170.2). Among the indices assessed, roughness, acoustic activity, and acoustic richness contributed most to the predictive ability of models. Performance of index models was negatively impacted by insect, weather, and anthropogenic sounds. For marine recordings, random forest models predicted Shannon diversity, richness, and total number of biological sounds with low accuracy (R 2 < = 0.40, MSE > = 195), indicating that alternative methods are necessary in marine habitats. Our results suggest that using a combination of relevant indices in a flexible model can accurately predict the diversity of biological sounds in temperate terrestrial acoustic recordings. Thus, acoustic approaches could be an important contribution to biodiversity monitoring in some habitats in the face of accelerating human-caused ecological change. This article is protected by copyright. All rights reserved.

Effect of MR Imaging Contrast Thresholds on Prediction of Neoadjuvant Chemotherapy Response in Breast Cancer Subtypes: A Subgroup Analysis of the ACRIN 6657/I-SPY 1 TRIAL

PubMed Central

Li, Wen; Arasu, Vignesh; Newitt, David C.; Jones, Ella F.; Wilmes, Lisa; Gibbs, Jessica; Kornak, John; Joe, Bonnie N.; Esserman, Laura J.; Hylton, Nola M.

2016-01-01

Functional tumor volume (FTV) measurements by dynamic contrast-enhanced magnetic resonance imaging can predict treatment outcomes for women receiving neoadjuvant chemotherapy for breast cancer. Here, we explore whether the contrast thresholds used to define FTV could be adjusted by breast cancer subtype to improve predictive performance. Absolute FTV and percent change in FTV (ΔFTV) at sequential time-points during treatment were calculated and investigated as predictors of pathologic complete response at surgery. Early percent enhancement threshold (PEt) and signal enhancement ratio threshold (SERt) were varied. The predictive performance of resulting FTV predictors was evaluated using the area under the receiver operating characteristic curve. A total number of 116 patients were studied both as a full cohort and in the following groups defined by hormone receptor (HR) and HER2 receptor subtype: 45 HR+/HER2−, 39 HER2+, and 30 triple negatives. High AUCs were found at different ranges of PEt and SERt levels in different subtypes. Findings from this study suggest that the predictive performance to treatment response by MRI varies by contrast thresholds, and that pathologic complete response prediction may be improved through subtype-specific contrast enhancement thresholds. A validation study is underway with a larger patient population. PMID:28066808

Genomic selection in sugar beet breeding populations

PubMed Central

2013-01-01

Background Genomic selection exploits dense genome-wide marker data to predict breeding values. In this study we used a large sugar beet population of 924 lines representing different germplasm types present in breeding populations: unselected segregating families and diverse lines from more advanced stages of selection. All lines have been intensively phenotyped in multi-location field trials for six agronomically important traits and genotyped with 677 SNP markers. Results We used ridge regression best linear unbiased prediction in combination with fivefold cross-validation and obtained high prediction accuracies for all except one trait. In addition, we investigated whether a calibration developed based on a training population composed of diverse lines is suited to predict the phenotypic performance within families. Our results show that the prediction accuracy is lower than that obtained within the diverse set of lines, but comparable to that obtained by cross-validation within the respective families. Conclusions The results presented in this study suggest that a training population derived from intensively phenotyped and genotyped diverse lines from a breeding program does hold potential to build up robust calibration models for genomic selection. Taken together, our results indicate that genomic selection is a valuable tool and can thus complement the genomics toolbox in sugar beet breeding. PMID:24047500

Indicators of breast cancer in patients undergoing microdochectomy for a pathological nipple discharge in a middle-income country.

PubMed

Lesetedi, Chiapo; Rayne, Sarah; Kruger, Deirdre; Benn, Carol-Ann

2017-12-01

The management of a pathological nipple discharge often involves surgery for the exclusion of a malignant etiology. This study aimed to determine the prevalence of cancer in patients who had microdochectomy for pathological nipple discharge in a population in South Africa and to evaluate patients' demographics and clinical characteristics as indicators of underlying cancer and make recommendations for their management in resource-limited settings. Clinical, radiological, and histological data from 153 patients who underwent a microdochectomy for a pathological nipple discharge at two South African breast clinics was collected. Invasive or in situ cancer was found in 12 patients (7.84%), and in all patients, cancer was associated with a bloody nipple discharge. Bloody discharge had a sensitivity of 100% in indicating cancer, specificity of 55.32%, positive predictive value of 16%, and negative predictive value of 100%. Patients with breast cancer were also more likely to be aged 55 y or older (P = 0.04). Preoperative mammogram and ultrasound were poor in detecting cancer (0/12). In our population, a bloody discharge in women aged 55 years or older should mandate a microdochectomy, with selective surgery for younger women and those with nonbloody discharges. Thorough clinical examination to determine the true color and nature of the discharge is vital in the initial assessment of these patients. Preoperative radiology is not helpful in determining the presence of cancer (in an isolated pathological nipple discharge), and microdochectomy still remains the gold standard in diagnosing cancer in these patients. Copyright © 2017 Elsevier Inc. All rights reserved.

Methods of developing core collections based on the predicted genotypic value of rice ( Oryza sativa L.).

PubMed

Li, C T; Shi, C H; Wu, J G; Xu, H M; Zhang, H Z; Ren, Y L

2004-04-01

The selection of an appropriate sampling strategy and a clustering method is important in the construction of core collections based on predicted genotypic values in order to retain the greatest degree of genetic diversity of the initial collection. In this study, methods of developing rice core collections were evaluated based on the predicted genotypic values for 992 rice varieties with 13 quantitative traits. The genotypic values of the traits were predicted by the adjusted unbiased prediction (AUP) method. Based on the predicted genotypic values, Mahalanobis distances were calculated and employed to measure the genetic similarities among the rice varieties. Six hierarchical clustering methods, including the single linkage, median linkage, centroid, unweighted pair-group average, weighted pair-group average and flexible-beta methods, were combined with random, preferred and deviation sampling to develop 18 core collections of rice germplasm. The results show that the deviation sampling strategy in combination with the unweighted pair-group average method of hierarchical clustering retains the greatest degree of genetic diversities of the initial collection. The core collections sampled using predicted genotypic values had more genetic diversity than those based on phenotypic values.

No Parent Left Behind: Predicting Parental Involvement in Adolescents' Education within a Sociodemographically Diverse Population

ERIC Educational Resources Information Center

Park, Sira; Holloway, Susan D.

2013-01-01

Numerous studies have investigated the utility of the Hoover-Dempsey and Sandler (HDS) model for predicting parents' involvement in students' education. Yet, the model has yet to be thoroughly evaluated with respect to youth who are (a) in high school and (b) from sociodemographically diverse families. Using a nationally representative sample of…

Frequency Effects or Context Effects in Second Language Word Learning: What Predicts Early Lexical Production?

ERIC Educational Resources Information Center

Crossley, Scott A.; Subtirelu, Nicholas; Salsbury, Tom

2013-01-01

This study examines frequency, contextual diversity, and contextual distinctiveness effects in predicting produced versus not-produced frequent nouns and verbs by early second language (L2) learners of English. The study analyzes whether word frequency is the strongest predictor of early L2 word production independent of contextual diversity and…

Validity of the Student Risk Screening Scale: Evidence of Predictive Validity in a Diverse, Suburban Elementary Setting

ERIC Educational Resources Information Center

Menzies, Holly M.; Lane, Kathleen Lynne

2012-01-01

In this study the authors examined the psychometric properties of the "Student Risk Screening Scale" (SRSS), including predictive validity in terms of student outcomes in behavioral and academic domains. The school, a diverse, suburban school in Southern California, administered the SRSS at three time points as part of regular school…

Detecting Human Hydrologic Alteration from Diversion Hydropower Requires Universal Flow Prediction Tools: A Proposed Framework for Flow Prediction in Poorly-gauged, Regulated Rivers

NASA Astrophysics Data System (ADS)

Kibler, K. M.; Alipour, M.

2016-12-01

Achieving the universal energy access Sustainable Development Goal will require great investment in renewable energy infrastructure in the developing world. Much growth in the renewable sector will come from new hydropower projects, including small and diversion hydropower in remote and mountainous regions. Yet, human impacts to hydrological systems from diversion hydropower are poorly described. Diversion hydropower is often implemented in ungauged rivers, thus detection of impact requires flow analysis tools suited to prediction in poorly-gauged and human-altered catchments. We conduct a comprehensive analysis of hydrologic alteration in 32 rivers developed with diversion hydropower in southwestern China. As flow data are sparse, we devise an approach for estimating streamflow during pre- and post-development periods, drawing upon a decade of research into prediction in ungauged basins. We apply a rainfall-runoff model, parameterized and forced exclusively with global-scale data, in hydrologically-similar gauged and ungauged catchments. Uncertain "soft" data are incorporated through fuzzy numbers and confidence-based weighting, and a multi-criteria objective function is applied to evaluate model performance. Testing indicates that the proposed framework returns superior performance (NSE = 0.77) as compared to models parameterized by rote calibration (NSE = 0.62). Confident that the models are providing `the right answer for the right reasons', our analysis of hydrologic alteration based on simulated flows indicates statistically significant hydrologic effects of diversion hydropower across many rivers. Mean annual flows, 7-day minimum and 7-day maximum flows decreased. Frequency and duration of flow exceeding Q25 decreased while duration of flows sustained below the Q75 increased substantially. Hydrograph rise and fall rates and flow constancy increased. The proposed methodology may be applied to improve diversion hydropower design in data-limited regions.

[Application of decision curve on evaluation of MRI predictive model for early assessing pathological complete response to neoadjuvant therapy in breast cancer].

PubMed

He, Y J; Li, X T; Fan, Z Q; Li, Y L; Cao, K; Sun, Y S; Ouyang, T

2018-01-23

Objective: To construct a dynamic enhanced MR based predictive model for early assessing pathological complete response (pCR) to neoadjuvant therapy in breast cancer, and to evaluate the clinical benefit of the model by using decision curve. Methods: From December 2005 to December 2007, 170 patients with breast cancer treated with neoadjuvant therapy were identified and their MR images before neoadjuvant therapy and at the end of the first cycle of neoadjuvant therapy were collected. Logistic regression model was used to detect independent factors for predicting pCR and construct the predictive model accordingly, then receiver operating characteristic (ROC) curve and decision curve were used to evaluate the predictive model. Results: ΔArea(max) and Δslope(max) were independent predictive factors for pCR, OR =0.942 (95% CI : 0.918-0.967) and 0.961 (95% CI : 0.940-0.987), respectively. The area under ROC curve (AUC) for the constructed model was 0.886 (95% CI : 0.820-0.951). Decision curve showed that in the range of the threshold probability above 0.4, the predictive model presented increased net benefit as the threshold probability increased. Conclusions: The constructed predictive model for pCR is of potential clinical value, with an AUC>0.85. Meanwhile, decision curve analysis indicates the constructed predictive model has net benefit from 3 to 8 percent in the likely range of probability threshold from 80% to 90%.

The Multi-Campus System's Role in Maintaining Institutional Diversity in Texas, Public Universities

ERIC Educational Resources Information Center

Lewis, Rebecca J.

2012-01-01

Institutional diversity is a long-held value in U.S. higher education with origins dating back 300 years to pre-Revolutionary colonial colleges. Institutional diversity is still valued today, but Institutional theory predicts that institutional organizations, such as universities, will homogenize without intervention to prevent loss of diversity.…

Severity of hydronephrosis correlates with tumour invasiveness and urinary bladder recurrence of ureteric cancer.

PubMed

Luo, Hao Lun; Kang, Chih Hsiung; Chen, Yen Ta; Chuang, Yao Chi; Lee, Wei Ching; Cheng, Yuan Tso; Chiang, Po Hui

2013-08-01

To explore the prognostic role of hydronephrosis grade in patients with pure ureteric cancer. The study included 162 patients with pure ureteric cancer who were treated between January 2005 and December 2010 at a single tertiary referral centre. The association between hydronephrosis grade with pathological findings and oncological outcomes was assessed using multivariate Cox regression analysis. Hydronephrosis grade >2 was independently associated with non-organ-confined ureteric cancer (P = 0.003). Hydronephrosis grade <2 was highly prevalent in organ-confined disease. Hydronephrosis grade >2 and bladder cancer history independently predict bladder cancer recurrence (P = 0.021 and P = 0.002, respectively) Hydronephrosis of grade >2 was found to be associated with local and distant recurrence only in univariate analysis; non-organ-confined pathology independently predicted local and distant oncological failure (P ≤ 0.001 and P = 0.002, respectively). Hydronephrosis grade >2 is associated with non-organ-confined ureteric cancer and with bladder cancer recurrence. Non-organ-confined pathology is still the most important predictor for local and distant oncological failure. © 2013 BJU International.

Reinforcer pathologies: Predicting alcohol related problems in college drinking men and women.

PubMed

Lemley, Shea M; Kaplan, Brent A; Reed, Derek D; Darden, Alexandria C; Jarmolowicz, David P

2016-10-01

Alcohol use in college is common, and problematic consequences of alcohol may affect college men and women differently. Approaches within behavioral economics have been used to improve our understanding of alcohol use in college students. The current study assessed relations between college students' delay discounting, demand for alcohol, and alcohol problems as measured by the Young Adult Alcohol Consequences Questionnaire (YAACQ). In this study, 80 college drinkers completed a monetary choice questionnaire that assessed delay discounting of money, a novel beer choice questionnaire that evaluated delay discounting of beer, and an alcohol purchase task that measured demand for alcohol. Behavioral economic measures associated with the reinforcer pathologies model (i.e., demand and discounting) predicted alcohol consequences as measured by the YAACQ. For men, these significant predictor variables included money discounting, beer discounting, and intensity of alcohol demand, whereas for women money discounting and essential value were significant predictors. These findings highlight the utility of the reinforcer pathologies approach for the study of alcohol use and the importance of considering gender differences in examining college drinking. Copyright © 2016. Published by Elsevier Ireland Ltd.

Use of Fetal Magnetic Resonance Image Analysis and Machine Learning to Predict the Need for Postnatal Cerebrospinal Fluid Diversion in Fetal Ventriculomegaly.

PubMed

Pisapia, Jared M; Akbari, Hamed; Rozycki, Martin; Goldstein, Hannah; Bakas, Spyridon; Rathore, Saima; Moldenhauer, Julie S; Storm, Phillip B; Zarnow, Deborah M; Anderson, Richard C E; Heuer, Gregory G; Davatzikos, Christos

2018-02-01

Which children with fetal ventriculomegaly, or enlargement of the cerebral ventricles in utero, will develop hydrocephalus requiring treatment after birth is unclear. To determine whether extraction of multiple imaging features from fetal magnetic resonance imaging (MRI) and integration using machine learning techniques can predict which patients require postnatal cerebrospinal fluid (CSF) diversion after birth. This retrospective case-control study used an institutional database of 253 patients with fetal ventriculomegaly from January 1, 2008, through December 31, 2014, to generate a predictive model. Data were analyzed from January 1, 2008, through December 31, 2015. All 25 patients who required postnatal CSF diversion were selected and matched by gestational age with 25 patients with fetal ventriculomegaly who did not require CSF diversion (discovery cohort). The model was applied to a sample of 24 consecutive patients with fetal ventriculomegaly who underwent evaluation at a separate institution (replication cohort) from January 1, 1998, through December 31, 2007. Data were analyzed from January 1, 1998, through December 31, 2009. To generate the model, linear measurements, area, volume, and morphologic features were extracted from the fetal MRI, and a machine learning algorithm analyzed multiple features simultaneously to find the combination that was most predictive of the need for postnatal CSF diversion. Accuracy, sensitivity, and specificity of the model in correctly classifying patients requiring postnatal CSF diversion. A total of 74 patients (41 girls [55%] and 33 boys [45%]; mean [SD] gestational age, 27.0 [5.6] months) were included from both cohorts. In the discovery cohort, median time to CSF diversion was 6 days (interquartile range [IQR], 2-51 days), and patients with fetal ventriculomegaly who did not develop symptoms were followed up for a median of 29 months (IQR, 9-46 months). The model correctly classified patients who required CSF diversion with 82% accuracy, 80% sensitivity, and 84% specificity. In the replication cohort, the model achieved 91% accuracy, 75% sensitivity, and 95% specificity. Image analysis and machine learning can be applied to fetal MRI findings to predict the need for postnatal CSF diversion. The model provides prognostic information that may guide clinical management and select candidates for potential fetal surgical intervention.

Nomograms to predict the pathological stage of clinically localized prostate cancer in Korean men: comparison with western predictive tools using decision curve analysis.

PubMed

Jeong, Chang Wook; Jeong, Seong Jin; Hong, Sung Kyu; Lee, Seung Bae; Ku, Ja Hyeon; Byun, Seok-Soo; Jeong, Hyeon; Kwak, Cheol; Kim, Hyeon Hoe; Lee, Eunsik; Lee, Sang Eun

2012-09-01

To develop and evaluate nomograms to predict the pathological stage of clinically localized prostate cancer after radical prostatectomy in Korean men. We reviewed the medical records of 2041 patients who had clinical stages T1c-T3a prostate cancer and were treated solely with radical prostatectomy at two hospitals. Logistic regressions were carried out to predict organ-confined disease, extraprostatic extension, seminal vesicle invasion, and lymph node metastasis using preoperative variables and resulting nomograms. Internal validations were assessed using the area under the receiver operating characteristic curve and calibration plot, and then external validations were carried out on 129 patients from another hospital. Head-to-head comparisons with 2007 Partin tables and Cancer of the Prostate Risk Assessment score were carried out using the area under the curve and decision curve analysis. The significant predictors for organ-confined disease and extraprostatic extension were clinical stage, prostate-specific antigen, Gleason score and a percent positive core of biopsy. Significant predictors for seminal vesicle invasion were prostate-specific antigen, Gleason score and percent positive core, and those for lymph node metastasis were prostate-specific antigen and percent positive core. The area under the curve of established nomograms for organ-confined disease, extraprostatic extension, seminal vesicle invasion and lymph node metastasis were 0.809, 0.804, 0.889 and 0.838, respectively. The nomograms were well calibrated and externally validated. These nomograms showed significantly higher accuracies and net benefits than two Western tools in Korean men. This is the first study to have developed and fully validated nomograms to predict the pathological stage of prostate cancer in an Asian population. These nomograms might be more accurate and useful for Korean men than other predictive models developed using Western populations. © 2012 The Japanese Urological Association.

Quantitative contrast-enhanced ultrasound evaluation of pathological complete response in patients with locally advanced breast cancer receiving neoadjuvant chemotherapy.

PubMed

Wan, Cai-Feng; Liu, Xue-Song; Wang, Lin; Zhang, Jie; Lu, Jin-Song; Li, Feng-Hua

2018-06-01

To clarify whether the quantitative parameters of contrast-enhanced ultrasound (CEUS) can be used to predict pathological complete response (pCR) in patients with locally advanced breast cancer receiving neoadjuvant chemotherapy (NAC). Fifty-one patients with histologically proved locally advanced breast cancer scheduled for NAC were enrolled. The quantitative data for CEUS and the tumor diameter were collected at baseline and before surgery, and compared with the pathological response. Multiple logistic regression analysis was performed to examine quantitative parameters at CEUS and the tumor diameter to predict the pCR, and receiver operating characteristic (ROC) curve analysis was used as a summary statistic. Multiple logistic regression analysis revealed that PEAK (the maximum intensity of the time-intensity curve during bolus transit), PEAK%, TTP% (time to peak), and diameter% were significant independent predictors of pCR, and the area under the ROC curve was 0.932(Az 1 ), and the sensitivity and specificity to predict pCR were 93.7% and 80.0%. The area under the ROC curve for the quantitative parameters was 0.927(Az 2 ), and the sensitivity and specificity to predict pCR were 81.2% and 94.3%. For diameter%, the area under the ROC curve was 0.786 (Az 3 ), and the sensitivity and specificity to predict pCR were 93.8% and 54.3%. The values of Az 1 and Az 2 were significantly higher than that of Az 3 (P = 0.027 and P = 0.034, respectively). However, there was no significant difference between the values of Az 1 and Az 2 (P = 0.825). Quantitative analysis of tumor blood perfusion with CEUS is superior to diameter% to predict pCR, and can be used as a functional technique to evaluate tumor response to NAC. Copyright © 2018. Published by Elsevier B.V.

Postglacial recolonization in a cold climate specialist in western Europe: patterns of genetic diversity in the adder (Vipera berus) support the central-marginal hypothesis.

PubMed

Ursenbacher, Sylvain; Guillon, Michaël; Cubizolle, Hervé; Dupoué, Andréaz; Blouin-Demers, Gabriel; Lourdais, Olivier

2015-07-01

Understanding the impact of postglacial recolonization on genetic diversity is essential in explaining current patterns of genetic variation. The central-marginal hypothesis (CMH) predicts a reduction in genetic diversity from the core of the distribution to peripheral populations, as well as reduced connectivity between peripheral populations. While the CMH has received considerable empirical support, its broad applicability is still debated and alternative hypotheses predict different spatial patterns of genetic diversity. Using microsatellite markers, we analysed the genetic diversity of the adder (Vipera berus) in western Europe to reconstruct postglacial recolonization. Approximate Bayesian Computation (ABC) analyses suggested a postglacial recolonization from two routes: a western route from the Atlantic Coast up to Belgium and a central route from the Massif Central to the Alps. This cold-adapted species likely used two isolated glacial refugia in southern France, in permafrost-free areas during the last glacial maximum. Adder populations further from putative glacial refugia had lower genetic diversity and reduced connectivity; therefore, our results support the predictions of the CMH. Our study also illustrates the utility of highly variable nuclear markers, such as microsatellites, and ABC to test competing recolonization hypotheses. © 2015 John Wiley & Sons Ltd.

CLINICAL BREAST EXAMINATION SCREENING BY TRAINED LAYWOMEN IN MALAWI INTEGRATED WITH OTHER HEALTH SERVICES.

PubMed

Gutnik, L; Lee, C; Msosa, J

2017-06-01

Breast cancer awareness and early detection are limited in Sub-Saharan Africa. Resource limitations make screening mammography or clinical breast examination (CBE) by physicians or nurses impractical in many settings. Four laywomen were trained to deliver breast cancer educational talks and conduct CBE. After training, screening was implemented in diverse urban health clinics. Eligible women were 30 years old, with no prior breast cancer or breast surgery, and clinic attendance for reasons other than a breast concern. Women with abnormal CBE were referred to a study surgeon. All palpable masses confirmed by surgeon examination were pathologically sampled. Patients with abnormal screening CBE but normal surgeon examination underwent breast ultrasound confirmation. In addition, 50 randomly selected women with normal screening CBE underwent breast ultrasound, and 45 different women with normal CBE were randomly assigned to surgeon examination. Among 1220 eligible women, 1000 (82%) agreed to CBE. Lack of time (69%) was the commonest reason for refusal. Educational talk attendance was associated with higher CBE participation (83% versus 77%, P ¼ 0.012). Among 1000 women screened, 7% had abnormal CBE. Of 45 women with normal CBE randomised to physician examination, 43 had normal examinations and two had axillary lymphadenopathy not detected by CBE. Sixty of 67 women (90%) with abnormal CBE attended the referral visit. Of these, 29 (48%) had concordant abnormal physician examination. Thirty-one women (52%) had discordant normal physician examination, all of whom also had normal breast ultrasounds. Compared with physician examination, sensitivity for CBE by laywomen was 94% (confidence interval [CI] 79%-99%), specificity 58% (CI, 46%-70%), positive predictive value 48% (CI, 35%-62%), and negative predictive value 96% (CI, 85%-100%). Of 13 women who underwent recommended pathologic sampling of a breast lesion, two had cytologic dysplasia and all others benign Results. CBE uptake in Lilongwe clinics was high. CBE by laywomen compared favourably with physician examination and followup was good. Our intervention can serve as a model for wider implementation. Performance in rural areas, effects on cancer stage and mortality, and cost effectiveness require evaluation.

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

Predicting Response to Neoadjuvant Chemoradiotherapy in Esophageal Cancer with Textural Features Derived from Pretreatment 18F-FDG PET/CT Imaging.

PubMed

Beukinga, Roelof J; Hulshoff, Jan B; van Dijk, Lisanne V; Muijs, Christina T; Burgerhof, Johannes G M; Kats-Ugurlu, Gursah; Slart, Riemer H J A; Slump, Cornelis H; Mul, Véronique E M; Plukker, John Th M

2017-05-01

Adequate prediction of tumor response to neoadjuvant chemoradiotherapy (nCRT) in esophageal cancer (EC) patients is important in a more personalized treatment. The current best clinical method to predict pathologic complete response is SUV max in 18 F-FDG PET/CT imaging. To improve the prediction of response, we constructed a model to predict complete response to nCRT in EC based on pretreatment clinical parameters and 18 F-FDG PET/CT-derived textural features. Methods: From a prospectively maintained single-institution database, we reviewed 97 consecutive patients with locally advanced EC and a pretreatment 18 F-FDG PET/CT scan between 2009 and 2015. All patients were treated with nCRT (carboplatin/paclitaxel/41.4 Gy) followed by esophagectomy. We analyzed clinical, geometric, and pretreatment textural features extracted from both 18 F-FDG PET and CT. The current most accurate prediction model with SUV max as a predictor variable was compared with 6 different response prediction models constructed using least absolute shrinkage and selection operator regularized logistic regression. Internal validation was performed to estimate the model's performances. Pathologic response was defined as complete versus incomplete response (Mandard tumor regression grade system 1 vs. 2-5). Results: Pathologic examination revealed 19 (19.6%) complete and 78 (80.4%) incomplete responders. Least absolute shrinkage and selection operator regularization selected the clinical parameters: histologic type and clinical T stage, the 18 F-FDG PET-derived textural feature long run low gray level emphasis, and the CT-derived textural feature run percentage. Introducing these variables to a logistic regression analysis showed areas under the receiver-operating-characteristic curve (AUCs) of 0.78 compared with 0.58 in the SUV max model. The discrimination slopes were 0.17 compared with 0.01, respectively. After internal validation, the AUCs decreased to 0.74 and 0.54, respectively. Conclusion: The predictive values of the constructed models were superior to the standard method (SUV max ). These results can be considered as an initial step in predicting tumor response to nCRT in locally advanced EC. Further research in refining the predictive value of these models is needed to justify omission of surgery. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Regional variation in the hierarchical partitioning of diversity in coral-dwelling fishes.

PubMed

Belmaker, Jonathan; Ziv, Yaron; Shashar, Nadav; Connolly, Sean R

2008-10-01

The size of the regional species pool may influence local patterns of diversity. However, it is unclear whether certain spatial scales are less sensitive to regional influences than others. Additive partitioning was used to separate coral-dwelling fish diversity to its alpha and beta components, at multiple scales, in several regions across the Indo-Pacific. We then examined how the relative contribution of these components changes with increased regional diversity. By employing specific random-placement null models, we overcome methodological problems with local-regional regressions. We show that, although alpha and beta diversities within each region are consistently different from random-placement null models, the increase in beta diversities among regions was similar to that predicted once heterogeneity in coral habitat was accounted for. In contrast, alpha diversity within single coral heads was limited and increased less than predicted by the null models. This was correlated with increased intraspecific aggregation in more diverse regions and is consistent with ecological limitations on the number of coexisting species at the local scale. These results suggest that, apart from very small spatial scales, variation in the partitioning of fish diversity along regional species richness gradients is driven overwhelmingly by the corresponding gradients in coral assemblage structure.

Neuropsychiatric symptoms predict hypometabolism in preclinical Alzheimer disease.

PubMed

Ng, Kok Pin; Pascoal, Tharick A; Mathotaarachchi, Sulantha; Chung, Chang-Oh; Benedet, Andréa L; Shin, Monica; Kang, Min Su; Li, Xiaofeng; Ba, Maowen; Kandiah, Nagaendran; Rosa-Neto, Pedro; Gauthier, Serge

2017-05-09

To identify regional brain metabolic dysfunctions associated with neuropsychiatric symptoms (NPS) in preclinical Alzheimer disease (AD). We stratified 115 cognitively normal individuals into preclinical AD (both amyloid and tau pathologies present), asymptomatic at risk for AD (either amyloid or tau pathology present), or healthy controls (no amyloid or tau pathology present) using [ 18 F]florbetapir PET and CSF phosphorylated tau biomarkers. Regression and voxel-based regression models evaluated the relationships between baseline NPS measured by the Neuropsychiatric Inventory (NPI) and baseline and 2-year change in metabolism measured by [ 18 F]fluorodeoxyglucose (FDG) PET. Individuals with preclinical AD with higher NPI scores had higher [ 18 F]FDG uptake in the posterior cingulate cortex (PCC), ventromedial prefrontal cortex, and right anterior insula at baseline. High NPI scores predicted subsequent hypometabolism in the PCC over 2 years only in individuals with preclinical AD. Sleep/nighttime behavior disorders and irritability and lability were the components of the NPI that drove this metabolic dysfunction. The magnitude of NPS in preclinical cases, driven by sleep behavior and irritability domains, is linked to transitory metabolic dysfunctions within limbic networks vulnerable to the AD process and predicts subsequent PCC hypometabolism. These findings support an emerging conceptual framework in which NPS constitute an early clinical manifestation of AD pathophysiology. Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

Prediction of alcohol and gambling problems in young adults by using a measure of decision making.

PubMed

Harvanko, Arit M; Schreiber, Liana R N; Grant, Jon E

2013-01-01

Individuals who regularly gamble, regularly consume alcohol, or meet criteria for an alcohol-use disorder or pathological gambling may make riskier decisions on cognitive tasks. What remains unclear in the literature is whether these decision-making deficits precede or result from these addictive behaviors. This study aimed to determine whether risky decision making on a cognitive task is predictive of increasing gambling behaviors and alcohol use. Fifty-eight young adults (aged 18-29 years) free from Axis I disorders and reporting no symptoms of at-risk gambling behavior or alcohol consumption, who were participating in a longitudinal study of impulsivity, were grouped as either high-risk decision makers (n = 29) or low-risk decision makers (n = 29) by using the Cambridge Gamble Task. Subjects were assessed at 1-year follow-up to examine gambling frequency, alcohol consumption, at-risk alcohol-use criteria, alcohol-use disorder criteria, at-risk gambling criteria, and pathological gambling criteria. High-risk decision makers were found to be more likely to meet at-risk criteria for alcohol use after 1 year. Decision-making group membership was not significantly correlated with frequency of gambling or development of pathological gambling or alcohol-use disorder over 1 year. A variable measuring risky decision making on the Cambridge Gambling Task may be able to predict who is more likely to increase alcohol use per session later in life.

Recurrent hepatocellular carcinoma after liver transplant: identifying the high-risk patient

PubMed Central

Nissen, Nicholas N; Menon, Vijay; Bresee, Catherine; Tran, Tram T; Annamalai, Alagappan; Poordad, Fred; Fair, Jeffrey H; Klein, Andrew S; Boland, Brendan; Colquhoun, Steven D

2011-01-01

Background Recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) is rarely curable. However, in view of the advent of new treatments, it is critical that patients at high risk for recurrence are identified. Methods Patients undergoing LT for HCC at a single centre between 2002 and 2010 were reviewed and data on clinical parameters and explant pathology were analysed to determine factors associated with HCC recurrence. All necrotic and viable tumour nodules were included in explant staging. All patients underwent LT according to the United Network for Organ Sharing (UNOS) Model for End-stage Liver Disease (MELD) tumour exception policies. Results Liver transplantation was performed in 122 patients with HCC during this period. Rates of recurrence-free survival in the entire cohort at 1 year and 3 years were 95% and 89%, respectively. Thirteen patients developed HCC recurrence at a median of 14 months post-LT. In univariate analysis the factors associated with HCC recurrence were bilobar tumours, vascular invasion, and stage exceeding either Milan or University of California San Francisco (UCSF) Criteria. Multivariate analysis showed pathology outside UCSF Criteria was the major predictor of recurrence; when pathology outside UCSF Criteria was found in combination with vascular invasion, the predicted 3-year recurrence-free survival was only 26%. Conclusions Explant pathology can be used to predict the risk for recurrent HCC after LT, which may allow for improved adjuvant and management strategies. PMID:21843263

Diagnostic value of the 2011 International Federation for Cervical Pathology and Colposcopy Terminology in predicting cervical lesions

PubMed Central

Zhang, Liqin; Yan, Ye; Han, Cha; Xue, Fengxia

2018-01-01

Objective To evaluate the diagnostic accuracy of the 2011 International Federation for Cervical Pathology and Colposcopy (IFCPC) colposcopic terminology. Methods The clinicopathological data of 2262 patients who underwent colposcopy from September 2012 to September 2016 were reviewed. The colposcopic findings, colposcopic impression, and cervical histopathology of the patients were analyzed. Correlations between variables were evaluated using cervical histopathology as the gold standard. Results Colposcopic diagnosis matched biopsy histopathology in 1482 patients (65.5%), and the weighted kappa strength of agreement was 0.480 (P<0.01). Colposcopic diagnoses more often underestimated (22.1%) than overestimated (12.3%) cervical pathology. There was no significant difference between the colposcopic diagnosis and cervical pathology agreement among the various grades of lesions (P=0.282). The sensitivity, specificity for detecting high-grade lesions/carcinoma was 71.6% and 98.0%, respectively. Multivariate analysis showed that major changes were independent factors in predicting high-grade lesion/carcinoma, whereas transformation zone, lesion size, and non-stained were not statistically related to high-grade lesion/carcinoma. Conclusions The 2011 IFCPC terminology can improve the diagnostic accuracy for all lesion severities. The categorization of major changes and minor changes is appropriate. However, colposcopic diagnosis remains unsatisfactory. Poor reproducibility of type 2 transformation zone and the significance of leukoplakia require further study. PMID:29507681

Undiagnosed cryptic diversity in small, microendemic frogs (Leptolalax) from the Central Highlands of Vietnam.

PubMed

Rowley, Jodi J L; Tran, Dao T A; Frankham, Greta J; Dekker, Anthony H; Le, Duong T T; Nguyen, Truong Q; Dau, Vinh Q; Hoang, Huy D

2015-01-01

A major obstacle in prioritizing species or habitats for conservation is the degree of unrecognized diversity hidden within complexes of morphologically similar, "cryptic" species. Given that amphibians are one of the most threatened groups of organisms on the planet, our inability to diagnose their true diversity is likely to have significant conservation consequences. This is particularly true in areas undergoing rapid deforestation, such as Southeast Asia. The Southeast Asian genus Leptolalax is a group of small-bodied, morphologically conserved frogs that inhabit the forest-floor. We examined a particularly small-bodied and morphologically conserved subset, the Leptolalax applebyi group, using a combination of molecular, morphometric, and acoustic data to identify previously unknown diversity within. In order to predict the geographic distribution of the group, estimate the effects of habitat loss and assess the degree of habitat protection, we used our locality data to perform ecological niche modelling using MaxEnt. Molecular (mtDNA and nuDNA), acoustic and subtle morphometric differences revealed a significant underestimation of diversity in the L. applebyi group; at least two-thirds of the diversity may be unrecognised. Patterns of diversification and microendemism in the group appear driven by limited dispersal, likely due to their small body size, with several lineages restricted to watershed basins. The L. applebyi group is predicted to have historically occurred over a large area of the Central Highlands of Vietnam, a considerable portion of which has already been deforested. Less than a quarter of the remaining forest predicted to be suitable for the group falls within current protected areas. The predicted distribution of the L. applebyi group extends into unsurveyed watershed basins, each potentially containing unsampled diversity, some of which may have already been lost due to deforestation. Current estimates of amphibian diversity based on morphology alone are misleading, and accurate alpha taxonomy is essential to accurately prioritize conservation efforts.

Undiagnosed Cryptic Diversity in Small, Microendemic Frogs (Leptolalax) from the Central Highlands of Vietnam

PubMed Central

Rowley, Jodi J. L.; Tran, Dao T. A.; Frankham, Greta J.; Dekker, Anthony H.; Le, Duong T. T.; Nguyen, Truong Q.; Dau, Vinh Q.; Hoang, Huy D.

2015-01-01

A major obstacle in prioritizing species or habitats for conservation is the degree of unrecognized diversity hidden within complexes of morphologically similar, “cryptic” species. Given that amphibians are one of the most threatened groups of organisms on the planet, our inability to diagnose their true diversity is likely to have significant conservation consequences. This is particularly true in areas undergoing rapid deforestation, such as Southeast Asia. The Southeast Asian genus Leptolalax is a group of small-bodied, morphologically conserved frogs that inhabit the forest-floor. We examined a particularly small-bodied and morphologically conserved subset, the Leptolalax applebyi group, using a combination of molecular, morphometric, and acoustic data to identify previously unknown diversity within. In order to predict the geographic distribution of the group, estimate the effects of habitat loss and assess the degree of habitat protection, we used our locality data to perform ecological niche modelling using MaxEnt. Molecular (mtDNA and nuDNA), acoustic and subtle morphometric differences revealed a significant underestimation of diversity in the L. applebyi group; at least two-thirds of the diversity may be unrecognised. Patterns of diversification and microendemism in the group appear driven by limited dispersal, likely due to their small body size, with several lineages restricted to watershed basins. The L. applebyi group is predicted to have historically occurred over a large area of the Central Highlands of Vietnam, a considerable portion of which has already been deforested. Less than a quarter of the remaining forest predicted to be suitable for the group falls within current protected areas. The predicted distribution of the L. applebyi group extends into unsurveyed watershed basins, each potentially containing unsampled diversity, some of which may have already been lost due to deforestation. Current estimates of amphibian diversity based on morphology alone are misleading, and accurate alpha taxonomy is essential to accurately prioritize conservation efforts. PMID:26020250

Quantitative image variables reflect the intratumoral pathologic heterogeneity of lung adenocarcinoma.

PubMed

Choi, E-Ryung; Lee, Ho Yun; Jeong, Ji Yun; Choi, Yoon-La; Kim, Jhingook; Bae, Jungmin; Lee, Kyung Soo; Shim, Young Mog

2016-10-11

We aimed to compare quantitative radiomic parameters from dual-energy computed tomography (DECT) of lung adenocarcinoma and pathologic complexity.A total 89 tumors with clinical stage I/II lung adenocarcinoma were prospectively included. Fifty one radiomic features were assessed both from iodine images and non-contrast images of DECT datasets. Comprehensive histologic subtyping was evaluated with all surgically resected tumors. The degree of pathologic heterogeneity was assessed using pathologic index and the number of mixture histologic subtypes in a tumor. Radiomic parameters were correlated with pathologic index. Tumors were classified as three groups according to the number of mixture histologic subtypes and radiomic parameters were compared between the three groups.Tumor density and 50th through 97.5th percentile Hounsfield units (HU) of histogram on non-contrast images showed strong correlation with the pathologic heterogeneity. Radiomic parameters including 75th and 97.5th percentile HU of histogram, entropy, and inertia on 1-, 2- and 3 voxel distance on non-contrast images showed incremental changes while homogeneity showed detrimental change according to the number of mixture histologic subtypes (all Ps < 0.05).Radiomic variables from DECT of lung adenocarcinoma reflect pathologic intratumoral heterogeneity, which may help in the prediction of intratumoral heterogeneity of the whole tumor.

Predicting acute aquatic toxicity of structurally diverse chemicals in fish using artificial intelligence approaches.

PubMed

Singh, Kunwar P; Gupta, Shikha; Rai, Premanjali

2013-09-01

The research aims to develop global modeling tools capable of categorizing structurally diverse chemicals in various toxicity classes according to the EEC and European Community directives, and to predict their acute toxicity in fathead minnow using set of selected molecular descriptors. Accordingly, artificial intelligence approach based classification and regression models, such as probabilistic neural networks (PNN), generalized regression neural networks (GRNN), multilayer perceptron neural network (MLPN), radial basis function neural network (RBFN), support vector machines (SVM), gene expression programming (GEP), and decision tree (DT) were constructed using the experimental toxicity data. Diversity and non-linearity in the chemicals' data were tested using the Tanimoto similarity index and Brock-Dechert-Scheinkman statistics. Predictive and generalization abilities of various models constructed here were compared using several statistical parameters. PNN and GRNN models performed relatively better than MLPN, RBFN, SVM, GEP, and DT. Both in two and four category classifications, PNN yielded a considerably high accuracy of classification in training (95.85 percent and 90.07 percent) and validation data (91.30 percent and 86.96 percent), respectively. GRNN rendered a high correlation between the measured and model predicted -log LC50 values both for the training (0.929) and validation (0.910) data and low prediction errors (RMSE) of 0.52 and 0.49 for two sets. Efficiency of the selected PNN and GRNN models in predicting acute toxicity of new chemicals was adequately validated using external datasets of different fish species (fathead minnow, bluegill, trout, and guppy). The PNN and GRNN models showed good predictive and generalization abilities and can be used as tools for predicting toxicities of structurally diverse chemical compounds. Copyright © 2013 Elsevier Inc. All rights reserved.

A Comparison of Inter-Professional Education Programs in Preparing Prospective Teachers and Speech and Language Pathologists for Collaborative Language-Literacy Instruction

ERIC Educational Resources Information Center

Wilson, Leanne; McNeill, Brigid; Gillon, Gail T.

2016-01-01

Ensuring teacher and speech and language pathology graduates are prepared to work collaboratively together to meet the diverse language literacy learning needs of children is an important goal. This study investigated the efficacy of a 3-h inter-professional education program focused on explicit instruction in the language skills that underpin…

In Praise of Diversity: Why Schools Should Seek Gay and Lesbian Teachers, and Why It's Still Difficult

ERIC Educational Resources Information Center

Nixon, David

2006-01-01

This article begins from imagining what it would be like to target recruitment for teachers at lesbian, gay, bisexual, transsexual (LGBT) people, and then examines in some detail two kinds of discrimination (or pathology) which makes life in the world of education problematic. It then turns to why, in spite of these difficulties, lesbian and gay…

Transmissible Spongiform Encephalopathy and Meat Safety

NASA Astrophysics Data System (ADS)

Ward, Hester J. T.; Knight, Richard S. G.

Prion diseases or transmissible spongiform encephalopathies (TSEs) comprise a wide-ranging group of neurodegenerative diseases found in animals and humans. They have diverse causes and geographical distributions, but have similar pathological features, transmissibility and, are ultimately, fatal. Central to all TSEs is the presence of an abnormal form of a normal host protein, namely the prion protein. Because of their potential transmissibility, these diseases have wide public health ramifications.

Understanding Caries From the Oral Microbiome Perspective.

PubMed

Tanner, Anne C R; Kressirer, Christine A; Faller, Lina L

2016-07-01

Dental caries is a major disease of the oral cavity with profound clinical significance. Caries results from a transition of a healthy oral microbiome into an acidogenic community of decreased microbial diversity in response to excessive dietary sugar intake. Microbiological cultivation, molecular identification, gene expression and metabolomic analyses show the importance of the entire microbial community in understanding the role of the microbiome in the pathology of caries.

Discourses of dementia: a call for an ethnographic, action research approach to care in linguistically and culturally diverse environments.

PubMed

Müller, Nicole; Guendouzi, Jacqueline A

2009-08-01

The methods of ethnography and action research have much to offer to the field of speech-language pathology, particularly as our clinical populations are becoming increasingly diverse. We suggest that practicing speech-language pathologists and students, as well as researchers, will benefit from strategies that use the methods of participatory action research and ethnography as guiding principles to their work. Ethnography seeks to discover meaningful structures in a culture from the perspective of those whose culture it is. Action research, which shares a methodological basis with ethnography, is undertaken with the aim of improving the functioning of the social institution, practice, or structure investigated for the benefit of those most closely involved with that institution or practice. By way of illustration, we use data collected during fieldwork in Louisiana, involving persons with dementia from linguistically and culturally diverse backgrounds.

The mycobiome of the human urinary tract: potential roles for fungi in urology

PubMed Central

Underhill, David M.

2017-01-01

The mycobiome, defined as the fungal microbiota within a host environment, is an important but understudied component of the human microbial ecosystem. New culture-independent approaches to determine microbial diversity, such as next-generation sequencing methods, have discovered specific, characteristic, commensal fungal populations present in different body sites. These studies have also identified diverse patterns in fungal communities associated with various diseases. While alterations in urinary bacterial communities have been noted in disease states, a comprehensive description of the urinary mycobiome has been lacking. Early evidence suggests the urinary mycobiome is a diverse community with high intraindividual variability. In other disease systems, the mycobiome is thought to interact with other biomes and the host to play a role in organ homeostasis and pathology; further study will be needed to elucidate the role fungi play in bladder health and disease. PMID:28217696

Sin Nombre Virus and Rodent Species Diversity: A Test of the Dilution and Amplification Hypotheses

PubMed Central

Clay, Christine A.; Lehmer, Erin M.; Jeor, Stephen St.; Dearing, M. Denise

2009-01-01

Background Species diversity is proposed to greatly impact the prevalence of pathogens. Two predominant hypotheses, the “Dilution Effect” and the “Amplification Effect”, predict divergent outcomes with respect to the impact of species diversity. The Dilution Effect predicts that pathogen prevalence will be negatively correlated with increased species diversity, while the Amplification Effect predicts that pathogen prevalence will be positively correlated with diversity. For many host-pathogen systems, the relationship between diversity and pathogen prevalence has not be empirically examined. Methodology/Principal Findings We tested the Dilution and Amplification Effect hypotheses by examining the prevalence of Sin Nombre virus (SNV) with respect to diversity of the nocturnal rodent community. SNV is directly transmitted primarily between deer mice (Peromyscus maniculatus). Using mark-recapture sampling in the Spring and Fall of 2003–2005, we measured SNV prevalence in deer mice at 16 landscape level sites (3.1 hectares each) that varied in rodent species diversity. We explored several mechanisms by which species diversity may affect SNV prevalence, including reduced host density, reduced host persistence, the presence of secondary reservoirs and community composition. We found a negative relationship between species diversity and SNV prevalence in deer mice, thereby supporting the Dilution Effect hypothesis. Deer mouse density and persistence were lower at sites with greater species diversity; however, only deer mouse persistence was positively correlated with SNV prevalence. Pinyon mice (P. truei) may serve as dilution agents, having a negative effect on prevalence, while kangaroo rats (Dipodomys ordii), may have a positive effect on the prevalence of SNV, perhaps through effects on deer mouse behavior. Conclusions/Significance While previous studies on host-pathogen systems have found patterns of diversity consistent with either the Dilution or Amplification Effects, the mechanisms by which species diversity influences prevalence have not been investigated. Our study indicates that changes in host persistence, coupled with interspecific interactions, are important mechanisms through which diversity may influence patterns of pathogens. Our results reveal the complexity of rodent community interactions with respect to SNV dynamics. PMID:19649283

Premorbid social adjustment and association with attenuated psychotic symptoms in clinical high-risk and help-seeking youth.

PubMed

Tarbox-Berry, S I; Perkins, D O; Woods, S W; Addington, J

2018-04-01

Attenuated positive symptom syndrome (APSS), characterized by 'putatively prodromal' attenuated psychotic-like pathology, indicates increased risk for psychosis. Poor premorbid social adjustment predicts severity of APSS symptoms and predicts subsequent psychosis in APSS-diagnosed individuals, suggesting application for improving detection of 'true' prodromal youth who will transition to psychosis. However, these predictive associations have not been tested in controls and therefore may be independent of the APSS diagnosis, negating utility for improving prediction in APSS-diagnosed individuals. Association between premorbid social maladjustment and severity of positive, negative, disorganized, and general APSS symptoms was tested in 156 individuals diagnosed with APSS and 76 help-seeking (non-APSS) controls enrolled in the Enhancing the Prospective Prediction of Psychosis (PREDICT) study using prediction analysis. Premorbid social maladjustment was associated with social anhedonia, reduced expression of emotion, restricted ideational richness, and deficits in occupational functioning, independent of the APSS diagnosis. Associations between social maladjustment and suspiciousness, unusual thought content, avolition, dysphoric mood, and impaired tolerance to normal stress were uniquely present in participants meeting APSS criteria. Social maladjustment was associated with odd behavior/appearance and diminished experience of emotions and self only in participants who did not meet APSS criteria. Predictive associations between poor premorbid social adjustment and attenuated psychotic-like pathology were identified, a subset of which were indicative of high risk for psychosis. This study offers a method for improving risk identification while ruling out low-risk individuals.

Anaplasia is rare and does not influence prognosis in adult medulloblastoma.

PubMed

Giordana, Maria Teresa; D'Agostino, Carla; Pollo, Bianca; Silvani, Antonio; Ferracini, Romano; Paiolo, Anna; Ghiglione, Paolo; Chiò, Adriano

2005-10-01

Histopathologic grading based on increasing anaplasia predicts clinical behavior of pediatric medulloblastomas. The present study was aimed at grading 86 medulloblastomas of adult patients (aged 18 and older) by anaplasia and analyzing the predictive power. Nodularity, desmoplasia, nuclear size, nuclear pleomorphism, necrosis, and endothelial proliferations have been evaluated. Morphometric analysis of nuclear size was performed using the Eclipse Net program. Patients treated with standard postoperative radiotherapy (35 Gy to craniospinal axis and 50 Gy to posterior fossa) were considered for correlation with survival. Pathologic data and total survival were compared by Kaplan-Meier and logrank analysis. No correlation was found between total survival duration and individual pathologic features. Cooccurrence of nuclear pleomorphism, large nuclear diameter, microvascular proliferations, and necroses did not predict outcome. Severe nuclear pleomorphism was found in 4 of 86 cases; the only large-cell medulloblastoma was from an 18-year-old patient. Histopathologic factors have no clinical use for stratification of patients in risk groups. The histologic spectrum of medulloblastoma in adults is different from that in children.

Local–global overlap in diversity informs mechanisms of bacterial biogeography

PubMed Central

Livermore, Joshua A; Jones, Stuart E

2015-01-01

Spatial variation in environmental conditions and barriers to organism movement are thought to be important factors for generating endemic species, thus enhancing global diversity. Recent microbial ecology research suggested that the entire diversity of bacteria in the global oceans could be recovered at a single site, thus inferring a lack of bacterial endemism. We argue this is not the case in the global ocean, but might be in other bacterial ecosystems with higher dispersal rates and lower global diversity, like the human gut. We quantified the degree to which local and global bacterial diversity overlap in a diverse set of ecosystems. Upon comparison of observed local–global diversity overlap with predictions from a neutral biogeography model, human-associated microbiomes (gut, skin, mouth) behaved much closer to neutral expectations whereas soil, lake and marine communities deviated strongly from the neutral expectations. This is likely a result of differences in dispersal rate among ‘patches', global diversity of these systems, and local densities of bacterial cells. It appears that overlap of local and global bacterial diversity is surprisingly large (but likely not one-hundred percent), and most importantly this overlap appears to be predictable based upon traditional biogeographic parameters like community size, global diversity, inter-patch environmental heterogeneity and patch connectivity. PMID:25848869

Quantification of localized vertebral deformities using a sparse wavelet-based shape model.

PubMed

Zewail, R; Elsafi, A; Durdle, N

2008-01-01

Medical experts often examine hundreds of spine x-ray images to determine existence of various pathologies. Common pathologies of interest are anterior osteophites, disc space narrowing, and wedging. By careful inspection of the outline shapes of the vertebral bodies, experts are able to identify and assess vertebral abnormalities with respect to the pathology under investigation. In this paper, we present a novel method for quantification of vertebral deformation using a sparse shape model. Using wavelets and Independent component analysis (ICA), we construct a sparse shape model that benefits from the approximation power of wavelets and the capability of ICA to capture higher order statistics in wavelet space. The new model is able to capture localized pathology-related shape deformations, hence it allows for quantification of vertebral shape variations. We investigate the capability of the model to predict localized pathology related deformations. Next, using support-vector machines, we demonstrate the diagnostic capabilities of the method through the discrimination of anterior osteophites in lumbar vertebrae. Experiments were conducted using a set of 150 contours from digital x-ray images of lumbar spine. Each vertebra is labeled as normal or abnormal. Results reported in this work focus on anterior osteophites as the pathology of interest.

An evolutionary approach to major histocompatibility diversity based on allele supertypes.

PubMed

Naugler, Christopher; Liwski, Robert

2008-01-01

Human leukocyte antigens are traditionally classified by serologic or molecular techniques into a bewildering variety of alleles. It is generally believed that this allelic diversity is maintained by selection pressures for inbreeding avoidance and/or maximal immune system diversity. While the usual antigen-based classification of individual alleles may be most appropriate in the artificial situation of tissue transplantation, we hypothesize that a functional classification based on allele supertypes may represent a more biologically relevant way to view MHC diversity in the contexts of mate choice and disease pathogenesis. Furthermore, immune system diversity could be quantitatively estimated by calculating a Supertype Diversity Index (SDI) which is the number of different MHC supertypes possessed by an individual. This hypothesis generates a number of testable predictions. First, it predicts that a reduced inherited diversity of MHC allele supertypes may predispose to the development of malignancies because of a decreased native ability to present different tumor-associated antigens. Furthermore, specific autoimmune diseases may be associated with the presence or absence of a particular MHC supertype rather than a particular MHC haplotype. In transplant medicine, it is possible that unmatched alleles may trigger a weaker foreign antigen response if they are matched by allele supertype. Finally, there have been several studies documenting dissortative mating in humans for dissimilar MHC alleles. We predict that natural selection should favor maximization of the heterozygosity of allele supertypes instead of the heterozygosity of individual alleles and that the previously observed dissortative mating may actually be an adaptive strategy to maximize allele supertype diversity.

Predicting mosaics and wildlife diversity resulting from fire disturbance to a forest ecosystem

NASA Astrophysics Data System (ADS)

Potter, Meredith W.; Kessell, Stephen R.

1980-05-01

A model for predicting community mosaics and wildlife diversity resulting from fire disturbance to a forest ecosystem is presented. It applies an algorithm that delineates the size and shape of each patch from grid-based input data and calculates standard diversity measures for the entire mosaic of community patches and their included animal species. The user can print these diversity calculations, maps of the current community-type-age-class mosaic, and maps of habitat utilization by each animal species. Furthermore, the user can print estimates of changes in each resulting from natural disturbance. Although data and resolution level independent, the model is demonstrated and tested with data from the Lewis and Clark National Forest in Montana.

Importance of early postnatal weight gain for normal retinal angiogenesis in very preterm infants: a multicenter study analyzing weight velocity deviations for the prediction of retinopathy of prematurity.

PubMed

Wu, Carolyn; Löfqvist, Chatarina; Smith, Lois E H; VanderVeen, Deborah K; Hellström, Ann

2012-08-01

To assess WINROP (https://winrop.com), an algorithm using postnatal weight measurements, as a tool for the prediction of retinopathy of prematurity (ROP) in a large geographically and racially diverse study population. WINROP analysis was performed retrospectively on conventionally at-risk infants from 10 neonatal intensive careunits.Weight measurements were entered into WINROP, which signals an alarm for an abnormal weight gain rate. Infants were classified into categories of no alarm (unlikely to develop type 1ROP)and alarm (at risk for developing type 1ROP).Use of WINROP requires that an infant has (1) gestational age less than 32 weeks at birth, (2) weekly weight measurements,(3) physiologic weight gain,and(4)absence of other pathologic retinal vascular disease. A total of 1706 infants with a median gestational age of 28 weeks (range, 22-31 weeks) and median birth weight of 1016 g (range, 378-2240 g) were included in the study analysis. An alarm occurred in 1101 infants (64.5%), with a median time from birth to alarm of 3 weeks (range, 0-12 weeks) and from alarm to treatment of 8 weeks (range, 1 day to 22 weeks). The sensitivity of WINROP was 98.6% and the negative predictive value was 99.7%. Two infants with type 1 ROP requiring treatment after 40 weeks' postmenstrual age did not receive an alarm. The WINROP system is a useful adjunct for ROP screening that identifies high-risk infants early to optimize care and potentially reduce the overall number of diagnostic ROP examinations.

Pathological and 3 Tesla Volumetric Magnetic Resonance Imaging Predictors of Biochemical Recurrence after Robotic Assisted Radical Prostatectomy: Correlation with Whole Mount Histopathology.

PubMed

Tan, Nelly; Shen, Luyao; Khoshnoodi, Pooria; Alcalá, Héctor E; Yu, Weixia; Hsu, William; Reiter, Robert E; Lu, David Y; Raman, Steven S

2018-05-01

We sought to identify the clinical and magnetic resonance imaging variables predictive of biochemical recurrence after robotic assisted radical prostatectomy in patients who underwent multiparametric 3 Tesla prostate magnetic resonance imaging. We performed an institutional review board approved, HIPAA (Health Insurance Portability and Accountability Act) compliant, single arm observational study of 3 Tesla multiparametric magnetic resonance imaging prior to robotic assisted radical prostatectomy from December 2009 to March 2016. Clinical, magnetic resonance imaging and pathological information, and clinical outcomes were compiled. Biochemical recurrence was defined as prostate specific antigen 0.2 ng/cc or greater. Univariate and multivariate regression analysis was performed. Biochemical recurrence had developed in 62 of the 255 men (24.3%) included in the study at a median followup of 23.5 months. Compared to the subcohort without biochemical recurrence the subcohort with biochemical recurrence had a greater proportion of patients with a high grade biopsy Gleason score, higher preoperative prostate specific antigen (7.4 vs 5.6 ng/ml), intermediate and high D'Amico classifications, larger tumor volume on magnetic resonance imaging (0.66 vs 0.30 ml), higher PI-RADS® (Prostate Imaging-Reporting and Data System) version 2 category lesions, a greater proportion of intermediate and high grade radical prostatectomy Gleason score lesions, higher pathological T3 stage (all p <0.01) and a higher positive surgical margin rate (19.3% vs 7.8%, p = 0.016). On multivariable analysis only tumor volume on magnetic resonance imaging (adjusted OR 1.57, p = 0.016), pathological T stage (adjusted OR 2.26, p = 0.02), positive surgical margin (adjusted OR 5.0, p = 0.004) and radical prostatectomy Gleason score (adjusted OR 2.29, p = 0.004) predicted biochemical recurrence. In this cohort tumor volume on magnetic resonance imaging and pathological variables, including Gleason score, staging and positive surgical margins, significantly predicted biochemical recurrence. This suggests an important new imaging biomarker. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Telangiectatic osteosarcoma: Outcome analyses and a diagnostic model for differentiation from aneurysmal bone cyst.

PubMed

Yin, Jun-Qiang; Fu, Yi-Wei; Xie, Xian-Biao; Cheng, Xiao-Yu; Yang, Xiao-Yu; Liu, Wei-Hai; Tu, Jian; Gao, Zhen-Hua; Shen, Jing-Nan

2018-06-01

Telangiectatic osteosarcoma (TOS), a rare variant of osteosarcoma, may be easily misdiagnosed as aneurysmal bone cyst (ABC). The aims of this study were to investigate the diagnostic and prognostic factors of TOS by reviewing our experience with TOS and to develop a diagnostic model that may distinguish TOS from ABC. We identified 51 cases of TOS treated at the First Affiliated Hospital of Sun Yat-Sen University from March 2001 to January 2016 and reviewed their records, imaging information and pathological studies. A diagnostic model was developed to differentiate TOS and ABC by Bayes discriminant analysis and was evaluated. The log-rank test was used to analyze the prognostic factors of TOS and to compare the outcome differences between TOS and other high-grade osteosarcoma subtypes. The multi-disciplinary diagnostic method employed that combined clinical, imaging, and pathological studies enhanced the diagnostic accuracy. Age 18 years or younger and pathologic fracture were more common among the TOS patients than among the ABC patients (P = .004 and .005, respectively). The average white blood cell (WBC), platelet, lactate dehydrogenase (LDH), and alkaline phosphatase (ALP) values of the TOS patients were higher than those of the ABC patients ( P = .002, .003, .007, and .007, respectively). Our diagnostic model, including the aforementioned factors, accurately predicted 62% and 78% of the TOS patients in the training and validation sets, respectively. The 5-year estimates of event-free survival and overall survival of the TOS patients were 52.5 ± 9.4% and 54.9 ± 8.8%, respectively, which were similar to those of patients with other osteosarcoma subtypes ( P = .950 and .615, respectively). Tumor volume and the LDH level were predictive prognostic factors ( P = .040 and .044) but not the presence of pathologic fracture or misdiagnosis ( P = .424 and .632, all respectively). The multi-disciplinary diagnostic method and diagnostic model based on predictive factors, i.e. , age, the presence of pathologic fracture, and platelet, LDH, ALP and WBC levels, aided the differentiation of TOS and ABC. Smaller tumors and normal LDH levels were associated with better outcomes.

Collagenous mucosal inflammatory diseases of the gastrointestinal tract.

PubMed

Freeman, Hugh J

2005-07-01

Collagenous mucosal inflammatory diseases involve the columnar-lined gastric and intestinal mucosa and have become recognized increasingly as a significant cause of symptomatic morbidity, particularly in middle-aged and elderly women, especially with watery diarrhea. Still, mechanisms involved in the pathogenesis of this diarrhea remain poorly understood and require further elucidation. The prognosis and long-term outcome of these disorders has been documented only to a limited extent. Recent clinical and pathologic studies have indicated that collagenous mucosal inflammatory disease is a more extensive pathologic process that concomitantly may involve several sites in the gastric and intestinal mucosa. The dominant pathologic lesion is a distinct subepithelial hyaline-like deposit that has histochemical and ultrastructural features of collagen overlying a microscopically defined inflammatory process. An intimate relationship with other autoimmune connective tissue disorders is evident, particularly celiac disease. This is intriguing because these collagenous disorders have not been shown to be gluten dependent. Collagenous mucosal inflammatory disorders may represent a relatively unique but generalized inflammatory response to a multitude of causes, including celiac disease, along with a diverse group of pharmacologic agents. Some recent reports have documented treatment success but histopathologic reversal has been more difficult to substantiate owing to the focal, sometimes extensive nature, of this pathologic process.

Pathological features of polyneuropathy in three dogs.

PubMed

Tsuboi, Masaya; Uchida, Kazuyuki; Ide, Tetsuya; Ogawa, Mizue; Inagaki, Takehiko; Tamura, Shinji; Saito, Miyoko; Chambers, James K; Nakayama, Hiroyuki

2013-01-01

Canine polyneuropathy is a neurological disorder characterized by a dysfunction of multiple peripheral nerves. The etiology of the disease is diverse; it may occur in cases of infectious, immune-mediated, or hereditary conditions or in association with endocrinopathy, neoplasm, or chemical intoxication. It is often difficult to determine the etiology through clinical symptoms. The aim of this study is to investigate pathological differences among three canine polyneuropathy cases with each presumably having a different etiology. Cases included a 13-month-old female border collie (Dog No.1), a 21-month-old male chihuahua (Dog No.2) and an 11-year-old male beagle (Dog No.3). Clinical examinations revealed hindlimb ataxia and sensory loss in Dog No.1, forelimb paralysis and vertebral pain in Dog No.2, and paddling-gait and hypothyroidism in Dog No.3. Histopathologically, axonal swelling and pale myelin were observed in Dog No.1. Giant axons mimicking giant axonal neuropathy were obvious in Dog No.2. Dog No.3 showed atrophic axons and severe interstitial edema. Distributions of peripheral nerve lesions coincided with respective clinical symptoms. According to their clinical and pathological features, Dogs No.1 and No.2 were suspected of hereditary polyneuropathy, while Dog No.3 seemed to have hypothyroidism-associated polyneuropathy. As each case demonstrated unique pathological features, different pathogeneses of peripheral nerve dysfunction were suggested.

STRESS RISK FACTORS AND STRESS-RELATED PATHOLOGY: NEUROPLASTICITY, EPIGENETICS AND ENDOPHENOTYPES

PubMed Central

Radley, Jason J.; Kabbaj, Mohamed; Jacobson, Lauren; Heydendael, Willem; Yehuda, Rachel; Herman, James P.

2013-01-01

This review highlights a symposium on stress risk factors and stress susceptibility, presented at the Neurobiology of Stress workshop in Boulder, Colorado, June 2010. This symposium addressed factors linking stress plasticity and reactivity to stress pathology in animal models and in humans. Dr. Jason Radley discussed studies demonstrating prefrontal cortical neuroplasticity and prefrontal control of hypothalamo-pituitary-adrenocortical axis function in rat, highlighting emerging evidence for a critical role of this region in normal and pathological stress integration. Dr. Mohamed Kabbaj summarized his studies of possible epigenetic mechanisms underlying behavioral differences in rat populations bred for differential stress reactivity. Dr. Lauren Jacobson described studies using a mouse model to explore the diverse actions of antidepressant action in brain, suggesting mechanisms whereby antidepressants may be differentially effective in treating specific depression endophenotypes. Dr. Rachel Yehuda discussed the role of glucocorticoids in post-traumatic stress disorder (PTSD), indicating that low cortisol may be a trait that predisposes the individual to development of the disorder. Furthermore, she presented evidence indicating that traumatic events can have transgenerational impact on cortisol reactivity and development of PTSD symptoms. Together, the symposium highlighted emerging themes regarding the role of brain reorganization, individual differences and epigenetics in determining stress plasticity and pathology. PMID:21848436

The role of immune cells, glia and neurons in white and gray matter pathology in multiple sclerosis

PubMed Central

Bernstock, Joshua D.; Pluchino, Stefano

2015-01-01

Multiple sclerosis is one of the most common causes of chronic neurological disability beginning in early to middle adult life. Multiple sclerosis is idiopathic in nature, yet increasing correlative evidence supports a strong association between one’s genetic predisposition, the environment and the immune system. Symptoms of multiple sclerosis have primarily been shown to result from a disruption in the integrity of myelinated tracts within the white matter of the central nervous system. However, recent research has also highlighted the hitherto underappreciated involvement of gray matter in multiple sclerosis disease pathophysiology, which may be especially relevant when considering the accumulation of irreversible damage and progressive disability. This review aims at providing a comprehensive overview of the interplay between inflammation, glial/neuronal damage and regeneration throughout the course of multiple sclerosis via the analysis of both white and gray matter lesional pathology. Further, we describe the common pathological mechanisms underlying both relapsing and progressive forms of multiple sclerosis, and analyze how current (as well as future) treatments may interact and/or interfere with its pathology. Understanding the putative mechanisms that drive disease pathogenesis will be key in helping to develop effective therapeutic strategies to prevent, mitigate, and treat the diverse morbidities associated with multiple sclerosis. PMID:25802011

Incorporating pathology in the practice of infectious disease: myths and reality.

PubMed

Guarner, Jeannette

2014-10-15

The role pathology plays in establishing or excluding infectious diseases has been established. However, as the practice of pathology has become subspecialized, there is not enough infectious disease specimen volume to have a pathologist dedicated full time to this crosscutting subspecialty. So, what are the myths and realities of a practicing infectious disease pathologist in the hospital setting? Infectious disease clinicians tend to consult pathologists when there are questions regarding terminology used in pathology reports; when there is the need to perform additional studies on formalin-fixed, paraffin-embedded tissues; and when there is an interest in seeing biopsies or resections obtained from patients and in obtaining photographs for presentations. Pathologists consult infectious disease pathologists when there is a need to review diverse inflammatory reactions; for identification of fungi, parasites, or unknown structures; to define the need to use special stains and other techniques in order to identify organisms in tissues that have been formalin fixed; and to help with terminology to be used in reports. This review explores in more detail why and how these consultations occur. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Hypoxia and Redox Signaling on Extracellular Matrix Remodeling: From Mechanisms to Pathological Implications.

PubMed

Labrousse-Arias, David; Martínez-Ruiz, Antonio; Calzada, María J

2017-10-20

The extracellular matrix (ECM) is an essential modulator of cell behavior that influences tissue organization. It has a strong relevance in homeostasis and translational implications for human disease. In addition to ECM structural proteins, matricellular proteins are important regulators of the ECM that are involved in a myriad of different pathologies. Recent Advances: Biochemical studies, animal models, and study of human diseases have contributed to the knowledge of molecular mechanisms involved in remodeling of the ECM, both in homeostasis and disease. Some of them might help in the development of new therapeutic strategies. This review aims to review what is known about some of the most studied matricellular proteins and their regulation by hypoxia and redox signaling, as well as the pathological implications of such regulation. Matricellular proteins have complex regulatory functions and are modulated by hypoxia and redox signaling through diverse mechanisms, in some cases with controversial effects that can be cell or tissue specific and context dependent. Therefore, a better understanding of these regulatory processes would be of great benefit and will open new avenues of considerable therapeutic potential. Characterizing the specific molecular mechanisms that modulate matricellular proteins in pathological processes that involve hypoxia and redox signaling warrants additional consideration to harness the potential therapeutic value of these regulatory proteins. Antioxid. Redox Signal. 27, 802-822.

CSF tau and β-amyloid predict cerebral synucleinopathy in autopsied Lewy body disorders.

PubMed

Irwin, David J; Xie, Sharon X; Coughlin, David; Nevler, Naomi; Akhtar, Rizwan S; McMillan, Corey T; Lee, Edward B; Wolk, David A; Weintraub, Daniel; Chen-Plotkin, Alice; Duda, John E; Spindler, Meredith; Siderowf, Andrew; Hurtig, Howard I; Shaw, Leslie M; Grossman, Murray; Trojanowski, John Q

2018-03-20

To test the association of antemortem CSF biomarkers with postmortem pathology in Lewy body disorders (LBD). Patients with autopsy-confirmed LBD (n = 24) and autopsy-confirmed Alzheimer disease (AD) (n = 23) and cognitively normal (n = 36) controls were studied. In LBD, neuropathologic criteria defined Lewy body α-synuclein (SYN) stages with medium/high AD copathology (SYN + AD = 10) and low/no AD copathology (SYN - AD = 14). Ordinal pathology scores for tau, β-amyloid (Aβ), and SYN pathology were averaged across 7 cortical regions to obtain a global cerebral score for each pathology. CSF total tau (t-tau), phosphorylated tau at threonine 181 , and Aβ 1-42 levels were compared between LBD and control groups and correlated with global cerebral pathology scores in LBD with linear regression. Diagnostic accuracy for postmortem categorization of LBD into SYN + AD vs SYN - AD or neocortical vs brainstem/limbic SYN stage was tested with receiver operating curves. SYN + AD had higher CSF t-tau (mean difference 27.0 ± 8.6 pg/mL) and lower Aβ 1-42 (mean difference -84.0 ± 22.9 g/mL) compared to SYN - AD ( p < 0.01, both). Increasing global cerebral tau and plaque scores were associated with higher CSF t-tau ( R 2 = 0.15-0.16, p < 0.05, both) and lower Aβ 1-42 ( R 2 = 0.43-0.49, p < 0.001, both), while increasing cerebral SYN scores were associated with lower CSF Aβ 1-42 ( R 2 = 0.31, p < 0.001) and higher CSF t-tau/Aβ 1-42 ratio ( R 2 = 0.27, p = 0.01). CSF t-tau/Aβ 1-42 ratio had 100% specificity and 90% sensitivity for SYN + AD, and CSF Aβ 1-42 had 77% specificity and 82% sensitivity for neocortical SYN stage. Higher antemortem CSF t-tau/Aβ 1-42 and lower Aβ 1-42 levels are predictive of increasing cerebral AD and SYN pathology. These biomarkers may identify patients with LBD vulnerable to cortical SYN pathology who may benefit from both SYN and AD-targeted disease-modifying therapies. © 2018 American Academy of Neurology.

Funding anatomic pathology research: a retrospective analysis of an intramural funding mechanism.

PubMed

McDaniel, Andrew; Fullen, Douglas R; Cho, Kathleen R; Lucas, David R; Giordano, Thomas J; Greenson, Joel; Lieberman, Andrew P; Kunju, Lakshmi P; Myers, Jeffrey L; Roh, Michael H

2013-09-01

In 2006, the department of pathology at our institution established an intramural research funding mechanism to support anatomic pathology research projects for faculty and trainee development. A review committee consisting of faculty members with diverse academic interests evaluated applications; proposals were eligible for a maximum award amount of $30 000 per project with a maximum program cost of $150 000 annually. To report our experience based on a retrospective review of the research proposals submitted to the committee since the inception of the Anatomic Pathology Research Fund and evaluate the outcomes of the funded projects. We retrospectively analyzed all project applications that were received by the committee. Outcome data were collected by reviewing progress reports, abstracts for national and international meetings, PubMed search results, and/or direct communication with investigators. To date, a total of 59 individual projects have been awarded funding, for a total amount of $349 792, with an average award amount of $5381 per project. A total of 26 faculty members have secured funding for projects through this mechanism, and 27 resident and fellow trainees have been engaged in the funded projects. Spanning 11 subspecialty disciplines in anatomic pathology, 32 abstracts (54%) have been presented at national meetings and 26 (44%) have been published in the peer-reviewed literature to date. One project generated data used to secure an extramural (R01) grant. Our funding mechanism could serve as a model used by other academic departments to support research activities, thereby fostering faculty development through scholarly activities.

MNDR v2.0: an updated resource of ncRNA–disease associations in mammals

PubMed Central

Cui, Tianyu; Zhang, Lin; Huang, Yan; Yi, Ying; Tan, Puwen; Zhao, Yue; Hu, Yongfei

2018-01-01

Abstract Accumulating evidence suggests that diverse non-coding RNAs (ncRNAs) are involved in the progression of a wide variety of diseases. In recent years, abundant ncRNA–disease associations have been found and predicted according to experiments and prediction algorithms. Diverse ncRNA–disease associations are scattered over many resources and mammals, whereas a global view of diverse ncRNA–disease associations is not available for any mammals. Hence, we have updated the MNDR v2.0 database (www.rna-society.org/mndr/) by integrating experimental and prediction associations from manual literature curation and other resources under one common framework. The new developments in MNDR v2.0 include (i) an over 220-fold increase in ncRNA–disease associations enhancement compared with the previous version (including lncRNA, miRNA, piRNA, snoRNA and more than 1400 diseases); (ii) integrating experimental and prediction evidence from 14 resources and prediction algorithms for each ncRNA–disease association; (iii) mapping disease names to the Disease Ontology and Medical Subject Headings (MeSH); (iv) providing a confidence score for each ncRNA–disease association and (v) an increase of species coverage to six mammals. Finally, MNDR v2.0 intends to provide the scientific community with a resource for efficient browsing and extraction of the associations between diverse ncRNAs and diseases, including >260 000 ncRNA–disease associations. PMID:29106639

What is the extent of prokaryotic diversity?

PubMed Central

Curtis, Thomas P; Head, Ian M; Lunn, Mary; Woodcock, Stephen; Schloss, Patrick D; Sloan, William T

2006-01-01

The extent of microbial diversity is an intrinsically fascinating subject of profound practical importance. The term ‘diversity’ may allude to the number of taxa or species richness as well as their relative abundance. There is uncertainty about both, primarily because sample sizes are too small. Non-parametric diversity estimators make gross underestimates if used with small sample sizes on unevenly distributed communities. One can make richness estimates over many scales using small samples by assuming a species/taxa-abundance distribution. However, no one knows what the underlying taxa-abundance distributions are for bacterial communities. Latterly, diversity has been estimated by fitting data from gene clone libraries and extrapolating from this to taxa-abundance curves to estimate richness. However, since sample sizes are small, we cannot be sure that such samples are representative of the community from which they were drawn. It is however possible to formulate, and calibrate, models that predict the diversity of local communities and of samples drawn from that local community. The calibration of such models suggests that migration rates are small and decrease as the community gets larger. The preliminary predictions of the model are qualitatively consistent with the patterns seen in clone libraries in ‘real life’. The validation of this model is also confounded by small sample sizes. However, if such models were properly validated, they could form invaluable tools for the prediction of microbial diversity and a basis for the systematic exploration of microbial diversity on the planet. PMID:17028084

Predation and landscape characteristics independently affect reef fish community organization.

PubMed

Stier, Adrian C; Hanson, Katharine M; Holbrook, Sally J; Schmitt, Russell J; Brooks, Andrew J

2014-05-01

Trophic island biogeography theory predicts that the effects of predators on prey diversity are context dependent in heterogeneous landscapes. Specifically, models predict that the positive effect of habitat area on prey diversity should decline in the presence of predators, and that predators should modify the partitioning of alpha and beta diversity across patchy landscapes. However, experimental tests of the predicted context dependency in top-down control remain limited. Using a factorial field experiment we quantify the effects of a focal predatory fish species (grouper) and habitat characteristics (patch size, fragmentation) on the partitioning of diversity and assembly of coral reef fish communities. We found independent effects of groupers and patch characteristics on prey communities. Groupers reduced prey abundance by 50% and gamma diversity by 45%, with a disproportionate removal of rare species relative to common species (64% and 36% reduction, respectively; an oddity effect). Further, there was a 77% reduction in beta diversity. Null model analysis demonstrated that groupers increased the importance of stochastic community assembly relative to patches without groupers. With regard to patch size, larger patches contained more fishes, but a doubling of patch size led to a modest (36%) increase in prey abundance. Patch size had no effect on prey diversity; however, fragmented patches had 50% higher species richness and modified species composition relative to unfragmented patches. Our findings suggest two different pathways (i.e., habitat or predator shifts) by which natural and/or anthropogenic processes can drive variation in fish biodiversity and community assembly.

Met synergizes with p53 loss to induce mammary tumors that possess features of claudin-low breast cancer

PubMed Central

Knight, Jennifer F.; Lesurf, Robert; Zhao, Hong; Pinnaduwage, Dushanthi; Davis, Ryan R.; Saleh, Sadiq M. I.; Zuo, Dongmei; Naujokas, Monica A.; Chughtai, Naila; Herschkowitz, Jason I.; Prat, Aleix; Mulligan, Anna Marie; Muller, William J.; Cardiff, Robert D.; Gregg, Jeff P.; Andrulis, Irene L.; Hallett, Michael T.; Park, Morag

2013-01-01

Triple-negative breast cancer (TNBC) accounts for ∼20% of cases and contributes to basal and claudin-low molecular subclasses of the disease. TNBCs have poor prognosis, display frequent mutations in tumor suppressor gene p53 (TP53), and lack targeted therapies. The MET receptor tyrosine kinase is elevated in TNBC and transgenic Met models (Metmt) develop basal-like tumors. To investigate collaborating events in the genesis of TNBC, we generated Metmt mice with conditional loss of murine p53 (Trp53) in mammary epithelia. Somatic Trp53 loss, in combination with Metmt, significantly increased tumor penetrance over Metmt or Trp53 loss alone. Unlike Metmt tumors, which are histologically diverse and enriched in a basal-like molecular signature, the majority of Metmt tumors with Trp53 loss displayed a spindloid pathology with a distinct molecular signature that resembles the human claudin-low subtype of TNBC, including diminished claudins, an epithelial-to-mesenchymal transition signature, and decreased expression of the microRNA-200 family. Moreover, although mammary specific loss of Trp53 promotes tumors with diverse pathologies, those with spindloid pathology and claudin-low signature display genomic Met amplification. In both models, MET activity is required for maintenance of the claudin-low morphological phenotype, in which MET inhibitors restore cell-cell junctions, rescue claudin 1 expression, and abrogate growth and dissemination of cells in vivo. Among human breast cancers, elevated levels of MET and stabilized TP53, indicative of mutation, correlate with highly proliferative TNBCs of poor outcome. This work shows synergy between MET and TP53 loss for claudin-low breast cancer, identifies a restricted claudin-low gene signature, and provides a rationale for anti-MET therapies in TNBC. PMID:23509284

Marital infidelity and its effect on pathogen diversity

NASA Astrophysics Data System (ADS)

Berryman, Matthew J.

2007-01-01

Marital infidelity is usually examined solely in terms of strategies of men and women, with an emphasis on the enhanced payoff for male infidelity (provided he can get away with it). What are not clear are the strategies used, in terms of how often to engage in extra-marital affairs. It has been proposed that female strategies are governed by a "decision" to maximize the genetic diversity of her offspring, in order to better guarantee that at least some will survive against a common pathogen. This strategy would then impact on the strategies and diversity of pathogens. I make a number of predictions about both strategies and the genetic diversity of humans and pathogens, couched in game-theoretic terms. These predictions are then compared with the existing evidence on the strategies used by women and also in terms of the genetic diversity of human populations.

Evolution of increased phenotypic diversity enhances population performance by reducing sexual harassment in damselflies.

PubMed

Takahashi, Yuma; Kagawa, Kotaro; Svensson, Erik I; Kawata, Masakado

2014-07-18

The effect of evolutionary changes in traits and phenotypic/genetic diversity on ecological dynamics has received much theoretical attention; however, the mechanisms and ecological consequences are usually unknown. Female-limited colour polymorphism in damselflies is a counter-adaptation to male mating harassment, and thus, is expected to alter population dynamics through relaxing sexual conflict. Here we show the side effect of the evolution of female morph diversity on population performance (for example, population productivity and sustainability) in damselflies. Our theoretical model incorporating key features of the sexual interaction predicts that the evolution of increased phenotypic diversity will reduce overall fitness costs to females from sexual conflict, which in turn will increase productivity, density and stability of a population. Field data and mesocosm experiments support these model predictions. Our study suggests that increased phenotypic diversity can enhance population performance that can potentially reduce extinction rates and thereby influence macroevolutionary processes.

Predicting temporal variation in zooplankton beta diversity is challenging

PubMed Central

Castelo Branco, Christina W.; Kozlowsky-Suzuki, Betina; Sousa-Filho, Izidro F.; Souza, Leonardo Coimbra e; Bini, Luis Mauricio

2017-01-01

Beta diversity, the spatial variation in species composition, has been related to different explanatory variables, including environmental heterogeneity, productivity and connectivity. Using a long-term time series of zooplankton data collected over 62 months in a tropical reservoir (Ribeirão das Lajes Reservoir, Rio de Janeiro State, Brazil), we tested whether beta diversity (as measured across six sites distributed along the main axis of the reservoir) was correlated with environmental heterogeneity (spatial environmental variation in a given month), chlorophyll-a concentration (a surrogate for productivity) and water level. We did not found evidence for the role of these predictors, suggesting the need to reevaluate predictions or at least to search for better surrogates of the processes that hypothetically control beta diversity variation. However, beta diversity declined over time, which is consistent with the process of biotic homogenization, a worldwide cause of concern. PMID:29095892

Predicting temporal variation in zooplankton beta diversity is challenging.

PubMed

Lopes, Vanessa Guimarães; Castelo Branco, Christina W; Kozlowsky-Suzuki, Betina; Sousa-Filho, Izidro F; Souza, Leonardo Coimbra E; Bini, Luis Mauricio

2017-01-01

Beta diversity, the spatial variation in species composition, has been related to different explanatory variables, including environmental heterogeneity, productivity and connectivity. Using a long-term time series of zooplankton data collected over 62 months in a tropical reservoir (Ribeirão das Lajes Reservoir, Rio de Janeiro State, Brazil), we tested whether beta diversity (as measured across six sites distributed along the main axis of the reservoir) was correlated with environmental heterogeneity (spatial environmental variation in a given month), chlorophyll-a concentration (a surrogate for productivity) and water level. We did not found evidence for the role of these predictors, suggesting the need to reevaluate predictions or at least to search for better surrogates of the processes that hypothetically control beta diversity variation. However, beta diversity declined over time, which is consistent with the process of biotic homogenization, a worldwide cause of concern.

Second branchial cleft anomaly with an ectopic tooth: a case report.

PubMed

Alyono, Jennifer C; Hong, Paul; Page, Nathan C; Malicki, Denise; Bothwell, Marcella R

2014-09-01

Branchial cleft cysts, sinuses, and fistulas are the most common congenital lateral neck lesions in children. They arise as a result of an abnormal development of the branchial arches and their corresponding ectoderm-lined branchial clefts. Of these diverse anomalies, second branchial cleft lesions are the most common, accounting for approximately 95% of all branchial arch pathologies. We describe what is to the best of our knowledge the first reported case of an ectopic tooth in a branchial cleft anomaly. The patient was a young girl who had other congenital abnormalities and syndromic features and who was eventually diagnosed with Townes-Brocks syndrome. We describe the clinical presentation, management, pathologic analysis, and postoperative outcomes of this case, and we present a brief review of Townes-Brocks syndrome.

Meeting the Curriculum Needs for Different Career Paths in Laboratory Medicine

PubMed Central

Smith, Brian R.

2008-01-01

There are a number of career paths in Laboratory Medicine and several clinical practice models for the discipline. This article summarizes the state of current training at the medical student and residency/post-graduate levels, emphasizing practice in the U.S., and the challenges of education in the discipline to meet the needs of diverse career paths. Data regarding effectiveness of current pedagogical Approaches are discussed along with a brief review of evolving didactic methodologies. The recently published curriculum in Laboratory Medicine (Clinical Pathology) by the Academy of Clinical Laboratory Physicians and Scientists is reviewed, including its major emphases and the importance of competency assessment. Finally, the future of Laboratory Medicine and Pathology and the need to train for that future is expanded upon. PMID:18410745

Use of Computed Tomography to Determine Perforation in Patients With Acute Appendicitis.

PubMed

Gaskill, Cameron E; Simianu, Vlad V; Carnell, Jonathan; Hippe, Daniel S; Bhargava, Puneet; Flum, David R; Davidson, Giana H

Urgent appendectomy has long been the standard of care for acute appendicitis. Six randomized trials have demonstrated that antibiotics can safely treat appendicitis, but approximately 1 in 4 of these patients eventually requires appendectomy. Overall treatment success may be limited by complex disease including perforation. Patients׳ success on antibiotic therapy may depend on preoperative identification of complex disease on imaging. However, the effectiveness of computed tomography (CT) in differentiating complex disease including perforated from nonperforated appendicitis remains to be determined. The purpose of this study was to assess the preoperative diagnostic accuracy of CT in determining appendiceal perforation in patients operated for acute appendicitis. We performed a retrospective review of pathology and radiology reports from consecutive patients who presented to the emergency department with suspicion for acute appendicitis between January 2012 and May 2015. CT scans were re-reviewed by abdominal imaging fellowship-trained radiologists using standardized criteria, and the radiologists were blinded to pathology and surgical findings. Radiologists specifically noted presence or absence of periappendiceal gas, abscess, appendicolith, fat stranding, and bowel wall thickening. The overall radiologic impression as well as these specific imaging findings was compared to results of pathology and operative reports. Pathology reports were considered the standard for diagnostic accuracy. Eighty-nine patients (65% male, average age of 34 years) presenting with right lower quadrant pain underwent CT imaging and prompt appendectomy. Final pathology reported perforation in 48% (n = 43) of cases. Radiologic diagnosis of perforation was reported in 9% (n = 8), correctly identifying perforation in 37.5% (n = 3), and incorrectly reporting perforation in 62.5% of nonperforated cases per pathology. Radiology missed 93% (n = 40) of perforations postoperatively diagnosed by pathology. There was no secondary finding (fat stranding, diameter >13mm, abscess, cecal wall thickening, periappendiceal gas, simple fluid collection, appendicolith, and phlegmon) with a clinically reliable sensitivity or specificity to predict perforated appendicitis. Surgeon׳s report of perforation was consistent with the pathology report of perforation in only 28% of cases. The usefulness of a CT for determining perforation in acute appendicitis is limited, and methods to improve precision in identifying patients with complicated appendicitis should be explored as this may help for improving risk prediction for failure of treatment with antibiotic therapy and help guide patients and providers in shared decision-making for treatment options. Copyright © 2017 Elsevier Inc. All rights reserved.

Rare pancreatic neoplasms: the utility of endoscopic ultrasound-guided fine-needle aspiration-a large single center study.

PubMed

Imaoka, Hiroshi; Yamao, Kenji; Bhatia, Vikram; Shimizu, Yasuhiro; Yatabe, Yasushi; Koshikawa, Takashi; Kinoshita, Yoshikazu

2009-01-01

Tumors other than ductal adenocarcinomas constitute 10%-15% of all pancreatic tumors. We describe the performance and pitfalls of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for diagnosis of these rare pancreatic tumors and their characteristic cytopathological features. The records of 455 pancreatic fine-needle aspiration procedures done between March 1997 and August 2006 at Aichi Cancer Center, Nagoya, Japan, were reviewed. Besides cytology, aspirated material was routinely submitted in formalin for cell-block analysis. The reference standard for final diagnosis was surgical pathology from resected specimens. Twenty-eight rare (nonductal adenocarcinomas) pancreatic tumors were identified. Overall, EUS-FNA with the results of cytology, cell-block processing, and immunohistochemistry could correctly diagnose the type of neoplasm in 19 (67.9%) cases. EUS-FNA could distinguish benign from malignant rare tumors with a sensitivity of 69.2%, a specificity of 100%, positive predictive value of 100%, negative predictive value of 79.0%, and accuracy of 85.7%. None of three malignant pancreatic endocrine neoplasms could be diagnosed as malignant. An adequate core tissue sample could be obtained in 21 cases (75.0%) and provide a histopathological diagnosis in 19 (67.9%) cases. EUS-FNA could change the presumptive diagnosis in 11 (39.3%) cases. Specific immunochemical studies were useful adjuncts to the diagnosis. No major or minor complication was noted in any patient. Pancreatic neoplasms other than ductal adenocarcinomas have diverse imaging and histopathological features. EUS-FNA is accurate and safe for their identification.

Fecal Calprotectin in Ileal Crohn's Disease: Relationship with Magnetic Resonance Enterography and a Pathology Score.

PubMed

Cerrillo, Elena; Beltrán, Belén; Pous, Salvador; Echarri, Ana; Gallego, Jose Carlos; Iborra, Marisa; Pamies, Jose; Nos, Pilar

2015-07-01

Magnetic resonance enterography (MRE) is an effective method of assessing small bowel Crohn's disease (CD). Fecal calprotectin (FC) correlates well with endoscopic disease activity. We aimed to evaluate the correlation between FC and disease activity according to MRE and surgical pathology in small bowel CD. One hundred twenty consecutive patients with ileal CD who underwent MRE assessment were included. Clinical data, C-reactive protein and FC, radiological and histological variables were obtained. Clinical activity was evaluated by the Harvey-Bradshaw Index and FC by enzyme-linked immunosorbent assay. MRE activity was assessed by means of the Magnetic Resonance Index of Activity score. Chiorean's score was used to grade pathological inflammation in surgical specimens. Seventy-five patients (62.5%) were in clinical remission (Harvey-Bradshaw Index < 5) and 45 (37.5%) had active disease (Harvey-Bradshaw Index ≥ 5). The Magnetic Resonance Index of Activity score was significantly associated with FC levels (P < 0.01), with a moderate overall correlation (Spearman's r = 0.56, P < 0.001). FC reflected MRE inflammatory activity with an area under the receiver operating characteristic curve of 0.914 (confidence interval, 0.849-0.958; P < 0.001). A cutoff value of 166.50 μg/g had 90% sensitivity, 74% specificity, 89% positive predictive value, and 76% negative predictive value for diagnosis of inflammation. Twenty-eight of 120 patients were operated. Surgical pathology showed a good agreement with FC for moderate (P = 0.03) and severe (P = 0.01) Chiorean's index. No relationship was detected for C-reactive protein. FC correlates with the degree of MRE inflammatory activity and with surgical pathology damage in ileal CD. Thus, FC could be a surrogate marker of disease control used to select patients for MRE assessment and therapeutic adjustment.

Internet-based motivation program for women with eating disorders: eating disorder pathology and depressive mood predict dropout.

PubMed

von Brachel, Ruth; Hötzel, Katrin; Hirschfeld, Gerrit; Rieger, Elizabeth; Schmidt, Ulrike; Kosfelder, Joachim; Hechler, Tanja; Schulte, Dietmar; Vocks, Silja

2014-03-31

One of the main problems of Internet-delivered interventions for a range of disorders is the high dropout rate, yet little is known about the factors associated with this. We recently developed and tested a Web-based 6-session program to enhance motivation to change for women with anorexia nervosa, bulimia nervosa, or related subthreshold eating pathology. The aim of the present study was to identify predictors of dropout from this Web program. A total of 179 women took part in the study. We used survival analyses (Cox regression) to investigate the predictive effect of eating disorder pathology (assessed by the Eating Disorders Examination-Questionnaire; EDE-Q), depressive mood (Hopkins Symptom Checklist), motivation to change (University of Rhode Island Change Assessment Scale; URICA), and participants' age at dropout. To identify predictors, we used the least absolute shrinkage and selection operator (LASSO) method. The dropout rate was 50.8% (91/179) and was equally distributed across the 6 treatment sessions. The LASSO analysis revealed that higher scores on the Shape Concerns subscale of the EDE-Q, a higher frequency of binge eating episodes and vomiting, as well as higher depression scores significantly increased the probability of dropout. However, we did not find any effect of the URICA or age on dropout. Women with more severe eating disorder pathology and depressive mood had a higher likelihood of dropping out from a Web-based motivational enhancement program. Interventions such as ours need to address the specific needs of women with more severe eating disorder pathology and depressive mood and offer them additional support to prevent them from prematurely discontinuing treatment.

Efficacy of Strain Elastography in Diagnosis and Staging of Acute Appendicitis in Pediatric Patients.

PubMed

Arslan, Harun; Akdemir, Zülküf; Yavuz, Alpaslan; Gökçal, Fahri; Parlakgümüş, Cemal; İslamoglu, Necat; Akdeniz, Hüseyin

2018-02-11

BACKGROUND In the present study, the role and efficiency of strain elastography (SE) were evaluated in diagnosis and staging of acute appendicitis in pediatric patients. MATERIAL AND METHODS We enrolled 225 pediatric patients with suspected clinical and laboratory findings of acute appendicitis. Gray-scale sonographic findings were recorded and staging was made by the colorization method of SE imaging. Appendectomy was performed in all patients and the results of the surgical pathology were compared with the imaging findings. The sensitivity, specificity, and accuracy of SE imaging were determined in terms of evaluating the "acute appendicitis". RESULTS Sonographic evaluation revealed acute appendicitis in 100 patients. Regarding the SE analysis, cases with appendicitis were classified into 3 groups as: mild (n=17), moderate (n=39), and severe (n=44). The pathological evaluation revealed 95 different stages of appendicitis and normal appendix in 5 cases: acute focal (n=10), acute suppurative (n=46), phlegmonous (n=27), and perforated (n=12), regarding the results of surgical pathology. Five patients with pathologically proven "normal" appendix were noted as "mild stage appendicitis" based on gray scale and SE analysis. In total, when gray-scale and SE results were compared with pathology results regardless of the stage of appendicitis, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy rates were 96%, 96%, 95%, 96.8%, and 96%, respectively. No statistically significant difference was detected between other groups (P<0.05). CONCLUSIONS In acute appendicitis, the use of SE imaging as a supportive method for the clinical approach can be useful in diagnosis, and its results are closely correlated with the histopathologic stage of appendix inflammation.

Internet-Based Motivation Program for Women With Eating Disorders: Eating Disorder Pathology and Depressive Mood Predict Dropout

PubMed Central

Hirschfeld, Gerrit; Rieger, Elizabeth; Schmidt, Ulrike; Kosfelder, Joachim; Hechler, Tanja; Schulte, Dietmar; Vocks, Silja

2014-01-01

Background One of the main problems of Internet-delivered interventions for a range of disorders is the high dropout rate, yet little is known about the factors associated with this. We recently developed and tested a Web-based 6-session program to enhance motivation to change for women with anorexia nervosa, bulimia nervosa, or related subthreshold eating pathology. Objective The aim of the present study was to identify predictors of dropout from this Web program. Methods A total of 179 women took part in the study. We used survival analyses (Cox regression) to investigate the predictive effect of eating disorder pathology (assessed by the Eating Disorders Examination-Questionnaire; EDE-Q), depressive mood (Hopkins Symptom Checklist), motivation to change (University of Rhode Island Change Assessment Scale; URICA), and participants’ age at dropout. To identify predictors, we used the least absolute shrinkage and selection operator (LASSO) method. Results The dropout rate was 50.8% (91/179) and was equally distributed across the 6 treatment sessions. The LASSO analysis revealed that higher scores on the Shape Concerns subscale of the EDE-Q, a higher frequency of binge eating episodes and vomiting, as well as higher depression scores significantly increased the probability of dropout. However, we did not find any effect of the URICA or age on dropout. Conclusions Women with more severe eating disorder pathology and depressive mood had a higher likelihood of dropping out from a Web-based motivational enhancement program. Interventions such as ours need to address the specific needs of women with more severe eating disorder pathology and depressive mood and offer them additional support to prevent them from prematurely discontinuing treatment. PMID:24686856

Quantification of Butyrylcholinesterase Activity as a Sensitive and Specific Biomarker of Alzheimer's Disease.

PubMed

Macdonald, Ian R; Maxwell, Selena P; Reid, George A; Cash, Meghan K; DeBay, Drew R; Darvesh, Sultan

2017-01-01

Amyloid-β (Aβ) plaques are a neuropathological hallmark of Alzheimer's disease (AD); however, a significant number of cognitively normal older adults can also have Aβ plaques. Thus, distinguishing AD from cognitively normal individuals with Aβ plaques (NwAβ) based on Aβ plaque detection is challenging. It has been observed that butyrylcholinesterase (BChE) accumulates in plaques preferentially in AD. Thus, detecting BChE-associated plaques has the potential as an improved AD biomarker. We present Aβ, thioflavin-S, and BChE quantification of 26 postmortem brain tissues; AD (n = 8), NwAβ (n = 6), cognitively normal without plaques (n = 8), and other common dementias including corticobasal degeneration, frontotemporal dementia with tau, dementia with Lewy bodies, and vascular dementia. Pathology burden in the orbitofrontal cortex, entorhinal cortex, amygdala, and hippocampal formation was determined and compared. The predictive value of Aβ and BChE quantification was determined, via receiver-operating characteristic plots, to evaluate their AD diagnostic performance using sensitivity, specificity, and area under curve (AUC) metrics. In general, Aβ and BChE-associated pathology were greater in AD, particularly in the orbitofrontal cortex. In this region, the largest increase (9.3-fold) was in BChE-associated pathology, observed between NwAβ and AD, due to the virtual absence of BChE-associated plaques in NwAβ brains. Furthermore, BChE did not associate with pathology of the other dementias. In this sample, BChE-associated pathology provided better diagnostic performance (AUC = 1.0, sensitivity/specificity = 100% /100%) when compared to Aβ (AUC = 0.98, 100% /85.7%). These findings highlight the predictive value of BChE as a biomarker for AD that could facilitate timely disease diagnosis and management.

Endoscopic ultrasound evaluation in the surgical treatment of duodenal and peri-ampullary adenomas

PubMed Central

Azih, Lilian C; Broussard, Brett L; Phadnis, Milind A; Heslin, Martin J; Eloubeidi, Mohamad A; Varadarajulu, Shayam; Arnoletti, Juan Pablo

2013-01-01

AIM: To investigate endoscopic ultrasound (EUS) for predicting depth of mucosal invasion and to analyze outcomes following endoscopic and transduodenal resection. METHODS: Records of 111 patients seen at our institution from November 1999 to July 2011 with the post-operative pathological diagnosis of benign ampullary and duodenal adenomas were reviewed. Records of patients who underwent preoperative EUS for diagnostic purposes were identified. The accuracy of EUS in predicting the absence of muscular invasion was assessed by comparing EUS reports to the final surgical pathological results. In addition, the incidence of the post-operative complications over a period of 30 d and the subsequent long-term outcome (recurrence) over a period of 30 mo associated with endoscopic and transduodenal surgical resection was recorded, compared and analyzed. RESULTS: Among 111 patients with benign ampullary and duodenal adenomas, 47 underwent preoperative EUS for 29 peri-ampullary lesions and 18 duodenal lesions. In addition, computed tomography was performed in 18 patients, endoscopic retrograde cholangio-pancreatography in 10 patients and esophagogastroduodenoscopy in 22 patients. There were 43 patients with sporadic adenomas and 4 patients with familial adenomatous polyposis (FAP)/other polyposis syndromes. In 38 (81%, P < 0.05) patients, EUS reliably identified absence of submucosal and muscularis invasion. In 4 cases, EUS underestimated submucosal invasion that was proven by pathology. In the other 5 patients, EUS predicted muscularis invasion which could not be demonstrated in the resected specimen. EUS predicted tumor muscularis invasion with a specificity of 88% and negative predictive value of 90% (P < 0.05). Types of resection performed included endoscopic resection in 22 cases, partial duodenectomy in 9 cases, transduodenal ampullectomy with sphincteroplasty in 10 cases and pancreaticoduodenectomy in 6 cases. The main post-operative final pathological results included villous adenoma (n = 5), adenoma (n = 8), tubulovillous adenoma (n = 10), tubular adenoma (n = 20) and hyperplastic polyp (n = 2). Among the 47 patients who underwent resection, 8 (17%, 5 of which corresponded to surgical resection) developed post-procedural complications which included retroperitoneal hematoma, intra-abdominal abscess, wound infection, delayed gastric emptying and prolonged ileus. After median follow-up of 20 mo there were 6 local recurrences (13%, median follow-up = 20 mo) 4 of which were in patients with FAP. CONCLUSION: EUS accurately predicts the depth of mucosal invasion in suspected benign ampullary and duodenal adenomas. These patients can safely undergo endoscopic or local resection. PMID:23382629

Predictive Value of Social Skills in Living Together at Primary School. Analysis in a Cultural Diversity Context

ERIC Educational Resources Information Center

Herrera Torres, Lucía; Bravo Antonio, Iván

2012-01-01

Coexistence at school stands out as one of the main goals in today's education (Carretero, 2008; Ortega, 2007). The aim of this study developed within a cultural diversity context is to identify the specific dimensions of social skills through which the different elements favouring or hindering coexistence at school can be predicted. A total of…

Classroom Dimensions Predict Early Peer Interaction when Children Are Diverse in Ethnicity, Race, and Home Language

ERIC Educational Resources Information Center

Howes, Carollee; Guerra, Alison Wishard; Fuligni, Allison; Zucker, Eleanor; Lee, Linda; Obregon, Nora B.; Spivak, Asha

2011-01-01

The purpose of this study was to test a model for predicting preschool-age children's behaviors with peers from dimensions of the classroom and teacher-child relationship quality when the children were from diverse race, ethnic, and home language backgrounds. Eight hundred children, (M=age 63 months, SD=8.1 months), part of the National Evaluation…

Gap formation following climatic events in spatially structured plant communities

PubMed Central

Liao, Jinbao; De Boeck, Hans J.; Li, Zhenqing; Nijs, Ivan

2015-01-01

Gaps play a crucial role in maintaining species diversity, yet how community structure and composition influence gap formation is still poorly understood. We apply a spatially structured community model to predict how species diversity and intraspecific aggregation shape gap patterns emerging after climatic events, based on species-specific mortality responses. In multispecies communities, average gap size and gap-size diversity increased rapidly with increasing mean mortality once a mortality threshold was exceeded, greatly promoting gap recolonization opportunity. This result was observed at all levels of species richness. Increasing interspecific difference likewise enhanced these metrics, which may promote not only diversity maintenance but also community invasibility, since more diverse niches for both local and exotic species are provided. The richness effects on gap size and gap-size diversity were positive, but only expressed when species were sufficiently different. Surprisingly, while intraspecific clumping strongly promoted gap-size diversity, it hardly influenced average gap size. Species evenness generally reduced gap metrics induced by climatic events, so the typical assumption of maximum evenness in many experiments and models may underestimate community diversity and invasibility. Overall, understanding the factors driving gap formation in spatially structured assemblages can help predict community secondary succession after climatic events. PMID:26114803

Pharmacogenetics Biomarkers and Their Specific Role in Neoadjuvant Chemoradiotherapy Treatments: An Exploratory Study on Rectal Cancer Patients

PubMed Central

Dreussi, Eva; Cecchin, Erika; Polesel, Jerry; Canzonieri, Vincenzo; Agostini, Marco; Boso, Caterina; Belluco, Claudio; Buonadonna, Angela; Lonardi, Sara; Bergamo, Francesca; Gagno, Sara; De Mattia, Elena; Pucciarelli, Salvatore; De Paoli, Antonino; Toffoli, Giuseppe

2016-01-01

Background: Pathological complete response (pCR) to neoadjuvant chemoradiotherapy (CRT) in locally advanced rectal cancer (LARC) is still ascribed to a minority of patients. A pathway based-approach could highlight the predictive role of germline single nucleotide polymorphisms (SNPs). The primary aim of this study was to define new predictive biomarkers considering treatment specificities. Secondary aim was to determine new potential predictive biomarkers independent from radiotherapy (RT) dosage and cotreatment with oxaliplatin. Methods: Thirty germ-line SNPs in twenty-one genes were selected according to a pathway-based approach. Genetic analyses were performed on 280 LARC patients who underwent fluoropyrimidine-based CRT. The potential predictive role of these SNPs in determining pathological tumor response was tested in Group 1 (94 patients undergoing also oxaliplatin), Group 2 (73 patients treated with high RT dosage), Group 3 (113 patients treated with standard RT dosage), and in the pooled population (280 patients). Results: Nine new predictive biomarkers were identified in the three groups. The most promising one was rs3136228-MSH6 (p = 0.004) arising from Group 3. In the pooled population, rs1801133-MTHFR showed only a trend (p = 0.073). Conclusion: This exploratory study highlighted new potential predictive biomarkers of neoadjuvant CRT and underlined the importance to strictly define treatment peculiarities in pharmacogenetic analyses. PMID:27608007

Aversive Startle Potentiation and Fear Pathology: Mediating Role of Threat Sensitivity and Moderating Impact of Depression

PubMed Central

Yancey, James R.; Vaidyanathan, Uma; Patrick, Christopher J.

2015-01-01

Enhanced startle during exposure to unpleasant cues (aversive startle potentiation; ASP) appears in the RDoC matrix as a physiological index of acute threat response. Increased ASP has been linked to focal fear disorders and to scale measures of dispositional fearfulness (i.e., threat sensitivity; THT+). However, some studies have reported reduced ASP for fear pathology accompanied by major depressive disorder (MDD) or pervasive distress. The current study evaluated whether (a) THT+ as indexed by reported dispositional fearfulness mediates the relationship between fear disorders (when unaccompanied by depression) and ASP, and (b) depression moderates relations of THT+ and fear disorders with ASP. Fear disorder participants without MDD showed enhanced ASP whereas those with MDD (or other distress conditions) showed evidence of reduced ASP. Continuous THT+ scores also predicted ASP, and this association: (a) was likewise moderated by depression/distress, and (b) accounted for the relationship between ASP and fear pathology without MDD. These findings point to a role for the RDoC construct of acute threat, operationalized dispositionally, in enhanced ASP shown by individuals with fear pathology unaccompanied by distress pathology. PMID:25448265

Developing and fostering a dynamic program for training in veterinary pathology and clinical pathology: veterinary students to post-graduate education.

PubMed

Lairmore, Michael D; Oglesbee, Michael; Weisbrode, Steve E; Wellman, Maxey; Rosol, Thomas; Stromberg, Paul

2007-01-01

Recent reports project a deficiency of veterinary pathologists, indicating a need to train highly qualified veterinary pathologists, particularly in academic veterinary medicine. The need to provide high-quality research training for veterinary pathologists has been recognized by the veterinary pathology training program of the Ohio State University (OSU) since its inception. The OSU program incorporates elements of both residency training and graduate education into a unified program. This review illustrates the components and structure of the training program and reflects on future challenges in training veterinary pathologists. Key elements of the OSU program include an experienced faculty, dedicated staff, and high-quality students who have a sense of common mission. The program is supported through cultural and infrastructure support. Financial compensation, limited research funding, and attractive work environments, including work-life balance, will undoubtedly continue to be forces in the marketplace for veterinary pathologists. To remain competitive and to expand the ability to train veterinary pathologists with research skills, programs must support strong faculty members, provide appropriate infrastructure support, and seek active partnerships with private industry to expand program opportunities. Shortages of trained faculty may be partially resolved by regional cooperation to share faculty expertise or through the use of communications technology to bridge distances between programs. To foster continued interest in academic careers, training programs will need to continue to evolve and respond to trainees' needs while maintaining strong allegiances to high-quality pathology training. Work-life balance, collegial environments that foster a culture of respect for veterinary pathology, and continued efforts to reach out to veterinary students to provide opportunities to learn about the diverse careers offered in veterinary pathology will pay long-term dividends for the future of the profession.

Developing and Fostering a Dynamic Program for Training in Veterinary Pathology and Clinical Pathology: Veterinary Students to Post-graduate Education

PubMed Central

Lairmore, Michael D.; Oglesbee, Michael; Weisbrode, Steve E.; Wellman, Maxey; Rosol, Thomas; Stromberg, Paul

2011-01-01

Recent reports project a deficiency of veterinary pathologists, indicating a need to train highly qualified veterinary pathologists, particularly in academic veterinary medicine. The need to provide high-quality research training for veterinary pathologists has been recognized by the veterinary pathology training program of the Ohio State University (OSU) since its inception. The OSU program incorporates elements of both residency training and graduate education into a unified program. This review illustrates the components and structure of the training program and reflects on future challenges in training veterinary pathologists. Key elements of the OSU program include an experienced faculty, dedicated staff, and high-quality students who have a sense of common mission. The program is supported through cultural and infrastructure support. Financial compensation, limited research funding, and attractive work environments, including work–life balance, will undoubtedly continue to be forces in the marketplace for veterinary pathologists. To remain competitive and to expand the ability to train veterinary pathologists with research skills, programs must support strong faculty members, provide appropriate infrastructure support, and seek active partnerships with private industry to expand program opportunities. Shortages of trained faculty may be partially resolved by regional cooperation to share faculty expertise or through the use of communications technology to bridge distances between programs. To foster continued interest in academic careers, training programs will need to continue to evolve and respond to trainees' needs while maintaining strong allegiances to high-quality pathology training. Work–life balance, collegial environments that foster a culture of respect for veterinary pathology, and continued efforts to reach out to veterinary students to provide opportunities to learn about the diverse careers offered in veterinary pathology will pay long-term dividends for the future of the profession. PMID:18287474

Psychological predictors of cultural diversity support at work.

PubMed

Hiemstra, Annemarie M F; Derous, Eva; Born, Marise Ph

2017-07-01

As diversity management activities become more prominent worldwide it is important to understand psychological reactions to them to ensure success, but empirical evidence is lacking. This study investigated employees' and managers' intentions and behavior to promote cultural diversity at work in a variety of organizations in the Netherlands, using Ajzen's theory of planned behavior. Predictors of intentions to promote cultural diversity at work (N = 670) and actual behavior after 6 months were assessed among managers and employees using self-reports in a 2-wave survey design. Participants' average age at Time 1 was 38.26 years (SD = 11.86), 56% was female, and there were 78.1% Dutch ethnic majority and 21.9% ethnic minority participants. Attitude to cultural diversity promotion at work and perceived behavioral control (PBC) related positively to both individuals' intentions to promote cultural diversity at work, which in turn predicted behavior. The strongest driver, however, was attitude. Managers' reported PBC and behavior were higher compared to employees. This study supported the applicability of the theory of planned behavior to predict intentions and behavior to promote cultural diversity at work. With an increasingly diverse workforce, this study aimed to advance our understanding of drivers of individual reactions and behavior to support cultural diversity at work. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Tau and Amyloid-β Cerebrospinal Fluid Biomarkers have Differential Relationships with Cognition in Mild Cognitive Impairment.

PubMed

Malpas, Charles B; Saling, Michael M; Velakoulis, Dennis; Desmond, Patricia; O'Brien, Terence J

2015-01-01

Alzheimer's disease (AD) is characterized by two primary pathologies: tau-related neurofibrillary tangles and the extracellular accumulation of amyloid-β (Aβ). The development of these pathologies is topologically distinct early in the disease, with Aβ beginning to accumulate as a diffuse, neocortical pathology, while tau-related pathology begins to form in mesial temporal regions. This study investigated the hypothesis that, by virtue of this distinction, there exist preferential associations between the primary pathologies and aspects of the cognitive phenotype. We investigated the relationship between cerebrospinal fluid (CSF) biomarkers for tau and Aβ pathologies with neurocognitive measures in 191 patients with mild cognitive impairment (MCI). Participants completed cognitive tests of new learning, information processing speed, and working memory. Separate regression models were computed and then followed up with mediation analyses to examine the predictive status of CSF biomarkers. The effect of Aβ on learning was mediated by phospho-tau (p = 0.008). In contrast, Aβ had a direct effect on information processing speed that was not mediated by phospho-tau (p = 0.59). No predictors were significant for working memory. This study provided evidence for a differential relationship of Aβ and phospho-tau pathologies on the neurocognitive phenotype of MCI. This supports the proposition that these primary AD pathologies maximally affect different aspects of cognition, and has potential implications for cognitive assessments and the use of biomarkers in disease-modifyingtherapeutic trials.

High-resolution Imaging of Neural Anatomy and Pathology of the Neck.

PubMed

Lee, Jeong Hyun; Cheng, Kai-Lung; Choi, Young Jun; Baek, Jung Hwan

2017-01-01

The neck has intricately connected neural structures, including cervical and brachial plexi, the sympathetic system, lower cranial nerves, and their branches. Except for brachial plexus, there has been little research regarding the normal imaging appearance or corresponding pathologies of neural structures in the neck. The development in imaging techniques with better spatial resolution and signal-to-noise ratio has made it possible to see many tiny nerves to predict complications related to image-guided procedures and to better assess treatment response, especially in the management of oncology patients. The purposes of this review is to present imaging-based anatomy of major nerves in the neck and explain their relevant clinical significance according to representative pathologies of regarded nerves in the neck.

Neurological soft signs in individuals with pathological gambling.

PubMed

Elman, Igor; Gurvits, Tamara V; Tschibelu, Evelyne; Spring, Justin D; Lasko, Natasha B; Pitman, Roger K

2013-01-01

Increased neurological soft signs (NSSs) have been found in a number of neuropsychiatric syndromes, including chemical addiction. The present study examined NSSs related to perceptual-motor and visuospatial processing in a behavioral addiction viz., pathological gambling (PG). As compared to mentally healthy individuals, pathological gamblers displayed significantly poorer ability to copy two- and three-dimensional figures, to recognize objects against a background noise, and to orient in space on a road-map test. Results indicated that PG is associated with subtle cerebral cortical abnormalities. Further prospective clinical research is needed to address the NSSs' origin and chronology (e.g., predate or follow the development of PG) as well as their response to therapeutic interventions and/or their ability to predict such a response.

Colorectal Cancer Classification and Cell Heterogeneity: A Systems Oncology Approach

PubMed Central

Blanco-Calvo, Moisés; Concha, Ángel; Figueroa, Angélica; Garrido, Federico; Valladares-Ayerbes, Manuel

2015-01-01

Colorectal cancer is a heterogeneous disease that manifests through diverse clinical scenarios. During many years, our knowledge about the variability of colorectal tumors was limited to the histopathological analysis from which generic classifications associated with different clinical expectations are derived. However, currently we are beginning to understand that under the intense pathological and clinical variability of these tumors there underlies strong genetic and biological heterogeneity. Thus, with the increasing available information of inter-tumor and intra-tumor heterogeneity, the classical pathological approach is being displaced in favor of novel molecular classifications. In the present article, we summarize the most relevant proposals of molecular classifications obtained from the analysis of colorectal tumors using powerful high throughput techniques and devices. We also discuss the role that cancer systems biology may play in the integration and interpretation of the high amount of data generated and the challenges to be addressed in the future development of precision oncology. In addition, we review the current state of implementation of these novel tools in the pathological laboratory and in clinical practice. PMID:26084042

Consensus Paper: Pathological Role of the Cerebellum in Autism

PubMed Central

Fatemi, S. Hossein; Aldinger, Kimberly A.; Ashwood, Paul; Bauman, Margaret L.; Blaha, Charles D.; Blatt, Gene J.; Chauhan, Abha; Chauhan, Ved; Dager, Stephen R.; Dickson, Price E.; Estes, Annette M.; Goldowitz, Dan; Heck, Detlef H.; Kemper, Thomas L.; King, Bryan H.; Martin, Loren A.; Millen, Kathleen J.; Mittleman, Guy; Mosconi, Matthew W.; Persico, Antonio M.; Sweeney, John A.; Webb, Sara J.; Welsh, John P.

2013-01-01

There has been significant advancement in various aspects of scientific knowledge concerning the role of cerebellum in the etiopathogenesis of autism. In the current consensus paper, we will observe the diversity of opinions regarding the involvement of this important site in the pathology of autism. Recent emergent findings in literature related to cerebellar involvement in autism are discussed, including: cerebellar pathology, cerebellar imaging and symptom expression in autism, cerebellar genetics, cerebellar immune function, oxidative stress and mitochondrial dysfunction, GABAergic and glutamatergic systems, cholinergic, dopaminergic, serotonergic, and oxytocin related changes in autism, motor control and cognitive deficits, cerebellar coordination of movements and cognition, gene-environment interactions, therapeutics in autism and relevant animal models of autism. Points of consensus include presence of abnormal cerebellar anatomy, abnormal neurotransmitter systems, oxidative stress, cerebellar motor and cognitive deficits, and neuroinflammation in subjects with autism. Undefined areas or areas requiring further investigation include lack of treatment options for core symptoms of autism, vermal hypoplasia and other vermal abnormalities as a consistent feature of autism, mechanisms underlying cerebellar contributions to cognition, and unknown mechanisms underlying neuroinflammation. PMID:22370873

[Gastritis and gastropathy].

PubMed

Mihály, Emese; Micsik, Tamás; Juhász, Márk; Herszényi, László; Tulassay, Zsolt

2014-01-12

Alterations of the stomach mucosa in response to different adverse effects result in various morphological and clinical symptoms. Gastric mucosa alterations can be classified on the bases of diverse viewpoints. It makes this overview difficult, that identical toxic effects may cause different mucosal changes and different toxic agents may produce similar mucosal appearance. The more accurate understanding of the pathological processes which develop in the stomach mucosa needs reconsideration. The authors make an attempt to define gastritis and gastropathy in order to classify and present their features. Gastritis is a histological definition indicating mucosal inflammation. Acute gastritis is caused by infections. The two most important forms of chronic gastritis are metaplastic atrophic gastritis with an autoimmune origin and Helicobacter pylori inflammation. Gastropathy is the name of different structural alterations of the mucosa. Its most important feature is the paucity of inflammatory signs. Gastropathies can be divided into 4 categories based on the nature of the underlying pathological effect, on its morphological appearance and the way of the development. Differential diagnosis is an important pathological and clinical task because different treatment methods and prognosis.

Nanoscale imaging of clinical specimens using pathology-optimized expansion microscopy

PubMed Central

Zhao, Yongxin; Bucur, Octavian; Irshad, Humayun; Chen, Fei; Weins, Astrid; Stancu, Andreea L.; Oh, Eun-Young; DiStasio, Marcello; Torous, Vanda; Glass, Benjamin; Stillman, Isaac E.; Schnitt, Stuart J.; Beck, Andrew H.; Boyden, Edward S.

2017-01-01

Expansion microscopy (ExM), a method for improving the resolution of light microscopy by physically expanding the specimen, has not been applied to clinical tissue samples. Here we report a clinically optimized form of ExM that supports nanoscale imaging of human tissue specimens that have been fixed with formalin, embedded in paraffin, stained with hematoxylin and eosin (H&E), and/or fresh frozen. The method, which we call expansion pathology (ExPath), converts clinical samples into an ExM-compatible state, then applies an ExM protocol with protein anchoring and mechanical homogenization steps optimized for clinical samples. ExPath enables ~70 nm resolution imaging of diverse biomolecules in intact tissues using conventional diffraction-limited microscopes, and standard antibody and fluorescent DNA in situ hybridization reagents. We use ExPath for optical diagnosis of kidney minimal-change disease, which previously required electron microscopy (EM), and demonstrate high-fidelity computational discrimination between early breast neoplastic lesions that to date have challenged human judgment. ExPath may enable the routine use of nanoscale imaging in pathology and clinical research. PMID:28714966

Consensus paper: pathological role of the cerebellum in autism.

PubMed

Fatemi, S Hossein; Aldinger, Kimberly A; Ashwood, Paul; Bauman, Margaret L; Blaha, Charles D; Blatt, Gene J; Chauhan, Abha; Chauhan, Ved; Dager, Stephen R; Dickson, Price E; Estes, Annette M; Goldowitz, Dan; Heck, Detlef H; Kemper, Thomas L; King, Bryan H; Martin, Loren A; Millen, Kathleen J; Mittleman, Guy; Mosconi, Matthew W; Persico, Antonio M; Sweeney, John A; Webb, Sara J; Welsh, John P

2012-09-01

There has been significant advancement in various aspects of scientific knowledge concerning the role of cerebellum in the etiopathogenesis of autism. In the current consensus paper, we will observe the diversity of opinions regarding the involvement of this important site in the pathology of autism. Recent emergent findings in literature related to cerebellar involvement in autism are discussed, including: cerebellar pathology, cerebellar imaging and symptom expression in autism, cerebellar genetics, cerebellar immune function, oxidative stress and mitochondrial dysfunction, GABAergic and glutamatergic systems, cholinergic, dopaminergic, serotonergic, and oxytocin-related changes in autism, motor control and cognitive deficits, cerebellar coordination of movements and cognition, gene-environment interactions, therapeutics in autism, and relevant animal models of autism. Points of consensus include presence of abnormal cerebellar anatomy, abnormal neurotransmitter systems, oxidative stress, cerebellar motor and cognitive deficits, and neuroinflammation in subjects with autism. Undefined areas or areas requiring further investigation include lack of treatment options for core symptoms of autism, vermal hypoplasia, and other vermal abnormalities as a consistent feature of autism, mechanisms underlying cerebellar contributions to cognition, and unknown mechanisms underlying neuroinflammation.

Nanoscale imaging of clinical specimens using pathology-optimized expansion microscopy.

PubMed

Zhao, Yongxin; Bucur, Octavian; Irshad, Humayun; Chen, Fei; Weins, Astrid; Stancu, Andreea L; Oh, Eun-Young; DiStasio, Marcello; Torous, Vanda; Glass, Benjamin; Stillman, Isaac E; Schnitt, Stuart J; Beck, Andrew H; Boyden, Edward S

2017-08-01

Expansion microscopy (ExM), a method for improving the resolution of light microscopy by physically expanding a specimen, has not been applied to clinical tissue samples. Here we report a clinically optimized form of ExM that supports nanoscale imaging of human tissue specimens that have been fixed with formalin, embedded in paraffin, stained with hematoxylin and eosin, and/or fresh frozen. The method, which we call expansion pathology (ExPath), converts clinical samples into an ExM-compatible state, then applies an ExM protocol with protein anchoring and mechanical homogenization steps optimized for clinical samples. ExPath enables ∼70-nm-resolution imaging of diverse biomolecules in intact tissues using conventional diffraction-limited microscopes and standard antibody and fluorescent DNA in situ hybridization reagents. We use ExPath for optical diagnosis of kidney minimal-change disease, a process that previously required electron microscopy, and we demonstrate high-fidelity computational discrimination between early breast neoplastic lesions for which pathologists often disagree in classification. ExPath may enable the routine use of nanoscale imaging in pathology and clinical research.

Methods for Maintaining Insect Cell Cultures

PubMed Central

Lynn, Dwight E.

2002-01-01

Insect cell cultures are now commonly used in insect physiology, developmental biology, pathology, and molecular biology. As the field has advanced from methods development to a standard procedure, so has the diversity of scientists using the technique. This paper describes methods that are effective for maintaining various insect cell lines. The procedures are differentiated between loosely or non-attached cell strains, attached cell strains, and strongly adherent cell strains. PMID:15455043

Macrophages - sensors and effectors coordinating skin damage and repair.

PubMed

Willenborg, Sebastian; Eming, Sabine A

2014-03-01

Restoration of skin integrity and homeostasis following injury is a vital process. Wound healing disorders, including chronic skin ulcers and pathological scarring, are of major clinical impact. The current therapeutic approaches are often not sufficient. The development of novel efficient therapies requires a thorough understanding of the underlying molecular mechanisms. A cardinal feature of non-healing skin ulcers and excessive scarring is a prolonged inflammatory response at the wound site, which aborts the healing response. Modulation of the local immune response may be an effective therapeutic strategy to correct impaired healing conditions. Yet, the specific mechanisms of inflammation, particularly the role of the diverse leukocyte lineages attracted to the site of tissue damage, have not been resolved. Recent findings in diverse experimental model systems and clinical studies have refined the understanding of monocyte/macrophage biology and the role of cells of the monocytic lineage in tissue regeneration. Thus, monocytes/macrophages are emerging as novel and interesting therapeutic targets to interfere in wound healing pathologies. In this article we will review the role of monocytes/macrophages in skin repair in the light of the recent literature and findings from our own group. This article will provide a rationale for monocyte/macrophage-based therapies to facilitate the healing response. © 2014 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

Telepathology Impacts and Implementation Challenges: A Scoping Review.

PubMed

Meyer, Julien; Paré, Guy

2015-12-01

Telepathology is a particular form of telemedicine that fundamentally alters the way pathology services are delivered. Prior reviews in this area have mostly focused on 2 themes, namely technical feasibility issues and diagnosis accuracy. To synthesize the literature on telepathology implementation challenges and broader organizational and societal impacts and to propose a research agenda to guide future efforts in this domain. Two complementary databases were systematically searched: MEDLINE (PubMed) and ABI/INFORM (ProQuest). Peer-reviewed articles and conference proceedings were considered. The final sample consisted of 159 papers published between 1992 and 2013. This review highlights the diversity of telepathology networks and the importance of considering these distinctions when interpreting research findings. Various network structures are associated with different benefits. Although the dominant rationale in single-site projects is financial, larger centralized and decentralized telepathology networks are targeting a more diverse set of benefits, including extending access to pathology to a whole region, achieving substantial economies of scale in workforce and equipment, and improving quality by standardizing care. Importantly, our synthesis reveals that the nature and scale of encountered implementation challenges also varies depending on the network structure. In smaller telepathology networks, organizational concerns are less prominent, and implementers are more focused on usability issues. As the network scope widens, organizational and legal issues gain prominence.

Beyond the zebrafish: diverse fish species for modeling human disease

PubMed Central

Schartl, Manfred

2014-01-01

ABSTRACT In recent years, zebrafish, and to a lesser extent medaka, have become widely used small animal models for human diseases. These organisms have convincingly demonstrated the usefulness of fish for improving our understanding of the molecular and cellular mechanisms leading to pathological conditions, and for the development of new diagnostic and therapeutic tools. Despite the usefulness of zebrafish and medaka in the investigation of a wide spectrum of traits, there is evidence to suggest that other fish species could be better suited for more targeted questions. With the emergence of new, improved sequencing technologies that enable genomic resources to be generated with increasing efficiency and speed, the potential of non-mainstream fish species as disease models can now be explored. A key feature of these fish species is that the pathological condition that they model is often related to specific evolutionary adaptations. By exploring these adaptations, new disease-causing and disease-modifier genes might be identified; thus, diverse fish species could be exploited to better understand the complexity of disease processes. In addition, non-mainstream fish models could allow us to study the impact of environmental factors, as well as genetic variation, on complex disease phenotypes. This Review will discuss the opportunities that such fish models offer for current and future biomedical research. PMID:24271780

Challenges in adapting existing clinical natural language processing systems to multiple, diverse health care settings.

PubMed

Carrell, David S; Schoen, Robert E; Leffler, Daniel A; Morris, Michele; Rose, Sherri; Baer, Andrew; Crockett, Seth D; Gourevitch, Rebecca A; Dean, Katie M; Mehrotra, Ateev

2017-09-01

Widespread application of clinical natural language processing (NLP) systems requires taking existing NLP systems and adapting them to diverse and heterogeneous settings. We describe the challenges faced and lessons learned in adapting an existing NLP system for measuring colonoscopy quality. Colonoscopy and pathology reports from 4 settings during 2013-2015, varying by geographic location, practice type, compensation structure, and electronic health record. Though successful, adaptation required considerably more time and effort than anticipated. Typical NLP challenges in assembling corpora, diverse report structures, and idiosyncratic linguistic content were greatly magnified. Strategies for addressing adaptation challenges include assessing site-specific diversity, setting realistic timelines, leveraging local electronic health record expertise, and undertaking extensive iterative development. More research is needed on how to make it easier to adapt NLP systems to new clinical settings. A key challenge in widespread application of NLP is adapting existing systems to new clinical settings. © The Author 2017. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com

A Common STEP in the Synaptic Pathology of Diverse Neuropsychiatric Disorders

PubMed Central

Johnson, Micah A.; Lombroso, Paul J.

2012-01-01

Synaptic function is critical for proper cognition, and synaptopathologies have been implicated in diverse neuropsychiatric disorders. STriatal-Enriched protein tyrosine Phosphatase (STEP) is a brain-enriched tyrosine phosphatase that normally opposes synaptic strengthening by dephosphorylating key neuronal signaling molecules. STEP targets include N-methyl D-aspartate receptors (NMDARs) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs), as well as extracellular signal-regulated kinase (ERK) and the tyrosine kinase Fyn. STEP-mediated dephosphorylation promotes the internalization of NMDARs and AMPARs and the inactivation of ERK and Fyn. Regulation of STEP is complex, and recent work has implicated STEP dysregulation in the pathophysiology of several neuropsychiatric disorders. Both high levels and low levels of STEP are found in a diverse group of illnesses. This review focuses on the role of STEP in three disorders in which STEP levels are elevated: Alzheimer’s disease, fragile X syndrome, and schizophrenia. The presence of elevated STEP in all three of these disorders raises the intriguing possibility that cognitive deficits resulting from diverse etiologies may share a common molecular pathway. PMID:23239949

Factors predictive of locoregional recurrence following neoadjuvant chemotherapy in patients with large operable or locally advanced breast cancer: An analysis of the EORTC 10994/BIG 1-00 study.

PubMed

Gillon, Pauline; Touati, Nathan; Breton-Callu, Christel; Slaets, Leen; Cameron, David; Bonnefoi, Hervé

2017-07-01

Identification of clinicopathological factors predicting for a locoregional recurrence (LRR) after neoadjuvant chemotherapy (NAC) could help to decide on the optimal locoregional radiotherapy. The objective of this trial is to identify those factors in the context of a phase III trial (European Organisation for Research and Treatment of Cancer 10994). Patients received NAC followed by surgery with or without radiotherapy. Radiotherapy was administered according to pre-specified guidelines. Patients with hormone receptor positive tumours received adjuvant hormonal therapy. A proportion of patients with human epidermal growth factor receptor 2 (HER2) positive cancer received adjuvant trastuzumab. The predictive factors for LRR were identified by multivariate analysis with time to LRR as first event as the primary end-point. The median follow-up was 4.4 years. In 1553 eligible patients, there were 76 LRRs with a 5-year cumulative incidence of 4.9% (95% confidence interval, CI [3.76-6.04]). In multivariate analysis, breast cancer subtype was a significant predictor of LRR (p < 0.0001): hazard ratio (HR) 6.44 (95% CI [2.83-14.69]) for triple negative, 6.26 (95% CI [2.81-13.93]) for HER2+ without trastuzumab (T) and 3.37 (95% CI [1.10-10.34]) for HER2+ with T cancers, all compared to luminal A patients. Lack of pathological response was also associated with significantly higher LRR risk in case of ≥4 pathologically positive nodes, HR 2.43 (95% CI [1.34-4.40], p < 0.0001). Breast cancer subtype and lack of pathological response are predictive factors for high LRR after NAC. Copyright © 2017 Elsevier Ltd. All rights reserved.

Tumor response ratio predicts overall survival in breast cancer patients treated with neoadjuvant chemotherapy.

PubMed

Miller, Marian; Ottesen, Rebecca A; Niland, Joyce C; Kruper, Laura; Chen, Steven L; Vito, Courtney

2014-10-01

Neoadjuvant chemotherapy (NAC) is commonly used to treat locally advanced breast cancer. Pathologic complete response (pCR) predicts improved overall survival (OS); however, prognosis of patients with partial response remains unclear. We evaluated whether tumor response ratio (TRR) is a better predictor of OS than current staging methods. Using the National Comprehensive Cancer Network Breast Cancer Outcomes Database, we identified patients with stage I-III breast cancer who had NAC and pretreatment imaging at City of Hope (1997-2010). Patient demographics, tumor characteristics, and OS were analyzed. TRR was calculated as residual in-breast disease divided by size on pre-NAC imaging. Four TRR groups were stratified; TRR 0 (pCR), TRR > 0-0.4 (strong partial response, SPR), TRR > 0.4-1.0 (weak partial response, WPR), or TRR > 1.0 (tumor growth, TG). OS was estimated by the Kaplan-Meier method and tested by the log-rank test. Cox regression was performed to evaluate associations between OS and TRR in a multivariable analysis while controlling for potential confounders. There were 218 eligible patients identified; 59 (27 %) had pCR, 61 (28 %) SPR, 72 (33 %) WPR, and 26 (12 %) TG. Five-year OS decreased continuously with increasing TRR:pCR (90 %), SPR (79 %), WPR (66 %), and TG (60 %). TRR was the only measure that significantly predicted OS (p = 0.0035); pathologic stage (p = 0.23) and pre-NAC clinical tumor stage (cT) (p = 0.87) were not significant. TRR continued to be statistically significant by multivariable analysis (p = 0.016). TRR takes into account both pretreatment and residual disease and more accurately predicts OS than pathologic stage and pre-NAC cT. TRR may be useful to more accurately assess prognosis and OS in breast cancer patients undergoing NAC.