Beyond "utilitarianism": maximizing the clinical impact of moral judgment research.

PubMed

Rosas, Alejandro; Koenigs, Michael

2014-01-01

The use of hypothetical moral dilemmas--which pit utilitarian considerations of welfare maximization against emotionally aversive "personal" harms--has become a widespread approach for studying the neuropsychological correlates of moral judgment in healthy subjects, as well as in clinical populations with social, cognitive, and affective deficits. In this article, we propose that a refinement of the standard stimulus set could provide an opportunity to more precisely identify the psychological factors underlying performance on this task, and thereby enhance the utility of this paradigm for clinical research. To test this proposal, we performed a re-analysis of previously published moral judgment data from two clinical populations: neurological patients with prefrontal brain damage and psychopathic criminals. The results provide intriguing preliminary support for further development of this assessment paradigm.

Effort-Based Decision-Making Paradigms for Clinical Trials in Schizophrenia: Part 1—Psychometric Characteristics of 5 Paradigms

PubMed Central

Reddy, L. Felice; Horan, William P.; Barch, Deanna M.; Buchanan, Robert W.; Dunayevich, Eduardo; Gold, James M.; Lyons, Naomi; Marder, Stephen R.; Treadway, Michael T.; Wynn, Jonathan K.; Young, Jared W.; Green, Michael F.

2015-01-01

Impairments in willingness to exert effort contribute to the motivational deficits characteristic of the negative symptoms of schizophrenia. The current study evaluated the psychometric properties of 5 new or adapted paradigms to determine their suitability for use in clinical trials of schizophrenia. This study included 94 clinically stable participants with schizophrenia and 40 healthy controls. The effort-based decision-making battery was administered twice to the schizophrenia group (baseline, 4-week retest) and once to the control group. The 5 paradigms included 1 that assesses cognitive effort, 1 perceptual effort, and 3 that assess physical effort. Each paradigm was evaluated on (1) patient vs healthy control group differences, (2) test-retest reliability, (3) utility as a repeated measure (ie, practice effects), and (4) tolerability. The 5 paradigms showed varying psychometric strengths and weaknesses. The Effort Expenditure for Rewards Task showed the best reliability and utility as a repeated measure, while the Grip Effort Task had significant patient-control group differences, and superior tolerability and administration duration. The other paradigms showed weaker psychometric characteristics in their current forms. These findings highlight challenges in adapting effort and motivation paradigms for use in clinical trials. PMID:26142081

The SickKids Genome Clinic: developing and evaluating a pediatric model for individualized genomic medicine.

PubMed

Bowdin, S C; Hayeems, R Z; Monfared, N; Cohn, R D; Meyn, M S

2016-01-01

Our increasing knowledge of how genomic variants affect human health and the falling costs of whole-genome sequencing are driving the development of individualized genomic medicine. This new clinical paradigm uses knowledge of an individual's genomic variants to anticipate, diagnose and manage disease. While individualized genetic medicine offers the promise of transformative change in health care, it forces us to reconsider existing ethical, scientific and clinical paradigms. The potential benefits of pre-symptomatic identification of at-risk individuals, improved diagnostics, individualized therapy, accurate prognosis and avoidance of adverse drug reactions coexist with the potential risks of uninterpretable results, psychological harm, outmoded counseling models and increased health care costs. Here we review the challenges, opportunities and limits of integrating genomic analysis into pediatric clinical practice and describe a model for implementing individualized genomic medicine. Our multidisciplinary team of bioinformaticians, health economists, health services and policy researchers, ethicists, geneticists, genetic counselors and clinicians has designed a 'Genome Clinic' research project that addresses multiple challenges in pediatric genomic medicine--ranging from development of bioinformatics tools for the clinical assessment of genomic variants and the discovery of disease genes to health policy inquiries, assessment of clinical care models, patient preference and the ethics of consent. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Design of clinical trials for therapeutic cancer vaccines development.

PubMed

Mackiewicz, Jacek; Mackiewicz, Andrzej

2009-12-25

Advances in molecular and cellular biology as well as biotechnology led to definition of a group of drugs referred to as medicinal products of advanced technologies. It includes gene therapy products, somatic cell therapeutics and tissue engineering. Therapeutic cancer vaccines including whole cell tumor cells vaccines or gene modified whole cells belong to somatic therapeutics and/or gene therapy products category. The drug development is a multistep complex process. It comprises of two phases: preclinical and clinical. Guidelines on preclinical testing of cell based immunotherapy medicinal products have been defined by regulatory agencies and are available. However, clinical testing of therapeutic cancer vaccines is still under debate. It presents a serious problem since recently clinical efficacy of the number of cancer vaccines has been demonstrated that focused a lot of public attention. In general clinical testing in the current form is very expensive, time consuming and poorly designed what may lead to overlooking of products clinically beneficial for patients. Accordingly regulatory authorities and researches including Cancer Vaccine Clinical Trial Working Group proposed three regulatory solutions to facilitate clinical development of cancer vaccines: cost-recovery program, conditional marketing authorization, and a new development paradigm. Paradigm includes a model in which cancer vaccines are investigated in two types of clinical trials: proof-of-principle and efficacy. The proof-of-principle trial objectives are: safety; dose selection and schedule of vaccination; and demonstration of proof-of-principle. Efficacy trials are randomized clinical trials with objectives of demonstrating clinical benefit either directly or through a surrogate. The clinical end points are still under debate.

Feminist poststructuralism: a methodological paradigm for examining clinical decision-making.

PubMed

Arslanian-Engoren, Cynthia

2002-03-01

To present the philosophical framework of feminist poststructuralism, discuss its use as an innovative research approach and its implications for nursing knowledge development and practice. This perspective examines the construction of meaning, power relationships, and the importance of language as it affects contemporary healthcare decisions. It seeks to identify and expose biases that marginalize the healthcare needs of women and contribute to healthcare disparities for this population. Additionally, a feminist poststructuralist perspective seeks to develop new knowledge for understanding gender differences. A feminist poststructuralist perspective represents an alternative paradigm for studying the phenomenon of clinical decision-making. An empirical application example of a feminist poststructuralist perspective is provided. This exemplar investigated emergency department registered nurses' triage decisions for men and women with symptoms suggestive of coronary heart disease.

Manufacturing, characterization and control of cell-based medicinal products: challenging paradigms toward commercial use.

PubMed

Salmikangas, Paula; Menezes-Ferreira, Margarida; Reischl, Ilona; Tsiftsoglou, Asterios; Kyselovic, Jan; Borg, John Joseph; Ruiz, Sol; Flory, Egbert; Trouvin, Jean-Hugues; Celis, Patrick; Ancans, Janis; Timon, Marcos; Pante, Guido; Sladowski, Dariusz; Lipnik-Stangelj, Metoda; Schneider, Christian K

2015-01-01

During the past decade, a large number of cell-based medicinal products have been tested in clinical trials for the treatment of various diseases and tissue defects. However, licensed products and those approaching marketing authorization are still few. One major area of challenge is the manufacturing and quality development of these complex products, for which significant manipulation of cells might be required. While the paradigms of quality, safety and efficacy must apply also to these innovative products, their demonstration may be demanding. Demonstration of comparability between production processes and batches may be difficult for cell-based medicinal products. Thus, the development should be built around a well-controlled manufacturing process and a qualified product to guarantee reproducible data from nonclinical and clinical studies.

Effort-Based Decision-Making Paradigms for Clinical Trials in Schizophrenia: Part 1—Psychometric Characteristics of 5 Paradigms.

PubMed

Reddy, L Felice; Horan, William P; Barch, Deanna M; Buchanan, Robert W; Dunayevich, Eduardo; Gold, James M; Lyons, Naomi; Marder, Stephen R; Treadway, Michael T; Wynn, Jonathan K; Young, Jared W; Green, Michael F

2015-09-01

Impairments in willingness to exert effort contribute to the motivational deficits characteristic of the negative symptoms of schizophrenia. The current study evaluated the psychometric properties of 5 new or adapted paradigms to determine their suitability for use in clinical trials of schizophrenia. This study included 94 clinically stable participants with schizophrenia and 40 healthy controls. The effort-based decision-making battery was administered twice to the schizophrenia group (baseline, 4-week retest) and once to the control group. The 5 paradigms included 1 that assesses cognitive effort, 1 perceptual effort, and 3 that assess physical effort. Each paradigm was evaluated on (1) patient vs healthy control group differences, (2) test-retest reliability, (3) utility as a repeated measure (ie, practice effects), and (4) tolerability. The 5 paradigms showed varying psychometric strengths and weaknesses. The Effort Expenditure for Rewards Task showed the best reliability and utility as a repeated measure, while the Grip Effort Task had significant patient-control group differences, and superior tolerability and administration duration. The other paradigms showed weaker psychometric characteristics in their current forms. These findings highlight challenges in adapting effort and motivation paradigms for use in clinical trials. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center 2015.

Renal blood flow, fractional excretion of sodium and acute kidney injury: time for a new paradigm?

PubMed

Prowle, John; Bagshaw, Sean M; Bellomo, Rinaldo

2012-12-01

Global renal blood flow is considered pivotal to renal function. Decreased global renal blood flow (decreased perfusion) is further considered the major mechanism of reduced glomerular filtration rate responsible for the development of acute kidney injury (AKI) in critically ill patients. Additionally, urinary biochemical tests are widely taught to allow the differential diagnosis of prerenal (functional) AKI and intrinsic [structural AKI (so-called acute tubular necrosis)]. In this review we will examine recent evidence regarding these two key clinical paradigms. Recent animal experiments and clinical studies in humans using cine-phase contrast magnetic resonance technology are not consistent with the decreased perfusion paradigm. They suggest instead that changes in the intra-renal circulation including modification in efferent arteriolar function and intra-renal shunting are much more likely to be responsible for AKI, especially in sepsis. Similarly, recent human studies indicate the urinary biochemistry has limited diagnostic or prognostic ability and is dissociated form biomarker and microscopic evidence of tubular injury. Intra-renal microcirculatory changes are likely more important than changes in global blood flow in the development of AKI. Urinary biochemistry is not a clinically useful diagnostic or prognostic tool in critically ill patients at risk of or with AKI.

Clinical Growth: An Evolutionary Concept Analysis.

PubMed

Barkimer, Jessica

2016-01-01

Clinical growth is an essential component of nursing education, although challenging to evaluate. Considering the paradigm shift toward constructivism and student-centered learning, clinical growth requires an examination within contemporary practices. A concept analysis of clinical growth in nursing education produced defining attributes, antecedents, and consequences. Attributes included higher-level thinking, socialization, skill development, self-reflection, self-investment, interpersonal communication, and linking theory to practice. Identification of critical attributes allows educators to adapt to student-centered learning in the clinical environment. These findings allow educators to determine significant research questions, develop situation-specific theories, and identify strategies to enhance student learning in the clinical environment.

Cancer research in need of a scientific revolution: Using 'paradigm shift' as a method of investigation.

PubMed

Wion, Didier; Appaix, Florence; Burruss, Meriwether; Berger, Francois; van der Sanden, Boudewijn

2015-09-01

Despite important human and financial resources and considerable accumulation of scientific publications, patents, and clinical trials, cancer research has been slow in achieving a therapeutic revolution similar to the one that occurred in the last century for infectious diseases. It has been proposed that science proceeds not only by accumulating data but also through paradigm shifts. Here, we propose to use the concept of 'paradigm shift' as a method of investigation when dominant paradigms fail to achieve their promises. The first step in using the 'paradigm shift' method in cancer research requires identifying its founding paradigms. In this review, two of these founding paradigms will be discussed: (i) the reification of cancer as a tumour mass and (ii) the translation of the concepts issued from infectious disease in cancer research. We show how these founding paradigms can generate biases that lead to over-diagnosis and over-treatment and also hamper the development of curative cancer therapies. We apply the 'paradigm shift' method to produce perspective reversals consistent with current experimental evidence. The 'paradigm shift' method enlightens the existence of a tumour physiologic-prophylactic-pathologic continuum. It integrates the target/antitarget concept and that cancer is also an extracellular disease. The 'paradigm shift' method has immediate implications for cancer prevention and therapy. It could be a general method of investigation for other diseases awaiting therapy.

Clinical Trials for Predictive Medicine—New Challenges and Paradigms*

PubMed Central

Simon, Richard

2014-01-01

Background Developments in biotechnology and genomics have increased the focus of biostatisticians on prediction problems. This has led to many exciting developments for predictive modeling where the number of variables is larger than the number of cases. Heterogeneity of human diseases and new technology for characterizing them presents new opportunities and challenges for the design and analysis of clinical trials. Purpose In oncology, treatment of broad populations with regimens that do not benefit most patients is less economically sustainable with expensive molecularly targeted therapeutics. The established molecular heterogeneity of human diseases requires the development of new paradigms for the design and analysis of randomized clinical trials as a reliable basis for predictive medicine[1, 2]. Results We have reviewed prospective designs for the development of new therapeutics with candidate predictive biomarkers. We have also outlined a prediction based approach to the analysis of randomized clinical trials that both preserves the type I error and provides a reliable internally validated basis for predicting which patients are most likely or unlikely to benefit from the new regimen. Conclusions Developing new treatments with predictive biomarkers for identifying the patients who are most likely or least likely to benefit makes drug development more complex. But for many new oncology drugs it is the only science based approach and should increase the chance of success. It may also lead to more consistency in results among trials and has obvious benefits for reducing the number of patients who ultimately receive expensive drugs which expose them risks of adverse events but no benefit. This approach also has great potential value for controlling societal expenditures on health care. Development of treatments with predictive biomarkers requires major changes in the standard paradigms for the design and analysis of clinical trials. Some of the key assumptions upon which current methods are based are no longer valid. In addition to reviewing a variety of new clinical trial designs for co-development of treatments and predictive biomarkers, we have outlined a prediction based approach to the analysis of randomized clinical trials. This is a very structured approach whose use requires careful prospective planning. It requires further development but may serve as a basis for a new generation of predictive clinical trials which provide the kinds of reliable individualized information which physicians and patients have long sought, but which have not been available from the past use of post-hoc subset analysis. PMID:20338899

Impact of Different Visual Field Testing Paradigms on Sample Size Requirements for Glaucoma Clinical Trials.

PubMed

Wu, Zhichao; Medeiros, Felipe A

2018-03-20

Visual field testing is an important endpoint in glaucoma clinical trials, and the testing paradigm used can have a significant impact on the sample size requirements. To investigate this, this study included 353 eyes of 247 glaucoma patients seen over a 3-year period to extract real-world visual field rates of change and variability estimates to provide sample size estimates from computer simulations. The clinical trial scenario assumed that a new treatment was added to one of two groups that were both under routine clinical care, with various treatment effects examined. Three different visual field testing paradigms were evaluated: a) evenly spaced testing, b) United Kingdom Glaucoma Treatment Study (UKGTS) follow-up scheme, which adds clustered tests at the beginning and end of follow-up in addition to evenly spaced testing, and c) clustered testing paradigm, with clusters of tests at the beginning and end of the trial period and two intermediary visits. The sample size requirements were reduced by 17-19% and 39-40% using the UKGTS and clustered testing paradigms, respectively, when compared to the evenly spaced approach. These findings highlight how the clustered testing paradigm can substantially reduce sample size requirements and improve the feasibility of future glaucoma clinical trials.

A suggested model for physical examination and conservative treatment of athletic pubalgia.

PubMed

Hegedus, Eric J; Stern, Ben; Reiman, Michael P; Tarara, Dan; Wright, Alexis A

2013-02-01

Athletic pubalgia (AP) is a chronic debilitating syndrome that affects many athletes. As a syndrome, AP is difficult to diagnose both with clinical examination and imaging. AP is also a challenge for conservative intervention with randomized controlled trials showing mixed success rates. In other syndromes where clinical diagnosis and conservative treatment have been less than clear, a paradigm has been suggested as a framework for clinical decision making. To propose a new clinical diagnostic and treatment paradigm for the conservative management of AP. Relevant studies were viewed with regard to diagnosis and intervention and where a gap in evidence existed, clinical expertise was used to fill that gap and duly noted. A new paradigm is proposed to assist with clinical diagnosis and non-surgical intervention in patients suffering with AP. The level of evidence supporting this paradigm, according to the SORT taxonomy, is primarily level 2B. Further testing is warranted but following the suggested paradigm should lead to a clearer diagnosis of AP and allow more meaningful research into homogeneous patient populations within the AP diagnostic cluster. Strength-of-Recommendation Taxonomy (SORT): 2B. Copyright © 2012 Elsevier Ltd. All rights reserved.

Role of semantic paradigms for optimization of language mapping in clinical FMRI studies.

PubMed

Zacà, D; Jarso, S; Pillai, J J

2013-10-01

The optimal paradigm choice for language mapping in clinical fMRI studies is challenging due to the variability in activation among different paradigms, the contribution to activation of cognitive processes other than language, and the difficulties in monitoring patient performance. In this study, we compared language localization and lateralization between 2 commonly used clinical language paradigms and 3 newly designed dual-choice semantic paradigms to define a streamlined and adequate language-mapping protocol. Twelve healthy volunteers performed 5 language paradigms: Silent Word Generation, Sentence Completion, Visual Antonym Pair, Auditory Antonym Pair, and Noun-Verb Association. Group analysis was performed to assess statistically significant differences in fMRI percentage signal change and lateralization index among these paradigms in 5 ROIs: inferior frontal gyrus, superior frontal gyrus, middle frontal gyrus for expressive language activation, middle temporal gyrus, and superior temporal gyrus for receptive language activation. In the expressive ROIs, Silent Word Generation was the most robust and best lateralizing paradigm (greater percentage signal change and lateralization index than semantic paradigms at P < .01 and P < .05 levels, respectively). In the receptive region of interest, Sentence Completion and Noun-Verb Association were the most robust activators (greater percentage signal change than other paradigms, P < .01). All except Auditory Antonym Pair were good lateralizing tasks (the lateralization index was significantly lower than other paradigms, P < .05). The combination of Silent Word Generation and ≥1 visual semantic paradigm, such as Sentence Completion and Noun-Verb Association, is adequate to determine language localization and lateralization; Noun-Verb Association has the additional advantage of objective monitoring of patient performance.

Computer-based analysis of general movements reveals stereotypies predicting cerebral palsy.

PubMed

Philippi, Heike; Karch, Dominik; Kang, Keun-Sun; Wochner, Katarzyna; Pietz, Joachim; Dickhaus, Hartmut; Hadders-Algra, Mijna

2014-10-01

To evaluate a kinematic paradigm of automatic general movements analysis in comparison to clinical assessment in 3-month-old infants and its prediction for neurodevelopmental outcome. Preterm infants at high risk (n=49; 26 males, 23 females) and term infants at low risk (n=18; eight males, 10 females) of developmental impairment were recruited from hospitals around Heidelberg, Germany. Kinematic analysis of general movements by magnet tracking and clinical video-based assessment of general movements were performed at 3 months of age. Neurodevelopmental outcome was evaluated at 2 years. By comparing the general movements of small samples of children with and without cerebral palsy (CP), we developed a kinematic paradigm typical for infants at risk of developing CP. We tested the validity of this paradigm as a tool to predict CP and neurodevelopmental impairment. Clinical assessment correctly identified almost all infants with neurodevelopmental impairment including CP, but did not predict if the infant would be affected by CP or not. The kinematic analysis, in particular the stereotypy score of arm movements, was an excellent predictor of CP, whereas stereotyped repetitive movements of the legs predicted any neurodevelopmental impairment. The automatic assessment of the stereotypy score by magnet tracking in 3-month-old spontaneously moving infants at high risk of developmental abnormalities allowed a valid detection of infants affected and unaffected by CP. © 2014 Mac Keith Press.

Adapting Social Neuroscience Measures for Schizophrenia Clinical Trials, Part 2: Trolling the Depths of Psychometric Properties

PubMed Central

Kern, Robert S.

2013-01-01

The psychometric properties of 4 paradigms adapted from the social neuroscience literature were evaluated to determine their suitability for use in clinical trials of schizophrenia. This 2-site study (University of California, Los Angeles and University of North Carolina) included 173 clinically stable schizophrenia outpatients and 88 healthy controls. The social cognition battery was administered twice to the schizophrenia group (baseline, 4-week retest) and once to the control group. The 4 paradigms included 2 that assess perception of nonverbal social and action cues (basic biological motion and emotion in biological motion) and 2 that involve higher level inferences about self and others’ mental states (self-referential memory and empathic accuracy). Each paradigm was evaluated on (1) patient vs healthy control group differences, (2) test-retest reliability, (3) utility as a repeated measure, and (4) tolerability. Of the 4 paradigms, empathic accuracy demonstrated the strongest characteristics, including large between-group differences, adequate test-retest reliability (.72), negligible practice effects, and good tolerability ratings. The other paradigms showed weaker psychometric characteristics in their current forms. These findings highlight challenges in adapting social neuroscience paradigms for use in clinical trials. PMID:24072805

On the relationship between the causal-inference and meta-analytic paradigms for the validation of surrogate endpoints.

PubMed

Alonso, Ariel; Van der Elst, Wim; Molenberghs, Geert; Buyse, Marc; Burzykowski, Tomasz

2015-03-01

The increasing cost of drug development has raised the demand for surrogate endpoints when evaluating new drugs in clinical trials. However, over the years, it has become clear that surrogate endpoints need to be statistically evaluated and deemed valid, before they can be used as substitutes of "true" endpoints in clinical studies. Nowadays, two paradigms, based on causal-inference and meta-analysis, dominate the scene. Nonetheless, although the literature emanating from these paradigms is wide, till now the relationship between them has largely been left unexplored. In the present work, we discuss the conceptual framework underlying both approaches and study the relationship between them using theoretical elements and the analysis of a real case study. Furthermore, we show that the meta-analytic approach can be embedded within a causal-inference framework on the one hand and that it can be heuristically justified why surrogate endpoints successfully evaluated using this approach will often be appealing from a causal-inference perspective as well, on the other. A newly developed and user friendly R package Surrogate is provided to carry out the evaluation exercise. © 2014, The International Biometric Society.

Prevalence of neuropathic features of back pain in clinical populations: implications for the diagnostic triage paradigm.

PubMed

Hush, Julia M; Marcuzzi, Anna

2012-07-01

SUMMARY Contemporary clinical assessment of back pain is based on the diagnostic triage paradigm. The most common diagnostic classification is nonspecific back pain, considered to be of nociceptive etiology. A small proportion are diagnosed with radicular pain, of neuropathic origin. In this study we review the body of literature on the prevalence of neuropathic features of back pain, revealing that the point prevalence is 17% in primary care, 34% in mixed clinical settings and 53% in tertiary care. There is evidence that neuropathic features of back pain are not restricted to typical clinical radicular pain phenotypes and may be under-recognized, particularly in primary care. The consequence of this is that in the clinic, diagnostic triage may erroneously classify patients with nonspecific back pain or radicular pain. A promising alternative is the development of mechanism-based pain phenotyping in patients with back pain. Timely identification of contributory pain mechanisms may enable greater opportunity to select appropriate therapeutic targets and improve patient outcomes.

Effort-Based Decision Making in Schizophrenia: Evaluation of Paradigms to Measure Motivational Deficits

PubMed Central

Green, Michael F.; Horan, William P.

2015-01-01

Effort-based decision making requires one to decide how much effort to expend for a certain amount of reward. As the amount of reward goes up most people are willing to exert more effort. This relationship between reward level and effort expenditure can be measured in specialized performance-based tasks that have only recently been applied to schizophrenia. Such tasks provide a way to measure objectively motivational deficits in schizophrenia, which now are only assessed with clinical interviews of negative symptoms. The articles in this theme provide reviews of the relevant animal and human literatures (first 2 articles), and then a psychometric evaluation of 5 effort-based decision making paradigms (last 2 articles). This theme section is intended to stimulate interest in this emerging area among basic scientists developing paradigms for preclinical studies, human experimentalists trying to disentangle factors that contribute to performance on effort-based tasks, and investigators looking for objective endpoints for clinical trials of negative symptoms in schizophrenia. PMID:26108868

Clinical Trials of Precision Medicine through Molecular Profiling: Focus on Breast Cancer.

PubMed

Zardavas, Dimitrios; Piccart-Gebhart, Martine

2015-01-01

High-throughput technologies of molecular profiling in cancer, such as gene-expression profiling and next-generation sequencing, are expanding our knowledge of the molecular landscapes of several cancer types. This increasing knowledge coupled with the development of several molecularly targeted agents hold the promise for personalized cancer medicine to be fully realized. Moreover, an expanding armamentarium of targeted agents has been approved for the treatment of specific molecular cancer subgroups in different diagnoses. According to this paradigm, treatment selection should be dictated by the specific molecular aberrations found in each patient's tumor. The classical clinical trials paradigm of patients' eligibility being based on clinicopathologic parameters is being abandoned, with current clinical trials enrolling patients on the basis of specific molecular aberrations. New, innovative trial designs have been generated to better tackle the multiple challenges induced by the increasing molecular fragmentation of cancer, namely: (1) longitudinal cohort studies with or without downstream trials, (2) studies assessing the clinical utility of molecular profiling, (3) master or umbrella trials, (4) basket trials, (5) N-of-1 trials, and (6) adaptive design trials. This article provides an overview of the challenges for clinical trials in the era of molecular profiling of cancer. Subsequently, innovative trial designs with respective examples and their potential to expedite efficient clinical development of targeted anticancer agents is discussed.

Challenges in the current antiangiogenic treatment paradigm for patients with non-small cell lung cancer.

PubMed

Wozniak, Antoinette

2012-05-01

Patients with non-small cell lung cancer (NSCLC) often present with advanced disease and cure rates are dismal with currently available treatment. Novel therapies including small molecule tyrosine kinase inhibitors and monoclonal antibodies are being developed to target angiogenesis, an essential step in tumorigenesis and metastasis. The only antiangiogenic agent currently approved for treatment of NSCLC is bevacizumab, although numerous other antiangiogenic inhibitors (e.g., sorafenib, sunitinib, cediranib, motesanib, BIBF 1120) are in clinical trials. Individualized treatment algorithms may improve patient outcomes and new evidence suggests that biomarkers may guide treatment decisions. We present an overview of the molecular pathways involved in angiogenesis, discuss clinical trials of bevacizumab and developmental antiangiogenic agents, and address the challenges of developing individualized treatment paradigms for NSCLC, particularly the use of biomarkers. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Pharmacogenomics: a new clinical or regulatory paradigm? European experiences of pharmacogenomics in drug regulation and regulatory initiatives.

PubMed

Prasad, Krishna; Breckenridge, Alasdair

2011-10-01

Are regulatory agencies and processes up to speed? This is an often asked question. Recent advances in science and the improved knowledge of the human genome have a considerable influence on drug development and their impact on the regulatory aspect is also significant for several reasons, including changing stakeholder expectations and treatment paradigms. One of the challenges faced by the regulators is the need to adapt regulatory processes to accommodate the newer methodologies and techniques while ensuring that the biomarkers, tests and/or diagnostics, and the clinical trials are appropriate and fit for purpose. The change in emphasis in pharmacological treatment from a phenotype-based approach to newer methods is attractive but is it ready for universal adoption? This paper details some of the regulatory responses to the developments in this area. Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.

Developmental origins of health and disease: a paradigm for understanding disease cause and prevention.

PubMed

Heindel, Jerrold J; Vandenberg, Laura N

2015-04-01

Although diseases may appear clinically throughout the lifespan, it is clear that many diseases have origins during development. Altered nutrition, as well as exposure to environmental chemicals, drugs, infections, or stress during specific times of development, can lead to functional changes in tissues, predisposing those tissues to diseases that manifest later in life. This review will focus on the role of altered nutrition and exposures to environmental chemicals during development in the role of disease and dysfunction. The effects of altered nutrition or exposure to environmental chemicals during development are likely because of altered programming of epigenetic marks, which persist across the lifespan. Indeed some changes can be transmitted to future generations. The evidence in support of the developmental origins of the health and disease paradigm is sufficiently robust and repeatable across species, including humans, to suggest a need for greater emphasis in the clinical area. As a result of these data, obesity, diabetes, cardiovascular morbidity, and neuropsychiatric diseases can all be considered pediatric diseases. Disease prevention must start with improved nutrition and reduced exposure to environmental chemicals during development.

Developmental Origins of Health and Disease: A Paradigm for Understanding Disease Etiology and Prevention

PubMed Central

Heindel, Jerrold J.; Vandenberg, Laura N.

2015-01-01

Purpose of Review While diseases may appear clinically throughout the lifespan, it is clear that many diseases have origins during development. Altered nutrition, as well as exposure to environmental chemicals, drugs, infections, or stress during specific times of development can lead to functional changes in tissues, predisposing those tissues to diseases that manifest later in life. This review will focus on the role of altered nutrition and exposures to environmental chemicals during development in the role of disease/dysfunctions. Recent Findings Effects of altered nutrition or exposure to environmental chemicals during development are likely due to altered programming of epigenetic marks which persist across the lifespan. Indeed some changes can be transmitted to future generations. Summary Evidence in support of the DOHaD paradigm is sufficiently robust and repeatable across species including humans, suggesting a need for greater emphasis in the clinical area. Because of these data, obesity, diabetes, cardiovascular morbidity, and neuropsychiatric diseases can all be considered pediatric diseases. Disease prevention must start with improved nutrition and reduced exposures to environmental chemicals during development. PMID:25635586

Empowerment of Patients with Hypertension through BPM, IoT and Remote Sensing.

PubMed

Ruiz-Fernández, Daniel; Marcos-Jorquera, Diego; Gilart-Iglesias, Virgilio; Vives-Boix, Víctor; Ramírez-Navarro, Javier

2017-10-04

Hypertension affects one in five adults worldwide. Healthcare processes require interdisciplinary cooperation and coordination between medical teams, clinical processes, and patients. The lack of patients' empowerment and adherence to treatment makes necessary to integrate patients, data collecting devices and clinical processes. For this reason, in this paper we propose a model based on Business Process Management paradigm, together with a group of technologies, techniques and IT principles which increase the benefits of the paradigm. To achieve the proposed model, the clinical process of the hypertension is analyzed with the objective of detecting weaknesses and improving the process. Once the process is analyzed, an architecture that joins health devices and environmental sensors, together with an information system, has been developed. To test the architecture, a web system connected with health monitors and environment sensors, and with a mobile app have been implemented.

Empowerment of Patients with Hypertension through BPM, IoT and Remote Sensing

PubMed Central

Ramírez-Navarro, Javier

2017-01-01

Hypertension affects one in five adults worldwide. Healthcare processes require interdisciplinary cooperation and coordination between medical teams, clinical processes, and patients. The lack of patients’ empowerment and adherence to treatment makes necessary to integrate patients, data collecting devices and clinical processes. For this reason, in this paper we propose a model based on Business Process Management paradigm, together with a group of technologies, techniques and IT principles which increase the benefits of the paradigm. To achieve the proposed model, the clinical process of the hypertension is analyzed with the objective of detecting weaknesses and improving the process. Once the process is analyzed, an architecture that joins health devices and environmental sensors, together with an information system, has been developed. To test the architecture, a web system connected with health monitors and environment sensors, and with a mobile app have been implemented. PMID:28976940

TU-C-18C-01: Medical Physics 1.0 to 2.0: Introduction and Panel Discussion

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

Samei, E; Pfeiffer, D; Frey, G

2014-06-15

Medical Physics 2.0, a new frontier in clinical imaging physics: Diagnostic imaging has always been a technological highlight of modern medicine. Imaging systems, with their ever-expanding advancement in terms of technology and application, increasingly require skilled expertise to understand the delicacy of their operation, monitor their performance, design their effective use, and ensure their overall quality and safety, scientifically and in quantitative terms. Physicists can play a crucial role in that process. But that role has largely remained a severely untapped resource. Many imaging centers fail to appreciate this potential, with medical physics groups either nonexistent or highly understaffed andmore » their services poorly integrated into the patient care process. As a field, we have yet to define and enact how the clinical physicist can engage as an active, effective, and integral member of the clinical team, and how the services that she/he provides can be financially accounted for. Physicists do and will always contribute to research and development. However, their indispensible contribution to clinical imaging operations is something that has not been adequately established. That, in conjunction with new realities of healthcare practice, indicates a growing need to establish an updated approach to clinical medical imaging physics. This presentation aims to describe a vision as how clinical imaging physics can expand beyond traditional insular models of inspection and acceptance testing, oriented toward compliance, towards team-based models of operational engagement addressing topics such as new non-classical challenges of new technologies, quantitative imaging, and operational optimization. The Medical Physics 2.0 paradigm extends clinical medical physics from isolated characterization of inherent properties of the equipment to effective use of the equipment and to retrospective evaluation of clinical performance. This is an existential transition of the field that speaks to the new paradigms of value-based and evidence-based medicine, comparative effectiveness, and meaningful use. The panel discussion that follows includes prominent practitioners, thinkers, and leaders that would lead the discussion on how Medical Physics 2.0 can be actualized. Topics of discussion will include the administrative, financial, regulatory, and accreditation requirements of the new paradigm, effective models of practice, and the steps that we need to take to make MP 2.0 a reality. Learning Objectives: To understand the new paradigm of clinical medical physics practice extending from traditional insular models of compliance towards teambased models of operational engagement. To understand how clinical physics can most effectively contribute to clinical care. Learn to identify strengths and weaknesses in studies designed to measure the effect of low doses of ionizing radiation To recognize the impediments to Medical Physics 2.0 paradigm.« less

American Society of Functional Neuroradiology-Recommended fMRI Paradigm Algorithms for Presurgical Language Assessment.

PubMed

Black, D F; Vachha, B; Mian, A; Faro, S H; Maheshwari, M; Sair, H I; Petrella, J R; Pillai, J J; Welker, K

2017-10-01

Functional MR imaging is increasingly being used for presurgical language assessment in the treatment of patients with brain tumors, epilepsy, vascular malformations, and other conditions. The inherent complexity of fMRI, which includes numerous processing steps and selective analyses, is compounded by institution-unique approaches to patient training, paradigm choice, and an eclectic array of postprocessing options from various vendors. Consequently, institutions perform fMRI in such markedly different manners that data sharing, comparison, and generalization of results are difficult. The American Society of Functional Neuroradiology proposes widespread adoption of common fMRI language paradigms as the first step in countering this lost opportunity to advance our knowledge and improve patient care. A taskforce of American Society of Functional Neuroradiology members from multiple institutions used a broad literature review, member polls, and expert opinion to converge on 2 sets of standard language paradigms that strike a balance between ease of application and clinical usefulness. The taskforce generated an adult language paradigm algorithm for presurgical language assessment including the following tasks: Sentence Completion, Silent Word Generation, Rhyming, Object Naming, and/or Passive Story Listening. The pediatric algorithm includes the following tasks: Sentence Completion, Rhyming, Antonym Generation, or Passive Story Listening. Convergence of fMRI language paradigms across institutions offers the first step in providing a "Rosetta Stone" that provides a common reference point with which to compare and contrast the usefulness and reliability of fMRI data. From this common language task battery, future refinements and improvements are anticipated, particularly as objective measures of reliability become available. Some commonality of practice is a necessary first step to develop a foundation on which to improve the clinical utility of this field. © 2017 by American Journal of Neuroradiology.

Mismatch Negativity and P3a in Adolescents and Young Adults with Autism Spectrum Disorders: Behavioral Correlates and Clinical Implications

ERIC Educational Resources Information Center

Chien, Yi-Ling; Hsieh, Ming Hsien; Gau, Susan Shur-Fen

2018-01-01

In a sample of 37 adolescents and young adults with autism spectrum disorder (ASD) and 35 typically-developing controls (TDC), we investigated sensory symptoms by clinical measures, and Mismatch Negativity and P3a component at Fz with the frequency and duration oddball paradigms of event-related potentials. Results showed that compared to TDC, ASD…

Chemical Dependency and Eating Disorders: Are They Really so Different?

ERIC Educational Resources Information Center

Cooper, Stewart E.

1989-01-01

Develops biopsychosocial perspective to help counselors integrate assessment, treatment, evaluation, and research with chemical dependency and eating disorders addictions. Claims that, although different in content and symptoms, the underlying similarities between these clinical syndromes are clearly seen through this paradigm. (Author)

Emergence of a scientific and commercial research and development infrastructure for human gene therapy.

PubMed

Crofts, Christine; Krimsky, Sheldon

2005-02-01

A research and clinical subfield known as "human gene therapy" has grown rapidly since 1990, when the first human trials were approved in the United States. Using quantitative data, this paper describes and analyzes the research and commercial infrastructure, including academic centers, publications, intellectual property, and biotechnology firms, that has developed around the goal of discovering clinical applications for the modification and transport of DNA to somatic cells. Despite setbacks and few documented successes, the subfield of human gene therapy continues to serve as an influential clinical paradigm for the treatment of inherited and noninherited diseases.

Multi-Step Usage of in Vivo Models During Rational Drug Design and Discovery

PubMed Central

Williams, Charles H.; Hong, Charles C.

2011-01-01

In this article we propose a systematic development method for rational drug design while reviewing paradigms in industry, emerging techniques and technologies in the field. Although the process of drug development today has been accelerated by emergence of computational methodologies, it is a herculean challenge requiring exorbitant resources; and often fails to yield clinically viable results. The current paradigm of target based drug design is often misguided and tends to yield compounds that have poor absorption, distribution, metabolism, and excretion, toxicology (ADMET) properties. Therefore, an in vivo organism based approach allowing for a multidisciplinary inquiry into potent and selective molecules is an excellent place to begin rational drug design. We will review how organisms like the zebrafish and Caenorhabditis elegans can not only be starting points, but can be used at various steps of the drug development process from target identification to pre-clinical trial models. This systems biology based approach paired with the power of computational biology; genetics and developmental biology provide a methodological framework to avoid the pitfalls of traditional target based drug design. PMID:21731440

New Paradigms in Medical Ethics.

PubMed

Howe, Edmund G

2016-01-01

As new technologies develop, new ethical paradigms may be needed. This article considers several examples, such as stopping venoarterial extracorporeal membrane oxygenation (VA-ECMO), treating patients who are in a locked-in-like state who have awareness, purposefully deceiving patients who have dementia, meeting the needs of transgender persons, showing loved ones patients' wounds, and doing research on controlled substances. I suggest that clinicians should identify the practices underlying their value assumptions so they can alter their assumptions when this might improve the care they offer to their patients. Copyright 2016 The Journal of Clinical Ethics. All rights reserved.

Integration of Primary Care and Psychiatry: A New Paradigm for Medical Student Clerkships.

PubMed

Wilkins, Kirsten M; Fenick, Ada M; Goldenberg, Matthew N; Ellis, Peter J; Barkil-Oteo, Andres; Rohrbaugh, Robert M

2018-01-01

Public health crises in primary care and psychiatry have prompted development of innovative, integrated care models, yet undergraduate medical education is not currently designed to prepare future physicians to work within such systems. To implement an integrated primary care-psychiatry clerkship for third-year medical students. Undergraduate medical education, amid institutional curriculum reform. Two hundred thirty-seven medical students participated in the clerkship in academic years 2015-2017. Educators in psychiatry, internal medicine, and pediatrics developed a 12-week integrated Biopsychosocial Approach to Health (BAH)/Primary Care-Psychiatry Clerkship. The clerkship provides students clinical experience in primary care, psychiatry, and integrated care settings, and a longitudinal, integrated didactic series covering key areas of interface between the two disciplines. Students reported satisfaction with the clerkship overall, rating it 3.9-4.3 on a 1-5 Likert scale, but many found its clinical curriculum and administrative organization disorienting. Students appreciated the conceptual rationale integrating primary care and psychiatry more in the classroom setting than in the clinical setting. While preliminary clerkship outcomes are promising, further optimization and evaluation of clinical and classroom curricula are ongoing. This novel educational paradigm is one model for preparing students for the integrated healthcare system of the twenty-first century.

Nuclear Molecular and Theranostic Imaging for Differentiated Thyroid Cancer

PubMed Central

Sheikh, Arif; Polack, Berna; Rodriguez, Yvette; Kuker, Russ

2017-01-01

Traditional nuclear medicine is rapidly being transformed by the evolving concepts in molecular imaging and theranostics. The utility of new approaches in differentiated thyroid cancer (DTC) diagnostics and therapy has not been fully appreciated. The clinical information, relevant to disease management and patient care, obtained by scintigraphy is still being underestimated. There has been a trend towards moving away from the use of radioactive iodine (RAI) imaging in the management of the disease. This paradigm shift is supported by the 2015 American Thyroid Association Guidelines (1). A more systematic and comprehensive understanding of disease pathophysiology and imaging methodologies is needed for optimal utilization of different imaging modalities in the management of DTC. There have been significant developments in radiotracer and imaging technology, clinically proven to contribute to the understanding of tumor biology and the clinical assessment of patients with DTC. The research and development in the field continues to evolve, with expected emergence of many novel diagnostic and therapeutic techniques. The role for nuclear imaging applications will continue to evolve and be reconfigured in the changing paradigm. This article aims to review the clinical uses and controversies surrounding the use of scintigraphy, and the information it can provide in assisting in the management and treatment of DTC. PMID:28117289

Converging Paradigms: A Reflection on Parallel Theoretical Developments in Psychoanalytic Metapsychology and Empirical Dream Research.

PubMed

Schmelowszky, Ágoston

2016-08-01

In the last decades one can perceive a striking parallelism between the shifting perspective of leading representatives of empirical dream research concerning their conceptualization of dreaming and the paradigm shift within clinically based psychoanalytic metapsychology with respect to its theory on the significance of dreaming. In metapsychology, dreaming becomes more and more a central metaphor of mental functioning in general. The theories of Klein, Bion, and Matte-Blanco can be considered as milestones of this paradigm shift. In empirical dream research, the competing theories of Hobson and of Solms respectively argued for and against the meaningfulness of the dream-work in the functioning of the mind. In the meantime, empirical data coming from various sources seemed to prove the significance of dream consciousness for the development and maintenance of adaptive waking consciousness. Metapsychological speculations and hypotheses based on empirical research data seem to point in the same direction, promising for contemporary psychoanalytic practice a more secure theoretical base. In this paper the author brings together these diverse theoretical developments and presents conclusions regarding psychoanalytic theory and technique, as well as proposing an outline of an empirical research plan for testing the specificity of psychoanalysis in developing dream formation.

A Conditioned Behavioral Paradigm for Assessing Onset and Lasting Tinnitus in Rats

PubMed Central

Pace, Edward; Luo, Hao; Bobian, Michael; Panekkad, Ajay; Zhang, Xueguo; Zhang, Huiming; Zhang, Jinsheng

2016-01-01

Numerous behavioral paradigms have been developed to assess tinnitus-like behavior in animals. Nevertheless, they are often limited by prolonged training requirements, as well as an inability to simultaneously assess onset and lasting tinnitus behavior, tinnitus pitch or duration, or tinnitus presence without grouping data from multiple animals or testing sessions. To enhance behavioral testing of tinnitus, we developed a conditioned licking suppression paradigm to determine the pitch(s) of both onset and lasting tinnitus-like behavior within individual animals. Rats learned to lick water during broadband or narrowband noises, and to suppress licking to avoid footshocks during silence. After noise exposure, rats significantly increased licking during silent trials, suggesting onset tinnitus-like behavior. Lasting tinnitus-behavior, however, was exhibited in about half of noise-exposed rats through 7 weeks post-exposure tested. Licking activity during narrowband sound trials remained unchanged following noise exposure, while ABR hearing thresholds fully recovered and were comparable between tinnitus(+) and tinnitus(-) rats. To assess another tinnitus inducer, rats were injected with sodium salicylate. They demonstrated high pitch tinnitus-like behavior, but later recovered by 5 days post-injection. Further control studies showed that 1): sham noise-exposed rats tested with footshock did not exhibit tinnitus-like behavior, and 2): noise-exposed or sham rats tested without footshocks showed no fundamental changes in behavior compared to those tested with shocks. Together, these results demonstrate that this paradigm can efficiently test the development of noise- and salicylate-induced tinnitus behavior. The ability to assess tinnitus individually, over time, and without averaging data enables us to realistically address tinnitus in a clinically relevant way. Thus, we believe that this optimized behavioral paradigm will facilitate investigations into the mechanisms of tinnitus and development of effective treatments. PMID:27835697

Experimental and clinical usefulness of crossmodal paradigms in psychiatry: an illustration from emotional processing in alcohol-dependence

PubMed Central

Maurage, Pierre; Campanella, Salvatore

2013-01-01

Crossmodal processing (i.e., the construction of a unified representation stemming from distinct sensorial modalities inputs) constitutes a crucial ability in humans' everyday life. It has been extensively explored at cognitive and cerebral levels during the last decade among healthy controls. Paradoxically however, and while difficulties to perform this integrative process have been suggested in a large range of psychopathological states (e.g., schizophrenia and autism), these crossmodal paradigms have been very rarely used in the exploration of psychiatric populations. The main aim of the present paper is thus to underline the experimental and clinical usefulness of exploring crossmodal processes in psychiatry. We will illustrate this proposal by means of the recent data obtained in the crossmodal exploration of emotional alterations in alcohol-dependence. Indeed, emotional decoding impairments might have a role in the development and maintenance of alcohol-dependence, and have been extensively investigated by means of experiments using separated visual or auditory stimulations. Besides these unimodal explorations, we have recently conducted several studies using audio-visual crossmodal paradigms, which has allowed us to improve the ecological validity of the unimodal experimental designs and to offer new insights on the emotional alterations among alcohol-dependent individuals. We will show how these preliminary results can be extended to develop a coherent and ambitious research program using crossmodal designs in various psychiatric populations and sensory modalities. We will finally end the paper by underlining the various potential clinical applications and the fundamental implications that can be raised by this emerging project. PMID:23898250

CHANGING OUR DIAGNOSTIC PARADIGM: MOVEMENT SYSTEM DIAGNOSTIC CLASSIFICATION

PubMed Central

Kamonseki, Danilo H.; Staker, Justin L.; Lawrence, Rebekah L.; Braman, Jonathan P.

2017-01-01

Proper diagnosis is a first step in applying best available treatments, and prognosticating outcomes for clients. Currently, the majority of musculoskeletal diagnoses are classified according to pathoanatomy. However, the majority of physical therapy treatments are applied toward movement system impairments or pain. While advocated within the physical therapy profession for over thirty years, diagnostic classification within a movement system framework has not been uniformly developed or adopted. We propose a basic framework and rationale for application of a movement system diagnostic classification for atraumatic shoulder pain conditions, as a case for the broader development of movement system diagnostic labels. Shifting our diagnostic paradigm has potential to enhance communication, improve educational efficiency, facilitate research, directly link to function, improve clinical care, and accelerate preventive interventions. PMID:29158950

Management framework paradigms for disorders of sex development.

PubMed

Telles-Silveira, Mariana; Knobloch, Felicia; Kater, Claudio E

2015-10-01

Until 2005, questions regarding medical treatment and diagnostic information on Disorders of Sex Development (DSD) were not systematically discussed with both the patients and their families; however, the way these patients are currently treated have been changing with time. Interventional changes in the clinical-psychotherapeutic-surgical areas of DSD determine not only different medical recommendations but also help to place the patient and the family into the decisional process of therapy. We must consider two paradigmatic periods that have influenced and transformed the clinical management framework of patients with DSD: a) The "Money era" (1955), which emphasized the role of the gonads as the diagnostic criterion, having the environment as determinant of the sex identity; and b) The Chicago Consensus (2005) phase, in which the role of genetics and molecular biology was critical for an early identification, as well as in building a proper sex identity, emphasizing ethical questions and the "stigma culture". In addition, recent data have focused on the importance of interdisciplinarity and statements on questions concerning Human Rights as key factors in treatment decision making. Despite each of these management models being able to determine specific directions and recommendations regarding the clinical handling of these patients, we verify that a composite of these several models is the clinical routine nowadays. In the present paper, we discuss these several paradigms, and pinpoint clinical differences and their unfolding regarding management of DSD patients and their families.

Gene Therapy and Targeted Toxins for Glioma

PubMed Central

Castro, Maria G.; Candolfi, Marianela; Kroeger, Kurt; King, Gwendalyn D.; Curtin, James F.; Yagiz, Kader; Mineharu, Yohei; Assi, Hikmat; Wibowo, Mia; Muhammad, AKM Ghulam; Foulad, David; Puntel, Mariana; Lowenstein, Pedro R.

2011-01-01

The most common primary brain tumor in adults is glioblastoma. These tumors are highly invasive and aggressive with a mean survival time of nine to twelve months from diagnosis to death. Current treatment modalities are unable to significantly prolong survival in patients diagnosed with glioblastoma. As such, glioma is an attractive target for developing novel therapeutic approaches utilizing gene therapy. This review will examine the available preclinical models for glioma including xenographs, syngeneic and genetic models. Several promising therapeutic targets are currently being pursued in pre-clinical investigations. These targets will be reviewed by mechanism of action, i.e., conditional cytotoxic, targeted toxins, oncolytic viruses, tumor suppressors/oncogenes, and immune stimulatory approaches. Preclinical gene therapy paradigms aim to determine which strategies will provide rapid tumor regression and long-term protection from recurrence. While a wide range of potential targets are being investigated preclinically, only the most efficacious are further transitioned into clinical trial paradigms. Clinical trials reported to date are summarized including results from conditionally cytotoxic, targeted toxins, oncolytic viruses and oncogene targeting approaches. Clinical trial results have not been as robust as preclinical models predicted; this could be due to the limitations of the GBM models employed. Once this is addressed, and we develop effective gene therapies in models that better replicate the clinical scenario, gene therapy will provide a powerful approach to treat and manage brain tumors. PMID:21453286

Management of inflammatory bowel disease in older persons: evolving paradigms

PubMed Central

Kedia, Saurabh; Limdi, Jimmy K.

2018-01-01

The incidence and prevalence of inflammatory bowel disease (IBD) is increasing, and considering the aging population, this number is set to increase further in the future. The clinical features and natural history of elderly-onset IBD have many similarities with those of IBD in younger patients, but with significant differences including a broader differential diagnosis. The relative lack of data specific to elderly patients with IBD, often stemming from their typical exclusion from clinical trials, has made clinical decision-making somewhat challenging. Treatment decisions in elderly patients with IBD must take into account age-specific concerns such as comorbidities, locomotor and cognitive function, and polypharmacy, to set realistic treatment targets in order to enable personalized treatment and minimize harm. Notwithstanding paucity of clinical data, recent studies have provided valuable insights, which, taken together with information gleaned from previous studies, can broaden our understanding of IBD. These insights may contribute to the development of paradigms for the holistic and, when possible, evidence-based management of this potentially vulnerable population and are the focus of this review. PMID:29743832

A new paradigm for clinical communication: critical review of literature in cancer care.

PubMed

Salmon, Peter; Young, Bridget

2017-03-01

To: (i) identify key assumptions of the scientific 'paradigm' that shapes clinical communication research and education in cancer care; (ii) show that, as general rules, these do not match patients' own priorities for communication; and (iii) suggest how the paradigm might change to reflect evidence better and thereby serve patients better. A critical review, focusing on cancer care. We identified assumptions about patients' and clinicians' roles in recent position and policy statements. We examined these in light of research evidence, focusing on inductive research that has not itself been constrained by those assumptions, and considering the institutionalised interests that the assumptions might serve. The current paradigm constructs patients simultaneously as needy (requiring clinicians' explicit emotional support) and robust (seeking information and autonomy in decision making). Evidence indicates, however, that patients generally value clinicians who emphasise expert clinical care rather than counselling, and who lead decision making. In denoting communication as a technical skill, the paradigm constructs clinicians as technicians; however, communication cannot be reduced to technical skills, and teaching clinicians 'communication skills' has not clearly benefited patients. The current paradigm is therefore defined by assumptions that that have not arisen from evidence. A paradigm for clinical communication that makes its starting point the roles that mortal illness gives patients and clinicians would emphasise patients' vulnerability and clinicians' goal-directed expertise. Attachment theory provides a knowledge base to inform both research and education. Researchers will need to be alert to political interests that seek to mould patients into 'consumers', and to professional interests that seek to add explicit psychological dimensions to clinicians' roles. New approaches to education will be needed to support clinicians' curiosity and goal-directed judgement in applying this knowledge. The test for the new paradigm will be whether the research and education it promotes benefit patients. © 2016 The Authors. Medical Education published by Association for the Study of Medical Education and John Wiley & Sons Ltd.

User-centered design in brain-computer interfaces-a case study.

PubMed

Schreuder, Martijn; Riccio, Angela; Risetti, Monica; Dähne, Sven; Ramsay, Andrew; Williamson, John; Mattia, Donatella; Tangermann, Michael

2013-10-01

The array of available brain-computer interface (BCI) paradigms has continued to grow, and so has the corresponding set of machine learning methods which are at the core of BCI systems. The latter have evolved to provide more robust data analysis solutions, and as a consequence the proportion of healthy BCI users who can use a BCI successfully is growing. With this development the chances have increased that the needs and abilities of specific patients, the end-users, can be covered by an existing BCI approach. However, most end-users who have experienced the use of a BCI system at all have encountered a single paradigm only. This paradigm is typically the one that is being tested in the study that the end-user happens to be enrolled in, along with other end-users. Though this corresponds to the preferred study arrangement for basic research, it does not ensure that the end-user experiences a working BCI. In this study, a different approach was taken; that of a user-centered design. It is the prevailing process in traditional assistive technology. Given an individual user with a particular clinical profile, several available BCI approaches are tested and - if necessary - adapted to him/her until a suitable BCI system is found. Described is the case of a 48-year-old woman who suffered from an ischemic brain stem stroke, leading to a severe motor- and communication deficit. She was enrolled in studies with two different BCI systems before a suitable system was found. The first was an auditory event-related potential (ERP) paradigm and the second a visual ERP paradigm, both of which are established in literature. The auditory paradigm did not work successfully, despite favorable preconditions. The visual paradigm worked flawlessly, as found over several sessions. This discrepancy in performance can possibly be explained by the user's clinical deficit in several key neuropsychological indicators, such as attention and working memory. While the auditory paradigm relies on both categories, the visual paradigm could be used with lower cognitive workload. Besides attention and working memory, several other neurophysiological and -psychological indicators - and the role they play in the BCIs at hand - are discussed. The user's performance on the first BCI paradigm would typically have excluded her from further ERP-based BCI studies. However, this study clearly shows that, with the numerous paradigms now at our disposal, the pursuit for a functioning BCI system should not be stopped after an initial failed attempt. Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

Overview of cancer vaccines

PubMed Central

Kudrin, Alex

2012-01-01

Cancer immunotherapy has seen a tremendous number of failures and only few recent regulatory successes. This is a review dedicated to determine major regulatory and developmental issues around cancer immunotherapeutics. A three pillar approach should be used in setting a development path: discovery platforms and sufficient pool of validated tumor antigens, product development strategy enabling to bring the product closer to the patient and clinical development strategy accounting for competitive landscape, treatment paradigm, technical and commercial risks. Regulatory framework existing around cancer vaccines in the EU, US, Japan and some developing countries is outlined. In addition, the review covers some specific issues on the design and conduct of clinical trials with cancer vaccines. PMID:22894970

On heterogeneity of treatment effects and clinical freedom.

PubMed

Sacristán, J A; Avendaño-Solá, C

2015-01-01

Three decades ago, John R Hampton announced the death of clinical freedom. Since then, evidence-based medicine has been the predominant paradigm in clinical research. By applying a population-based approach, the randomised controlled trial has become the cornerstone for demonstrating the overall effect of a treatment and for developing guidelines. The new patient-centred medicine movement is rediscovering the important implications of heterogeneity of treatment effects for clinical practice and that a better understanding of such variability can contribute to improve health outcomes for individual patients through practicing a science-based clinical freedom. © 2015 The Authors. International Journal of Clinical Practice Published by John Wiley & Sons Ltd.

The Preparation of Educational Leaders: What's Needed and What's Next?

ERIC Educational Resources Information Center

Hills, Jean

This essay formulates some recommendations for educational administrator preparation programs and predicts the course of their future development. While the case of medical practice as a paradigm for the practice of educational administration is found only generally useful, the clinical analogy yields the suggestion that educational leader…

Expansion of the consultation-liaison psychiatry paradigm at a university medical center: integration of diversified clinical and funding models.

PubMed

Bourgeois, James A; Hilty, Donald M; Klein, Sally C; Koike, Alan K; Servis, Mark E; Hales, Robert E

2003-01-01

The perspective of the contemporary Consultation-Liason Service (CLS) psychiatrist is increasingly one of consultant to medical and surgical colleagues in models other than inpatient medical and surgical units. Simultaneously, the need for a clinically and educationally robust inpatient CLS persists despite funding pressures. The University of California, Davis Medical Center Department of Psychiatry has made use of creative organizational and financial models to accomplish the inpatient CLS clinical and educational missions in a fiscally responsible manner. In addition, the department has in recent years expanded the delivery of psychiatry consultation-liaison clinical and educational services to other models of care delivery, broadening the role and influence of the CLS. Several of the initiatives described in this paper parallel an overall evolution of the practice of consultation-liaison psychiatry in response to managed care influences and other systems pressures. This consultation-liaison paradigm expansion with diversified sources of funding support facilitates the development of consultation-liaison psychiatry along additional clinical, administrative, research, and educational dimensions. Other university medical centers may consider adaptation of some of the initiatives described here to their institutions.

Perceptual Measurement in Schizophrenia: Promising Electrophysiology and Neuroimaging Paradigms From CNTRICS

PubMed Central

Butler, Pamela D.; Chen, Yue; Ford, Judith M.; Geyer, Mark A.; Silverstein, Steven M.; Green, Michael F.

2012-01-01

The sixth meeting of the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS) focused on selecting promising imaging paradigms for each of the cognitive constructs selected in the first CNTRICS meeting. In the domain of perception, the 2 constructs of interest were “gain control” and “visual integration.” CNTRICS received 6 task nominations for imaging paradigms for gain control and 3 task nominations for integration. The breakout group for perception evaluated the degree to which each of these tasks met prespecified criteria. For gain control, the breakout group believed that one task (mismatch negativity) was already mature and was being incorporated into multisite clinical trials. The breakout group recommended that 1 visual task (steady-state visual evoked potentials to magnocellular- vs parvocellular-biased stimuli) and 2 auditory measures (an event-related potential (ERP) measure of corollary discharge and a functional magnetic resonance imaging (fMRI) version of prepulse inhibition of startle) be adapted for use in clinical trials in schizophrenia research. For visual integration, the breakout group recommended that fMRI and ERP versions of a contour integration test and an fMRI version of a coherent motion test be adapted for use in clinical trials. This manuscript describes the ways in which each of these tasks met the criteria used in the breakout group to evaluate and recommend tasks for further development. PMID:21890745

A new paradigm (Westphal-Paradigm) to study the neural correlates of panic disorder with agoraphobia.

PubMed

Wittmann, A; Schlagenhauf, F; John, T; Guhn, A; Rehbein, H; Siegmund, A; Stoy, M; Held, D; Schulz, I; Fehm, L; Fydrich, T; Heinz, A; Bruhn, H; Ströhle, A

2011-04-01

Agoraphobia (with and without panic disorder) is a highly prevalent and disabling anxiety disorder. Its neural complexity can be characterized by specific cues in fMRI studies. Therefore, we developed a fMRI paradigm with agoraphobia-specific stimuli. Pictures of potential agoraphobic situations were generated. Twenty-six patients, suffering from panic disorder and agoraphobia, and 22 healthy controls rated the pictures with respect to arousal, valence, and agoraphobia-related anxiety. The 96 pictures, which discriminated best between groups were chosen, split into two parallel sets and supplemented with matched neutral pictures from the International Affective Picture System. Reliability, criterion, and construct validity of the picture set were determined in a second sample (44 patients, 28 controls). The resulting event-related "Westphal-Paradigm" with cued and uncued pictures was tested in a fMRI pilot study with 16 patients. Internal consistency of the sets was very high; parallelism was given. Positive correlations of picture ratings with Mobility Inventory and Hamilton anxiety scores support construct validity. FMRI data revealed activations in areas associated with the fear circuit including amygdala, insula, and hippocampal areas. Psychometric properties of the Westphal-Paradigm meet necessary quality requirements for further scientific use. The paradigm reliably produces behavioral and fMRI patterns in response to agoraphobia-specific stimuli. To our knowledge, it is the first fMRI paradigm with these properties. This paradigm can be used to further characterize the functional neuroanatomy of panic disorder and agoraphobia and might be useful to contribute data to the differentiation of panic disorder and agoraphobia as related, but conceptually different clinical disorders.

Is it time for a new paradigm for systemic cancer treatment? Lessons from a century of cancer chemotherapy

PubMed Central

Crawford, Sarah

2013-01-01

U.S. SEER (Surveillance Epidemiology and End Results) data for age-adjusted mortality rates for all cancers combined for all races show only a modest overall 13% decline over the past 35 years. Moreover, the greatest contributor to cancer mortality is treatment-resistant metastatic disease. The accepted therapeutic paradigm for the past half-century for the treatment of advanced cancers has involved the use of systemic chemotherapy drugs cytotoxic for cycling cells (both normal and malignant) during DNA synthesis and/or mitosis. The failure of this therapeutic modality to achieve high-level, consistent rates of disease-free survival for some of the most common cancers, including tumors of the lung, colon breast, brain, melanoma, and others is the focus of this paper. A retrospective assessment of critical milestones in cancer chemotherapy indicates that most successful therapeutic regimens use cytotoxic cell cycle inhibitors in combined, maximum tolerated, dose-dense acute treatment regimens originally developed to treat acute lymphoblastic leukemia and some lymphomas. Early clinical successes in this area led to their wholesale application to the treatment of solid tumor malignancies that, unfortunately, has not produced consistent, long-term high cure rates for many common cancers. Important differences in therapeutic sensitivity of leukemias/lymphomas versus solid tumors can be explained by key biological differences that define the treatment-resistant solid tumor phenotype. A review of these clinical outcome data in the context of recent developments in our understanding of drug resistance mechanisms characteristic of solid tumors suggests the need for a new paradigm for the treatment of chemotherapy-resistant cancers. In contrast to reductionist approaches, the systemic approach targets both microenvironmental and systemic factors that drive and sustain tumor progression. These systemic factors include dysregulated inflammatory and oxidation pathways shown to be directly implicated in the development and maintenance of the cancer phenotype. The paradigm stresses the importance of a combined preventive/therapeutic approach involving adjuvant chemotherapies that incorporate anti-inflammatory and anti-oxidant therapeutics. PMID:23805101

Motor Priming in Neurorehabilitation

PubMed Central

Stoykov, Mary Ellen; Madhavan, Sangeetha

2014-01-01

Priming is a type of implicit learning wherein a stimulus prompts a change in behavior. Priming has been long studied in the field of psychology. More recently, rehabilitation researchers have studied motor priming as a possible way to facilitate motor learning. For example, priming of the motor cortex is associated with changes in neuroplasticity that are associated with improvements in motor performance. Of the numerous motor priming paradigms under investigation, only a few are practical for the current clinical environment, and the optimal priming modalities for specific clinical presentations are not known. Accordingly, developing an understanding of the various types of motor priming paradigms and their underlying neural mechanisms is an important step for therapists in neurorehabilitation. Most importantly, an understanding of the methods and their underlying mechanisms is essential for optimizing rehabilitation outcomes. The future of neurorehabilitation is likely to include these priming methods, which are delivered prior to or in conjunction with primary neurorehabilitation therapies. In this Special Interest article we discuss those priming paradigms that are supported by the greatest amount of evidence including: (i) stimulation-based priming, (ii) motor imagery and action observation, (iii) sensory priming, (iv) movement-based priming, and (v) pharmacological priming. PMID:25415551

Effort-Based Decision Making in Schizophrenia: Evaluation of Paradigms to Measure Motivational Deficits.

PubMed

Green, Michael F; Horan, William P

2015-09-01

Effort-based decision making requires one to decide how much effort to expend for a certain amount of reward. As the amount of reward goes up most people are willing to exert more effort. This relationship between reward level and effort expenditure can be measured in specialized performance-based tasks that have only recently been applied to schizophrenia. Such tasks provide a way to measure objectively motivational deficits in schizophrenia, which now are only assessed with clinical interviews of negative symptoms. The articles in this theme provide reviews of the relevant animal and human literatures (first 2 articles), and then a psychometric evaluation of 5 effort-based decision making paradigms (last 2 articles). This theme section is intended to stimulate interest in this emerging area among basic scientists developing paradigms for preclinical studies, human experimentalists trying to disentangle factors that contribute to performance on effort-based tasks, and investigators looking for objective endpoints for clinical trials of negative symptoms in schizophrenia. © The Author 2015. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Functional MRI Motor Imagery Tasks to Detect Command Following in Traumatic Disorders of Consciousness.

PubMed

Bodien, Yelena G; Giacino, Joseph T; Edlow, Brian L

2017-01-01

Severe traumatic brain injury impairs arousal and awareness, the two components of consciousness. Accurate diagnosis of a patient's level of consciousness is critical for determining treatment goals, access to rehabilitative services, and prognosis. The bedside behavioral examination, the current clinical standard for diagnosis of disorders of consciousness, is prone to misdiagnosis, a finding that has led to the development of advanced neuroimaging techniques aimed at detection of conscious awareness. Although a variety of paradigms have been used in functional magnetic resonance imaging (fMRI) to reveal covert consciousness, the relative accuracy of these paradigms in the patient population is unknown. Here, we compare the rate of covert consciousness detection by hand squeezing and tennis playing motor imagery paradigms in 10 patients with traumatic disorders of consciousness [six male, six acute, mean ± SD age = 27.9 ± 9.1 years, one coma, four unresponsive wakefulness syndrome, two minimally conscious without language function, and three minimally conscious with language function, per bedside examination with the Coma Recovery Scale-Revised (CRS-R)]. We also tested the same paradigms in 10 healthy subjects (nine male, mean ± SD age = 28.5 ± 9.4 years). In healthy subjects, the hand squeezing paradigm detected covert command following in 7/10 and the tennis playing paradigm in 9/10 subjects. In patients who followed commands on the CRS-R, the hand squeezing paradigm detected covert command following in 2/3 and the tennis playing paradigm in 0/3 subjects. In patients who did not follow commands on the CRS-R, the hand squeezing paradigm detected command following in 1/7 and the tennis playing paradigm in 2/7 subjects. The sensitivity, specificity, and accuracy (ACC) of detecting covert command following in patients who demonstrated this behavior on the CRS-R was 66.7, 85.7, and 80% for the hand squeezing paradigm and 0, 71.4, and 50% for the tennis playing paradigm, respectively. Overall, the tennis paradigm performed better than the hand squeezing paradigm in healthy subjects, but in patients, the hand squeezing paradigm detected command following with greater ACC. These findings indicate that current fMRI motor imagery paradigms frequently fail to detect command following and highlight the need for paradigm optimization to improve the accuracy of covert consciousness detection.

Functional MRI Motor Imagery Tasks to Detect Command Following in Traumatic Disorders of Consciousness

PubMed Central

Bodien, Yelena G.; Giacino, Joseph T.; Edlow, Brian L.

2017-01-01

Severe traumatic brain injury impairs arousal and awareness, the two components of consciousness. Accurate diagnosis of a patient’s level of consciousness is critical for determining treatment goals, access to rehabilitative services, and prognosis. The bedside behavioral examination, the current clinical standard for diagnosis of disorders of consciousness, is prone to misdiagnosis, a finding that has led to the development of advanced neuroimaging techniques aimed at detection of conscious awareness. Although a variety of paradigms have been used in functional magnetic resonance imaging (fMRI) to reveal covert consciousness, the relative accuracy of these paradigms in the patient population is unknown. Here, we compare the rate of covert consciousness detection by hand squeezing and tennis playing motor imagery paradigms in 10 patients with traumatic disorders of consciousness [six male, six acute, mean ± SD age = 27.9 ± 9.1 years, one coma, four unresponsive wakefulness syndrome, two minimally conscious without language function, and three minimally conscious with language function, per bedside examination with the Coma Recovery Scale-Revised (CRS-R)]. We also tested the same paradigms in 10 healthy subjects (nine male, mean ± SD age = 28.5 ± 9.4 years). In healthy subjects, the hand squeezing paradigm detected covert command following in 7/10 and the tennis playing paradigm in 9/10 subjects. In patients who followed commands on the CRS-R, the hand squeezing paradigm detected covert command following in 2/3 and the tennis playing paradigm in 0/3 subjects. In patients who did not follow commands on the CRS-R, the hand squeezing paradigm detected command following in 1/7 and the tennis playing paradigm in 2/7 subjects. The sensitivity, specificity, and accuracy (ACC) of detecting covert command following in patients who demonstrated this behavior on the CRS-R was 66.7, 85.7, and 80% for the hand squeezing paradigm and 0, 71.4, and 50% for the tennis playing paradigm, respectively. Overall, the tennis paradigm performed better than the hand squeezing paradigm in healthy subjects, but in patients, the hand squeezing paradigm detected command following with greater ACC. These findings indicate that current fMRI motor imagery paradigms frequently fail to detect command following and highlight the need for paradigm optimization to improve the accuracy of covert consciousness detection. PMID:29326648

[Considerations concerning medical knowledge inherited in Mexico from 19th century: the diabetes mellitus case].

PubMed

García de Alba-García, Javier Eduardo; Salcedo-Rocha, Ana Leticia; Milke-Najar, María Eugenia; Alonso-Reynoso, Carlos; García de Alba-Verduzco, Javier Eugenio

2017-01-01

In Mexico, as in the entire Western world, during the 19th century and the beginnings of the 20th century, medical knowledge developed in a remarkable way and the case of diabetes mellitus was not the exception. This situation, which arose on the basis of the antique paradigm, and which in turn was overthrown by the positivism as the emergent paradigm (with its clinical and anatomical, as well as physiopathological and etiopathological viewpoints), was reflected during the 19th the century through its actors and the communications that opened the access of Mexican medicine to the modernity.

A change roadmap towards research paradigm in low-resource countries: retinoblastoma model in Egypt.

PubMed

Alfaar, Ahmad Samir; Nour, Radwa; Bakry, Mohamed Sabry; Kamal, Mohamed; Hassanain, Omneya; Labib, Rania M; Rashed, Wafaa M; Elzomor, Hossam; Alieldin, Adel; Taha, Hala; Zaghloul, Mohamed Saad; Ezzat, Sameera; AboElnaga, Sherif

2017-02-01

Research on childhood diseases represents a great global challenge. This challenge is maximized in both childhood cancer disciplines and developing world. In this paper, we aim at describing our institution experience in starting a structured childhood cancer research program in one of the developing countries in a short time based on philanthropic efforts. We used retinoblastoma as an example for what was conducted in this program. Starting in 2008, this program included improving clinical practice and its related supporting services besides developing new research services that both complement the clinical activities and pave the way towards creating a research foundation in the country. Results included developing hospital standard treatment protocols, developing national clinical trials, joining international consortia for childhood cancers clinical trials, developing data collection tools and real-time analytics, establishing a biobanking facility, and developing highly qualified team for conducting clinical, epidemiologic, and translational research studies. Moreover, this effort resulted in improving both clinical practice and patients' awareness nationally. This model can be used for other startup facilities that aim at finding answers for their national health problems in low-resource setting.

Introduction: Toward an Understanding of Epistemology and Deafness

ERIC Educational Resources Information Center

Paul, Peter V.; Moores, Donald F.

2010-01-01

The major concept of epistemology--or epistemologies--is discussed, as well as related terms such as "paradigm" and "science". Also covered are two broad paradigms, the clinical and the cultural, that seem to drive theorizing, research, and practice regarding individuals who are d/Deaf or hard of hearing. The two paradigms emanate from different…

Common Ground of Two Paradigms: Incorporating Critical Theory into Current Art Therapy Practices

ERIC Educational Resources Information Center

Nolan, Emily

2013-01-01

Clinical art therapy and studio-based community art therapy represent two major paradigms in art therapy practice. This viewpoint explores how critical theory can be incorporated into both paradigms and result in common ground between them. Critical theory encompasses an understanding of oppression in psychological, social, and cultural contexts…

Molecular Pathology Informatics.

PubMed

Roy, Somak

2015-06-01

Molecular informatics (MI) is an evolving discipline that will support the dynamic landscape of molecular pathology and personalized medicine. MI provides a fertile ground for development of clinical solutions to bridge the gap between clinical informatics and bioinformatics. Rapid adoption of next generation sequencing (NGS) in the clinical arena has triggered major endeavors in MI that are expected to bring a paradigm shift in the practice of pathology. This brief review presents a broad overview of various aspects of MI, particularly in the context of NGS based testing. Copyright © 2015 Elsevier Inc. All rights reserved.

From Metabonomics to Pharmacometabonomics: The Role of Metabolic Profiling in Personalized Medicine

PubMed Central

Everett, Jeremy R.

2016-01-01

Variable patient responses to drugs are a key issue for medicine and for drug discovery and development. Personalized medicine, that is the selection of medicines for subgroups of patients so as to maximize drug efficacy and minimize toxicity, is a key goal of twenty-first century healthcare. Currently, most personalized medicine paradigms rely on clinical judgment based on the patient's history, and on the analysis of the patients' genome to predict drug effects i.e., pharmacogenomics. However, variability in patient responses to drugs is dependent upon many environmental factors to which human genomics is essentially blind. A new paradigm for predicting drug responses based on individual pre-dose metabolite profiles has emerged in the past decade: pharmacometabonomics, which is defined as “the prediction of the outcome (for example, efficacy or toxicity) of a drug or xenobiotic intervention in an individual based on a mathematical model of pre-intervention metabolite signatures.” The new pharmacometabonomics paradigm is complementary to pharmacogenomics but has the advantage of being sensitive to environmental as well as genomic factors. This review will chart the discovery and development of pharmacometabonomics, and provide examples of its current utility and possible future developments. PMID:27660611

Systems healthcare: a holistic paradigm for tomorrow.

PubMed

Fiandaca, Massimo S; Mapstone, Mark; Connors, Elenora; Jacobson, Mireille; Monuki, Edwin S; Malik, Shaista; Macciardi, Fabio; Federoff, Howard J

2017-12-19

Systems healthcare is a holistic approach to health premised on systems biology and medicine. The approach integrates data from molecules, cells, organs, the individual, families, communities, and the natural and man-made environment. Both extrinsic and intrinsic influences constantly challenge the biological networks associated with wellness. Such influences may dysregulate networks and allow pathobiology to evolve, resulting in early clinical presentation that requires astute assessment and timely intervention for successful mitigation. Herein, we describe the components of relevant biological systems and the nature of progression from at-risk to manifest disease. We illustrate the systems approach by examining two relevant clinical examples: Alzheimer's and cardiovascular diseases. The implications of systems healthcare management are examined through the lens of economics, ethics, policy and the law. Finally, we propose the need to develop new educational paradigms to enhance the training of the health professional in an era of systems medicine.

Paradigm shifts and the development of the diagnostic and statistical manual of mental disorders: past experiences and future aspirations.

PubMed

First, Michael B

2010-11-01

Work is currently under way on the Diagnostic and Statistical Manual of Mental Disorders (DSM), Fifth Edition, due to be published by the American Psychiatric Association in 2013. Dissatisfaction with the current categorical descriptive approach has led to aspirations for a paradigm shift for DSM-5. A historical review of past revisions of the DSM was performed. Efforts undertaken before the start of the DSM-5 development process to conduct a state-of-the science review and set a research agenda were examined to determine if results supported a paradigm shift for DSM-5. Proposals to supplement DSM-5 categorical diagnosis with dimensional assessments are reviewed and critiqued. DSM revisions have alternated between paradigm shifts (the first edition of the DSM in 1952 and DSM-III in 1980) and incremental improvements (DSM-II in 1968, DSM-III-R in 1987, and DSM-IV in 1994). The results of the review of the DSM-5 research planning initiatives suggest that despite the scientific advances that have occurred since the descriptive approach was first introduced in 1980, the field lacks a sufficiently deep understanding of mental disorders to justify abandoning the descriptive approach in favour of a more etiologically based alternative. Proposals to add severity and cross-cutting dimensions throughout DSM-5 are neither paradigm shifting, given that simpler versions of such dimensions are already a component of DSM-IV, nor likely to be used by busy clinicians without evidence that they improve clinical outcomes. Despite initial aspirations that DSM would undergo a paradigm shift with this revision, DSM-5 will continue to adopt a descriptive categorical approach, albeit with a greatly expanded dimensional component.

NEURAL SUBSTRATES OF CUE-REACTIVITY: ASSOCIATION WITH TREATMENT OUTCOMES AND RELAPSE

PubMed Central

Courtney, Kelly E.; Schacht, Joseph P.; Hutchison, Kent; Roche, Daniel J.O.; Ray, Lara A.

2016-01-01

Given the strong evidence for neurological alterations at the basis of drug dependence, functional magnetic resonance imaging (fMRI) represents an important tool in the clinical neuroscience of addiction. fMRI cue-reactivity paradigms represent an ideal platform to probe the involvement of neurobiological pathways subserving the reward/motivation system in addiction and potentially offer a translational mechanism by which interventions and behavioral predictions can be tested. Thus, this review summarizes the research that has applied fMRI cue-reactivity paradigms to the study of adult substance use disorder treatment responses. Studies utilizing fMRI cue-reactivity paradigms for the prediction of relapse, and as a means to investigate psychosocial and pharmacological treatment effects on cue-elicited brain activation are presented within four primary categories of substances: alcohol, nicotine, cocaine, and opioids. Lastly, suggestions for how to leverage fMRI technology to advance addiction science and treatment development are provided. PMID:26435524

'Mind the gap' between the development of therapeutic innovations and the clinical practice in oncology: A proposal of the European Organisation for Research and Treatment of Cancer (EORTC) to optimise cancer clinical research.

PubMed

Kempf, Emmanuelle; Bogaerts, Jan; Lacombe, Denis; Liu, Lifang

2017-11-01

In Europe, most of the cancer clinical research dedicated to therapeutic innovations aims primarily at regulatory approval. Once an anticancer drug enters the common market, each member state determines its real-world use based on its own criteria: pricing, reimbursement and clinical indications. Such an innovation-centred clinical research landscape might neglect patient-relevant issues in real-world setting, such as comparative effectiveness of distinct treatment options or long-term safety monitoring. The European Organisation for Research and Treatment of Cancer (EORTC) advocates reforming the current 'innovation-centred' system to a truly 'patient-centred' paradigm with systematically coordinated applied clinical research in conjunction with drug development, featuring the following strategy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Phacilitate Barcelona active immunotherapeutics forum. 11-13 May 2011, Barcelona, Spain.

PubMed

Shore, Neal D

2011-08-01

The era of active immunotherapy has now been successfully ushered into the clinical realm of advanced prostate cancer. The successful clinical trial development and US FDA approval of sipuleucel-T (Provenge®) has revamped the therapeutic paradigm for advanced prostate cancer. Nonetheless, physician and patient education as well as regulatory pathways and manufacturing efficiencies are still required in order to optimize patient care. These topics were covered at the Phacilitate Barcelona Active Immunotherapeutics Forum.

Self-injurious behaviour in people with intellectual disability and autism spectrum disorder.

PubMed

Oliver, Chris; Licence, Lucy; Richards, Caroline

2017-03-01

This review summarises the recent trends in research in the field of self-injurious behaviour in people with intellectual disability and autism spectrum disorder. New data on incidence, persistence and severity add to studies of prevalence to indicate the large scale of the clinical need. A number of person characteristics have been repeatedly identified in prevalence and cohort studies that: can be considered as risk markers (e.g. stereotyped behaviour, autism spectrum disorder) and indicate possible causal mechanisms (e.g. sleep disorder, anxiety). Studies have started to integrate traditional operant learning paradigms with known person characteristics and reviews and meta-analyses of applied behaviour analytic procedures can now inform practice. Despite these positive developments interventions and appropriate support falls far short of the required need. Expansions in applied research are warranted to develop and evaluate innovative service delivery models that can translate knowledge of risk markers and operant learning paradigms into widespread, low cost routine clinical practice. Alongside this, further pure research is needed to elucidate the direction of causality of implicated risk factors, in order to understand and intervene more effectively in self-injury.

Improved Endpoints for Cancer Immunotherapy Trials

PubMed Central

Eggermont, Alexander M. M.; Janetzki, Sylvia; Hodi, F. Stephen; Ibrahim, Ramy; Anderson, Aparna; Humphrey, Rachel; Blumenstein, Brent; Wolchok, Jedd

2010-01-01

Unlike chemotherapy, which acts directly on the tumor, cancer immunotherapies exert their effects on the immune system and demonstrate new kinetics that involve building a cellular immune response, followed by changes in tumor burden or patient survival. Thus, adequate design and evaluation of some immunotherapy clinical trials require a new development paradigm that includes reconsideration of established endpoints. Between 2004 and 2009, several initiatives facilitated by the Cancer Immunotherapy Consortium of the Cancer Research Institute and partner organizations systematically evaluated an immunotherapy-focused clinical development paradigm and created the principles for redefining trial endpoints. On this basis, a body of clinical and laboratory data was generated that supports three novel endpoint recommendations. First, cellular immune response assays generate highly variable results. Assay harmonization in multicenter trials may minimize variability and help to establish cellular immune response as a reproducible biomarker, thus allowing investigation of its relationship with clinical outcomes. Second, immunotherapy may induce novel patterns of antitumor response not captured by Response Evaluation Criteria in Solid Tumors or World Health Organization criteria. New immune-related response criteria were defined to more comprehensively capture all response patterns. Third, delayed separation of Kaplan–Meier curves in randomized immunotherapy trials can affect results. Altered statistical models describing hazard ratios as a function of time and recognizing differences before and after separation of curves may allow improved planning of phase III trials. These recommendations may improve our tools for cancer immunotherapy trials and may offer a more realistic and useful model for clinical investigation. PMID:20826737

The Challenge of Infectious Diseases to the Biomedical Paradigm

ERIC Educational Resources Information Center

Foladori, Guillermo

2005-01-01

The resurgence of infectious diseases and the emergence of infectious diseases raise questions on how to cope with the situation. The germ or clinical approach is the hegemonic biomedical paradigm. In this article, the author argues that the spread of infectious diseases has posted a challenge to the biomedical paradigm and shows how lock-in…

Ebonics and Dr. Ernie Adolphus Smith toward Acomparative and Holistic Paradigm in Black Linguistics

ERIC Educational Resources Information Center

Minamoto, Kunihiko

2017-01-01

One African-centered linguistic paradigm argues the primary language of most descendants of enslaved Africans in the United States is not English but an African language. The language is called "Ebonics." Clinical linguist Dr. Ernie Adolphus Smith (1938-) is the most conspicuous figure in the history of the paradigm. The reconstructed…

Computational models and motor learning paradigms: Could they provide insights for neuroplasticity after stroke? An overview.

PubMed

Kiper, Pawel; Szczudlik, Andrzej; Venneri, Annalena; Stozek, Joanna; Luque-Moreno, Carlos; Opara, Jozef; Baba, Alfonc; Agostini, Michela; Turolla, Andrea

2016-10-15

Computational approaches for modelling the central nervous system (CNS) aim to develop theories on processes occurring in the brain that allow the transformation of all information needed for the execution of motor acts. Computational models have been proposed in several fields, to interpret not only the CNS functioning, but also its efferent behaviour. Computational model theories can provide insights into neuromuscular and brain function allowing us to reach a deeper understanding of neuroplasticity. Neuroplasticity is the process occurring in the CNS that is able to permanently change both structure and function due to interaction with the external environment. To understand such a complex process several paradigms related to motor learning and computational modeling have been put forward. These paradigms have been explained through several internal model concepts, and supported by neurophysiological and neuroimaging studies. Therefore, it has been possible to make theories about the basis of different learning paradigms according to known computational models. Here we review the computational models and motor learning paradigms used to describe the CNS and neuromuscular functions, as well as their role in the recovery process. These theories have the potential to provide a way to rigorously explain all the potential of CNS learning, providing a basis for future clinical studies. Copyright © 2016 Elsevier B.V. All rights reserved.

Design of a Randomized Controlled Trial for Ebola Virus Disease Medical Countermeasures: PREVAIL II, the Ebola MCM Study.

PubMed

Dodd, Lori E; Proschan, Michael A; Neuhaus, Jacqueline; Koopmeiners, Joseph S; Neaton, James; Beigel, John D; Barrett, Kevin; Lane, Henry Clifford; Davey, Richard T

2016-06-15

Unique challenges posed by emerging infectious diseases often expose inadequacies in the conventional phased investigational therapeutic development paradigm. The recent Ebola outbreak in West Africa presents a critical case-study highlighting barriers to faster development. During the outbreak, clinical trials were implemented with unprecedented speed. Yet, in most cases, this fast-tracked approach proved too slow for the rapidly evolving epidemic. Controversy abounded as to the most appropriate study designs to yield safety and efficacy data, potentially causing delays in pivotal studies. Preparation for research during future outbreaks may require acceptance of a paradigm that circumvents, accelerates, or reorders traditional phases, without losing sight of the traditional benchmarks by which drug candidates must be assessed for activity, safety and efficacy. We present the design of an adaptive, parent protocol, ongoing in West Africa until January 2016. The exigent circumstances of the outbreak and limited prior clinical experience with experimental treatments, led to more direct bridging from preclinical studies to human trials than the conventional paradigm would typically have sanctioned, and required considerable design flexibility. Preliminary evaluation of the "barely Bayesian" design was provided through computer simulation studies. The understanding and public discussion of the study design will help its future implementation. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

The Evolution of an Interprofessional Shared Decision-Making Research Program: Reflective Case Study of an Emerging Paradigm

PubMed Central

Menear, Matthew; Stacey, Dawn; Brière, Nathalie; Légaré, France

2016-01-01

Introduction: Healthcare research increasingly focuses on interprofessional collaboration and on shared decision making, but knowledge gaps remain about effective strategies for implementing interprofessional collaboration and shared decision-making together in clinical practice. We used Kuhn’s theory of scientific revolutions to reflect on how an integrated interprofessional shared decision-making approach was developed and implemented over time. Methods: In 2007, an interdisciplinary team initiated a new research program to promote the implementation of an interprofessional shared decision-making approach in clinical settings. For this reflective case study, two new team members analyzed the team’s four projects, six research publications, one unpublished and two published protocols and organized them into recognizable phases according to Kuhn’s theory. Results: The merging of two young disciplines led to challenges characteristic of emerging paradigms. Implementation of interprofessional shared-decision making was hindered by a lack of conceptual clarity, a dearth of theories and models, little methodological guidance, and insufficient evaluation instruments. The team developed a new model, identified new tools, and engaged knowledge users in a theory-based approach to implementation. However, several unresolved challenges remain. Discussion: This reflective case study sheds light on the evolution of interdisciplinary team science. It offers new approaches to implementing emerging knowledge in the clinical context. PMID:28435417

The Evolution of an Interprofessional Shared Decision-Making Research Program: Reflective Case Study of an Emerging Paradigm.

PubMed

Dogba, Maman Joyce; Menear, Matthew; Stacey, Dawn; Brière, Nathalie; Légaré, France

2016-07-19

Healthcare research increasingly focuses on interprofessional collaboration and on shared decision making, but knowledge gaps remain about effective strategies for implementing interprofessional collaboration and shared decision-making together in clinical practice. We used Kuhn's theory of scientific revolutions to reflect on how an integrated interprofessional shared decision-making approach was developed and implemented over time. In 2007, an interdisciplinary team initiated a new research program to promote the implementation of an interprofessional shared decision-making approach in clinical settings. For this reflective case study, two new team members analyzed the team's four projects, six research publications, one unpublished and two published protocols and organized them into recognizable phases according to Kuhn's theory. The merging of two young disciplines led to challenges characteristic of emerging paradigms. Implementation of interprofessional shared-decision making was hindered by a lack of conceptual clarity, a dearth of theories and models, little methodological guidance, and insufficient evaluation instruments. The team developed a new model, identified new tools, and engaged knowledge users in a theory-based approach to implementation. However, several unresolved challenges remain. This reflective case study sheds light on the evolution of interdisciplinary team science. It offers new approaches to implementing emerging knowledge in the clinical context.

[Clinical neuropsychology in perspective: future challenges based on current developments].

PubMed

Verdejo-García, Antonio; Tirapu-Ustárroz, Javier

2012-02-01

New lines of translational, interdisciplinary research are emerging among different fields of the neurosciences, which often point at clinical neuropsychology as the hinge discipline capable of linking the basic findings with their clinical implications and thereby endow them with some meaning for phenomenological experience. To establish the great lines of progress made in the fields of neuroscience and neuropsychology in recent years, so as to be able to foresee the strategic lines and priorities of neuroscience in the near future. To achieve this aim, the first step will be to identify the changes of paradigm that have taken place in the areas of neuroscience and psychology in the last two decades. The next step will be to propose new topics and fields of application that these changes in paradigm offer and demand from neuroscience. The false dichotomies of genes versus environment, mind versus brain, and reason versus emotion are considered, as are the new applications of neuropsychology to the understanding of psychopathological disorders, from the neurodegenerative to neurodevelopment, from 'dirty' drugs to cognitive and affective enhancers.

Trial Watch: Adoptive cell transfer for oncological indications

PubMed Central

Aranda, Fernando; Buqué, Aitziber; Bloy, Norma; Castoldi, Francesca; Eggermont, Alexander; Cremer, Isabelle; Fridman, Wolf Hervé; Fucikova, Jitka; Galon, Jérôme; Spisek, Radek; Tartour, Eric; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

2015-01-01

One particular paradigm of anticancer immunotherapy relies on the administration of (potentially) tumor-reactive immune effector cells. Generally, these cells are obtained from autologous peripheral blood lymphocytes (PBLs) ex vivo (in the context of appropriate expansion, activation and targeting protocols), and re-infused into lymphodepleted patients along with immunostimulatory agents. In spite of the consistent progress achieved throughout the past two decades in this field, no adoptive cell transfer (ACT)-based immunotherapeutic regimen is currently approved by regulatory agencies for use in cancer patients. Nonetheless, the interest of oncologists in ACT-based immunotherapy continues to increase. Accumulating clinical evidence indicates indeed that specific paradigms of ACT, such as the infusion of chimeric antigen receptor (CAR)-expressing autologous T cells, are associated with elevated rates of durable responses in patients affected by various neoplasms. In line with this notion, clinical trials investigating the safety and therapeutic activity of ACT in cancer patients are being initiated at an ever increasing pace. Here, we review recent preclinical and clinical advances in the development of ACT-based immunotherapy for oncological indications. PMID:26451319

Trial Watch: Adoptive cell transfer for oncological indications.

PubMed

Aranda, Fernando; Buqué, Aitziber; Bloy, Norma; Castoldi, Francesca; Eggermont, Alexander; Cremer, Isabelle; Fridman, Wolf Hervé; Fucikova, Jitka; Galon, Jérôme; Spisek, Radek; Tartour, Eric; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

2015-11-01

One particular paradigm of anticancer immunotherapy relies on the administration of (potentially) tumor-reactive immune effector cells. Generally, these cells are obtained from autologous peripheral blood lymphocytes (PBLs) ex vivo (in the context of appropriate expansion, activation and targeting protocols), and re-infused into lymphodepleted patients along with immunostimulatory agents. In spite of the consistent progress achieved throughout the past two decades in this field, no adoptive cell transfer (ACT)-based immunotherapeutic regimen is currently approved by regulatory agencies for use in cancer patients. Nonetheless, the interest of oncologists in ACT-based immunotherapy continues to increase. Accumulating clinical evidence indicates indeed that specific paradigms of ACT, such as the infusion of chimeric antigen receptor (CAR)-expressing autologous T cells, are associated with elevated rates of durable responses in patients affected by various neoplasms. In line with this notion, clinical trials investigating the safety and therapeutic activity of ACT in cancer patients are being initiated at an ever increasing pace. Here, we review recent preclinical and clinical advances in the development of ACT-based immunotherapy for oncological indications.

The scope for qualitative methods in research and clinical trials in dementia.

PubMed

Gibson, Grant; Timlin, Alison; Curran, Stephen; Wattis, John

2004-07-01

In the evaluation of drugs, the randomised double-blind placebo controlled trial is the 'gold standard'. This method, based on a positivist paradigm, answers questions about efficacy and side-effects of treatments that are accepted as valid, reliable and generalisable, provided the study is well designed and properly conducted. In contrast, qualitative research methodologies, originating from the social sciences, embrace a variety of approaches, including phenomenological and other paradigms. Within clinical and health services research, qualitative approaches view the world more subjectively, acknowledging that the researcher is part of what is researched, focusing on meanings and understanding of experience, rather than on what can be reduced to quantitative measures. They can develop new ideas through induction from data, rather than confirming or refuting hypotheses. Qualitative methods have improved our understanding of the experiences of people with dementia and, if used alongside clinical trials, could be used to improve the relevance of outcomes to patients, compliance and user involvement. They could also possibly generate new measures of efficacy and effectiveness in severe dementia.

Technological choices for mobile clinical applications.

PubMed

Ehrler, Frederic; Issom, David; Lovis, Christian

2011-01-01

The rise of cheaper and more powerful mobile devices make them a new and attractive platform for clinical applications. The interaction paradigm and portability of the device facilitates bedside human-machine interactions. The better accessibility to information and decision-support anywhere in the hospital improves the efficiency and the safety of care processes. In this study, we attempt to find out what are the most appropriate Operating System (OS) and Software Development Kit (SDK) to support the development of clinical applications on mobile devices. The Android platform is a Linux-based, open source platform that has many advantages. Two main SDKs are available on this platform: the native Android and the Adobe Flex SDK. Both of them have interesting features, but the latter has been preferred due its portability at comparable performance and ease of development.

Tuberculosis as a three-act play: A new paradigm for the pathogenesis of pulmonary tuberculosis.

PubMed

Hunter, Robert L

2016-03-01

Lack of access to human tissues with untreated tuberculosis (TB) has forced generations of researchers to use animal models and to adopt a paradigm that granulomas are the characteristic lesion of both primary and post primary TB. An extended search of studies of human lung tissues failed to find any reports that support this paradigm. We found scores of publications from gross pathology in 1804 through high resolution CT scans in 2015 that identify obstructive lobular pneumonia, not granulomas, as the characteristic lesion of developing post-primary TB. This paper reviews this literature together with other relevant observations to formulate a new paradigm of TB with three distinct stages: a three-act play. First, primary TB, a war of attrition, begins with infection that spreads via lymphatics and blood stream before inducing systemic immunity that contains and controls the organisms within granulomas. Second, post-primary TB, a sneak attack, develops during latent TB as an asymptomatic obstructive lobular pneumonia in persons with effective systemic immunity. It is a paucibacillary process with no granulomas that spreads via bronchi and accumulates mycobacterial antigens and host lipids for 1-2 years before suddenly undergoing caseous necrosis. Third, the fallout, is responsible for nearly all clinical post primary disease. It begins with caseous necrotic pneumonia that is either retained to become the focus of fibrocaseous disease or is coughed out to leave a cavity. This three-stage paradigm suggests testable hypotheses and plausible answers to long standing questions of immunity to TB. Copyright © 2015 The Author. Published by Elsevier Ltd.. All rights reserved.

Breast Imaging: A Paradigm for Accountable Care Organizations.

PubMed

Parikh, Jay R; Yang, Wei T

2016-02-01

Accountable care organizations (ACOs) are being promoted by the Centers of Medicare Services as alternative payment models for radiology reimbursement. Because of its clinical orientation, focus on prevention, standardized reporting, quality orientation through mandatory accreditation, and value demonstration through established outcome metrics, breast imaging offers a unique paradigm for the ACO model in radiology. In radiology, breast imaging represents the paradigm for ACOs.

Clinical research of traditional Chinese medicine in big data era.

PubMed

Zhang, Junhua; Zhang, Boli

2014-09-01

With the advent of big data era, our thinking, technology and methodology are being transformed. Data-intensive scientific discovery based on big data, named "The Fourth Paradigm," has become a new paradigm of scientific research. Along with the development and application of the Internet information technology in the field of healthcare, individual health records, clinical data of diagnosis and treatment, and genomic data have been accumulated dramatically, which generates big data in medical field for clinical research and assessment. With the support of big data, the defects and weakness may be overcome in the methodology of the conventional clinical evaluation based on sampling. Our research target shifts from the "causality inference" to "correlativity analysis." This not only facilitates the evaluation of individualized treatment, disease prediction, prevention and prognosis, but also is suitable for the practice of preventive healthcare and symptom pattern differentiation for treatment in terms of traditional Chinese medicine (TCM), and for the post-marketing evaluation of Chinese patent medicines. To conduct clinical studies involved in big data in TCM domain, top level design is needed and should be performed orderly. The fundamental construction and innovation studies should be strengthened in the sections of data platform creation, data analysis technology and big-data professionals fostering and training.

Telomeres and age-related disease: how telomere biology informs clinical paradigms

PubMed Central

Armanios, Mary

2013-01-01

Telomere length shortens with age and predicts the onset of replicative senescence. Recently, short telomeres have been linked to the etiology of degenerative diseases such as idiopathic pulmonary fibrosis, bone marrow failure, and cryptogenic liver cirrhosis. These disorders have recognizable clinical manifestations, and the telomere defect explains their genetics and informs the approach to their treatment. Here, I review how telomere biology has become intimately connected to clinical paradigms both for understanding pathophysiology and for individualizing therapy decisions. I also critically examine nuances of interpreting telomere length measurement in clinical studies. PMID:23454763

Molecular Markers and Targeted Therapeutics in Metastatic Tumors of the Spine: Changing the Treatment Paradigms.

PubMed

Goodwin, C Rory; Abu-Bonsrah, Nancy; Rhines, Laurence D; Verlaan, Jorrit-Jan; Bilsky, Mark H; Laufer, Ilya; Boriani, Stefano; Sciubba, Daniel M; Bettegowda, Chetan

2016-10-15

A review of the literature. The aim of this study was to discuss the evolution of molecular signatures and the history and development of targeted therapeutics in metastatic tumor types affecting the spinal column. Molecular characterization of metastatic spine tumors is expected to usher in a revolution in diagnostic and treatment paradigms. Molecular characterization will provide critical information that can be used for initial diagnosis, prognosticating the ideal treatment strategy, assessment of treatment efficacy, surveillance and monitoring recurrence, and predicting complications, clinical outcome, and overall survival in patients diagnosed with metastatic cancers to the spinal column. A review of the literature was performed focusing on illustrative examples of the role that molecular-based therapeutics have played in clinical outcomes for patients diagnosed with metastatic tumor types affecting the spinal column. The impact of molecular therapeutics including receptor tyrosine kinases and immune checkpoint inhibitors and the ability of molecular signatures to provide prognostic information are discussed in metastatic breast cancer, lung cancer, prostate cancer, melanoma, and renal cell cancer affecting the spinal column. For the providers who will ultimately counsel patients diagnosed with metastases to the spinal column, molecular advancements will radically alter the management/surgical paradigms utilized. Ultimately, the translation of these molecular advancements into routine clinical care will greatly improve the quality and quantity of life for patients diagnosed with spinal malignancies and provide better overall outcomes and counseling for treating physicians. N/A.

Renovating Alzheimer's: "Constructive" Reflections on the New Clinical and Research Diagnostic Guidelines

ERIC Educational Resources Information Center

George, Daniel R.; Qualls, Sara H.; Camp, Cameron J.; Whitehouse, Peter J.

2013-01-01

The development of disease concepts for conditions such as Alzheimer's disease (AD) is an ongoing social process that evolves over time. The biomedical paradigm about AD that has informed our culture's understanding of brain aging for the past several decades is currently undergoing a major and timely renovation in the early 21st century. This…

Clinical Trials in Late Life: New Science in Old Paradigms

ERIC Educational Resources Information Center

Lebowitz, Barry D.

2004-01-01

This article, based on a Lawton Award Lecture, addresses the subject of the need to enhance the evidence base in our field in order to influence processes of policy development. Four issues are identified as critical to this: theory-driven targets of public health significance, use of appropriate and sophisticated approaches to research design and…

An Experimental Approach to Detecting Dementia in Down Syndrome: A Paradigm for Alzheimer's Disease

ERIC Educational Resources Information Center

Nelson, Linda D.; Scheibel, Kevin E.; Ringman, John M.; Sayre, James W.

2007-01-01

Measures developed from animal models of aging may detect dementia of the Alzheimer's type in a population at-risk for Alzheimer's disease (AD). Although, by middle age, individuals with Down syndrome (DS) show an extraordinarily high prevalence of AD-type pathology, their severe idiopathic cognitive deficits tend to confound the "clinical"…

Community forensic psychiatry: restoring some sanity to forensic psychiatric rehabilitation.

PubMed

Skipworth, J; Humberstone, V

2002-01-01

To review clinical and legal paradigms of community forensic mental health care, with specific focus on New Zealand, and to develop a clinically based set of guiding principles for service development in this area. The general principles of rehabilitating mentally disordered offenders, and assertive community care programmes were reviewed and applied to the law and policy in a New Zealand forensic mental health setting. There is a need to develop comprehensive community treatment programmes for mentally disordered offenders. The limited available research supports assertive community treatment models, with specialist forensic input. Ten clinically based principles of care provision important to forensic mental health assertive community treatment were developed. Deinstitutionalization in forensic psychiatry lags behind the rest of psychiatry, but can only occur with well-supported systems in place to assess and manage risk in the community setting. The development of community-based forensic rehabilitation services in conjunction with general mental health is indicated.

The Social Value of Knowledge and International Clinical Research.

PubMed

Wenner, Danielle M

2015-08-01

In light of the growth in the conduct of international clinical research in developing populations, this paper seeks to explore what is owed to developing world communities who host international clinical research. Although existing paradigms for assigning and assessing benefits to host communities offer valuable insight, I criticize their failure to distinguish between those benefits which can justify the conduct of research in a developing world setting and those which cannot. I argue that the justification for human subjects research is fundamentally grounded in the social value of knowledge, and that this value is context-dependent in a manner which should inform our ethical evaluation of the conduct of research in specific settings. I propose a new framework for the assessment of research benefits assigned to developing world host communities, a natural implication of which is to limit the types of research projects which may permissibly be conducted in developing world settings. © 2013 John Wiley & Sons Ltd.

An alternate pathophysiologic paradigm of sepsis and septic shock

PubMed Central

Kumar, Anand

2014-01-01

The advent of modern antimicrobial therapy following the discovery of penicillin during the 1940s yielded remarkable improvements in case fatality rate of serious infections including septic shock. Since then, pathogens have continuously evolved under selective antimicrobial pressure resulting in a lack of significant improvement in clinical effectiveness in the antimicrobial therapy of septic shock despite ever more broad-spectrum and potent drugs. In addition, although substantial effort and money has been expended on the development novel non-antimicrobial therapies of sepsis in the past 30 years, clinical progress in this regard has been limited. This review explores the possibility that the current pathophysiologic paradigm of septic shock fails to appropriately consider the primacy of the microbial burden of infection as the primary driver of septic organ dysfunction. An alternate paradigm is offered that suggests that has substantial implications for optimizing antimicrobial therapy in septic shock. This model of disease progression suggests the key to significant improvement in the outcome of septic shock may lie, in great part, with improvements in delivery of existing antimicrobials and other anti-infectious strategies. Recognition of the role of delays in administration of antimicrobial therapy in the poor outcomes of septic shock is central to this effort. However, therapeutic strategies that improve the degree of antimicrobial cidality likely also have a crucial role. PMID:24184742

Potential Use of γ-Secretase Modulators in the Treatment of Alzheimer Disease

PubMed Central

Wagner, Steven L.; Tanzi, Rudolph E.; Mobley, William C.; Galasko, Douglas

2013-01-01

Although significant progress has occurred in the past 20 years regarding our understanding of Alzheimer disease pathogenesis, we have yet to identify disease-modifying therapeutics capable of substantially altering the clinical course of this prevalent neurodegenerative disease. In this short review, we discuss 2 approaches that are currently being tested clinically (γ-secretase inhibition and γ-secretase modulation) and emphasize the significant differences between these 2 therapeutic approaches. We also discuss certain genetic- and biomarker-based translational and clinical trial paradigms that may assist in developing a useful therapeutic agent. PMID:22801784

[History of clinical pharmacology in France: adaptation, evaluation, defense and illustration of drug in France 1978-1981].

PubMed

Montastruc, Paul

2014-01-01

This text illustrates some unknown aspects of the history and beginnings of clinical pharmacology in France in the late 1970s and early 1980s From the current situation, development and objectives of clinical pharmacology are recalled as well as obstacles necessary to overcome to change the paradigm in the field of drug evaluation and appropriate use in France. The text recalls this important moment where French medicine and medical pharmacology entered the modern era. © 2014 Société Française de Pharmacologie et de Thérapeutique.

White Paper: Recommendations on the Conduct of Superiority and Organism-Specific Clinical Trials of Antibacterial Agents for the Treatment of Infections Caused by Drug-Resistant Bacterial Pathogens

PubMed Central

2012-01-01

There is a critical need for new pathways to develop antibacterial agents to treat life-threatening infections caused by highly resistant bacteria. Traditionally, antibacterial agents have been studied in noninferiority clinical trials that focus on one site of infection (eg, pneumonia, intra-abdominal infection). Conduct of superiority trials for infections caused by highly antibiotic-resistant bacteria represents a new, and as yet, untested paradigm for antibacterial drug development. We sought to define feasible trial designs of antibacterial agents that could enable conduct of superiority and organism-specific clinical trials. These recommendations are the results of several years of active dialogue among the white paper's drafters as well as external collaborators and regulatory officials. Our goal is to facilitate conduct of new types of antibacterial clinical trials to enable development and ultimately approval of critically needed new antibacterial agents. PMID:22891041

A wearable computing platform for developing cloud-based machine learning models for health monitoring applications.

PubMed

Patel, Shyamal; McGinnis, Ryan S; Silva, Ikaro; DiCristofaro, Steve; Mahadevan, Nikhil; Jortberg, Elise; Franco, Jaime; Martin, Albert; Lust, Joseph; Raj, Milan; McGrane, Bryan; DePetrillo, Paolo; Aranyosi, A J; Ceruolo, Melissa; Pindado, Jesus; Ghaffari, Roozbeh

2016-08-01

Wearable sensors have the potential to enable clinical-grade ambulatory health monitoring outside the clinic. Technological advances have enabled development of devices that can measure vital signs with great precision and significant progress has been made towards extracting clinically meaningful information from these devices in research studies. However, translating measurement accuracies achieved in the controlled settings such as the lab and clinic to unconstrained environments such as the home remains a challenge. In this paper, we present a novel wearable computing platform for unobtrusive collection of labeled datasets and a new paradigm for continuous development, deployment and evaluation of machine learning models to ensure robust model performance as we transition from the lab to home. Using this system, we train activity classification models across two studies and track changes in model performance as we go from constrained to unconstrained settings.

ATOM - Accelerating therapeutics through opportunities in medicine

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

Mcmahon, Benjamin Hamilton; Dotson, Paul Jeffrey

Create a new paradigm of drug discovery that would reduce the time from an identified drug target to clinical candidate from the current ~6 years to just 12 months. ATOM will develop, test, and validate a multidisciplinary approach to drug discovery in which modern science, technology and engineering, supercomputing, simulations, data science, and artificial intelligence are highly integrated into a single drug-discovery platform that can ultimately be shared with the drug development community at-large.

Quantifying motivation with effort-based decision-making paradigms in health and disease.

PubMed

Chong, T T-J; Bonnelle, V; Husain, M

2016-01-01

Motivation can be characterized as a series of cost-benefit valuations, in which we weigh the amount of effort we are willing to expend (the cost of an action) in return for particular rewards (its benefits). Human motivation has traditionally been measured with self-report and questionnaire-based tools, but an inherent limitation of these methods is that they are unable to provide a mechanistic explanation of the processes underlying motivated behavior. A major goal of current research is to quantify motivation objectively with effort-based decision-making paradigms, by drawing on a rich literature from nonhuman animals. Here, we review this approach by considering the development of these paradigms in the laboratory setting over the last three decades, and their more recent translation to understanding choice behavior in humans. A strength of this effort-based approach to motivation is that it is capable of capturing the wide range of individual differences, and offers the potential to dissect motivation into its component elements, thus providing the basis for more accurate taxonomic classifications. Clinically, modeling approaches might provide greater sensitivity and specificity to diagnosing disorders of motivation, for example, in being able to detect subclinical disorders of motivation, or distinguish a disorder of motivation from related but separate syndromes, such as depression. Despite the great potential in applying effort-based paradigms to index human motivation, we discuss several caveats to interpreting current and future studies, and the challenges in translating these approaches to the clinical setting. © 2016 Elsevier B.V. All rights reserved.

The 2014 ESPEN Arvid Wretlind Lecture: Metabolism & nutrition: Shifting paradigms in COPD management.

PubMed

Schols, Annemie M W J

2015-12-01

COPD is a chronic disease of the lungs, but heterogeneous with respect to clinical manifestations and disease progression. This has consequences for health risk assessment, stratification and management. Heterogeneity can be driven by pulmonary events but also by systemic consequences (e.g. cachexia and muscle weakness) and co-morbidity (e.g. osteoporosis, diabetes and cardiovascular disease). This paper shows how a metabolic perspective on COPD has contributed significantly to understanding clinical heterogeneity and the need for a paradigm shift from reactive medicine towards predictive, preventive, personalized and participatory medicine. These insights have also lead to a paradigm shift in nutritional therapy for COPD from initial ignorance or focusing on putative adverse effects of carbohydrate overload on the ventilatory system to beneficial effects of nutritional intervention on body composition and physical functioning as integral part of disease management. The wider implications beyond COPD as disease have been as clinical model for translational cachexia research. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

[Paradigm Transformation of Cancer Research and Development, Treatment, and Clinical Trials toward Total Cure - The Role of ARO].

PubMed

Kojima, Shinsuke; Fukushima, Masanori

2016-08-01

We are living in an era characterized by an unprecedented scientific and technological revolution, which is also affecting both the health and medical fields. The revolution surrounding the cancer field is drastically changing not only the research and development sector, but also the manner in which malignancies are diagnosed and treated. This is due to achievements in genome, molecular immunology, and stem cell research. Here are some examples of molecular targeted therapy drugs. The targeted drug crizotinib, developed after the discovery of driver genes and genotype identification, opened up a newera of genome clinical sequencing. Mogamulizumab not only targets the chemokine receptor CCR4 but also modifies host antitumor immunity by suppressing Tregs. Trametinib is a molecular targeted therapy drug that controls molecules associated with the control system responsible for tumor maintenance. The creation of an assay system resulted in a breakthrough in this field, which led to the development of trametinib and crizotinib. The checkpoint inhibitor nivolumab acts on the immune system of the host and promotes tumor targeting. As exemplified by these developments, the paradigm of cancer drug therapy is changing from a probabilistic approach(ie, administering a general anticancer drug), to a deterministic approach(ie, administering the most adequate drug after diagnosing the specific mechanisms responsible for tumor generation, sustenance, and progression). The latter requires a drastic change in the way clinical trials are performed. Thus, we are now entering a newphase: the era of precision medicine. Herewe discuss the present state of the cancer medical revolution and the academic progress in research and development and cancer therapy in our country.

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

Tan, J; Pompos, A; Jiang, S

Purpose: To put forth an innovative clinical paradigm for weekly chart checking so that treatment status is periodically checked accurately and efficiently. This study also aims to help optimize the chart checking clinical workflow in a busy radiation therapy clinic. Methods: It is mandated by the Texas Administrative code to check patient charts of radiation therapy once a week or every five fractions, however it varies drastically among institutions in terms of when and how it is done. Some do it every day, but a lot of efforts are wasted on opening ineligible charts; some do it on a fixedmore » day but the distribution of intervals between subsequent checks is not optimal. To establish an optimal chart checking procedure, a new paradigm was developed to achieve 1) charts are checked more accurately and more efficiently; 2) charts are checked on optimal days without any miss; 3) workload is evened out throughout a week when multiple physicists are involved. All active charts will be accessed by querying the R&V system. Priority is assigned to each chart based on the number of days before the next due date followed by sorting and workload distribution steps. New charts are also taken into account when distributing the workload so it is reasonably even throughout the week. Results: Our clinical workflow became more streamlined and smooth. In addition, charts get checked in a more timely fashion so that errors would get caught earlier should they occur. Conclusion: We developed a new weekly chart checking diagram. It helps physicists check charts in a timely manner, saves their time in busy clinics, and consequently reduces possible errors.« less

Bridging the gap. The separate worlds of evidence-based medicine and patient-centered medicine.

PubMed

Bensing, J

2000-01-01

Modern medical care is influenced by two paradigms: 'evidence-based medicine' and 'patient-centered medicine'. In the last decade, both paradigms rapidly gained in popularity and are now both supposed to affect the process of clinical decision making during the daily practice of physicians. However, careful analysis shows that they focus on different aspects of medical care and have, in fact, little in common. Evidence-based medicine is a rather young concept that entered the scientific literature in the early 1990s. It has basically a positivistic, biomedical perspective. Its focus is on offering clinicians the best available evidence about the most adequate treatment for their patients, considering medicine merely as a cognitive-rational enterprise. In this approach the uniqueness of patients, their individual needs and preferences, and their emotional status are easily neglected as relevant factors in decision-making. Patient-centered medicine, although not a new phenomenon, has recently attracted renewed attention. It has basically a humanistic, biopsychosocial perspective, combining ethical values on 'the ideal physician', with psychotherapeutic theories on facilitating patients' disclosure of real worries, and negotiation theories on decision making. It puts a strong focus on patient participation in clinical decision making by taking into account the patients' perspective, and tuning medical care to the patients' needs and preferences. However, in this approach the ideological base is better developed than its evidence base. In modern medicine both paradigms are highly relevant, but yet seem to belong to different worlds. The challenge for the near future is to bring these separate worlds together. The aim of this paper is to give an impulse to this integration. Developments within both paradigms can benefit from interchanging ideas and principles from which eventually medical care will benefit. In this process a key role is foreseen for communication and communication research.

Development of ipilimumab: contribution to a new paradigm for cancer immunotherapy.

PubMed

Hoos, Axel; Ibrahim, Ramy; Korman, Alan; Abdallah, Kald; Berman, David; Shahabi, Vafa; Chin, Kevin; Canetta, Renzo; Humphrey, Rachel

2010-10-01

Identification of cytotoxic T-lymphocyte antigen-4 (CTLA-4) as a key negative regulator of T-cell activity led to development of the fully human, monoclonal antibody ipilimumab to block CTLA-4 and potentiate antitumor T-cell responses. Animal studies first provided insight into the ability of an anti-CTLA-4 antibody to cause tumor regression, particularly in combination regimens. Early clinical studies defined ipilimumab pharmacokinetics and possibilities for combinability. Phase II trials of ipilimumab in advanced melanoma showed objective responses, but a greater number of patients had disease stabilization. In a phase III trial, ipilimumab was the first agent to demonstrate an improvement in overall survival in patients with previously treated, advanced melanoma. The adverse event profile associated with ipilimumab was primarily immune-related. Adverse events can be severe and life-threatening, but most were reversible using treatment guidelines. Ipilimumab monotherapy exhibits conventional and new patterns of activity in advanced melanoma, with a delayed separation of Kaplan-Meier survival curves. The observation of some new response patterns with ipilimumab, which are not captured by standard response criteria, led to novel criteria for the evaluation of immunotherapy in solid tumors. Overall, lessons from the development of ipilimumab contributed to a new clinical paradigm for cancer immunotherapy evolved by the Cancer Immunotherapy Consortium. Copyright © 2010 Elsevier Inc. All rights reserved.

A burn center paradigm to fulfill deferred consent public disclosure and community consultation requirements for emergency care research.

PubMed

Blackford, Martha G; Falletta, Lynn; Andrews, David A; Reed, Michael D

2012-09-01

To fulfill Food and Drug Administration and Department of Health and Human Services emergency care research informed consent requirements, our burn center planned and executed a deferred consent strategy gaining Institutional Review Board (IRB) approval to proceed with the clinical study. These federal regulations dictate public disclosure and community consultation unique to acute care research. Our regional burn center developed and implemented a deferred consent public notification and community consultation paradigm appropriate for a burn study. Published accounts of deferred consent strategies focus on acute care resuscitation practices. We adapted those strategies to design and conduct a comprehensive public notification/community consultation plan to satisfy deferred consent requirements for burn center research. To implement a robust media campaign we engaged the hospital's public relations department, distributed media materials, recruited hospital staff for speaking engagements, enlisted community volunteers, and developed initiatives to inform "hard-to-reach" populations. The hospital's IRB determined we fulfilled our obligation to notify the defined community. Our communication strategy should provide a paradigm other burn centers may appropriate and adapt when planning and executing a deferred consent initiative. Copyright © 2012 Elsevier Ltd and ISBI. All rights reserved.

European League against rheumatism - selected presentation and poster a highlights June 11th to 13th 2013.

PubMed

Braddock, Martin

2014-02-01

The heterogeneous pathology of many autoimmune diseases warrants the continual discovery and development of new drugs. Drawing on selected oral presentations and selected poster displays, this article highlights some new developments in the pharmacological validation of molecular targets implicated in inflammatory autoimmune disease and may be of direct importance to scientists working in this field. This report describes the current state of the pharmacology of selected drugs and targets which may have utility in modulating immune function and autoimmune inflammatory disease. Many new molecules are progressing through clinical development for the treatment of rheumatological diseases. The value of the basic nonclinical and clinical research presented is to further pharmacological knowledge of the molecule, better understand the benefit-risk associated with clinical development and to assist in supporting the potential position of a new drug in the current treatment paradigm.

Development and validation of risk models and molecular diagnostics to permit personalized management of cancer.

PubMed

Pu, Xia; Ye, Yuanqing; Wu, Xifeng

2014-01-01

Despite the advances made in cancer management over the past few decades, improvements in cancer diagnosis and prognosis are still poor, highlighting the need for individualized strategies. Toward this goal, risk prediction models and molecular diagnostic tools have been developed, tailoring each step of risk assessment from diagnosis to treatment and clinical outcomes based on the individual's clinical, epidemiological, and molecular profiles. These approaches hold increasing promise for delivering a new paradigm to maximize the efficiency of cancer surveillance and efficacy of treatment. However, they require stringent study design, methodology development, comprehensive assessment of biomarkers and risk factors, and extensive validation to ensure their overall usefulness for clinical translation. In the current study, the authors conducted a systematic review using breast cancer as an example and provide general guidelines for risk prediction models and molecular diagnostic tools, including development, assessment, and validation. © 2013 American Cancer Society.

Development and Pilot Testing of the Dual Task Screen in Healthy Adolescents.

PubMed

Stephens, Jaclyn; Nicholson, Rachel; Slomine, Beth; Suskauer, Stacy

Athletes with mild traumatic brain injury (mTBI) should refrain from high-risk activities until recovered (symptom free and cognitive and physical exam findings normalize). Studies have suggested that this examination may not be sufficiently sensitive because dual-task paradigms, which typically assess motor performance while a person simultaneously completes a distractor task, can detect residual deficits in athletes who otherwise appear recovered from mTBI. Paradigms used to date are time-intensive procedures conducted in laboratory settings. Here, we report findings from a pilot study of the Dual Task Screen (DTS), which is a brief evaluation with two dual-task paradigms. In 32 healthy female adolescents, the DTS was administered in a mean of 5.63 min in the community, and every participant had poorer dual-condition performance on at least one of the motor tasks. The DTS is a clinically feasible measure and merits additional study regarding utility in adolescents with mTBIs. Copyright © 2018 by the American Occupational Therapy Association, Inc.

The fuzzy cube and causal efficacy: representation of concomitant mechanisms in stroke.

PubMed

Jobe, Thomas H.; Helgason, Cathy M.

1998-04-01

Twentieth century medical science has embraced nineteenth century Boolean probability theory based upon two-valued Aristotelian logic. With the later addition of bit-based, von Neumann structured computational architectures, an epistemology based on randomness has led to a bivalent epidemiological methodology that dominates medical decision making. In contrast, fuzzy logic, based on twentieth century multi-valued logic, and computational structures that are content addressed and adaptively modified, has advanced a new scientific paradigm for the twenty-first century. Diseases such as stroke involve multiple concomitant causal factors that are difficult to represent using conventional statistical methods. We tested which paradigm best represented this complex multi-causal clinical phenomenon-stroke. We show that the fuzzy logic paradigm better represented clinical complexity in cerebrovascular disease than current probability theory based methodology. We believe this finding is generalizable to all of clinical science since multiple concomitant causal factors are involved in nearly all known pathological processes.

Evolving healthcare delivery paradigms and the optimization of 'value' in anesthesiology.

PubMed

Alem, Navid; Kain, Zeev

2017-04-01

Healthcare worldwide is evolving to yield enhanced care provided at a lowered cost. Patient-centric paradigms that hasten surgical recovery and strengthen collaboration amongst medical professionals are gaining impetus. This review will discuss the changing healthcare landscape and outline its implications on anesthesiology practice. Anesthesiologists must be nimble and versatile as they adapt to healthcare redesign. An increased responsibility for patient outcomes should be embraced by extending the breadth and depth of clinical practice throughout the surgical care continuum. The perioperative surgical home and enhanced recovery after surgery provide paradigms to further integrate expanding clinical opportunities and improved patient outcomes. Investment is needed in perioperative medical education and research efforts to best position anesthesiologists for success both now and in the future. Exemplifying opportunities to demonstrate value-added care, the scope of anesthesiology education and clinical practice should diversify to further integrate perioperative care of surgical patients.

Distributed user interfaces for clinical ubiquitous computing applications.

PubMed

Bång, Magnus; Larsson, Anders; Berglund, Erik; Eriksson, Henrik

2005-08-01

Ubiquitous computing with multiple interaction devices requires new interface models that support user-specific modifications to applications and facilitate the fast development of active workspaces. We have developed NOSTOS, a computer-augmented work environment for clinical personnel to explore new user interface paradigms for ubiquitous computing. NOSTOS uses several devices such as digital pens, an active desk, and walk-up displays that allow the system to track documents and activities in the workplace. We present the distributed user interface (DUI) model that allows standalone applications to distribute their user interface components to several devices dynamically at run-time. This mechanism permit clinicians to develop their own user interfaces and forms to clinical information systems to match their specific needs. We discuss the underlying technical concepts of DUIs and show how service discovery, component distribution, events and layout management are dealt with in the NOSTOS system. Our results suggest that DUIs--and similar network-based user interfaces--will be a prerequisite of future mobile user interfaces and essential to develop clinical multi-device environments.

Kahlbaum, Hecker, and Kraepelin and the Transition From Psychiatric Symptom Complexes to Empirical Disease Forms.

PubMed

Kendler, Kenneth S; Engstrom, Eric J

2017-02-01

The nosology for major psychiatric disorders developed by Emil Kraepelin in the 1890s has substantially shaped psychiatry. His theories, however, did not arise de novo, being strongly influenced by Karl Kahlbaum and Ewald Hecker. From the 1860-1880s, they articulated a paradigm shift in the conceptualization of psychiatric diagnosis, from symptom-based syndromes, popular since the late 18th century, to proto-disease entities. This effort was influenced by parallel developments in general medicine, especially the rise of bacterial theories of disease where different syndromes had distinctive symptoms, courses, and etiologies. Their thinking was particularly shaped by the increasing understanding of general paresis of the insane. Indeed, this disorder, with its distinct course and characteristic symptoms, was paradigmatic for them. Their hope was that a similar progression of medical understanding would evolve for the other major psychiatric syndromes. Their thinking and its connection with Kraepelin's nosology are illustrated through a close reading of their essays on hebephrenia, catatonia, and cyclic insanity. Kahlbaum, Hecker, and Kraepelin shared both a commitment to a clinical research agenda for psychiatry (to utilize methods of clinical assessment and follow-up to help define disease forms) and a skepticism for the brain-based neuropathological paradigm of psychiatric research then dominant in most European centers. Understanding the historical origins of our key diagnostic concepts can help us to evaluate their strengths and limitations. It remains to be determined whether this "Kahlbaum-Hecker-Kraepelin paradigm"-defining disorders based on distinctive symptoms and course-will produce psychiatric syndromes of sufficient homogeneity to yield their etiologic secrets.

Standardized exchange of clinical documents--towards a shared care paradigm in glaucoma treatment.

PubMed

Gerdsen, F; Müller, S; Jablonski, S; Prokosch, H-U

2006-01-01

The exchange of medical data from research and clinical routine across institutional borders is essential to establish an integrated healthcare platform. In this project we want to realize the standardized exchange of medical data between different healthcare institutions to implement an integrated and interoperable information system supporting clinical treatment and research of glaucoma. The central point of our concept is a standardized communication model based on the Clinical Document Architecture (CDA). Further, a communication concept between different health care institutions applying the developed document model has been defined. With our project we have been able to prove that standardized communication between an Electronic Medical Record (EMR), an Electronic Health Record (EHR) and the Erlanger Glaucoma Register (EGR) based on the established conceptual models, which rely on CDA rel.1 level 1 and SCIPHOX, could be implemented. The HL7-tool-based deduction of a suitable CDA rel.2 compliant schema showed significant differences when compared with the manually created schema. Finally fundamental requirements, which have to be implemented for an integrated health care platform, have been identified. An interoperable information system can enhance both clinical treatment and research projects. By automatically transferring screening findings from a glaucoma research project to the electronic medical record of our ophthalmology clinic, clinicians could benefit from the availability of a longitudinal patient record. The CDA as a standard for exchanging clinical documents has demonstrated its potential to enhance interoperability within a future shared care paradigm.

Towards a 21 century paradigm of chiropractic: stage 1, redesigning clinical learning.

PubMed

Ebrall, Phillip; Draper, Barry; Repka, Adrian

2008-01-01

To describe a formal process designed to determine the nature and extent of change that may enhance the depth of student learning in the pre-professional, clinical chiropractic environment. Project teams in the Royal Melbourne Institute of Technology (RMIT) School of Health Sciences and the Division of Chiropractic explored questions of clinical assessment in several health care disciplines of the School and the issue of implementing change in a manner that would be embraced by the clinicians who supervise student-learning in the clinical environment. The teams applied to RMIT for grant funding within the Learning and Teaching Investment Fund to support two proposed studies. Both research proposals were fully funded and are in process. The genesis of this work is the discovery that the predominant management plan in the chiropractic teaching clinics is based on diagnostic reductionism. It is felt this is counter-productive to the holistic dimensions of chiropractic practice taught in the classroom and non-supportive of chiropractic's paradigm shift towards wellness. A need is seen to improve processes around student assessment in the contemporary work-integrated learning that is a prime element of learning within the clinical disciplines of the School of Health Sciences, including chiropractic. Any improvements in the manner of clinical assessment within the chiropractic discipline will need to be accompanied by improvement in the training and development of the clinicians responsible for managing the provision of quality patient care by Registered Chiropractic Students.

Emerging pathways and future targets for the molecular therapy of pancreatic cancer.

PubMed

Vaccaro, Vanja; Melisi, Davide; Bria, Emilio; Cuppone, Federica; Ciuffreda, Ludovica; Pino, Maria Simona; Gelibter, Alain; Tortora, Giampaolo; Cognetti, Francesco; Milella, Michele

2011-10-01

Pancreatic cancer treatment remains a challenge for clinicians and researchers. Despite undisputable advances in the comprehension of the molecular mechanisms underlying cancer development and progression, early disease detection and clinical management of patients has made little, if any, progress in the past 20 years. Clinical development of targeted agents directed against validated pathways, such as the EGF/EGF receptor axis, the mutant KRAS protein, MMPs, and VEGF-mediated angiogenesis, alone or in combination with gemcitabine-based standard chemotherapy, has been disappointing. This review explores the preclinical rationale for clinical approaches aimed at targeting the TGF-β, IGF, Hedgehog, Notch and NF-κB signaling pathways, to develop innovative therapeutic strategies for pancreatic cancer. Although some of the already clinically explored approaches (particularly EGFR and KRAS targeting) deserve further clinical consideration, by employing more innovative and creative clinical trial designs than the gemcitabine-targeted agent paradigm that has thus far invariably failed, the targeting of emerging and relatively unexplored signaling pathways holds great promise to increase our understanding of the complex molecular biology and to advance the clinical management of pancreatic cancer.

Insights into the Functional Anatomy Behind the PREEMPT Injection Paradigm: Guidance on Achieving Optimal Outcomes.

PubMed

Blumenfeld, Andrew M; Silberstein, Stephen D; Dodick, David W; Aurora, Sheena K; Brin, Mitchell F; Binder, William J

2017-05-01

To provide clinically relevant insights on the identification of the muscles and techniques involved in the safe and effective use of onabotulinumtoxinA for chronic migraine prophylaxis. Although guidance on the use of onabotulinumtoxinA for chronic migraine is available, based on the Phase III Research Evaluating Migraine Prophylaxis Therapy (PREEMPT) clinical program, clinical experience has shown that insufficient understanding of the anatomy and function of the head and neck muscles may lead to undesirable outcomes and suboptimal efficacy. Each muscle involved in the standardized PREEMPT injection paradigm is reviewed with a thorough description of each muscle's anatomy (ie, muscle description and location, innervation, vascular supply) and function. Key insights based on clinical experience are also provided to help improve outcomes. The identification of the muscles in the PREEMPT injection paradigm should be based on each patient's unique anatomy and injections should be administered using the advised techniques. A thorough examination of the patient prior to treatment is also critical to determine if any preexisting conditions may increase the risk for unwanted outcomes and appropriate expectations should be communicated. Thorough knowledge of the functional anatomy of the muscles involved in the standardized PREEMPT injection paradigm is critical to achieve the efficacy and safety observed in clinical trials. In addition, it is important to assess a patient's baseline condition to anticipate the risk for unwanted outcomes that may result from treatment. © 2017 Allergan plc. Headache published by Wiley Periodicals, Inc. on behalf of American Headache Society.

Insights into the Functional Anatomy Behind the PREEMPT Injection Paradigm: Guidance on Achieving Optimal Outcomes

PubMed Central

Silberstein, Stephen D.; Dodick, David W.; Aurora, Sheena K.; Brin, Mitchell F.; Binder, William J.

2017-01-01

Objective To provide clinically relevant insights on the identification of the muscles and techniques involved in the safe and effective use of onabotulinumtoxinA for chronic migraine prophylaxis. Background Although guidance on the use of onabotulinumtoxinA for chronic migraine is available, based on the Phase III Research Evaluating Migraine Prophylaxis Therapy (PREEMPT) clinical program, clinical experience has shown that insufficient understanding of the anatomy and function of the head and neck muscles may lead to undesirable outcomes and suboptimal efficacy. Design/Methods Each muscle involved in the standardized PREEMPT injection paradigm is reviewed with a thorough description of each muscle's anatomy (ie, muscle description and location, innervation, vascular supply) and function. Key insights based on clinical experience are also provided to help improve outcomes. Results The identification of the muscles in the PREEMPT injection paradigm should be based on each patient's unique anatomy and injections should be administered using the advised techniques. A thorough examination of the patient prior to treatment is also critical to determine if any preexisting conditions may increase the risk for unwanted outcomes and appropriate expectations should be communicated. Conclusions Thorough knowledge of the functional anatomy of the muscles involved in the standardized PREEMPT injection paradigm is critical to achieve the efficacy and safety observed in clinical trials. In addition, it is important to assess a patient's baseline condition to anticipate the risk for unwanted outcomes that may result from treatment. PMID:28387038

Evolving paradigms in clinical pharmacology and therapeutics for the treatment of Duchenne muscular dystrophy.

PubMed

Huard, J; Mu, X; Lu, A

2016-08-01

Progressive muscle weakness and degeneration due to the lack of dystrophin eventually leads to the loss of independent ambulation by the middle of the patient's second decade, and a fatal outcome due to cardiac or respiratory failure by the third decade. More specifically, loss of sarcolemmal dystrophin and the dystrophin-associated glycoprotein (DAG) complex promotes muscle fiber damage during muscle contraction. This process results in an efflux of creatine kinase (CK), an influx of calcium ions, and the recruitment of T cells, macrophages, and mast cells to the damaged muscle, causing progressive myofiber necrosis. For the last 20 years, the major goal in the development of therapeutic approaches to alleviate muscle weakness in DMD has been centered on the restoration of dystrophin or proteins that are analogous to dystrophin, such as utrophin, through a variety of modalities including cell therapy, gene therapy, gene correction, and the highly promising techniques utilizing CRISPR/Cas9 technology. Despite the development of new therapeutic options, there still exist numerous challenges that we must face with regard to these new strategies and, consequently, we still do not have any feasible options available to ultimately slow the progression of this devastating disease. The purpose of this article is to highlight the current knowledge and advancements in the evolving paradigms in clinical pharmacology and therapeutics for this devastating musculoskeletal disease. © 2016 American Society for Clinical Pharmacology and Therapeutics.

Current nonclinical testing paradigm enables safe entry to First-In-Human clinical trials: The IQ consortium nonclinical to clinical translational database.

PubMed

Monticello, Thomas M; Jones, Thomas W; Dambach, Donna M; Potter, David M; Bolt, Michael W; Liu, Maggie; Keller, Douglas A; Hart, Timothy K; Kadambi, Vivek J

2017-11-01

The contribution of animal testing in drug development has been widely debated and challenged. An industry-wide nonclinical to clinical translational database was created to determine how safety assessments in animal models translate to First-In-Human clinical risk. The blinded database was composed of 182 molecules and contained animal toxicology data coupled with clinical observations from phase I human studies. Animal and clinical data were categorized by organ system and correlations determined. The 2×2 contingency table (true positive, false positive, true negative, false negative) was used for statistical analysis. Sensitivity was 48% with a 43% positive predictive value (PPV). The nonhuman primate had the strongest performance in predicting adverse effects, especially for gastrointestinal and nervous system categories. When the same target organ was identified in both the rodent and nonrodent, the PPV increased. Specificity was 84% with an 86% negative predictive value (NPV). The beagle dog had the strongest performance in predicting an absence of clinical adverse effects. If no target organ toxicity was observed in either test species, the NPV increased. While nonclinical studies can demonstrate great value in the PPV for certain species and organ categories, the NPV was the stronger predictive performance measure across test species and target organs indicating that an absence of toxicity in animal studies strongly predicts a similar outcome in the clinic. These results support the current regulatory paradigm of animal testing in supporting safe entry to clinical trials and provide context for emerging alternate models. Copyright © 2017 Elsevier Inc. All rights reserved.

The treatment of Parkinson's disease with deep brain stimulation: current issues.

PubMed

Moldovan, Alexia-Sabine; Groiss, Stefan Jun; Elben, Saskia; Südmeyer, Martin; Schnitzler, Alfons; Wojtecki, Lars

2015-07-01

Deep brain stimulation has become a well-established symptomatic treatment for Parkinson's disease during the last 25 years. Besides improving motor symptoms and long-term motor complications, positive effects on patients' mobility, activities of daily living, emotional well-being and health-related quality of life have been recognized. Apart from that, numerous clinical trials analyzed effects on non-motor symptoms and side effects of deep brain stimulation. Several technical issues and stimulation paradigms have been and are still being developed to optimize the therapeutic effects, minimize the side effects and facilitate handling. This review summarizes current therapeutic issues, i.e., patient and target selection, surgical procedure and programming paradigms. In addition it focuses on neuropsychological effects and side effects of deep brain stimulation.

The Shifting Paradigm of Prognostic Factors of Colorectal Liver Metastases: From Tumor-Centered to Host Immune-Centered Factors

PubMed Central

Donadon, Matteo; Lleo, Ana; Di Tommaso, Luca; Soldani, Cristiana; Franceschini, Barbara; Roncalli, Massimo; Torzilli, Guido

2018-01-01

The determinants of prognosis in patients with colorectal liver metastases (CLM) have been traditionally searched among the tumoral factors, either of the primary colorectal tumor or of the CLM. While many different scoring systems have been developed based on those clinic-pathological factors with disparate results, there has been the introduction of genetic biological markers that added a theranostic perspective. More recently, other important elements, such as those factors related to the host immune system, have been proposed as determinants of prognosis of CLM patients. In the present work, we review the current prognostic factors of CLM patients as well as the burgeoning shifting paradigm of prognostication that relies on the host immune system. PMID:29892573

Cerebrovascular reactivity measurement in cerebral small vessel disease: Rationale and reproducibility of a protocol for MRI acquisition and image processing.

PubMed

Thrippleton, Michael J; Shi, Yulu; Blair, Gordon; Hamilton, Iona; Waiter, Gordon; Schwarzbauer, Christian; Pernet, Cyril; Andrews, Peter Jd; Marshall, Ian; Doubal, Fergus; Wardlaw, Joanna M

2018-02-01

Background Impaired autoregulation may contribute to the pathogenesis of cerebral small vessel disease. Reliable protocols for measuring microvascular reactivity are required to test this hypothesis and for providing secondary endpoints in clinical trials. Aims To develop and assess a protocol for acquisition and processing of cerebrovascular reactivity by MRI, in subcortical tissue of patients with small vessel disease and minor stroke. Methods We recruited 15 healthy volunteers, testing paradigms using 1- and 3-min 6% CO 2 challenges with repeat scanning, and 15 patients with history of minor stroke. We developed a protocol to measure cerebrovascular reactivity and delay times, assessing tolerability and reproducibility in grey and white matter areas. Results The 3-min paradigm yielded more reproducible data than the 1-min paradigm (CV respectively: 7.9-15.4% and 11.7-70.2% for cerebrovascular reactivity in grey matter), and was less reproducible in white matter (16.1-24.4% and 27.5-141.0%). Tolerability was similar for the two paradigms, but mean cerebrovascular reactivity and cerebrovascular reactivity delay were significantly higher for the 3-min paradigm in most regions. Patient tolerability was high with no evidence of greater failure rate (1/15 patients vs. 2/15 volunteers withdrew at the first visit). Grey matter cerebrovascular reactivity was lower in patients than in volunteers (0.110-0.234 vs. 0.172-0.313%/mmHg; p < 0.05 in 6/8 regions), as was the white matter cerebrovascular reactivity delay (16.2-43.9 vs. 31.1-47.9 s; p < 0.05 in 4/8 regions). Conclusions An effective and well-tolerated protocol for measurement of cerebrovascular reactivity was developed for use in ongoing and future trials to investigate small vessel disease pathophysiology and to measure treatment effects.

[Prospects for applications in human health of nanopore-based sequencing].

PubMed

Audebert, Christophe; Hot, David; Caboche, Ségolène

2018-04-01

High throughput sequencing has opened up new clinical opportunities moving towards a medicine of precision. Oncology, infectious diseases or human genomics, many applications have been developed in recent years. The introduction of a third generation of nanopore-based sequencing technology, addressing some of the weaknesses of the previous generation, heralds a new revolution. Portability, real time, long reads and marginal investment costs, these promising new technologies point to a new shift of paradigm. What are the perspectives opened up by nanopores for clinical applications? © 2018 médecine/sciences – Inserm.

The search for understanding: the role of paradigms.

PubMed

Kelly, Marcella; Dowling, Maura; Millar, Michelle

2018-03-16

Kuhn's ( 1962 ) acknowledgement of a paradigm as a way that scientists make sense of their world and its reality gave recognition to the idea of 'paradigm shift'. This shift exposes the transience of paradigm development shaped by societal and scientific evolution. This ongoing evolutionary development provides the researcher with many paradigms to consider regarding how research is undertaken and the search for understanding achieved. An understanding of paradigm development is necessary when planning a study and can shape the search for understanding. It is hoped that the discussion presented here will assist novice and experienced researchers in articulating the rationales for their paradigm choices. An overview of the dominant paradigms is presented, reflecting ongoing paradigm development shaped by ontological, epistemological and methodological perspectives. Potential paradigm choices that shape research aims, objectives and focus in the search for understanding are considered. The inherent debates about paradigm shift, division, war and synthesis leave the researcher many perspectives to consider. Articulating the world views underpinning constructivism, interpretivism and pragmatism is particularly challenging because of the blurring of boundaries between them. The evolutionary nature of paradigmatic development has provided nurse researchers with the opportunity for methodological openness to the myriad research approaches, methods and designs that they may choose to answer their research question. However, it is imperative that researchers consider their ontological stances and the nature of their research questions. This is challenging in constructivism, interpretivism and pragmatism, where there is often an overlap of paradigm world views. ©2018 RCN Publishing Company Ltd. All rights reserved. Not to be copied, transmitted or recorded in any way, in whole or part, without prior permission of the publishers.

New statistical learning theory paradigms adapted to breast cancer diagnosis/classification using image and non-image clinical data.

PubMed

Land, Walker H; Heine, John J; Raway, Tom; Mizaku, Alda; Kovalchuk, Nataliya; Yang, Jack Y; Yang, Mary Qu

2008-01-01

The automated decision paradigms presented in this work address the false positive (FP) biopsy occurrence in diagnostic mammography. An EP/ES stochastic hybrid and two kernelized Partial Least Squares (K-PLS) paradigms were investigated with following studies: methodology performance comparisonsautomated diagnostic accuracy assessments with two data sets. The findings showed: the new hybrid produced comparable results more rapidlythe new K-PLS paradigms train and operate Essentially in real time for the data sets studied. Both advancements are essential components for eventually achieving the FP reduction goal, while maintaining acceptable diagnostic sensitivities.

New statistical learning theory paradigms adapted to breast cancer diagnosis/classification using image and non-image clinical data

PubMed Central

Raway, Tom; Mizaku, Alda; Kovalchuk, Nataliya; Yang, Jack Y.; Yang, Mary Qu

2015-01-01

The automated decision paradigms presented in this work address the false positive (FP) biopsy occurrence in diagnostic mammography. An EP/ES stochastic hybrid and two kernelized Partial Least Squares (K-PLS) paradigms were investigated with following studies: methodology performance comparisonsautomated diagnostic accuracy assessments with two data sets. The findings showed: the new hybrid produced comparable results more rapidlythe new K-PLS paradigms train and operate Essentially in real time for the data sets studied. Both advancements are essential components for eventually achieving the FP reduction goal, while maintaining acceptable diagnostic sensitivities. PMID:26430470

Social scientific paradigms of masculinity and their implications for research and practice in men's mental health.

PubMed

Addis, Michael E; Cohane, Geoffrey H

2005-06-01

Clinical researchers and practitioners are increasingly aware of the need for quality theory, research, and intervention in men's mental health. Successful work in this area requires an understanding of the multitude of ways that gender, and more specifically masculinities, can be conceptualized beyond a sole focus on sex differences between men and women. Drawing from a range of social sciences in addition to psychology, the authors consider several theoretical, research, and clinical directions that can follow from social learning, psychodynamic, social constructionist, and feminist paradigms. It is concluded that thinking deeply and critically within different paradigms of masculinity is critical for progress in both research and practice. Copyright 2005 Wiley Periodicals, Inc.

A new paradigm for improved co-ordination and efficacy of European biomedical research: taking diabetes as a model.

PubMed

Halban, P A; Boulton, A J M; Smith, U

2013-03-01

Today, European biomedical and health-related research is insufficiently well funded and is fragmented, with no common vision, less-than-optimal sharing of resources, and inadequate support and training in clinical research. Improvements to the competitiveness of European biomedical research will depend on the creation of new infrastructures that must be dynamic and free of bureaucracy, involve all stakeholders and facilitate faster delivery of new discoveries from bench to bedside. Taking diabetes research as the model, a new paradigm for European biomedical research is presented, which offers improved co-ordination and common resources that will benefit both academic and industrial clinical research. This includes the creation of a European Council for Health Research, first proposed by the Alliance for Biomedical Research in Europe, which will bring together and consult with all health stakeholders to develop strategic and multidisciplinary research programmes addressing the full innovation cycle. A European Platform for Clinical Research in Diabetes is proposed by the Alliance for European Diabetes Research (EURADIA) in response to the special challenges and opportunities presented by research across the European region, with the need for common standards and shared expertise and data.

Trial watch: Naked and vectored DNA-based anticancer vaccines

PubMed Central

Bloy, Norma; Buqué, Aitziber; Aranda, Fernando; Castoldi, Francesca; Eggermont, Alexander; Cremer, Isabelle; Sautès-Fridman, Catherine; Fucikova, Jitka; Galon, Jérôme; Spisek, Radek; Tartour, Eric; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

2015-01-01

One type of anticancer vaccine relies on the administration of DNA constructs encoding one or multiple tumor-associated antigens (TAAs). The ultimate objective of these preparations, which can be naked or vectored by non-pathogenic viruses, bacteria or yeast cells, is to drive the synthesis of TAAs in the context of an immunostimulatory milieu, resulting in the (re-)elicitation of a tumor-targeting immune response. In spite of encouraging preclinical results, the clinical efficacy of DNA-based vaccines employed as standalone immunotherapeutic interventions in cancer patients appears to be limited. Thus, efforts are currently being devoted to the development of combinatorial regimens that allow DNA-based anticancer vaccines to elicit clinically relevant immune responses. Here, we discuss recent advances in the preclinical and clinical development of this therapeutic paradigm. PMID:26155408

Trial watch: Naked and vectored DNA-based anticancer vaccines.

PubMed

Bloy, Norma; Buqué, Aitziber; Aranda, Fernando; Castoldi, Francesca; Eggermont, Alexander; Cremer, Isabelle; Sautès-Fridman, Catherine; Fucikova, Jitka; Galon, Jérôme; Spisek, Radek; Tartour, Eric; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

2015-05-01

One type of anticancer vaccine relies on the administration of DNA constructs encoding one or multiple tumor-associated antigens (TAAs). The ultimate objective of these preparations, which can be naked or vectored by non-pathogenic viruses, bacteria or yeast cells, is to drive the synthesis of TAAs in the context of an immunostimulatory milieu, resulting in the (re-)elicitation of a tumor-targeting immune response. In spite of encouraging preclinical results, the clinical efficacy of DNA-based vaccines employed as standalone immunotherapeutic interventions in cancer patients appears to be limited. Thus, efforts are currently being devoted to the development of combinatorial regimens that allow DNA-based anticancer vaccines to elicit clinically relevant immune responses. Here, we discuss recent advances in the preclinical and clinical development of this therapeutic paradigm.

Simplistic and complex thought in medicine: the rationale for a person-centered care model as a medical revolution

PubMed Central

Reach, Gérard

2016-01-01

According to the concept developed by Thomas Kuhn, a scientific revolution occurs when scientists encounter a crisis due to the observation of anomalies that cannot be explained by the generally accepted paradigm within which scientific progress has thereto been made: a scientific revolution can therefore be described as a change in paradigm aimed at solving a crisis. Described herein is an application of this concept to the medical realm, starting from the reflection that during the past decades, the medical community has encountered two anomalies that, by their frequency and consequences, represent a crisis in the system, as they deeply jeopardize the efficiency of care: nonadherence of patients who do not follow the prescriptions of their doctors, and clinical inertia of doctors who do not comply with good practice guidelines. It is proposed that these phenomena are caused by a contrast between, on the one hand, the complex thought of patients and doctors that sometimes escapes rationalization, and on the other hand, the simplification imposed by the current paradigm of medicine dominated by the technical rationality of evidence-based medicine. It is suggested therefore that this crisis must provoke a change in paradigm, inventing a new model of care defined by an ability to take again into account, on an individual basis, the complex thought of patients and doctors. If this overall analysis is correct, such a person-centered care model should represent a solution to the two problems of patients’ nonadherence and doctors’ clinical inertia, as it tackles their cause. These considerations may have important implications for the teaching and the practice of medicine. PMID:27103790

Translational Radiomics: Defining the Strategy Pipeline and Considerations for Application-Part 2: From Clinical Implementation to Enterprise.

PubMed

Shaikh, Faiq; Franc, Benjamin; Allen, Erastus; Sala, Evis; Awan, Omer; Hendrata, Kenneth; Halabi, Safwan; Mohiuddin, Sohaib; Malik, Sana; Hadley, Dexter; Shrestha, Rasu

2018-03-01

Enterprise imaging has channeled various technological innovations to the field of clinical radiology, ranging from advanced imaging equipment and postacquisition iterative reconstruction tools to image analysis and computer-aided detection tools. More recently, the advancement in the field of quantitative image analysis coupled with machine learning-based data analytics, classification, and integration has ushered in the era of radiomics, a paradigm shift that holds tremendous potential in clinical decision support as well as drug discovery. However, there are important issues to consider to incorporate radiomics into a clinically applicable system and a commercially viable solution. In this two-part series, we offer insights into the development of the translational pipeline for radiomics from methodology to clinical implementation (Part 1) and from that point to enterprise development (Part 2). In Part 2 of this two-part series, we study the components of the strategy pipeline, from clinical implementation to building enterprise solutions. Copyright © 2017 American College of Radiology. Published by Elsevier Inc. All rights reserved.

Recent early clinical drug development for acute kidney injury.

PubMed

Gallagher, Kevin M; O'neill, Stephen; Harrison, Ewen M; Ross, James A; Wigmore, Stephen J; Hughes, Jeremy

2017-02-01

Despite significant need and historical trials, there are no effective drugs in use for the prevention or treatment of acute kidney injury (AKI). There are several promising agents in early clinical development for AKI and two trials have recently been terminated. There are also exciting new findings in pre-clinical AKI research. There is a need to take stock of current progress in the field to guide future drug development for AKI. Areas covered: The main clinical trial registries, PubMed and pharmaceutical company website searches were used to extract the most recent clinical trials for sterile, transplant and sepsis-associated AKI. We summarise the development of the agents recently in clinical trial, update on their trial progress, consider reasons for failed efficacy of two agents, and discuss new paradigms in pre-clinical targets for AKI. Agents covered include- QPI-1002, THR-184, BB-3, heme arginate, human recombinant alkaline phosphatase (recAP), ciclosporin A, AB103, levosimendan, AC607 and ABT-719. Expert opinion: Due to the heterogenous nature of AKI, agents with the widest pleiotropic effects on multiple pathophysiological pathways are likely to be most effective. Linking preclinical models to clinical indication and improving AKI definition and diagnosis are key areas for improvement in future clinical trials.

A systems change: leading the way to meeting health needs.

PubMed

Deisher, Mirella

2013-01-01

Demonstrating the efficacy of our practice requires a paradigm shift. Becoming an effective leader and clinician can facilitate opportunities for program development and clinical research. The use of strategic planning strategies, such as needs assessment and SWOT analysis, can help lead the way to such change. The following illustrates the use of strategic planning to develop The Carpal and Cubital Tunnel Syndrome Program (CCTSP) within a growing orthopedic practice. Copyright © 2013 Hanley & Belfus. Published by Elsevier Inc. All rights reserved.

Contact heat-evoked temporal summation: tonic versus repetitive-phasic stimulation.

PubMed

Granot, Michal; Granovsky, Yelena; Sprecher, Elliot; Nir, Rony-Reuven; Yarnitsky, David

2006-06-01

Temporal summation (TS) is usually evoked by repetitive mechanical or electrical stimuli, and less commonly by tonic heat pain. The present study aimed to examine the TS induction by repetitive-phasic versus tonic heat pain stimuli. Using 27 normal volunteers, we compared the extent of summation by three calculation methods: start-to-end pain rating difference, percent change, and double-logarithmic regression of successive ratings along the stimulation. Subjects were tested twice, and the reliability of each of the paradigms was obtained. In addition, personality factors related to pain catastrophizing and anxiety level were also correlated with the psychophysical results. Both paradigms induced significant TS, with similar increases for the repetitive-phasic and the tonic paradigms, as measured on 0-100 numerical pain scale (from 52.9+/-11.7 to 80.2+/-15.5, p<0.001; and from 38.5+/-13.3 to 75.8+/-18.3, p<0.001, respectively). The extent of summation was significantly correlated between the two paradigms, when calculated by absolute change (r=0.543, p=0.004) and by regression (r=0.438, p=0.025). Session-to-session variability was similar for both paradigms, relatively large, yet not biased. As with other psychophysical parameters, this poses some limitations on TS assessment in individual patients over time. The extent of TS induced by both paradigms was found to be associated with anxiety level and pain catastrophizing. Despite some dissimilarity between the repetitive-phasic and the tonic paradigms, the many similarities suggest that the two represent a similar physiological process, even if not precisely the same. Future clinical applications of these tests will determine the clinical relevance of the TS paradigms presented in this study.

Early insights into the characteristics and evolution of clinical parameters in a cohort of patients prescribed sacubitril/valsartan in Germany.

PubMed

Wachter, Rolf; Viriato, Daniel; Klebs, Sven; Grunow, Stefanie S; Schindler, Matthias; Engelhard, Johanna; Proenca, Catia C; Calado, Frederico; Schlienger, Raymond; Dworak, Markus; Balas, Bogdan; Bruce Wirta, Sara

2018-04-01

This study aimed to provide early insights into sacubitril/valsartan (sac/val) prescription patterns and the demographic and clinical characteristics of patients prescribed sac/val in primary care and cardiology settings in Germany. The study used electronic medical records from the German IMS® Disease Analyzer database. Patients with ≥1 prescription for sac/val during 1 January-31 December 2016 (n = 1643) were identified and followed up for ≤12 months from first prescription. Patients with ≥1 heart failure (HF) diagnosis during the study period, ≥1 additional HF diagnosis in the full history of the database, and ≥1 prescription for an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker and a β-blocker during the study period, without a prescription for sac/val (n = 25,264), were included as a reference cohort. Changes in clinical parameters in the 12 months before and after sac/val initiation were investigated and compared with those from the PARADIGM-HF study. The characteristics of patients prescribed sac/val more closely resembled those of patients enrolled in PARADIGM-HF (e.g. younger age, higher proportion of men than women, lower systolic blood pressure) than patients in the reference cohort. Most patients were initiated on the lowest dose of sac/val irrespective of clinical setting. Significant decreases (p < 0.001) in NT-proBNP and glycated haemoglobin levels were observed following sac/val initiation. Patients prescribed sac/val had similar baseline demographics and clinical characteristics to those from PARADIGM-HF, and most patients were initiated on the lowest dose. Changes in clinical parameters before and after initiation mirrored findings from the PARADIGM-HF study.

Bioinformatics Approaches for Fetal DNA Fraction Estimation in Noninvasive Prenatal Testing

PubMed Central

Peng, Xianlu Laura; Jiang, Peiyong

2017-01-01

The discovery of cell-free fetal DNA molecules in plasma of pregnant women has created a paradigm shift in noninvasive prenatal testing (NIPT). Circulating cell-free DNA in maternal plasma has been increasingly recognized as an important proxy to detect fetal abnormalities in a noninvasive manner. A variety of approaches for NIPT using next-generation sequencing have been developed, which have been rapidly transforming clinical practices nowadays. In such approaches, the fetal DNA fraction is a pivotal parameter governing the overall performance and guaranteeing the proper clinical interpretation of testing results. In this review, we describe the current bioinformatics approaches developed for estimating the fetal DNA fraction and discuss their pros and cons. PMID:28230760

Bioinformatics Approaches for Fetal DNA Fraction Estimation in Noninvasive Prenatal Testing.

PubMed

Peng, Xianlu Laura; Jiang, Peiyong

2017-02-20

The discovery of cell-free fetal DNA molecules in plasma of pregnant women has created a paradigm shift in noninvasive prenatal testing (NIPT). Circulating cell-free DNA in maternal plasma has been increasingly recognized as an important proxy to detect fetal abnormalities in a noninvasive manner. A variety of approaches for NIPT using next-generation sequencing have been developed, which have been rapidly transforming clinical practices nowadays. In such approaches, the fetal DNA fraction is a pivotal parameter governing the overall performance and guaranteeing the proper clinical interpretation of testing results. In this review, we describe the current bioinformatics approaches developed for estimating the fetal DNA fraction and discuss their pros and cons.

Yearning for the Vastness of the Sea: Reflections and Commentary on Professional Training in Hypnosis.

PubMed

Baker, Elgan L

2017-01-01

Educational programs are a major focus of most professional hypnosis societies. Many of these programs rely on traditional curricula and teaching strategies with variable success. The articles in this special issue examine and critique these training models and suggest innovative approaches to professional education with an emphasis on more uniform course content and goals and more dynamic and effective educational processes. A convergence of themes is noted and examined including the need to continue to expand the acceptance and utilization of clinical hypnosis, the importance of attending to broader clinical competence beyond hypnosis skills, the need for faculty development and evaluation, and the imperative that course content reflects academic rigor and contemporary science as well as providing for demonstration and supervised clinical practice. These themes are explicated for the development of new training paradigms and for continued programs in the field of clinical hypnosis.

Product-Related Impurities in Clinical-Grade Recombinant AAV Vectors: Characterization and Risk Assessment

PubMed Central

Wright, J. Fraser

2014-01-01

Adeno-associated virus (AAV)-based vectors expressing therapeutic genes continue to demonstrate great promise for the treatment of a wide variety of diseases and together with other gene transfer vectors represent an emerging new therapeutic paradigm comparable in potential impact on human health to that achieved by recombinant proteins and vaccines. A challenge for the current pipeline of AAV-based investigational products as they advance through clinical development is the identification, characterization and lot-to-lot control of the process- and product-related impurities present in even highly purified preparations. Especially challenging are AAV vector product-related impurities that closely resemble the vector itself and are, in some cases, without clear precedent in established biotherapeutic products. The determination of acceptable levels of these impurities in vectors prepared for human clinical product development, with the goal of new product licensure, requires careful risk and feasibility assessment. This review focuses primarily on the AAV product-related impurities that have been described in vectors prepared for clinical development. PMID:28548061

A Model of Teaching-Learning Transactions in Generalist-Specialist Consultations

ERIC Educational Resources Information Center

Shershneva, Marianna B.; Carnes, Molly; Bakken, Lori L.

2006-01-01

Introduction: A new paradigm in continuing medical education is characterized by emphasis on physicians' learning in practice. Consistent with this paradigm, our study examined a subset of clinical practice--generalist-specialist consultations--from an educational perspective. Methods: We applied the grounded-theory method with semistructured…

Virtual reality jogging as a novel exposure paradigm for the acute urge to be physically active in patients with eating disorders: Implications for treatment.

PubMed

Paslakis, Georgios; Fauck, Vanessa; Röder, Kathrin; Rauh, Elisabeth; Rauh, Manfred; Erim, Yesim

2017-11-01

The acute urge to be physically active is a relevant clinical phenomenon in patients suffering from eating disorders. In this study with n = 20 female patients with anorexia nervosa and n = 10 female patients with bulimia nervosa, a virtual reality (VR) jogging paradigm was applied as a novel highly immersive 3D exposure paradigm. Patients were asked to rate their acute urge to be physically active during the exposure procedure. A 10-item self-report questionnaire (smQ) was developed to capture the cognitive, emotional, and behavioral aspects of the acute urge to move. We hypothesized that exposure would lead to habituation of the urge to be physically active. We also hypothesized that leptin levels would be associated with the degree of the subjective urge to be physically active, while habituation would be associated with a decrease in stress hormones (α-amylase, cortisol, and cortisone in saliva). A statistically significant change in subjective scores in the smQ from baseline to postexposure was seen. Our novel VR paradigm may serve as a therapeutic tool for exposure and habituation of the urge of acutely engaging in physical activity in patients with eating disorders. © 2017 Wiley Periodicals, Inc.

After pluralism: towards a new, integrated psychoanalytic paradigm.

PubMed

Jiménez, Juan Pablo

2006-12-01

After a restatement of the isolationism of psychoanalysis from allied disciplines, and an examination of some of the reasons for the diversity of schools of thought and the fragmentation of psychoanalytic knowledge, the author suggests the need to adopt principles of correspondence or external coherence along with those of hermeneutic coherence to validate psychoanalytic hypotheses. Recent developments in neurocognitive science have come to the aid of psychoanalysis in this period of crisis, resulting in the proposition of integrating both areas to form a new paradigm for the construction of the theory of the mind. This emerging paradigm tries to integrate clinical knowledge with neurocognitive science, findings from studies on the process and outcome of psychotherapy, research into the early mother-infant relationship, and developmental psychopathology. The author examines theoretical- technical models based on the concept of drives and of relationships in the light of interdisciplinary findings. He concludes that the relational model has a broad empirical base, except when the concept of drives is discredited. Interdisciplinary findings have led to the positing of the replacement of the Freudian model of drives with a model of motivational systems centred on affective processes. He draws certain conclusions which have a bearing on the technique of psychoanalytic treatment. These arise from the adoption of the new integrated paradigm.

Exercise training and immune crosstalk in breast cancer microenvironment: exploring the paradigms of exercise-induced immune modulation and exercise-induced myokines.

PubMed

Goh, Jorming; Niksirat, Negin; Campbell, Kristin L

2014-01-01

Observational research suggests that exercise may reduce the risk of breast cancer and improve survival. One proposed mechanism for the protective effect of aerobic exercise related to cancer risk and outcomes, but has not been examined definitively, is the immune response to aerobic exercise. Two prevailing paradigms are proposed. The first considers the host immune response as modifiable by aerobic exercise training. This exercise-modulated immune-tumor crosstalk in the mammary microenvironment may alter the balance between tumor initiation and progression versus tumor suppression. The second paradigm considers the beneficial role of exercise-induced, skeletal muscle-derived cytokines, termed "myokines". These myokines exert endocrine-like effects on multiple organs, including the mammary glands. In this systematic review, we i) define the role of macrophages and T-cells in breast cancer initiation and progression; ii) address the two paradigms that support exercise-induced immunomodulation; iii) systematically assessed the literature for exercise intervention that assessed biomarkers relevant to both paradigms in human intervention trials of aerobic exercise training, in healthy women and women with breast cancer; iv) incorporated pre-clinical animal studies and non-RCTs for background discussion of putative mechanisms, through which aerobic exercise training modulates the immunological crosstalk, or the myokine-tumor interaction in the tumor microenvironment; and v) speculated on the potential biomarkers and mechanisms that define an exercise-induced, anti-tumor "signature", with a view toward developing relevant biomarkers for future aerobic exercise intervention trials.

Philosophy of science and the emerging paradigm: implications for hypnosis.

PubMed

Osowiec, Darlene A

2014-01-01

Within the hypnosis field, there is a disparity between clinical and research worldviews. Clinical practitioners work with patients who are dealing with serious, often unique, real-world problems-lived experience. Researchers adhere to objective measurements, standardization, data, and statistics. Although there is overlap, an ongoing divergence can be counterproductive to the hypnosis field and to the larger professional and social contexts. The purpose of this article is: (1) to examine some of the major assumptions, the history, and the philosophy that undergird the definition of science, which was constructed in the mid-17th century; (2) to discover how science is a product of prevailing social forces and is undergoing a paradigm shift; and (3) to understand the more encompassing, holistic paradigm with implications for the hypnosis field.

Treating Patients Who Strain the Research Psychotherapy Paradigm

PubMed Central

Markowitz, John C.; Kaplowitz, Matthew; Suh, Eun-Jung; Meehan, Kevin; Neria, Yuval; Jonker, Hanske; Rafaeli, Alexandra; Lovell, Karina

2013-01-01

Background Clinical trials of psychotherapy require diagnostic homogeneity, which implies a convergence of clinical presentations. Yet research study patients present diversely, and patients who do not fit a treatment paradigm may greatly complicate delivery of the study psychotherapy. The research literature has not addressed this issue. Methods The authors use case illustrations of three psychotherapies – Prolonged Exposure, Relaxation Therapy, and Interpersonal Psychotherapy – from an ongoing psychotherapy outcome trial of posttraumatic stress disorder to describe psychotherapeutic responses to complex, “atypical” patients who strain standard treatment paradigms. Results Therapists required flexibility, and occasionally deviations from strict protocol, in treating heterodox patients. Conclusions Such heterogeneity of presentation may have implications for psychotherapy outcome in research trials. Despite lack of discussion in the literature, many trials may face such issues. PMID:22759936

DNA vaccination for prostate cancer, from preclinical to clinical trials - where we stand?

PubMed Central

2012-01-01

Development of various vaccines for prostate cancer (PCa) is becoming an active research area. PCa vaccines are perceived to have less toxicity compared with the available cytotoxic agents. While various immune-based strategies can elicit anti-tumour responses, DNA vaccines present increased efficacy, inducing both humoural and cellular immunity. This immune activation has been proven effective in animal models and initial clinical trials are encouraging. However, to validate the role of DNA vaccination in currently available PCa management paradigms, strong clinical evidence is still lacking. This article provides an overview of the basic principles of DNA vaccines and aims to provide a summary of preclinical and clinical trials outlining the benefits of this immunotherapy in the management of PCa. PMID:23046944

Partnering with patients to promote holistic diabetes management: changing paradigms.

PubMed

Lorenzo, Lenora

2013-07-01

To provide a review of best practice for clinical management of diabetes mellitus (DM) for nurse practitioners (NPs) and accelerate incorporation of key findings into current practice. A search was conducted in Pub Med, Ovid, CINAHL, and Cochrane's Database of Systematic Reviews. There are many challenges for DM care identified in the current health system. There is a great need to change care paradigms to engage patients in partnership for enhanced management and self-management in DM. A review of the best practice evidence revealed numerous models of care, strategies, and tools available to enhance diabetes care and promote health and well-being. The primary focus of this article is to engage NP clinicians to incorporate new strategies to augment management and improve clinical outcomes. Incorporation of best practice for DM management may accelerate the paradigm shift to more patient-focused care. Engaged, informed, and activated patients along with clinicians working in partnerships may enhance clinical outcomes. ©2013 The Author ©2013 American Association of Nurse Practitioners.

Game Theory Paradigm: A New Tool for Investigating Social Dysfunction in Major Depressive Disorders

PubMed Central

Wang, Yun; Yang, Liu-Qing; Li, Shu; Zhou, Yuan

2015-01-01

Social dysfunction is a prominent source of distress and disability in patients with major depressive disorder (MDD) but is commonly omitted from current clinical studies, although some researchers propose an evolutionary strategy to understand these negative outcomes. Limited knowledge about the neural basis of social dysfunction in MDD results from traditional paradigms, which lack insights into social interactions. Game theoretical modeling offers a new tool for investigating social-interaction impairments in neuropsychiatric disorders. This review first introduces three widely used games from game theory and the major behavioral and neuroimaging findings obtained using these games in healthy populations. We also address the factors that modulate behaviors in games and their neural bases. We then summarize the current findings obtained by using these games in depressed patients and discuss the clinical implications of these abnormal game behaviors. Finally, we briefly discuss future prospects that may further elucidate the clinical use of a game theory paradigm in MDD. PMID:26441689

Game Theory Paradigm: A New Tool for Investigating Social Dysfunction in Major Depressive Disorders.

PubMed

Wang, Yun; Yang, Liu-Qing; Li, Shu; Zhou, Yuan

2015-01-01

Social dysfunction is a prominent source of distress and disability in patients with major depressive disorder (MDD) but is commonly omitted from current clinical studies, although some researchers propose an evolutionary strategy to understand these negative outcomes. Limited knowledge about the neural basis of social dysfunction in MDD results from traditional paradigms, which lack insights into social interactions. Game theoretical modeling offers a new tool for investigating social-interaction impairments in neuropsychiatric disorders. This review first introduces three widely used games from game theory and the major behavioral and neuroimaging findings obtained using these games in healthy populations. We also address the factors that modulate behaviors in games and their neural bases. We then summarize the current findings obtained by using these games in depressed patients and discuss the clinical implications of these abnormal game behaviors. Finally, we briefly discuss future prospects that may further elucidate the clinical use of a game theory paradigm in MDD.

Biomedical and development paradigms in AIDS prevention.

PubMed Central

Wolffers, I.

2000-01-01

In the fight against the HIV/AIDS pandemic different approaches can be distinguished, reflecting professional backgrounds, world views and political interests. One important distinction is between the biomedical and the development paradigms. The biomedical paradigm is characterized by individualization and the concept of "risk". This again is related to the concept of the market where health is a product of services and progress a series of new discoveries that can be marketed. The development paradigm is characterized by participation of the different stakeholders and by community work. The concept "vulnerability" is important in the development paradigm and emphasis is placed on efforts to decrease this vulnerability in a variety of sustainable ways. Biomedical technology is definitely one of the tools in these efforts. In the beginning of the pandemic the biomedical approach was important for the discovery of the virus and understanding its epidemiology. Later, stakeholders became involved. In the light of absence of treatment or vaccines, the development paradigm became more important and the two approaches were more in balance. However, since the reports about effective treatment of AIDS and hope of development of vaccines, the biomedical paradigm has become a leading principle in many HIV/AIDS prevention programmes. There is a need for a better balance between the two paradigms. Especially in developing countries, where it is not realistic to think that sustainable biomedical interventions can be organized on a short-term basis, it would be counterproductive to base our efforts to deal with HIV/AIDS exclusively on the biomedical approach. PMID:10743300

Integrative Mental Health (IMH): paradigm, research, and clinical practice.

PubMed

Lake, James; Helgason, Chanel; Sarris, Jerome

2012-01-01

This paper provides an overview of the rapidly evolving paradigm of "Integrative Mental Health (IMH)." The paradigm of contemporary biomedical psychiatry and its contrast to non-allopathic systems of medicine is initially reviewed, followed by an exploration of the emerging paradigm of IMH, which aims to reconcile the bio-psycho-socio-spiritual model with evidence-based methods from traditional healing practices. IMH is rapidly transforming conventional understandings of mental illness and has significant positive implications for the day-to-day practice of mental health care. IMH incorporates mainstream interventions such as pharmacologic treatments, psychotherapy, and psychosocial interventions, as well as alternative therapies such as acupuncture, herbal and nutritional medicine, dietary modification, meditation, etc. Two recent international conferences in Europe and the United States show that interest in integrative mental health care is growing rapidly. In response, the International Network of Integrative Mental Health (INIMH: www.INIMH.org) was established in 2010 with the objective of creating an international network of clinicians, researchers, and public health advocates to advance a global agenda for research, education, and clinical practice of evidence-based integrative mental health care. The paper concludes with a discussion of emerging opportunities for research in IMH, and an exploration of potential clinical applications of integrative mental health care. Copyright © 2012 Elsevier Inc. All rights reserved.

Learning about Expectation Violation from Prediction Error Paradigms – A Meta-Analysis on Brain Processes Following a Prediction Error

PubMed Central

D’Astolfo, Lisa; Rief, Winfried

2017-01-01

Modifying patients’ expectations by exposing them to expectation violation situations (thus maximizing the difference between the expected and the actual situational outcome) is proposed to be a crucial mechanism for therapeutic success for a variety of different mental disorders. However, clinical observations suggest that patients often maintain their expectations regardless of experiences contradicting their expectations. It remains unclear which information processing mechanisms lead to modification or persistence of patients’ expectations. Insight in the processing could be provided by Neuroimaging studies investigating prediction error (PE, i.e., neuronal reactions to non-expected stimuli). Two methods are often used to investigate the PE: (1) paradigms, in which participants passively observe PEs (”passive” paradigms) and (2) paradigms, which encourage a behavioral adaptation following a PE (“active” paradigms). These paradigms are similar to the methods used to induce expectation violations in clinical settings: (1) the confrontation with an expectation violation situation and (2) an enhanced confrontation in which the patient actively challenges his expectation. We used this similarity to gain insight in the different neuronal processing of the two PE paradigms. We performed a meta-analysis contrasting neuronal activity of PE paradigms encouraging a behavioral adaptation following a PE and paradigms enforcing passiveness following a PE. We found more neuronal activity in the striatum, the insula and the fusiform gyrus in studies encouraging behavioral adaptation following a PE. Due to the involvement of reward assessment and avoidance learning associated with the striatum and the insula we propose that the deliberate execution of action alternatives following a PE is associated with the integration of new information into previously existing expectations, therefore leading to an expectation change. While further research is needed to directly assess expectations of participants, this study provides new insights into the information processing mechanisms following an expectation violation. PMID:28804467

Learning about Expectation Violation from Prediction Error Paradigms - A Meta-Analysis on Brain Processes Following a Prediction Error.

PubMed

D'Astolfo, Lisa; Rief, Winfried

2017-01-01

Modifying patients' expectations by exposing them to expectation violation situations (thus maximizing the difference between the expected and the actual situational outcome) is proposed to be a crucial mechanism for therapeutic success for a variety of different mental disorders. However, clinical observations suggest that patients often maintain their expectations regardless of experiences contradicting their expectations. It remains unclear which information processing mechanisms lead to modification or persistence of patients' expectations. Insight in the processing could be provided by Neuroimaging studies investigating prediction error (PE, i.e., neuronal reactions to non-expected stimuli). Two methods are often used to investigate the PE: (1) paradigms, in which participants passively observe PEs ("passive" paradigms) and (2) paradigms, which encourage a behavioral adaptation following a PE ("active" paradigms). These paradigms are similar to the methods used to induce expectation violations in clinical settings: (1) the confrontation with an expectation violation situation and (2) an enhanced confrontation in which the patient actively challenges his expectation. We used this similarity to gain insight in the different neuronal processing of the two PE paradigms. We performed a meta-analysis contrasting neuronal activity of PE paradigms encouraging a behavioral adaptation following a PE and paradigms enforcing passiveness following a PE. We found more neuronal activity in the striatum, the insula and the fusiform gyrus in studies encouraging behavioral adaptation following a PE. Due to the involvement of reward assessment and avoidance learning associated with the striatum and the insula we propose that the deliberate execution of action alternatives following a PE is associated with the integration of new information into previously existing expectations, therefore leading to an expectation change. While further research is needed to directly assess expectations of participants, this study provides new insights into the information processing mechanisms following an expectation violation.

The treatment of Parkinson's disease with deep brain stimulation: current issues

PubMed Central

Moldovan, Alexia-Sabine; Groiss, Stefan Jun; Elben, Saskia; Südmeyer, Martin; Schnitzler, Alfons; Wojtecki, Lars

2015-01-01

Deep brain stimulation has become a well-established symptomatic treatment for Parkinson's disease during the last 25 years. Besides improving motor symptoms and long-term motor complications, positive effects on patients’ mobility, activities of daily living, emotional well-being and health-related quality of life have been recognized. Apart from that, numerous clinical trials analyzed effects on non-motor symptoms and side effects of deep brain stimulation. Several technical issues and stimulation paradigms have been and are still being developed to optimize the therapeutic effects, minimize the side effects and facilitate handling. This review summarizes current therapeutic issues, i.e., patient and target selection, surgical procedure and programming paradigms. In addition it focuses on neuropsychological effects and side effects of deep brain stimulation. PMID:26330809

How to report and discuss ADME data in medicinal chemistry publications: in vitro data or in vivo extrapolations?

PubMed

Svennebring, Andreas M

2015-01-01

Early drug discovery projects often utilize data from ADME (absorption, distribution, metabolism, elimination) assays to benchmark data and guide discussion, rather than the predicted in vivo consequences of these data. Here, the two paradigms are compared, using evaluations of metabolic stability based on either microsomal clearance assay data or from the predicted in vivo hepatic clearance and half-life calculated through the combination of the venous well-stirred model and Øie-Tozer's model. The need for a shift in paradigm is presented, and its implications discussed. It is suggested that discussions about ADME data should revolve around potential clinical problems that are most likely to surface during the development phase, each benchmarked with a suitable variable derived from the assay data.

Bridging the practitioner-scientist gap in group psychotherapy research.

PubMed

Lau, Mark A; Ogrodniczuk, John; Joyce, Anthony S; Sochting, Ingrid

2010-04-01

Bridging the practitioner-scientist gap requires a different clinical research paradigm: participatory research that encourages community agency-academic partnerships. In this context, clinicians help define priorities, determine the type of evidence that will have an impact on their practice (affecting the methods that are used to produce the evidence), and develop strategies for translating, implementing, and disseminating their findings into evidence-based practice. Within this paradigm, different roles are assumed by the partners, and sometimes these roles are blended. This paper will consider the perspectives of people who assume these different roles (clinician, researcher, and clinician-researcher) with group psychotherapy as the specific focus. Finally, the establishment of a practice-research network will be discussed as a potentially promising way to better engage group therapists in research.

Speech-feature discrimination in children with Asperger syndrome as determined with the multi-feature mismatch negativity paradigm.

PubMed

Kujala, T; Kuuluvainen, S; Saalasti, S; Jansson-Verkasalo, E; von Wendt, L; Lepistö, T

2010-09-01

Asperger syndrome, belonging to the autistic spectrum of disorders, involves deficits in social interaction and prosodic use of language but normal development of formal language abilities. Auditory processing involves both hyper- and hypoactive reactivity to acoustic changes. Responses composed of mismatch negativity (MMN) and obligatory components were recorded for five types of deviations in syllables (vowel, vowel duration, consonant, syllable frequency, syllable intensity) with the multi-feature paradigm from 8-12-year old children with Asperger syndrome. Children with Asperger syndrome had larger MMNs for intensity and smaller MMNs for frequency changes than typically developing children, whereas no MMN group differences were found for the other deviant stimuli. Furthermore, children with Asperger syndrome performed more poorly than controls in Comprehension of Instructions subtest of a language test battery. Cortical speech-sound discrimination is aberrant in children with Asperger syndrome. This is evident both as hypersensitive and depressed neural reactions to speech-sound changes, and is associated with features (frequency, intensity) which are relevant for prosodic processing. The multi-feature MMN paradigm, which includes variation and thereby resembles natural speech hearing circumstances, suggests abnormal pattern of speech discrimination in Asperger syndrome, including both hypo- and hypersensitive responses for speech features. 2010 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

CNTRICS Final Biomarker Selection: Control of Attention

PubMed Central

Luck, Steven J.; Ford, Judith M.; Sarter, Martin; Lustig, Cindy

2012-01-01

Attention is widely believed to be dysfunctional in schizophrenia. The Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS) group previously concluded that the processes involved in the top-down control of attention are particularly impaired in schizophrenia and should be the focus of future research. These processes determine which sources of input should be attended, linking goal representations in prefrontal cortex with more posterior regions that implement the actual selection of attended information. A more recent meeting of the CNTRICS group assessed several paradigms that might be useful for identifying biomarkers of attentional control and that could be used for treatment development and assessment. Two types of paradigms were identified as being particularly promising. In one approach, neural activity is measured (using electroencephalography or functional magnetic resonance imaging) during the period between an attention-directing cue and a target. In a second approach, neural activity is measured under low- and high-distraction conditions. These approaches make it possible to identify the goal representations that guide attention and the interactions between these goal representations and the implementation of selection. Although more basic science research with healthy volunteers and preclinical research with schizophrenia patients is needed before these paradigms will be ready to provide clinically useful biomarkers, they hold substantial promise for aiding in the development and assessment of new treatments. PMID:21765166

Critical Questions about PARADIGM-HF and the Future

PubMed Central

Chen, Chen-Huan

2016-01-01

Cardiovascular (CV) diseases in general and heart failure (HF) in particular are major contributors to death and morbidity and are also recognized as important drivers of health care expenditure. The PARADIGM-HF trial was a pivotal trial designed to compare the long-term effects of LCZ696 with enalapril in patients with symptomatic HF with reduced ejection fraction (HFrEF). This review article presents an in-depth view of the PARADIGM-HF trial and the implications of the results in the management of patients with HF and is based on peer reviewed manuscripts, editorials, perspectives and opinions written about the PARADIGM-HF trial. The article presents the key safety and efficacy results of the trial with specific emphasis on the clinical implications of these findings. The review highlights the highly statistically significant, 20% reduction in the primary composite endpoint of cardiovascular death or HF hospitalization, and a 16% reduction in the risk of death from any cause. It also provides an overview of the design, clinical findings, limitations and special areas of clinical interest. The review discusses the future of LCZ696 and additional trials that seek to answer questions in other sub-populations of patients with HF. The article reiterates what has been concluded by many experts in the field of HF- the introduction of LCZ696 into routine clinical care, while dependent on the regulatory approvals in various countries as well as acceptance by physicians, payers and patients, will change the treatment landscape for patients with HFrEF. PMID:27471351

Dissonance-based interventions for health behaviour change: a systematic review.

PubMed

Freijy, Tanya; Kothe, Emily J

2013-05-01

Increasing evidence suggests that various health behaviours are amenable to change following the induction of cognitive dissonance. This systematic review sought to evaluate the effectiveness and methodological quality of dissonance-based health behaviour interventions and to explore identified sources of heterogeneity in intervention effects. Bibliographic databases were searched for relevant articles from inception to March 2012. Only studies targeting non-clinical health behaviour in non-clinical populations were included in the review. One author extracted data and assessed quality of evidence and a second author verified all content. Reports of 20 studies were included. A variety of health behaviours and outcome measures were addressed across studies. Most studies produced one or more significant effects on measures of behaviour, attitude or intention. Across studies, methodological risk for bias was frequently high, particularly for selection bias. Gender and self-esteem were identified as potential moderator variables. The evidence for the effectiveness of dissonance-based interventions was generally positive. The hypocrisy paradigm was found to be the most commonly applied research paradigm and was most effective at inciting change across a range of health behaviours. There was no observable link between type of target behaviour and positive outcomes. Researchers are encouraged to minimize potential for bias in future studies and explore moderators of the dissonance effect. What is already known on this subject? A recent meta-analysis indicates that dissonance-based interventions primarily based on the induced compliance paradigm are effective for eating disorder prevention (Stice, Shaw, Becker, & Rohde, 2008, Prev. Sci., 9, 114). However, it is currently unclear whether such outcomes are generalizable to interventions targeting non-clinical health behaviours such as smoking, sun protection and sexual risk taking. Other research indicates that studies based on the hypocrisy paradigm may lead to changes in non-clinical health behaviours (Stone & Fernandez, 2008, Soc. Personal. Psychol. Compass, 2, 1024; Stone & Focella, 2011, Self Identity, 10, 295) although this literature lacks systematic evaluation of interventions across a range of experimental paradigms. What does this study add? The hypocrisy paradigm appears most effective in inciting change across a range of non-clinical health behaviours. The dissonance effect may be moderated by variables such as self-esteem and gender. Risk of bias needs to be minimised to increase the validity of studies within this topic area. © 2013 The British Psychological Society.

Development of inexpensive blood imaging systems: where are we now?

PubMed

Chu, Kaiqin; Smith, Zachary J; Wachsmann-Hogiu, Sebastian

2015-01-01

Clinical applications in the developing world, such as malaria and anemia diagnosis, demand a change in the medical paradigm of expensive care given in central locations by highly trained professionals. There has been a recent explosion in optical technologies entering the consumer market through the widespread adoption of smartphones and LEDs. This technology commoditization has enabled the development of small, portable optical imaging systems at an unprecedentedly low cost. Here, we review the state-of-the-field of the application of these systems for low-cost blood imaging with an emphasis on cellular imaging systems. In addition to some promising results addressing specific clinical issues, an overview of the technology landscape is provided. We also discuss several key issues that need to be addressed before these technologies can be commercialized.

A SOA-Based Platform to Support Clinical Data Sharing.

PubMed

Gazzarata, R; Giannini, B; Giacomini, M

2017-01-01

The eSource Data Interchange Group, part of the Clinical Data Interchange Standards Consortium, proposed five scenarios to guide stakeholders in the development of solutions for the capture of eSource data. The fifth scenario was subdivided into four tiers to adapt the functionality of electronic health records to support clinical research. In order to develop a system belonging to the "Interoperable" Tier, the authors decided to adopt the service-oriented architecture paradigm to support technical interoperability, Health Level Seven Version 3 messages combined with LOINC (Logical Observation Identifiers Names and Codes) vocabulary to ensure semantic interoperability, and Healthcare Services Specification Project standards to provide process interoperability. The developed architecture enhances the integration between patient-care practice and medical research, allowing clinical data sharing between two hospital information systems and four clinical data management systems/clinical registries. The core is formed by a set of standardized cloud services connected through standardized interfaces, involving client applications. The system was approved by a medical staff, since it reduces the workload for the management of clinical trials. Although this architecture can realize the "Interoperable" Tier, the current solution actually covers the "Connected" Tier, due to local hospital policy restrictions.

A SOA-Based Platform to Support Clinical Data Sharing

PubMed

Gazzarata, R; Giannini, B; Giacomini, M

2017-01-01

The eSource Data Interchange Group, part of the Clinical Data Interchange Standards Consortium, proposed five scenarios to guide stakeholders in the development of solutions for the capture of eSource data. The fifth scenario was subdivided into four tiers to adapt the functionality of electronic health records to support clinical research. In order to develop a system belonging to the “Interoperable” Tier, the authors decided to adopt the service-oriented architecture paradigm to support technical interoperability, Health Level Seven Version 3 messages combined with LOINC (Logical Observation Identifiers Names and Codes) vocabulary to ensure semantic interoperability, and Healthcare Services Specification Project standards to provide process interoperability. The developed architecture enhances the integration between patient-care practice and medical research, allowing clinical data sharing between two hospital information systems and four clinical data management systems/clinical registries. The core is formed by a set of standardized cloud services connected through standardized interfaces, involving client applications. The system was approved by a medical staff, since it reduces the workload for the management of clinical trials. Although this architecture can realize the “Interoperable” Tier, the current solution actually covers the “Connected” Tier, due to local hospital policy restrictions. © 2017 R. Gazzarata et al.

Clinical social networking--a new revolution in provider communication and delivery of clinical information across providers of care?

PubMed

Kolowitz, Brian J; Lauro, Gonzalo Romero; Venturella, James; Georgiev, Veliyan; Barone, Michael; Deible, Christopher; Shrestha, Rasu

2014-04-01

The adoption of social media technologies appears to enhance clinical outcomes through improved communications as reported by Bacigalupe (Fam Syst Heal 29(1):1-14, 2011). The ability of providers to more effectively, directly, and rapidly communicate among themselves as well as with patients should strengthen collaboration and treatment as reported by Bacigalupe (Fam Syst Heal 29(1):1-14, 2011). This paper is a case study in one organization's development of an internally designed and developed social technology solution termed "Unite." The Unite system combines social technologies' features including push notifications, messaging, community groups, and user lists with clinical workflow and applications to construct dynamic provider networks, simplify communications, and facilitate clinical workflow optimization. Modeling Unite as a social technology may ease adoption barriers. Developing a social network that is integrated with healthcare information systems in the clinical space opens the doors to capturing and studying the way in which providers communicate. The Unite system appears to have the potential to breaking down existing communication paradigms. With Unite, a rich set of usage data tied to clinical events may unravel alternative networks that can be leveraged to advance patient care.

A SOA-Based Platform to Support Clinical Data Sharing

PubMed Central

Gazzarata, R.; Giannini, B.

2017-01-01

The eSource Data Interchange Group, part of the Clinical Data Interchange Standards Consortium, proposed five scenarios to guide stakeholders in the development of solutions for the capture of eSource data. The fifth scenario was subdivided into four tiers to adapt the functionality of electronic health records to support clinical research. In order to develop a system belonging to the “Interoperable” Tier, the authors decided to adopt the service-oriented architecture paradigm to support technical interoperability, Health Level Seven Version 3 messages combined with LOINC (Logical Observation Identifiers Names and Codes) vocabulary to ensure semantic interoperability, and Healthcare Services Specification Project standards to provide process interoperability. The developed architecture enhances the integration between patient-care practice and medical research, allowing clinical data sharing between two hospital information systems and four clinical data management systems/clinical registries. The core is formed by a set of standardized cloud services connected through standardized interfaces, involving client applications. The system was approved by a medical staff, since it reduces the workload for the management of clinical trials. Although this architecture can realize the “Interoperable” Tier, the current solution actually covers the “Connected” Tier, due to local hospital policy restrictions. PMID:29065576

XML-based scripting of multimodality image presentations in multidisciplinary clinical conferences

NASA Astrophysics Data System (ADS)

Ratib, Osman M.; Allada, Vivekanand; Dahlbom, Magdalena; Marcus, Phillip; Fine, Ian; Lapstra, Lorelle

2002-05-01

We developed a multi-modality image presentation software for display and analysis of images and related data from different imaging modalities. The software is part of a cardiac image review and presentation platform that supports integration of digital images and data from digital and analog media such as videotapes, analog x-ray films and 35 mm cine films. The software supports standard DICOM image files as well as AVI and PDF data formats. The system is integrated in a digital conferencing room that includes projections of digital and analog sources, remote videoconferencing capabilities, and an electronic whiteboard. The goal of this pilot project is to: 1) develop a new paradigm for image and data management for presentation in a clinically meaningful sequence adapted to case-specific scenarios, 2) design and implement a multi-modality review and conferencing workstation using component technology and customizable 'plug-in' architecture to support complex review and diagnostic tasks applicable to all cardiac imaging modalities and 3) develop an XML-based scripting model of image and data presentation for clinical review and decision making during routine clinical tasks and multidisciplinary clinical conferences.

21st century paradigm of tissue banking: the Clinical Breast Care Project.

PubMed

Shriver, Craig D

2010-07-01

The Clinical Breast Care Project (CBCP) is a congressionally mandated program that began in the year 2000. The military-civilian collaboration was founded on five pillars: (1) center of excellence in clinical care, (2) risk reduction for women at risk for developing breast cancer, (3) tissue banking to develop and maintain the world's finest repository of human biospecimens of breast diseases, (4) targeted research into the molecular signatures of breast diseases and cancer, and (5) biomedical informatics core to support the data warehouse needs of the project. Now in its eighth year of operation, these efforts have resulted in more than 300 peer-reviewed scientific publications and dozens of collaborations with world leaders in cancer research. In this short time, CBCP has created what is believed to be the world's largest breast tissue biorepository.

Simulation-based medical education: time for a pedagogical shift.

PubMed

Kalaniti, Kaarthigeyan; Campbell, Douglas M

2015-01-01

The purpose of medical education at all levels is to prepare physicians with the knowledge and comprehensive skills, required to deliver safe and effective patient care. The traditional 'apprentice' learning model in medical education is undergoing a pedagogical shift to a 'simulation-based' learning model. Experiential learning, deliberate practice and the ability to provide immediate feedback are the primary advantages of simulation-based medical education. It is an effective way to develop new skills, identify knowledge gaps, reduce medical errors, and maintain infrequently used clinical skills even among experienced clinical teams, with the overall goal of improving patient care. Although simulation cannot replace clinical exposure as a form of experiential learning, it promotes learning without compromising patient safety. This new paradigm shift is revolutionizing medical education in the Western world. It is time that the developing countries embrace this new pedagogical shift.

Paradigms for adaptive statistical information designs: practical experiences and strategies.

PubMed

Wang, Sue-Jane; Hung, H M James; O'Neill, Robert

2012-11-10

In the last decade or so, interest in adaptive design clinical trials has gradually been directed towards their use in regulatory submissions by pharmaceutical drug sponsors to evaluate investigational new drugs. Methodological advances of adaptive designs are abundant in the statistical literature since the 1970s. The adaptive design paradigm has been enthusiastically perceived to increase the efficiency and to be more cost-effective than the fixed design paradigm for drug development. Much interest in adaptive designs is in those studies with two-stages, where stage 1 is exploratory and stage 2 depends upon stage 1 results, but where the data of both stages will be combined to yield statistical evidence for use as that of a pivotal registration trial. It was not until the recent release of the US Food and Drug Administration Draft Guidance for Industry on Adaptive Design Clinical Trials for Drugs and Biologics (2010) that the boundaries of flexibility for adaptive designs were specifically considered for regulatory purposes, including what are exploratory goals, and what are the goals of adequate and well-controlled (A&WC) trials (2002). The guidance carefully described these distinctions in an attempt to minimize the confusion between the goals of preliminary learning phases of drug development, which are inherently substantially uncertain, and the definitive inference-based phases of drug development. In this paper, in addition to discussing some aspects of adaptive designs in a confirmatory study setting, we underscore the value of adaptive designs when used in exploratory trials to improve planning of subsequent A&WC trials. One type of adaptation that is receiving attention is the re-estimation of the sample size during the course of the trial. We refer to this type of adaptation as an adaptive statistical information design. Specifically, a case example is used to illustrate how challenging it is to plan a confirmatory adaptive statistical information design. We highlight the substantial risk of planning the sample size for confirmatory trials when information is very uninformative and stipulate the advantages of adaptive statistical information designs for planning exploratory trials. Practical experiences and strategies as lessons learned from more recent adaptive design proposals will be discussed to pinpoint the improved utilities of adaptive design clinical trials and their potential to increase the chance of a successful drug development. Published 2012. This article is a US Government work and is in the public domain in the USA.

The Effect of Glycolytic Modulation on Prostate Cancer

DTIC Science & Technology

2010-07-01

this paradigm in the clinic, we completed a phase I study of 2-deoxyglucose (2DG), and assessed 2DG uptake with fluorodeoxyglucose (FDG) positron ...efficacy. In vitro studies with 2DG have demonstrated activity in osteosarcoma cells that were defective in oxidative phosphorylation implying that cells...diagnostic studies developing positron emission tomography (PET), which uses a trapped glucose analogue, 2-deoxy-D-glucose (2DG), for detec- tion of

Fanconi anaemia: genetics, molecular biology, and cancer – implications for clinical management in children and adults.

PubMed

Schneider, M; Chandler, K; Tischkowitz, M; Meyer, S

2015-07-01

Fanconi anaemia (FA) is an inherited disease with congenital and developmental abnormalities, cross-linker hypersensitivity and extreme cancer predisposition. With better understanding of the genetic and molecular basis of the disease, and improved clinical management, FA has been transformed from a life-limiting paediatric disease to an uncommon chronic condition that needs lifelong multidisciplinary management, and a paradigm condition for the understanding of the gene-environment interaction in the aetiology of congenital anomalies, haematopoiesis and cancer development. Here we review genetic, molecular and clinical aspects of FA, and discuss current controversies and future prospects. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Stem cell therapies in cardiovascular disease A "realistic" appraisal.

PubMed

Partovian, Chohreh; Simons, Michael

2008-01-01

The possibility of reconstituting the damaged heart has introduced a new paradigm in cardiovascular biology and created the potential for a new therapeutic approach in the cardiovascular field, where there is a compelling need for innovative treatments. While the results of animal and early clinical studies are encouraging, the more direct use of cell-based therapies in patients is still long-reached. Gaps in our basic understanding of mechanisms, lack of important randomized, double blind, and controlled clinical trials, as well as technology development for cell production are among challenges to be overcome before full translation of cell based therapies in clinical arena. This review focuses on summarizing the latest knowledge in stem cell therapy for cardiovascular diseases.

Current external beam radiation therapy quality assurance guidance: does it meet the challenges of emerging image-guided technologies?

PubMed

Palta, Jatinder R; Liu, Chihray; Li, Jonathan G

2008-01-01

The traditional prescriptive quality assurance (QA) programs that attempt to ensure the safety and reliability of traditional external beam radiation therapy are limited in their applicability to such advanced radiation therapy techniques as three-dimensional conformal radiation therapy, intensity-modulated radiation therapy, inverse treatment planning, stereotactic radiosurgery/radiotherapy, and image-guided radiation therapy. The conventional QA paradigm, illustrated by the American Association of Physicists in Medicine Radiation Therapy Committee Task Group 40 (TG-40) report, consists of developing a consensus menu of tests and device performance specifications from a generic process model that is assumed to apply to all clinical applications of the device. The complexity, variation in practice patterns, and level of automation of high-technology radiotherapy renders this "one-size-fits-all" prescriptive QA paradigm ineffective or cost prohibitive if the high-probability error pathways of all possible clinical applications of the device are to be covered. The current approaches to developing comprehensive prescriptive QA protocols can be prohibitively time consuming and cost ineffective and may sometimes fail to adequately safeguard patients. It therefore is important to evaluate more formal error mitigation and process analysis methods of industrial engineering to more optimally focus available QA resources on process components that have a significant likelihood of compromising patient safety or treatment outcomes.

Recent developments leading toward a paradigm switch in the diagnostic and therapeutic approach to human leishmaniasis

PubMed Central

Schriefer, Albert; Wilson, Mary E.; Carvalho, Edgar M.

2008-01-01

Purpose of review To identify recent papers showing how human and parasite genetics influence leishmaniasis, and how understanding of the immunopathology may be utilized in immunotherapy for these diseases. Recent findings Progress has been made in recent years showing the complexity within populations of Leishmania spp. and indicating that different strains lead to diverse clinical pictures and responses to treatment. Thus detection of parasite genetic tags for the precise identification of infecting strains, and for predictive diagnosis of clinical and therapeutic fates seems now possible. Host genetic loci involved in disease outcome have been detected, which may also be explored for better case management. These developments in diagnosis will demand expanding the therapeutic arsenal to take their expected effect. This is starting to be fulfilled by immunotherapies successfully employed to treat cases refractory to standard first line drugs, as the result of a more profound comprehension of the immunopathology of the leishmaniases. Summary The knowledge mounting has already helped explain why different patients present different forms of leishmaniasis and respond differently to treatment, and may be on the verge of catalyzing a major change in the already over a century old paradigm of diagnosing and managing these patients. PMID:18725797

Twenty-five years of optical coherence tomography: the paradigm shift in sensitivity and speed provided by Fourier domain OCT [Invited

PubMed Central

de Boer, Johannes F.; Leitgeb, Rainer; Wojtkowski, Maciej

2017-01-01

Optical coherence tomography (OCT) has become one of the most successful optical technologies implemented in medicine and clinical practice mostly due to the possibility of non-invasive and non-contact imaging by detecting back-scattered light. OCT has gone through a tremendous development over the past 25 years. From its initial inception in 1991 [Science 254, 1178 (1991)1957169] it has become an indispensable medical imaging technology in ophthalmology. Also in fields like cardiology and gastro-enterology the technology is envisioned to become a standard of care. A key contributor to the success of OCT has been the sensitivity and speed advantage offered by Fourier domain OCT. In this review paper the development of FD-OCT will be revisited, providing a single comprehensive framework to derive the sensitivity advantage of both SD- and SS-OCT. We point out the key aspects of the physics and the technology that has enabled a more than 2 orders of magnitude increase in sensitivity, and as a consequence an increase in the imaging speed without loss of image quality. This speed increase provided a paradigm shift from point sampling to comprehensive 3D in vivo imaging, whose clinical impact is still actively explored by a large number of researchers worldwide. PMID:28717565

Peptide vaccines and peptidomimetics targeting HER and VEGF proteins may offer a potentially new paradigm in cancer immunotherapy

PubMed Central

Kaumaya, Pravin TP; Foy, Kevin Chu

2013-01-01

The ErbB family (HER-1, HER-2, HER-3 and HER-4) of receptor tyrosine kinases has been the focus of cancer immunotherapeutic strategies while antiangiogenic therapies have focused on VEGF and its receptors VEGFR-1 and VEGFR-2. Agents targeting receptor tyrosine kinases in oncology include therapeutic antibodies to receptor tyrosine kinase ligands or the receptors themselves, and small-molecule inhibitors. Many of the US FDA-approved therapies targeting HER-2 and VEGF exhibit unacceptable toxicities, and show problems of efficacy, development of resistance and unacceptable safety profiles that continue to hamper their clinical progress. The combination of dif ferent peptide vaccines and peptidomimetics targeting specific molecular pathways that are dysregulated in tumors may potentiate anticancer immune responses, bypass immune tolerance and circumvent resistance mechanisms. The focus of this review is to discuss efforts in our laboratory spanning two decades of rationally developing peptide vaccines and therapeutics for breast cancer. This review highlights the prospective benefit of a new, untapped category of therapies biologically targeted to EGF receptor (HER-1), HER-2 and VEGF with potential peptide ‘blockbusters‘ that could lay the foundation of a new paradigm in cancer immunotherapy by creating clinical breakthroughs for safe and efficacious cancer cures. PMID:22894670

Pharmacological validation of a novel nonhuman primate measure of thermal responsivity with utility for predicting analgesic effects.

PubMed

Vardigan, Joshua D; Houghton, Andrea K; Lange, Henry S; Adarayan, Emily D; Pall, Parul S; Ballard, Jeanine E; Henze, Darrell A; Uslaner, Jason M

2018-01-01

The development of novel analgesics to treat acute or chronic pain has been a challenge due to a lack of translatable measurements. Preclinical end points with improved translatability are necessary to more accurately inform clinical testing paradigms, which may help guide selection of viable drug candidates. In this study, a nonhuman primate biomarker which is sensitive to standard analgesics at clinically relevant plasma concentrations, can differentiate analgesia from sedation and utilizes a protocol very similar to that which can be employed in human clinical studies is described. Specifically, acute heat stimuli were delivered to the volar forearm using a contact heat thermode in the same manner as the clinical setting. Clinically efficacious exposures of morphine, fentanyl, and tramadol produced robust analgesic effects, whereas doses of diazepam that produce sedation had no effect. We propose that this assay has predictive utility that can help improve the probability of success for developing novel analgesics.

Clinical research in small genomically stratified patient populations.

PubMed

Martin-Liberal, J; Rodon, J

2017-07-01

The paradigm of early drug development in cancer is shifting from 'histology-oriented' to 'molecularly oriented' clinical trials. This change can be attributed to the vast amount of tumour biology knowledge generated by large international research initiatives such as The Cancer Genome Atlas (TCGA) and the use of next generation sequencing (NGS) techniques developed in recent years. However, targeting infrequent molecular alterations entails a series of special challenges. The optimal molecular profiling method, the lack of standardised biological thresholds, inter- and intra-tumor heterogeneity, availability of enough tumour material, correct clinical trials design, attrition rate, logistics or costs are only some of the issues that need to be taken into consideration in clinical research in small genomically stratified patient populations. This article examines the most relevant challenges inherent to clinical research in these populations. Moreover, perspectives from the Academia point of view are reviewed as well as initiatives to be taken in forthcoming years. Copyright © 2017 Elsevier Ltd. All rights reserved.

Pharmacological validation of a novel nonhuman primate measure of thermal responsivity with utility for predicting analgesic effects

PubMed Central

Vardigan, Joshua D; Houghton, Andrea K; Lange, Henry S; Adarayan, Emily D; Pall, Parul S; Ballard, Jeanine E; Henze, Darrell A; Uslaner, Jason M

2018-01-01

Introduction The development of novel analgesics to treat acute or chronic pain has been a challenge due to a lack of translatable measurements. Preclinical end points with improved translatability are necessary to more accurately inform clinical testing paradigms, which may help guide selection of viable drug candidates. Methods In this study, a nonhuman primate biomarker which is sensitive to standard analgesics at clinically relevant plasma concentrations, can differentiate analgesia from sedation and utilizes a protocol very similar to that which can be employed in human clinical studies is described. Specifically, acute heat stimuli were delivered to the volar forearm using a contact heat thermode in the same manner as the clinical setting. Results Clinically efficacious exposures of morphine, fentanyl, and tramadol produced robust analgesic effects, whereas doses of diazepam that produce sedation had no effect. Conclusion We propose that this assay has predictive utility that can help improve the probability of success for developing novel analgesics. PMID:29692626

Challenges in the clinical development of new antiepileptic drugs.

PubMed

Franco, Valentina; French, Jacqueline A; Perucca, Emilio

2016-01-01

Despite the current availability in the market of over two dozen antiepileptic drugs (AEDs), about one third of people with epilepsy fail to achieve complete freedom from seizures with existing medications. Moreover, currently available AEDs have significant limitations in terms of safety, tolerability and propensity to cause or be a target for clinically important adverse drug interactions. A review of the evidence shows that there are many misperceptions about the viability of investing into new therapies for epilepsy. In fact, there are clear incentives to develop newer and more efficacious medications. Developing truly innovative drugs requires a shift in the paradigms for drug discovery, which is already taking place by building on greatly expanded knowledge about the mechanisms involved in epileptogenesis, seizure generation, seizure spread and development of co-morbidities. AED development can also benefit by a review of the methodology currently applied in clinical AED development, in order to address a number of ethical and scientific concerns. As discussed in this article, many processes of clinical drug development, from proof-of-concept-studies to ambitious programs aimed at demonstrating antiepileptogenesis and disease-modification, can be facilitated by a greater integration of preclinical and clinical science, and by application of knowledge acquired during decades of controlled epilepsy trials. Copyright © 2015 Elsevier Ltd. All rights reserved.

Systems Pharmacology-Based Discovery of Natural Products for Precision Oncology Through Targeting Cancer Mutated Genes.

PubMed

Fang, J; Cai, C; Wang, Q; Lin, P; Zhao, Z; Cheng, F

2017-03-01

Massive cancer genomics data have facilitated the rapid revolution of a novel oncology drug discovery paradigm through targeting clinically relevant driver genes or mutations for the development of precision oncology. Natural products with polypharmacological profiles have been demonstrated as promising agents for the development of novel cancer therapies. In this study, we developed an integrated systems pharmacology framework that facilitated identifying potential natural products that target mutated genes across 15 cancer types or subtypes in the realm of precision medicine. High performance was achieved for our systems pharmacology framework. In case studies, we computationally identified novel anticancer indications for several US Food and Drug Administration-approved or clinically investigational natural products (e.g., resveratrol, quercetin, genistein, and fisetin) through targeting significantly mutated genes in multiple cancer types. In summary, this study provides a powerful tool for the development of molecularly targeted cancer therapies through targeting the clinically actionable alterations by exploiting the systems pharmacology of natural products. © 2017 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

Statistical considerations for a trial of Ebola virus disease therapeutics.

PubMed

Proschan, Michael A; Dodd, Lori E; Price, Dionne

2016-02-01

The 2014 West African outbreak of Ebola virus ravaged Liberia, Sierra Leone, and Guinea, causing hemorrhagic fever and death. The need to identify effective therapeutics was acute. The usual drug development paradigm of phase I, followed by phase II, and then phase III trials would take too long. These and other factors led to the design of a clinical trial of Ebola virus disease therapeutics that differs from more conventional clinical trial designs. This article describes the Ebola virus disease medical countermeasures trial design and the thinking behind it. © The Author(s) 2016.

Collaborative Paradigm of Preventive, Personalized, and Precision Medicine With Point-of-Care Technologies.

PubMed

Dhawan, Atam P

2016-01-01

Recent advances in biosensors, medical instrumentation, and information processing and communication technologies (ICT) have enabled significant improvements in healthcare. However, these technologies have been mainly applied in clinical environments, such as hospitals and healthcare facilities, under managed care by well-trained and specialized individuals. The global challenge of providing quality healthcare at affordable cost leads to the proposed paradigm of P reventive, Personalized, and Precision Medicine that requires a seamless use of technology and infrastructure support for patients and healthcare providers at point-of-care (POC) locations including homes, semi or pre-clinical facilities, and hospitals. The complexity of the global healthcare challenge necessitates strong collaborative interdisciplinary synergies involving all stakeholder groups including academia, federal research institutions, industry, regulatory agencies, and clinical communities. It is critical to evolve with collaborative efforts on the translation of research to technology development toward clinical validation and potential healthcare applications. This special issue is focused on technology innovation and translational research for POC applications with potential impact in improving global healthcare in the respective areas. Some of these papers were presented at the NIH-IEEE Strategic Conference on Healthcare Innovations and POC Technologies for Precision Medicine (HI-POCT) held at the NIH on November 9-10, 2015. The papers included in the Special Issue provide a spectrum of critical issues and collaborative resources on translational research of advanced POC devices and ICT into global healthcare environment.

Comorbidity of psychiatric disorders with Internet addiction in a clinical sample: the effect of personality, defense style and psychopathology.

PubMed

Floros, Georgios; Siomos, Konstantinos; Stogiannidou, Ariadni; Giouzepas, Ioannis; Garyfallos, Georgios

2014-12-01

This study aims to contribute to the understanding of underlying causes for the development of Internet Addiction Disorder (IAD) and assess comorbidity with other mental disorders through the analysis of data from a clinical sample of college students who presented for treatment of IAD. The clinical sample of our study has demonstrated a high percentage of comorbidity with Axis I and II disorders, while the temporal precedence of the establishment of those disorders cannot lead to specific conclusions. Half of the sample (25/50) presented with comorbidity of another Axis I disorder and 38% (19/50) with a concurrent Axis II personality disorder. The majority of Axis I disorders (51.85%) were reported before the onset of IAD, 33.3% after the onset while it was unclear in 14.81% of cases. The examination of a path model demonstrated that important contributions to the understanding of this disorder can be made through concepts from the neurobiological, trait personality paradigm, as well as from the psychodynamic defense style paradigm. Comorbid psychopathology can further exacerbate the presentation of IAD through a direct link, regardless of the underlying personality structure. The clinician treating IAD patients should complete a clinical evaluation for comorbid Axis I and II diagnoses since their presence may signify a more serious presentation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Medications Development for the Treatment of Alcohol Use Disorder: Insights into the Predictive Value of Animal and Human Laboratory Models

PubMed Central

Yardley, Megan M.; Ray, Lara A.

2016-01-01

Development of effective treatments for alcohol use disorder (AUD) represents an important public health goal. This review provides a summary of completed preclinical and clinical studies testing pharmacotherapies for treatment of AUD. We discuss opportunities for improving the translation from preclinical findings to clinical trial outcomes, focusing on the validity and predictive value of animal and human laboratory models of AUD. Specifically, while preclinical studies of medications development have offered important insights into the neurobiology of the disorder and alcohol's molecular targets, limitations include the lack of standardized methods and streamlined processes whereby animal studies can readily inform human studies. Behavioral pharmacology studies provide a less expensive and valuable opportunity to assess the feasibility of a pharmacotherapy prior to initiating larger scale clinical trials by providing insights into the mechanism of the drug, which can then inform recruitment, analyses, and assessments. Summary tables are provided to illustrate the wide range of preclinical, human laboratory, and clinical studies of medications development for alcoholism. Taken together, this review highlights the challenges associated with animal paradigms, human laboratory studies and clinical trials with the overarching goal of advancing treatment development and highlighting opportunities to bridge the gap between preclinical and clinical research. PMID:26833803

New strategies in drug discovery.

PubMed

Ohlstein, Eliot H; Johnson, Anthony G; Elliott, John D; Romanic, Anne M

2006-01-01

Gene identification followed by determination of the expression of genes in a given disease and understanding of the function of the gene products is central to the drug discovery process. The ability to associate a specific gene with a disease can be attributed primarily to the extraordinary progress that has been made in the areas of gene sequencing and information technologies. Selection and validation of novel molecular targets have become of great importance in light of the abundance of new potential therapeutic drug targets that have emerged from human gene sequencing. In response to this revolution within the pharmaceutical industry, the development of high-throughput methods in both biology and chemistry has been necessitated. Further, the successful translation of basic scientific discoveries into clinical experimental medicine and novel therapeutics is an increasing challenge. As such, a new paradigm for drug discovery has emerged. This process involves the integration of clinical, genetic, genomic, and molecular phenotype data partnered with cheminformatics. Central to this process, the data generated are managed, collated, and interpreted with the use of informatics. This review addresses the use of new technologies that have arisen to deal with this new paradigm.

Neuroimaging-based biomarkers in psychiatry: clinical opportunities of a paradigm shift.

PubMed

Fu, Cynthia H Y; Costafreda, Sergi G

2013-09-01

Neuroimaging research has substantiated the functional and structural abnormalities underlying psychiatric disorders but has, thus far, failed to have a significant impact on clinical practice. Recently, neuroimaging-based diagnoses and clinical predictions derived from machine learning analysis have shown significant potential for clinical translation. This review introduces the key concepts of this approach, including how the multivariate integration of patterns of brain abnormalities is a crucial component. We survey recent findings that have potential application for diagnosis, in particular early and differential diagnoses in Alzheimer disease and schizophrenia, and the prediction of clinical response to treatment in depression. We discuss the specific clinical opportunities and the challenges for developing biomarkers for psychiatry in the absence of a diagnostic gold standard. We propose that longitudinal outcomes, such as early diagnosis and prediction of treatment response, offer definite opportunities for progress. We propose that efforts should be directed toward clinically challenging predictions in which neuroimaging may have added value, compared with the existing standard assessment. We conclude that diagnostic and prognostic biomarkers will be developed through the joint application of expert psychiatric knowledge in addition to advanced methods of analysis.

Interpretation of lung cancer study outcomes.

PubMed

Cortinovis, Diego; Abbate, Marida; Bidoli, Paolo; Pelizzoni, Davide; Canova, Stefania

2015-11-01

Lung cancer is the leading cause of cancer death in developed countries. However, in the last few years we observed an important acceleration in drug development due to oncogenic driver tumors discovery. Sharing and putting together preclinical data from benchmark and data from clinical research is the scientific paradigm that allows real breakthrough in clinical practice in this field, but only a few targeted agents are worthy and practice changing. The clinical research and proper use of statistical methodology are the pillars to continue to achieve important goals like improvement of overall survival. A good medical oncologist should be able to critically read a scientific paper and move from the observed outcomes into clinical perspective. Despite clinical improvements, sometimes the union of promising targeted agents and optimistic expectations misrepresent the reality and the value of clinical research. In this article, we try to analyze the meaning of statistical assumptions from clinical trials, especially in lung cancer, through a critical review of the concept of value-based medicine. We also attempt to give the reader some practical tools to weigh scientific value of literature reports.

Ischaemic conditioning: pitfalls on the path to clinical translation

PubMed Central

Przyklenk, Karin

2015-01-01

The development of novel adjuvant strategies capable of attenuating myocardial ischaemia-reperfusion injury and reducing infarct size remains a major, unmet clinical need. A wealth of preclinical evidence has established that ischaemic ‘conditioning’ is profoundly cardioprotective, and has positioned the phenomenon (in particular, the paradigms of postconditioning and remote conditioning) as the most promising and potent candidate for clinical translation identified to date. However, despite this preclinical consensus, current phase II trials have been plagued by heterogeneity, and the outcomes of recent meta-analyses have largely failed to confirm significant benefit. As a result, the path to clinical application has been perceived as ‘disappointing’ and ‘frustrating’. The goal of the current review is to discuss the pitfalls that may be stalling the successful clinical translation of ischaemic conditioning, with an emphasis on concerns regarding: (i) appropriate clinical study design and (ii) the choice of the ‘right’ preclinical models to facilitate clinical translation. PMID:25560903

Understanding paradigms used for nursing research.

PubMed

Weaver, Kathryn; Olson, Joanne K

2006-02-01

The aims of this paper are to add clarity to the discussion about paradigms for nursing research and to consider integrative strategies for the development of nursing knowledge. Paradigms are sets of beliefs and practices, shared by communities of researchers, which regulate inquiry within disciplines. The various paradigms are characterized by ontological, epistemological and methodological differences in their approaches to conceptualizing and conducting research, and in their contribution towards disciplinary knowledge construction. Researchers may consider these differences so vast that one paradigm is incommensurable with another. Alternatively, researchers may ignore these differences and either unknowingly combine paradigms inappropriately or neglect to conduct needed research. To accomplish the task of developing nursing knowledge for use in practice, there is a need for a critical, integrated understanding of the paradigms used for nursing inquiry. We describe the evolution and influence of positivist, postpositivist, interpretive and critical theory research paradigms. Using integrative review, we compare and contrast the paradigms in terms of their philosophical underpinnings and scientific contribution. A pragmatic approach to theory development through synthesis of cumulative knowledge relevant to nursing practice is suggested. This requires that inquiry start with assessment of existing knowledge from disparate studies to identify key substantive content and gaps. Knowledge development in under-researched areas could be accomplished through integrative strategies that preserve theoretical integrity and strengthen research approaches associated with various philosophical perspectives. These strategies may include parallel studies within the same substantive domain using different paradigms; theoretical triangulation to combine findings from paradigmatically diverse studies; integrative reviews; and mixed method studies. Nurse scholars are urged to consider the benefits and limitations of inquiry within each paradigm, and the theoretical needs of the discipline.

Chronic, Wireless Recordings of Large Scale Brain Activity in Freely Moving Rhesus Monkeys

PubMed Central

Schwarz, David A.; Lebedev, Mikhail A.; Hanson, Timothy L.; Dimitrov, Dragan F.; Lehew, Gary; Meloy, Jim; Rajangam, Sankaranarayani; Subramanian, Vivek; Ifft, Peter J.; Li, Zheng; Ramakrishnan, Arjun; Tate, Andrew; Zhuang, Katie; Nicolelis, Miguel A.L.

2014-01-01

Advances in techniques for recording large-scale brain activity contribute to both the elucidation of neurophysiological principles and the development of brain-machine interfaces (BMIs). Here we describe a neurophysiological paradigm for performing tethered and wireless large-scale recordings based on movable volumetric three-dimensional (3D) multielectrode implants. This approach allowed us to isolate up to 1,800 units per animal and simultaneously record the extracellular activity of close to 500 cortical neurons, distributed across multiple cortical areas, in freely behaving rhesus monkeys. The method is expandable, in principle, to thousands of simultaneously recorded channels. It also allows increased recording longevity (5 consecutive years), and recording of a broad range of behaviors, e.g. social interactions, and BMI paradigms in freely moving primates. We propose that wireless large-scale recordings could have a profound impact on basic primate neurophysiology research, while providing a framework for the development and testing of clinically relevant neuroprostheses. PMID:24776634

The role of dental hygiene in caries management: a new paradigm.

PubMed

Young, Douglas A; Lyon, Lucinda; Azevedo, Shelly

2010-01-01

Dental caries is the most common disease of children and remains a significant oral health problem worldwide for both children and adults. The traditional paradigm of treating dental caries solely by "drilling and filling," brushing and flossing and lowering sugar intake has evolved. Current science in the management of dental caries suggests a clear focus on the reduction of responsible infectious agents, remineralization of non-cavitated lesions and minimally invasive restorative approaches whenever possible. The paradigm shift is away from a purely surgical approach toward more preventive and curative clinical protocols. This paper provides a review of this caries management methodology and explores the role of the dental hygienist in this paradigm change.

Treating impaired cognition in schizophrenia: the case for combining cognitive-enhancing drugs with cognitive remediation.

PubMed

Michalopoulou, Panayiota G; Lewis, Shôn W; Wykes, Til; Jaeger, Judith; Kapur, Shitij

2013-08-01

Cognitive impairment is a well-documented feature of schizophrenia and represents a major impediment to the functional recovery of patients. The therapeutic strategies to improve cognition in schizophrenia have either used medications (collectively referred to as 'cognitive-enhancing drugs' in this article) or non-pharmacological training approaches ('cognitive remediation'). Cognitive-enhancing drugs have not as yet been successful and cognitive remediation has shown modest success. Therefore, we may need to explore new therapeutic paradigms to improve cognition in schizophrenia. The optimal approach may require a combination of cognitive-enhancing drugs with cognitive remediation. We review the available data from animal and human studies that provide the conceptual basis, proof-of-concept and illustrations of success of such combination strategies in experimental and clinical paradigms in other conditions. We address the major design issues relevant to the choice of the cognitive-enhancing drugs and cognitive remediation, as well as the timing and the duration of the intervention as will be relevant for schizophrenia. Finally, we address the practical realities of the development and testing of such combined approaches in the real-world clinical situation and conclude that while scientifically attractive, there are several practical difficulties to be overcome for this approach to be clinically feasible. Copyright © 2013 Elsevier B.V. and ECNP. All rights reserved.

Insights into implementation of sacubitril/valsartan into clinical practice.

PubMed

Martens, Pieter; Beliën, Hanne; Dupont, Matthias; Mullens, Wilfried

2018-06-01

Sacubitril/valsartan significantly reduced heart failure hospitalization and mortality in PARADIGM-HF (Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor With an Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure). However, real-world data from its use are lacking. We retrospectively assessed all baseline and follow-up data of consecutive heart failure patients with reduced ejection fraction receiving therapy with sacubitril/valsartan for Class I recommendation between December 2016 and July 2017. Baseline characteristics and dose titration of sacubitril/valsartan were compared between patients in clinical practice and in PARADIGM-HF. A total of 120 patients (81% male) were switched from angiotensin-converting enzyme inhibitor or angiotensin receptor blocker to sacubitril/valsartan. A total of 20.1% of patients received dose uptitration. Patients were treated with an equipotential dose of renin-angiotensin system blockers before and after uptitration of sacubitril/valsartan (57 ± 29% vs. 53 ± 29% of target dose indicated by European Society of Cardiology guidelines; P = 0.286). However, they received a lower dose of sacubitril/valsartan in comparison with those in the PARADIGM-HF (219 ± 12 vs. 375 ± 75 mg; P < 0.001). In comparison with the patients receiving sacubitril/valsartan in PARADIGM-HF, patients in clinical practice were older and had a higher serum creatinine, higher New York Heart Association functional classification, and lower left ventricular ejection fraction (all P-value <0.05). Even in comparison with patients who experienced dropout during the run-in phase of PARADIGM-HF, real-world patients exhibited baseline characteristics indicative of more disease severity. Patients were at high absolute baseline risk for adverse outcome as illustrated by the EMPHASIS-HF (Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure) risk score of 6 (inter-quartile range 3), in comparison with 5 (inter-quartile range 4) in PARADIGM-HF. After initiation of sacubitril/valsartan, New York Heart Association class significantly improved (P < 0.001), but systolic blood pressure dropped more than was reported in PARADIGM-HF (7.1 ± 8.0 vs. 3.2 ± 0.4 mmHg; P < 0.001). Patients in clinical practice exhibit baseline characteristics associated with more severe disease, which might lead to prescription of lower doses. Nevertheless, patients in clinical practice are at high risk of adverse outcome as illustrated by the EMPHASIS-HF risk score, underscoring the large potential for sacubitril/valsartan therapy to reduce the risk of heart failure hospitalization and all-cause mortality. © 2018 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

[Nursing knowledge: the evolution of scientific philosophies and paradigm trends].

PubMed

Hung, Hsuan-Man; Wang, Hui-Ling; Chang, Yun-Hsuan; Chen, Chung-Hey

2010-02-01

Different aspects of philosophy are derived from different paradigms that contain various main points, some of which are repeated or overlap. Belief and practice are two components of a paradigm that provide perspective and framework and lead to nursing research. Changes in healthcare have popularized empirical and evidence-based research in the field of nursing research. However, the evidence-base study approach has given rise to a certain level of debate. Until now, no standard paradigm has been established for the nursing field, as different professionals use different paradigms in their studies. Such provides certain limitations as well as advantages. The quantitative aspects of a nursing paradigm were developed by Peplau and Henderson (1950) and Orem (1980). Such remained the standard until 1990, when Guba and Parse proposed qualitative viewpoints in contextual features. Therefore, the nursing paradigm has made great contributions to the development of knowledge in nursing care, although debate continues due to incomplete knowledge attributable to the presentation of knowledge and insight within individually developed paradigms. It is better to apply multiple paradigms to different research questions. It is suggested that better communication amongst experts regarding their individual points of view would help nursing members to integrate findings within the global pool of knowledge and allow replication over multiple studies.

The Development of Genetics in the Light of Thomas Kuhn's Theory of Scientific Revolutions.

PubMed

Portin, Petter

2015-01-01

The concept of a paradigm is in the key position in Thomas Kuhn's theory of scientific revolutions. A paradigm is the framework within which the results, concepts, hypotheses and theories of scientific research work are understood. According to Kuhn, a paradigm guides the working and efforts of scientists during the time period which he calls the period of normal science. Before long, however, normal science leads to unexplained matters, a situation that then leads the development of the scientific discipline in question to a paradigm shift--a scientific revolution. When a new theory is born, it has either gradually emerged as an extension of the past theory, or the old theory has become a borderline case in the new theory. In the former case, one can speak of a paradigm extension. According to the present author, the development of modern genetics has, until very recent years, been guided by a single paradigm, the Mendelian paradigm which Gregor Mendel launched 150 years ago, and under the guidance of this paradigm the development of genetics has proceeded in a normal fashion in the spirit of logical positivism. Modern discoveries in genetics have, however, created a situation which seems to be leading toward a paradigm shift. The most significant of these discoveries are the findings of adaptive mutations, the phenomenon of transgenerational epigenetic inheritance, and, above all, the present deeply critical state of the concept of the gene.

Clinical trials for drug registrations in Asian-Pacific countries: proposal for a new paradigm from a statistical perspective.

PubMed

Shih, W J

2001-08-01

The world has become more interdependent in the movement of free trade and global markets. The regulations for approval of new drugs in the Asian markets have always been an important issue in the free trade negotiation between the U.S.- and E.U.-based international manufacturers and the Asian-Pacific countries, since pharmaceuticals are of large trade value for them. In 1998 the University of Hong Kong and the Singapore National Medical Research Council jointly hosted the first Asian Clinical Trials Conference. The Society for Clinical Trials was invited as a collaborator for the event, which signified a milestone for interaction between the East and West in the discussion of clinical trials. Many have participated in the discussion of drug approval and registration issues for the Asian region based on the drug development experience in the United States. However, there are many interesting differences between the two regions, which lead to different approval processes for new drugs developed by the U.S.- and E.U.-based international manufacturers. This article highlights some regulatory dilemmas and some key statistical concepts pertinent to these differences. The purpose of this paper is to resolve the regional regulatory and scientific dilemma. A new paradigm of sample size design and data analysis for drug approval for countries in the Asian-Pacific region is proposed. The central premise is that substantial information from multicenter studies has already shown efficacy in the United States or the European Union when a drug manufacturer seeks marketing approval in an Asian country. This leads to the idea of a "consistency trial" using the method of Bayesian most plausible prediction. The method is illustrated with an example.

Rethinking School Effectiveness and Improvement: A Question of Paradigms

ERIC Educational Resources Information Center

Wrigley, Terry

2013-01-01

The purpose of this article is to contribute to progressive school change by developing a more systematic critique of school effectiveness (SE) and school improvement (SI) as paradigms. Diverse examples of paradigms and paradigm change in non-educational fields are used to create a model of paradigms for application to SE and SI, and to explore…

Changing paradigm of cancer therapy: precision medicine by next-generation sequencing

PubMed Central

Xue, Yuan; Wilcox, William R.

2016-01-01

Precision medicine aims to identify the right drug, for the right patient, at the right dose, at the right time, which is particularly important in cancer therapy. Problems such as the variability of treatment response and resistance to medication have been long-standing challenges in oncology, especially for development of new medications. Solid tumors, unlike hematologic malignancies or brain tumors, are remarkably diverse in their cellular origins and developmental timing. The ability of next-generation sequencing (NGS) to analyze the comprehensive landscape of genetic alterations brings promises to diseases that have a highly complex and heterogeneous genetic composition such as cancer. Here we provide an overview of how NGS is able to facilitate precision medicine and change the paradigm of cancer therapy, especially for solid tumors, through technical advancements, molecular diagnosis, response monitoring and clinical trials. PMID:27144059

Shifting from the single- to the multitarget paradigm in drug discovery

PubMed Central

Medina-Franco, José L.; Giulianotti, Marc A.; Welmaker, Gregory S.; Houghten, Richard A.

2013-01-01

Increasing evidence that several drug compounds exert their effects through interactions with multiple targets is boosting the development of research fields that challenge the data reductionism approach. In this article, we review and discuss the concepts of drug repurposing, polypharmacology, chemogenomics, phenotypic screening and highthroughput in vivo testing of mixture-based libraries in an integrated manner. These research fields offer alternatives to the current paradigm of drug discovery, from a one target–one drug model to a multiple-target approach. Furthermore, the goals of lead identification are being expanded accordingly to identify not only ‘key’ compounds that fit with a single-target ‘lock’, but also ‘master key’ compounds that favorably interact with multiple targets (i.e. operate a set of desired locks to gain access to the expected clinical effects). PMID:23340113

Drug safety assurance through clinical genotyping: near-term considerations for a system-wide implementation of personalized medicine.

PubMed

Kane, Michael D; Springer, John A; Sprague, Jon E

2008-07-01

The rationale and overall system-wide behavior of a clinical genotyping information system (both DNA analysis and data management) requires a near-term, scalable approach, which is emerging in the focused implementation of pharmacogenomics and drug safety assurance. The challenges to implementing a successful clinical genotyping system are described, as are how the benefits of a focused, near-term system for drug safety assessment and assurance overcome the logistical and operational challenges that perpetually hinder the development of a societal-scale clinical genotyping system. This rationale is based on the premise that a focused application domain for clinical genotyping, specifically drug safety assurance, provides a transition paradigm for both professionals and consumers of healthcare, thereby facilitating the movement of genotyping from bench to bedside and paving the way for the adoption of prognostic and diagnostic applications in clinical genomics.

Maximizing potential impact of experimental research into cognitive processes in health psychology: A systematic approach to material development.

PubMed

Hughes, Alicia M; Gordon, Rola; Chalder, Trudie; Hirsch, Colette R; Moss-Morris, Rona

2016-11-01

There is an abundance of research into cognitive processing biases in clinical psychology including the potential for applying cognitive bias modification techniques to assess the causal role of biases in maintaining anxiety and depression. Within the health psychology field, there is burgeoning interest in applying these experimental methods to assess potential cognitive biases in relation to physical health conditions and health-related behaviours. Experimental research in these areas could inform theoretical development by enabling measurement of implicit cognitive processes that may underlie unhelpful illness beliefs and help drive health-related behaviours. However, to date, there has been no systematic approach to adapting existing experimental paradigms for use within physical health research. Many studies fail to report how materials were developed for the population of interest or have used untested materials developed ad hoc. The lack of protocol for developing stimuli specificity has contributed to large heterogeneity in methodologies and findings. In this article, we emphasize the need for standardized methods for stimuli development and replication in experimental work, particularly as it extends beyond its original anxiety and depression scope to other physical conditions. We briefly describe the paradigms commonly used to assess cognitive biases in attention and interpretation and then describe the steps involved in comprehensive/robust stimuli development for attention and interpretation paradigms using illustrative examples from two conditions: chronic fatigue syndrome and breast cancer. This article highlights the value of preforming rigorous stimuli development and provides tools to aid researchers engage in this process. We believe this work is worthwhile to establish a body of high-quality and replicable experimental research within the health psychology literature. Statement of contribution What is already known on this subject? Cognitive biases (e.g., tendencies to attend to negative information and/or interpret ambiguous information in negative ways) have a causal role in maintaining anxiety and depression. There is mixed evidence of cognitive biases in physical health conditions and chronic illness; one reason for this may be the heterogeneous stimuli used to assess attention and interpretation biases in these conditions. What does this study add? Steps for comprehensive/robust stimuli development for attention and interpretation paradigms are presented. Illustrative examples are provided from two conditions: chronic fatigue syndrome and breast cancer. We provide tools to help researchers develop condition-specific materials for experimental studies. © 2016 The British Psychological Society.

Community Involvement in School Development: Modifying School Improvement Concepts to the Needs of South African Township Schools

ERIC Educational Resources Information Center

Prew, Martin

2009-01-01

The article posits a paradigm for school development (SD) in the context of a developing country, which is somewhat different from the dominant SD and school improvement (SI) paradigm in the West. Within this paradigm the norm of a school-parent engagement over pedagogical issues as in the West is replaced by imperatives based on full community…

Measuring the software process and product: Lessons learned in the SEL

NASA Technical Reports Server (NTRS)

Basili, V. R.

1985-01-01

The software development process and product can and should be measured. The software measurement process at the Software Engineering Laboratory (SEL) has taught a major lesson: develop a goal-driven paradigm (also characterized as a goal/question/metric paradigm) for data collection. Project analysis under this paradigm leads to a design for evaluating and improving the methodology of software development and maintenance.

Entering medical practice for the very first time: emotional talk, meaning and identity development.

PubMed

Helmich, Esther; Bolhuis, Sanneke; Dornan, Tim; Laan, Roland; Koopmans, Raymond

2012-11-01

During early clinical exposure, medical students have many emotive experiences. Through participation in social practice, they learn to give personal meaning to their emotional states. This meaningful social act of participation may lead to a sense of belonging and identity construction. The aim of this study was to broaden and deepen our understanding of the interplay between those experiences and students' identity development. Our research questions asked how medical students give meaning to early clinical experiences and how that affects their professional identity development. Our method was phenomenology. Within that framework we used a narrative interviewing technique. Interviews with 17 medical students on Year 1 attachments to nurses in hospitals and nursing homes were analysed by listening to audio-recordings and reading transcripts. Nine transcripts, which best exemplified the students' range of experiences, were purposively sampled for deeper analysis. Two researchers carried out a systematic analysis using qualitative research software. Finally, cases representing four paradigms were chosen to exemplify the study findings. Students experienced their relationships with the people they met during early clinical experiences in very different ways, particularly in terms of feeling and displaying emotions, adjusting, role finding and participation. The interplay among emotions, meaning and identity was complex and four different 'paradigms' of lived experience were apparent: feeling insecure; complying; developing, and participating. We found large differences in the way students related to other people and gave meaning to their first experiences as doctors-to-be. They differed in their ability to engage in ward practices, the way they experienced their roles as medical students and future doctors, and how they experienced and expressed their emotions. Medical educators should help students to be sensitive to their emotions, offer space to explore different meanings, and be ready to suggest alternative interpretations that foster the development of desired professional identities. © Blackwell Publishing Ltd 2012.

Advances towards the design and development of personalized non-small-cell lung cancer drug therapy.

PubMed

Vari, Sabrina; Pilotto, Sara; Maugeri-Saccà, Marcello; Ciuffreda, Ludovica; Cesta Incani, Ursula; Falcone, Italia; Del Curatolo, Anais; Ceribelli, Anna; Gelibter, Alain; De Maria, Ruggero; Tortora, Giampaolo; Cognetti, Francesco; Bria, Emilio; Milella, Michele

2013-11-01

Non-small-cell lung cancer (NSCLC) subtypes are driven by specific genetic aberrations. For reasons such as this, there is a call for treatment personalization. The ability to instigate NSCLC fragmentation poses new methodological problems, and new 'driver' molecular aberrations are being discovered at an unprecedented pace. This article describes the clinical development of epidermal growth factor-tyrosine kinase inhibitors (EGFR-TKIs) and crizotinib for EGFR-mutant and anaplastic lymphoma kinase (ALK)-rearranged NSCLC. Further, the authors briefly describe the emerging molecular targets in NSCLC, in terms of both rationale for therapeutic targeting and strategies, for clinical development. Target identification and validation in NSCLC still requires considerable effort, as not all of the molecular alterations are clear 'drivers' nor can they be efficiently targeted with available drugs. However, 50% of the NSCLC cases are without clear-defined molecular aberrations. Clinical trial methodology will need to develop novel paradigms for targeted drug development, aiming at the validation of an ideal 'biology-to-trial' approach. Despite significant challenges, a truly 'personalized' approach to NSCLC therapy appears to be within our reach.

Experimental Psychopathology Paradigms for Alcohol Use Disorders: Applications for Translational Research

PubMed Central

Bujarski, Spencer; Ray, Lara A.

2016-01-01

In spite of high prevalence and disease burden, scientific consensus on the etiology and treatment of Alcohol Use Disorder (AUD) has yet to be reached. The development and utilization of experimental psychopathology paradigms in the human laboratory represents a cornerstone of AUD research. In this review, we describe and critically evaluate the major experimental psychopathology paradigms developed for AUD, with an emphasis on their implications, strengths, weaknesses, and methodological considerations. Specifically we review alcohol administration, self-administration, cue-reactivity, and stress-reactivity paradigms. We also provide an introduction to the application of experimental psychopathology methods to translational research including genetics, neuroimaging, pharmacological and behavioral treatment development, and translational science. Through refining and manipulating key phenotypes of interest, these experimental paradigms have the potential to elucidate AUD etiological factors, improve the efficiency of treatment developments, and refine treatment targets thus advancing precision medicine. PMID:27266992

Experimental psychopathology paradigms for alcohol use disorders: Applications for translational research.

PubMed

Bujarski, Spencer; Ray, Lara A

2016-11-01

In spite of high prevalence and disease burden, scientific consensus on the etiology and treatment of Alcohol Use Disorder (AUD) has yet to be reached. The development and utilization of experimental psychopathology paradigms in the human laboratory represents a cornerstone of AUD research. In this review, we describe and critically evaluate the major experimental psychopathology paradigms developed for AUD, with an emphasis on their implications, strengths, weaknesses, and methodological considerations. Specifically we review alcohol administration, self-administration, cue-reactivity, and stress-reactivity paradigms. We also provide an introduction to the application of experimental psychopathology methods to translational research including genetics, neuroimaging, pharmacological and behavioral treatment development, and translational science. Through refining and manipulating key phenotypes of interest, these experimental paradigms have the potential to elucidate AUD etiological factors, improve the efficiency of treatment developments, and refine treatment targets thus advancing precision medicine. Copyright © 2016 Elsevier Ltd. All rights reserved.

Targeted therapies for Parkinson's disease: From genetics to the clinic.

PubMed

Sardi, S Pablo; Cedarbaum, Jesse M; Brundin, Patrik

2018-04-27

The greatest unmet medical need in Parkinson's disease (PD) is treatments that slow the relentless progression of symptoms. The discovery of genetic variants causing and/or increasing the risk for PD has provided the field with a new arsenal of potential therapies ready to be tested in clinical trials. We highlight 3 of the genetic discoveries (α-synuclein, glucocerebrosidase, and leucine-rich repeat kinase) that have prompted new therapeutic approaches now entering the clinical stages. We are at an exciting juncture in the journey to developing disease-modifying treatments based on knowledge of PD genetics and pathology. This review focuses on therapeutic paradigms that are under clinical development and highlights a wide range of key outstanding questions in PD. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Mesenchymal Stem Cells in Lipogems, a Reverse Story: from Clinical Practice to Basic Science.

PubMed

Tremolada, Carlo; Ricordi, Camillo; Caplan, Arnold I; Ventura, Carlo

2016-01-01

The idea that basic science should be the starting point for modern clinical approaches has been consolidated over the years, and emerged as the cornerstone of Molecular Medicine. Nevertheless, there is increasing concern over the low efficiency and inherent costs related to the translation of achievements from the bench to the bedside. These burdens are also perceived with respect to the effectiveness of translating basic discoveries in stem cell biology to the newly developing field of advanced cell therapy or Regenerative Medicine. As an alternative paradigm, past and recent history in Medical Science provides remarkable reverse stories in which clinical observations at the patient's bedside have fed major advances in basic research which, in turn, led to consistent progression in clinical practice. Within this context, we discuss our recently developed method and device, which forms the core of a system (Lipogems) for processing of human adipose tissue solely with the aid of mild mechanical forces to yield a microfractured tissue product.

Clinical Applications of Personalized Medicine: A New Paradigm and Challenge.

PubMed

Di Sanzo, Mariantonia; Cipolloni, Luigi; Borro, Marina; La Russa, Raffaele; Santurro, Alessandro; Scopetti, Matteo; Simmaco, Maurizio; Frati, Paola

2017-01-01

The personalized medicine is an emergent and rapidly developing method of clinical practice that uses new technologies to provide decisions in regard to the prediction, prevention, diagnosis and treatment of disease. A continuous evolution of technology and the developments in molecular diagnostics and genomic analysis increased the possibility of an even more understanding and interpretation of the human genome and exome, allowing a "personalized" approach to clinical care, so that the concepts of "Systems Medicine" and "System Biology" are actually increasing. The purpose of this study is to evaluate the personalized medicine about its indications and benefits, actual clinical applications and future perspectives as well as its issues and health care implications. A careful review of the scientific literature on this field that highlighted the applicability and usefulness of this new medical approach as well as the fact that personalized medicine strategy is even more increasing in numerous fields of applications. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Cognitive remediation versus active computer control in bipolar disorder with psychosis: study protocol for a randomized controlled trial.

PubMed

Lewandowski, Kathryn Eve; Sperry, Sarah H; Ongur, Dost; Cohen, Bruce M; Norris, Lesley A; Keshavan, Matcheri S

2016-03-12

Cognitive dysfunction is a major feature of bipolar disorder with psychosis and is strongly associated with functional outcomes. Computer-based cognitive remediation has shown promise in improving cognition in patients with schizophrenia. However, despite similar neurocognitive deficits between patients with schizophrenia and bipolar disorder, few studies have extended neuroscience-based cognitive remediation programs to this population. The Treatment to Enhance Cognition in Bipolar Disorder study is an investigator-initiated, parallel group, randomized, blinded clinical trial of an Internet-based cognitive remediation protocol for patients with bipolar disorder I with psychosis (n = 100). We also describe the development of our dose-matched active control paradigm. Both conditions involve 70 sessions of computer-based activities over 24 weeks. The control intervention was developed to mirror the treatment condition in dose and format but without the neuroplasticity-based task design and structure. All participants undergo neuropsychological and clinical assessment at baseline, after approximately 25 hours of study activities, post treatment, and after 6 months of no study contact to assess durability. Neuroimaging at baseline and post treatment are offered in an "opt-in" format. The primary outcomes are scores on the MATRICS battery; secondary and exploratory outcomes include measures of clinical symptoms, community functioning, and neuroimaging changes. Associations between change in cognitive measures and change in community functioning will be assessed. Baseline predictors of treatment response will be examined. The present study is the first we are aware of to implement an Internet-based cognitive remediation program in patients with bipolar disorder with psychosis and to develop a comparable web-based control paradigm. The mixed online and study-site format allows accessible treatment while providing weekly staff contact and bridging. Based on user-provided feedback, participant blinding is feasible. ClinicalTrials.gov NCT01470781 ; 11 July 2011.

Advancing tuberculosis drug regimen development through innovative quantitative translational pharmacology methods and approaches.

PubMed

Hanna, Debra; Romero, Klaus; Schito, Marco

2017-03-01

The development of novel tuberculosis (TB) multi-drug regimens that are more efficacious and of shorter duration requires a robust drug development pipeline. Advances in quantitative modeling and simulation can be used to maximize the utility of patient-level data from prior and contemporary clinical trials, thus optimizing study design for anti-TB regimens. This perspective article highlights the work of seven project teams developing first-in-class translational and quantitative methodologies that aim to inform drug development decision-making, dose selection, trial design, and safety assessments, in order to achieve shorter and safer therapies for patients in need. These tools offer the opportunity to evaluate multiple hypotheses and provide a means to identify, quantify, and understand relevant sources of variability, to optimize translation and clinical trial design. When incorporated into the broader regulatory sciences framework, these efforts have the potential to transform the development paradigm for TB combination development, as well as other areas of global health. Copyright © 2016. Published by Elsevier Ltd.

A New Paradigm for Ovarian Sex Cord-Stromal Tumor Development

DTIC Science & Technology

2016-05-01

1 AWARD NUMBER: W81XWH-15-1-0082 TITLE: A New Paradigm for Ovarian Sex Cord-Stromal Tumor Development PRINCIPAL INVESTIGATOR: Qinglei Li...5a. CONTRACT NUMBER A New Paradigm for Ovarian Sex Cord-Stromal Tumor Development 5b. GRANT NUMBER W81XWH-15-1-0082 5c. PROGRAM ELEMENT NUMBER 6...role of sustained activation of oocyte TGFBR1 in ovarian tumor development using an in vitro approach. 2. Keywords Ovarian tumor, Sex cord

Clinical Characteristics and Current Treatment of Age-Related Macular Degeneration

PubMed Central

Yonekawa, Yoshihiro; Kim, Ivana K.

2015-01-01

Age-related macular degeneration (AMD) is a multifactorial degeneration of photoreceptors and retinal pigment epithelium. The societal impact is significant, with more than 2 million individuals in the United States alone affected by advanced stages of AMD. Recent progress in our understanding of this complex disease and parallel developments in therapeutics and imaging have translated into new management paradigms in recent years. However, there are many unanswered questions, and diagnostic and prognostic precision and treatment outcomes can still be improved. In this article, we discuss the clinical features of AMD, provide correlations with modern imaging and histopathology, and present an overview of treatment strategies. PMID:25280900

Can Functional Magnetic Resonance Imaging Improve Success Rates in CNS Drug Discovery?

PubMed Central

Borsook, David; Hargreaves, Richard; Becerra, Lino

2011-01-01

Introduction The bar for developing new treatments for CNS disease is getting progressively higher and fewer novel mechanisms are being discovered, validated and developed. The high costs of drug discovery necessitate early decisions to ensure the best molecules and hypotheses are tested in expensive late stage clinical trials. The discovery of brain imaging biomarkers that can bridge preclinical to clinical CNS drug discovery and provide a ‘language of translation’ affords the opportunity to improve the objectivity of decision-making. Areas Covered This review discusses the benefits, challenges and potential issues of using a science based biomarker strategy to change the paradigm of CNS drug development and increase success rates in the discovery of new medicines. The authors have summarized PubMed and Google Scholar based publication searches to identify recent advances in functional, structural and chemical brain imaging and have discussed how these techniques may be useful in defining CNS disease state and drug effects during drug development. Expert opinion The use of novel brain imaging biomarkers holds the bold promise of making neuroscience drug discovery smarter by increasing the objectivity of decision making thereby improving the probability of success of identifying useful drugs to treat CNS diseases. Functional imaging holds the promise to: (1) define pharmacodynamic markers as an index of target engagement (2) improve translational medicine paradigms to predict efficacy; (3) evaluate CNS efficacy and safety based on brain activation; (4) determine brain activity drug dose-response relationships and (5) provide an objective evaluation of symptom response and disease modification. PMID:21765857

Information Management and the Biological Warfare Threat

DTIC Science & Technology

2002-03-01

24 2. Scientific-Security Paradigm Interaction........................................ 25 3. Business - Security Paradigm...policies of openness and guardedness and discuss the three paradigms (scientific, business , security ) as a developing factor for information sharing...Trade Center. 3. Business - Security Paradigm Interaction Gene patenting (discussed previously) is utilized by business to protect their

A deep learning model observer for use in alterative forced choice virtual clinical trials

NASA Astrophysics Data System (ADS)

Alnowami, M.; Mills, G.; Awis, M.; Elangovanr, P.; Patel, M.; Halling-Brown, M.; Young, K. C.; Dance, D. R.; Wells, K.

2018-03-01

Virtual clinical trials (VCTs) represent an alternative assessment paradigm that overcomes issues of dose, high cost and delay encountered in conventional clinical trials for breast cancer screening. However, to fully utilize the potential benefits of VCTs requires a machine-based observer that can rapidly and realistically process large numbers of experimental conditions. To address this, a Deep Learning Model Observer (DLMO) was developed and trained to identify lesion targets from normal tissue in small (200 x 200 pixel) image segments, as used in Alternative Forced Choice (AFC) studies. The proposed network consists of 5 convolutional layers with 2x2 kernels and ReLU (Rectified Linear Unit) activations, followed by max pooling with size equal to the size of the final feature maps and three dense layers. The class outputs weights from the final fully connected dense layer are used to consider sets of n images in an n-AFC paradigm to determine the image most likely to contain a target. To examine the DLMO performance on clinical data, a training set of 2814 normal and 2814 biopsy-confirmed malignant mass targets were used. This produced a sensitivity of 0.90 and a specificity of 0.92 when presented with a test data set of 800 previously unseen clinical images. To examine the DLMOs minimum detectable contrast, a second dataset of 630 simulated backgrounds and 630 images with simulated lesion and spherical targets (4mm and 6mm diameter), produced contrast thresholds equivalent to/better than human observer performance for spherical targets, and comparable (12 % difference) for lesion targets.

Applying Evidence-Based Medicine in Telehealth: An Interactive Pattern Recognition Approximation

PubMed Central

Fernández-Llatas, Carlos; Meneu, Teresa; Traver, Vicente; Benedi, José-Miguel

2013-01-01

Born in the early nineteen nineties, evidence-based medicine (EBM) is a paradigm intended to promote the integration of biomedical evidence into the physicians daily practice. This paradigm requires the continuous study of diseases to provide the best scientific knowledge for supporting physicians in their diagnosis and treatments in a close way. Within this paradigm, usually, health experts create and publish clinical guidelines, which provide holistic guidance for the care for a certain disease. The creation of these clinical guidelines requires hard iterative processes in which each iteration supposes scientific progress in the knowledge of the disease. To perform this guidance through telehealth, the use of formal clinical guidelines will allow the building of care processes that can be interpreted and executed directly by computers. In addition, the formalization of clinical guidelines allows for the possibility to build automatic methods, using pattern recognition techniques, to estimate the proper models, as well as the mathematical models for optimizing the iterative cycle for the continuous improvement of the guidelines. However, to ensure the efficiency of the system, it is necessary to build a probabilistic model of the problem. In this paper, an interactive pattern recognition approach to support professionals in evidence-based medicine is formalized. PMID:24185841

An official American Thoracic Society research statement: comparative effectiveness research in pulmonary, critical care, and sleep medicine.

PubMed

Carson, Shannon S; Goss, Christopher H; Patel, Sanjay R; Anzueto, Antonio; Au, David H; Elborn, Stuart; Gerald, Joe K; Gerald, Lynn B; Kahn, Jeremy M; Malhotra, Atul; Mularski, Richard A; Riekert, Kristin A; Rubenfeld, Gordon D; Weaver, Terri E; Krishnan, Jerry A

2013-11-15

Comparative effectiveness research (CER) is intended to inform decision making in clinical practice, and is central to patient-centered outcomes research (PCOR). To summarize key aspects of CER definitions and provide examples highlighting the complementary nature of efficacy and CER studies in pulmonary, critical care, and sleep medicine. An ad hoc working group of the American Thoracic Society with experience in clinical trials, health services research, quality improvement, and behavioral sciences in pulmonary, critical care, and sleep medicine was convened. The group used an iterative consensus process, including a review by American Thoracic Society committees and assemblies. The traditional efficacy paradigm relies on clinical trials with high internal validity to evaluate interventions in narrowly defined populations and in research settings. Efficacy studies address the question, "Can it work in optimal conditions?" The CER paradigm employs a wide range of study designs to understand the effects of interventions in clinical settings. CER studies address the question, "Does it work in practice?" The results of efficacy and CER studies may or may not agree. CER incorporates many attributes of outcomes research and health services research, while placing greater emphasis on meeting the expressed needs of nonresearcher stakeholders (e.g., patients, clinicians, and others). CER complements traditional efficacy research by placing greater emphasis on the effects of interventions in practice, and developing evidence to address the needs of the many stakeholders involved in health care decisions. Stakeholder engagement is an important component of CER.

Narratives of neoliberalism: ‘clinical labour’ in context

PubMed Central

Parry, Bronwyn

2015-01-01

Cross-border reproductive care has been thrust under the international spotlight by a series of recent scandals. These have prompted calls to develop more robust means of assessing the exploitative potential of such practices and the need for overarching and normative forms of national and international regulation. Allied theorisations of the emergence of forms of clinical labour have cast the outsourcing of reproductive services such as gamete donation and gestational surrogacy as artefacts of a wider neoliberalisation of service provision. These accounts share with many other narratives of neoliberalism a number of key assertions that relate to the presumed organisation of labour relations within this paradigm. This article critically engages with four assumptions implicit in these accounts: that clinical labourers constitute a largely homogeneous underclass of workers; that reproductive labour has been contractualised in ways that disembed it from wider social and communal relations; that contractualisation can provide protection for clinical labour lessening the need for formal regulatory oversight; and that the transnationalisation of reproductive service labour is largely unidirectional and characterised by a dynamic of provision in which ‘the rest’ services ‘the West’. Drawing on the first findings of a large-scale ethnographic research project into assisted reproduction in India I provide evidence to refute these assertions. In so doing the article demonstrates that while the outsourcing and contractualisation of reproductive labour may be embedded in a wider neoliberal paradigm these practices cannot be understood nor their impacts be fully assessed in isolation from their social and cultural contexts. PMID:26052118

Collaborative Paradigm of Preventive, Personalized, and Precision Medicine With Point-of-Care Technologies

PubMed Central

2016-01-01

Recent advances in biosensors, medical instrumentation, and information processing and communication technologies (ICT) have enabled significant improvements in healthcare. However, these technologies have been mainly applied in clinical environments, such as hospitals and healthcare facilities, under managed care by well-trained and specialized individuals. The global challenge of providing quality healthcare at affordable cost leads to the proposed paradigm of P reventive, Personalized, and Precision Medicine that requires a seamless use of technology and infrastructure support for patients and healthcare providers at point-of-care (POC) locations including homes, semi or pre-clinical facilities, and hospitals. The complexity of the global healthcare challenge necessitates strong collaborative interdisciplinary synergies involving all stakeholder groups including academia, federal research institutions, industry, regulatory agencies, and clinical communities. It is critical to evolve with collaborative efforts on the translation of research to technology development toward clinical validation and potential healthcare applications. This special issue is focused on technology innovation and translational research for POC applications with potential impact in improving global healthcare in the respective areas. Some of these papers were presented at the NIH-IEEE Strategic Conference on Healthcare Innovations and POC Technologies for Precision Medicine (HI-POCT) held at the NIH on November 9–10, 2015. The papers included in the Special Issue provide a spectrum of critical issues and collaborative resources on translational research of advanced POC devices and ICT into global healthcare environment. PMID:28560119

Practical considerations in clinical strategy to support the development of injectable drug-device combination products for biologics.

PubMed

Li, Zhaoyang; Easton, Rachael

2018-01-01

The development of an injectable drug-device combination (DDC) product for biologics is an intricate and evolving process that requires substantial investments of time and money. Consequently, the commercial dosage form(s) or presentation(s) are often not ready when pivotal trials commence, and it is common to have drug product changes (manufacturing process or presentation) during clinical development. A scientifically sound and robust bridging strategy is required in order to introduce these changes into the clinic safely. There is currently no single developmental paradigm, but a risk-based hierarchical approach has been well accepted. The rigor required of a bridging package depends on the level of risk associated with the changes. Clinical pharmacokinetic/pharmacodynamic comparability or outcome studies are only required when important changes occur at a late stage. Moreover, an injectable DDC needs to be user-centric, and usability assessment in real-world clinical settings may be required to support the approval of a DDC. In this review, we discuss the common issues during the manufacturing process and presentation development of an injectable DDC and practical considerations in establishing a clinical strategy to address these issues, including key elements of clinical studies. We also analyze the current practice in the industry and review relevant and status of regulatory guidance in the DDC field.

Practical considerations in clinical strategy to support the development of injectable drug-device combination products for biologics

PubMed Central

Easton, Rachael

2018-01-01

ABSTRACT The development of an injectable drug-device combination (DDC) product for biologics is an intricate and evolving process that requires substantial investments of time and money. Consequently, the commercial dosage form(s) or presentation(s) are often not ready when pivotal trials commence, and it is common to have drug product changes (manufacturing process or presentation) during clinical development. A scientifically sound and robust bridging strategy is required in order to introduce these changes into the clinic safely. There is currently no single developmental paradigm, but a risk-based hierarchical approach has been well accepted. The rigor required of a bridging package depends on the level of risk associated with the changes. Clinical pharmacokinetic/pharmacodynamic comparability or outcome studies are only required when important changes occur at a late stage. Moreover, an injectable DDC needs to be user-centric, and usability assessment in real-world clinical settings may be required to support the approval of a DDC. In this review, we discuss the common issues during the manufacturing process and presentation development of an injectable DDC and practical considerations in establishing a clinical strategy to address these issues, including key elements of clinical studies. We also analyze the current practice in the industry and review relevant and status of regulatory guidance in the DDC field. PMID:29035675

Conversive disorders among children and adolescents: towards new "complementarist" paradigms?

PubMed

Ouss, L; Tordjman, E

2014-10-01

This paper aims to describe current questions concerning conversive disorders among children and adolescents. We first describe prevalence and clinical characteristics of these. Many unresolved questions remain. Why do patients show excess, or loss of function? Attachment theory offers a relevant framework to answer this question. Does neurobiology of conversion disorders shed light on conversive processes? Current neurobiological research paradigms focus on the symptom, trying to infer processes, instead of proposing paradigms that test theoretical hypotheses. The most convincing theoretical framework that has already proposed a coherent theory of conversion is a psychodynamic one, which has not yet been tested with neurobiological paradigms. The interest of studying child and adolescent conversive disorders is to provide a means to more deeply investigate the two challenges we face: theoretical, and clinical ones. It provides the opportunity to access a pathopsychological process at its roots, not yet hidden by many defensive, rationalizing attitudes, and to better explore environmental features. We propose a "complementarist" model, which allows the combination of different approaches (neural, cognitive, environmental, attachment, intra-psychic) and permits proposal of different levels of therapeutic targets and means. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Gene Editing: A View Through the Prism of Inherited Metabolic Disorders.

PubMed

Davison, James

2018-04-01

Novel technological developments mean that gene editing - making deliberately targeted alterations in specific genes - is now a clinical reality. The inherited metabolic disorders, a group of clinically significant, monogenic disorders, provide a useful paradigm to explore some of the many ethical issues that arise from this technological capability. Fundamental questions about the significance of the genome, and of manipulating it by selection or editing, are reviewed, and a particular focus on the legislative process that has permitted the development of mitochondrial donation techniques is considered. Ultimately, decisions about what we should do with gene editing must be determined by reference to other non-genomic texts that determine what it is to be human - rather than simply to undertake gene editing because it can be done.

Quality improvement in neonatal care - a new paradigm for developing countries.

PubMed

Chawla, Deepak; Suresh, Gautham K

2014-12-01

Infrastructure for facility-based neonatal care has rapidly grown in India over last few years. Experience from developed countries indicates that different health facilities have varying clinical outcomes despite accounting for differences in illness severity of admitted neonates and random variation. Variation in quality of care provided at different neonatal units may account for variable clinical outcomes. Monitoring quality of care, comparing outcomes across different centers and conducting collaborative quality improvement projects can improve outcome of neonates in health facilities. Top priority should be given to establishing quality monitoring and improvement procedures at special care neonatal units and neonatal intensive care units of the country. This article presents an overview of methods of quality improvement. Literature reports of successful collaborative quality improvement projects in neonatal health are also reviewed.

Therapeutic antibodies: A new era in the treatment of respiratory diseases?

PubMed

Sécher, T; Guilleminault, L; Reckamp, K; Amanam, I; Plantier, L; Heuzé-Vourc'h, N

2018-05-04

Respiratory diseases affect millions of people worldwide, and account for significant levels of disability and mortality. The treatment of lung cancer and asthma with therapeutic antibodies (Abs) is a breakthrough that opens up new paradigms for the management of respiratory diseases. Antibodies are becoming increasingly important in respiratory medicine; dozens of Abs have received marketing approval, and many more are currently in clinical development. Most of these Abs target asthma, lung cancer and respiratory infections, while very few target chronic obstructive pulmonary disease - one of the most common non-communicable causes of death - and idiopathic pulmonary fibrosis. Here, we review Abs approved for or in clinical development for the treatment of respiratory diseases. We notably highlight their molecular mechanisms, strengths, and likely future trends. Copyright © 2018 Elsevier Inc. All rights reserved.

Novel Androgen Deprivation Therapy (ADT) in the Treatment of Advanced Prostate Cancer.

PubMed

Aragon-Ching, Jeanny B; Dahut, William L

2010-07-01

Androgen deprivation therapy has been the mainstay of treatment for advanced and metastatic prostate cancer. The use of novel agents targeting the androgen receptor and its signaling pathways offers a promising approach that is both safe and effective. We describe the rationale behind the use of these compounds in clinical development and the existing challenges as to how best to incorporate these new and emerging therapies in the changing treatment paradigm of metastatic prostate cancer.

Strategic Intellectual Capital Development: A Defining Paradigm for HRD?

ERIC Educational Resources Information Center

Holton, Elwood F., III; Yamkovenko, Bogdan

2008-01-01

The performance paradigm of human resource development (HRD) practice has served the field well, particularly in enhancing the relevance and impact of HRD interventions. However, in this article, it is argued that the time has come for a new defining paradigm to advance the field of HRD to a higher level of organizational impact. This article…

The role of motor memory in action selection and procedural learning: insights from children with typical and atypical development.

PubMed

Tallet, Jessica; Albaret, Jean-Michel; Rivière, James

2015-01-01

Motor memory is the process by which humans can adopt both persistent and flexible motor behaviours. Persistence and flexibility can be assessed through the examination of the cooperation/competition between new and old motor routines in the motor memory repertoire. Two paradigms seem to be particularly relevant to examine this competition/cooperation. First, a manual search task for hidden objects, namely the C-not-B task, which allows examining how a motor routine may influence the selection of action in toddlers. The second paradigm is procedural learning, and more precisely the consolidation stage, which allows assessing how a previously learnt motor routine becomes resistant to subsequent programming or learning of a new - competitive - motor routine. The present article defends the idea that results of both paradigms give precious information to understand the evolution of motor routines in healthy children. Moreover, these findings echo some clinical observations in developmental neuropsychology, particularly in children with Developmental Coordination Disorder. Such studies suggest that the level of equilibrium between persistence and flexibility of motor routines is an index of the maturity of the motor system.

Historical ESWT Paradigms Are Overcome: A Narrative Review

PubMed Central

Nauck, Tanja; Korakakis, Vasileios; Malliaropoulos, Nikos

2016-01-01

Extracorporeal Shock Wave Therapy (ESWT) is a conservative treatment modality with still growing interest in musculoskeletal disorders. This narrative review aims to present an overview covering 20-year development in the field of musculoskeletal ESWT. Eight historical paradigms have been identified and put under question from a current perspective: energy intensity, focus size, anesthesia, imaging, growth plates, acuteness, calcifications, and number of sessions. All paradigms as set in a historical consensus meeting in 1995 are to be revised. First, modern musculoskeletal ESWT is divided into focused and radial technology and the physical differences are about 100-fold with respect to the applied energy. Most lesions to be treated are easy to reach and clinical focusing plays a major role today. Lesion size is no longer a matter of concern. With the exception of nonunion fractures full, regional, or even local anesthesia is not helpful in musculoskeletal indications. Juvenile patients can also effectively be treated without risk of epiphyseal damage. Further research is needed to answer the question about if and which acute injuries can be managed effectively. Treatment parameters like the number of sessions are still relying on empirical data and have to be further elucidated. PMID:27493955

[Botulinum toxin: from drug to poison].

PubMed

Dressler, D; Saberi, F A

2009-08-01

For most of its time, the history of botulinum toxin (BT) has been the history of botulism, i. e. of an intoxication with BT. By the end of the 1960's a paradigm shift took place which in this radicalness had never occurred before in the history of mankind. At that time BT was first used therapeutically to treat strabismus. From ophthalmology BT rapidly spread into numerous medical specialties. For most of its indications BT is the therapy of choice, for some it has revolutionized their treatment altogether. The widespread therapeutic use of BT allowed detailed clinical and technical investigations of BT's action upon the human body. Applying this knowledge we diagnosed for the first time chronic botulism in adults living on a farm with chronic bovine botulism. This constitutes another radical paradigm shift. The history of BT is the history of a dual paradigm shift each time induced by a complete reversal of the viewing perspective. Knowledge gain can be a linear process. It can, however, also be a circular one. Changes of the viewing perspective are crucial. Changing the viewing perspective may facilitate knowledge gain. This might be used to develop an instrument to facilitate knowledge gain. (c) Georg Thieme Verlag KG Stuttgart-New York.

Engineering paradigms and anthropogenic global change

NASA Astrophysics Data System (ADS)

Bohle, Martin

2016-04-01

This essay discusses 'paradigms' as means to conceive anthropogenic global change. Humankind alters earth-systems because of the number of people, the patterns of consumption of resources, and the alterations of environments. This process of anthropogenic global change is a composite consisting of societal (in the 'noosphere') and natural (in the 'bio-geosphere') features. Engineering intercedes these features; e.g. observing stratospheric ozone depletion has led to understanding it as a collateral artefact of a particular set of engineering choices. Beyond any specific use-case, engineering works have a common function; e.g. civil-engineering intersects economic activity and geosphere. People conceive their actions in the noosphere including giving purpose to their engineering. The 'noosphere' is the ensemble of social, cultural or political concepts ('shared subjective mental insights') of people. Among people's concepts are the paradigms how to shape environments, production systems and consumption patterns given their societal preferences. In that context, engineering is a means to implement a given development path. Four paradigms currently are distinguishable how to make anthropogenic global change happening. Among the 'engineering paradigms' for anthropogenic global change, 'adaptation' is a paradigm for a business-as-usual scenario and steady development paths of societies. Applying this paradigm implies to forecast the change to come, to appropriately design engineering works, and to maintain as far as possible the current production and consumption patterns. An alternative would be to adjust incrementally development paths of societies, namely to 'dovetail' anthropogenic and natural fluxes of matter and energy. To apply that paradigm research has to identify 'natural boundaries', how to modify production and consumption patterns, and how to tackle process in the noosphere to render alterations of common development paths acceptable. A further alternative, the paradigm of 'ecomodernism' implies to accentuate some of the current development paths of societies with the goal to 'decouple' anthropogenic and natural fluxes of matter and energy. Applying the paradigm 'geoengineering', engineering works shall 'modulate' natural fluxes of matter to counter the effect of anthropogenic fluxes of matter instead to alter the development paths of societies. Thus, anthropogenic global change is a composite process in which engineering intercedes the 'noosphere' and in the 'bio-geosphere'. Paradigms 'how to engineering earth systems' reflect different concepts ('shared subjective insights') how to combine knowledge with use, function and purpose. Currently, four paradigms are distinguishable how to engineer anthropogenic global change. They convene recipes human activity and bio-geosphere should intersect.

What proportion of patients with chronic heart failure are eligible for sacubitril-valsartan?

PubMed

Pellicori, Pierpaolo; Urbinati, Alessia; Shah, Parin; MacNamara, Alexandra; Kazmi, Syed; Dierckx, Riet; Zhang, Jufen; Cleland, John G F; Clark, Andrew L

2017-06-01

The PARADIGM-HF trial showed that sacubitril-valsartan, an ARB-neprilysin inhibitor, is more effective than enalapril for some patients with heart failure (HF). It is uncertain what proportion of patients with HF would be eligible for sacubitril-valsartan in clinical practice. Between 2001 and 2014, 6131 patients consecutively referred to a community HF clinic with suspected HF were assessed. The criteria required to enter the randomized phase of PARADIGM-HF, including symptoms, NT-proBNP, and current treatment with or without target doses of ACE inhibitors or ARBs, were applied to identify the proportion of patients eligible for sacubitril-valsartan. Recognizing the diversity of clinical opinion and guideline recommendations concerning this issue, entry criteria were applied singly and in combination. Of 1396 patients with reduced left ventricular ejection fraction (≤40%, HFrEF) and contemporary measurement of NT-proBNP, 379 were on target doses of an ACE inhibitor or ARB at their initial visit and, of these, 172 (45%) fulfilled the key entry criteria for the PARADIGM-HF trial. Lack of symptoms (32%) and NT-proBNP <600 ng/L (49%) were common reasons for failure to fulfil criteria. A further 122 patients became eligible during follow-up (n = 294, 21%). However, if background medication and doses were ignored, then 701 (50%) were eligible initially and a further 137 became eligible during follow-up. Of patients with HFrEF referred to a clinic such as ours, only 21% fulfilled the PARADIGM-HF randomization criteria, on which the ESC Guidelines are based; this proportion rises to 60% if background medication is ignored. © 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.

Bayesian prediction of placebo analgesia in an instrumental learning model

PubMed Central

Jung, Won-Mo; Lee, Ye-Seul; Wallraven, Christian; Chae, Younbyoung

2017-01-01

Placebo analgesia can be primarily explained by the Pavlovian conditioning paradigm in which a passively applied cue becomes associated with less pain. In contrast, instrumental conditioning employs an active paradigm that might be more similar to clinical settings. In the present study, an instrumental conditioning paradigm involving a modified trust game in a simulated clinical situation was used to induce placebo analgesia. Additionally, Bayesian modeling was applied to predict the placebo responses of individuals based on their choices. Twenty-four participants engaged in a medical trust game in which decisions to receive treatment from either a doctor (more effective with high cost) or a pharmacy (less effective with low cost) were made after receiving a reference pain stimulus. In the conditioning session, the participants received lower levels of pain following both choices, while high pain stimuli were administered in the test session even after making the decision. The choice-dependent pain in the conditioning session was modulated in terms of both intensity and uncertainty. Participants reported significantly less pain when they chose the doctor or the pharmacy for treatment compared to the control trials. The predicted pain ratings based on Bayesian modeling showed significant correlations with the actual reports from participants for both of the choice categories. The instrumental conditioning paradigm allowed for the active choice of optional cues and was able to induce the placebo analgesia effect. Additionally, Bayesian modeling successfully predicted pain ratings in a simulated clinical situation that fits well with placebo analgesia induced by instrumental conditioning. PMID:28225816

Evolution of psychology and counseling in infertility.

PubMed

Boivin, Jacky; Gameiro, Sofia

2015-08-01

Five key paradigm shifts are described to illustrate the evolution of psychology and counseling in infertility. The first paradigm shift was in the 1930s when psychosomatic concepts were introduced in obstetrics and gynecology as causal factors to explain why some couples could not conceive despite the absence of organic pathology. In the second shift, the nurse advocacy movement of the 1970s stimulated the investigation of the psychosocial consequences of infertility and promoted counseling to help couples grieve childlessness when medical treatments often could not help them conceive. The third shift occurred with the advent of IVF, which created a demand for mental health professionals in fertility clinics. Mental health professionals assessed the ability of couples to withstand the demands of this new high technology treatment as well as their suitability as potential parents. The fourth shift, in the 1990s, saw reproductive medicine embrace the principles of evidence-based medicine, which introduced a much more rigorous approach to medical practice (effectiveness and safety) that extended to psychosocial interventions. The most recent paradigm shift, in the new millennium, occurred with the realization that compliance with protracted fertility treatment depended on the adoption of an integrated approach to fertility care. An integrated approach could reduce treatment burden arising from multiple sources (i.e., patient, clinic, and treatment). This review describes these paradigm shifts and reflects on future clinical and research directions for mental health professionals. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Viewing the art and the science of pediatric nursing through the lens of paradigms: the impact on hope for the future.

PubMed

Bally, Jill M G

2012-07-01

The purpose of this study was to examine the strengths and limitations of common research paradigms used in the study of the hope of parents who have children with a variety of illnesses. Research findings on parental hope extracted from only one paradigm present limitations to related knowledge development. To take into account the contributions from each paradigm and to allow for a multidimensional understanding of parental hope, a multiparadigmatic approach is needed. The complementary findings from multiple research paradigms can lead to a comprehensive base of knowledge that can guide future research and develop effective, family-centered pediatric nursing care. © 2012, Wiley Periodicals, Inc.

Advanced Bioinks for 3D Printing: A Materials Science Perspective.

PubMed

Chimene, David; Lennox, Kimberly K; Kaunas, Roland R; Gaharwar, Akhilesh K

2016-06-01

Advanced bioinks for 3D printing are rationally designed materials intended to improve the functionality of printed scaffolds outside the traditional paradigm of the "biofabrication window". While the biofabrication window paradigm necessitates compromise between suitability for fabrication and ability to accommodate encapsulated cells, recent developments in advanced bioinks have resulted in improved designs for a range of biofabrication platforms without this tradeoff. This has resulted in a new generation of bioinks with high print fidelity, shear-thinning characteristics, and crosslinked scaffolds with high mechanical strength, high cytocompatibility, and the ability to modulate cellular functions. In this review, we describe some of the promising strategies being pursued to achieve these goals, including multimaterial, interpenetrating network, nanocomposite, and supramolecular bioinks. We also provide an overview of current and emerging trends in advanced bioink synthesis and biofabrication, and evaluate the potential applications of these novel biomaterials to clinical use.

The biomedical model of mental disorder: a critical analysis of its validity, utility, and effects on psychotherapy research.

PubMed

Deacon, Brett J

2013-11-01

The biomedical model posits that mental disorders are brain diseases and emphasizes pharmacological treatment to target presumed biological abnormalities. A biologically-focused approach to science, policy, and practice has dominated the American healthcare system for more than three decades. During this time, the use of psychiatric medications has sharply increased and mental disorders have become commonly regarded as brain diseases caused by chemical imbalances that are corrected with disease-specific drugs. However, despite widespread faith in the potential of neuroscience to revolutionize mental health practice, the biomedical model era has been characterized by a broad lack of clinical innovation and poor mental health outcomes. In addition, the biomedical paradigm has profoundly affected clinical psychology via the adoption of drug trial methodology in psychotherapy research. Although this approach has spurred the development of empirically supported psychological treatments for numerous mental disorders, it has neglected treatment process, inhibited treatment innovation and dissemination, and divided the field along scientist and practitioner lines. The neglected biopsychosocial model represents an appealing alternative to the biomedical approach, and an honest and public dialog about the validity and utility of the biomedical paradigm is urgently needed. Copyright © 2013 Elsevier Ltd. All rights reserved.

High-Throughput Testing of Novel-Novel Combination Therapies for Cancer: An Idea Whose Time Has Come.

PubMed

Scarlett, Uciane K; Chang, Dennis C; Murtagh, Thomas J; Flaherty, Keith T

2016-09-01

Combination therapies are essential to address the genetic complexity, plasticity, and heterogeneity of tumors and to overcome resistance mechanisms that confound single-agent approaches, and are a paradigm that became well established in the era of conventional cytotoxic chemotherapies. Today, we are well equipped to address many of the scientific, clinical, and collaboration challenges that have existed historically; however, the pace of testing rational combinations is modest. Our analysis shows that the volume of clinical trials testing multiple investigational pipeline agents ("novel-novel" combinations) is dismally low, as out of approximately 1,500 phase I to III investigational combination trials initiated in 2014-2015, only 80 were for novel-novel combinations, and only 9 of those involved more than one company. The Collaborative Novel-Novel Combination Therapies (CoNNCT) initiative aims to alleviate this bottleneck by developing a new, faster paradigm for early investigation of scientifically informed, novel-novel drug combinations. The initiative kicked off on March 7, 2016, when representatives from top academic centers, biopharma, nonprofits, the FDA, and other groups gathered to define an actionable path forward. Cancer Discov; 6(9); 956-62. ©2016 AACR. ©2016 American Association for Cancer Research.

Coronary artery disease: new insights into the pathophysiology, prevalence and early detection of a monster menace.

PubMed

Slater, James; Rill, Velisar

2003-04-01

Coronary artery disease (CAD) is the leading cause of morbidity and mortality in the United States and industrialized countries. In the undeveloped world a similar epidemic is brewing. A new pathophysiologic paradigm has emerged, which assigns the mediators of inflammation a much larger role in the disease process. This paradigm has helped explain the unpredictable nature of many adverse consequences of CAD. The long latent phase of the disease and often sudden initial presentation make efforts at early detection extremely important. Considerable work has been devoted to identify as well as influence predisposing risk factors for developing arteriosclerosis. Novel markers of inflammation, like C-reactive protein, have been identified and compared to traditional risk factors. In addition, new imaging modalities introduce the possibility of screening for sub-clinical disease. Electron-beam and spiral CT scanners, as well as other techniques, are emerging as powerful tools to detect early disease presence and allow intervention to take place before major clinical events occur. Advances in our understanding of the pathophysiology and our ability to image the stages of silent disease will go hand in hand to revolutionize our approach to prevention and treatment of this deadly disease.

Cue-induced craving in pathological buying: empirical evidence and clinical implications.

PubMed

Trotzke, Patrick; Starcke, Katrin; Pedersen, Anya; Brand, Matthias

2014-01-01

Pathological buying is associated with marked distress and impaired functioning in important life domains. It is currently under debate whether pathological buying can be considered a behavioral addiction. In analogy to results reported in addicted individuals, craving reactions elicited by addiction-related cues might be an underlying mechanism for the etiology and pathogenesis of pathological buying. In the present study, 30 pathological buyers and 30 matched control participants were examined with a cue-reactivity paradigm consisting of shopping and control cues. Skin conductance responses, as well as subjective ratings for arousal, valence, and urge to buy, were assessed. Subjective craving reactions were measured before and after the cue-reactivity paradigm. On a physiological level, skin conductance responses toward shopping cues were higher in pathological buyers (mean [M; standard deviation {SD}] = 0.26 [0.13]) compared with control participants (M [SD] = 0.19 [0.09]; t(58) = 2.29, p = .025, d = 0.60). On a behavioral level, the individuals with pathological buying rated the shopping cues as more arousing and more positive, and reported a greater urge to buy compared with control participants and with control cues. An increase in subjective craving after completing the cue-reactivity paradigm was observed only in the pathological buyers (Mpre [SD] = 1.95 [1.47], Mpost [SD] = 2.87 [1.79]; t(29) = 5.07, p < .001, d = 0.97). Cue-reactivity and craving might be potential correlates for the development and maintenance of pathological buying. The results demonstrate similarities between pathological buying and substance or behavioral addictions and provide implications for clinical treatment.

Lifelong learning in obstetrics and gynaecology: how theory can influence clinical practice.

PubMed

Mukhopadhyay, S; Smith, S; Cresswell, J

2011-08-01

Lifelong learning refers to the systematic acquisition, renewal, updating and completion of knowledge. It is synonymous with the term 'self-directed learning'. This is a new educational strategy meant to consolidate knowledge in a fashion that is reproducible for a lifetime with successful application to both known and unknown clinical exercises. The development of lifelong learning is based on the principles of andragogy (autonomy and independence in one's learning activities), reflection and learning from experience. This paper deals with the development of these theories culminating in the advent of self-directed learning. Evidence to support experiential, reflective and self-directed learning is provided, including the use of rating scales. An example from obstetrics is used to highlight the application of these principles. There are barriers to adopting a new educational paradigm, however, lifelong learning remains an excellent tool for continuous professional development.

The druggable genome and support for target identification and validation in drug development.

PubMed

Finan, Chris; Gaulton, Anna; Kruger, Felix A; Lumbers, R Thomas; Shah, Tina; Engmann, Jorgen; Galver, Luana; Kelley, Ryan; Karlsson, Anneli; Santos, Rita; Overington, John P; Hingorani, Aroon D; Casas, Juan P

2017-03-29

Target identification (determining the correct drug targets for a disease) and target validation (demonstrating an effect of target perturbation on disease biomarkers and disease end points) are important steps in drug development. Clinically relevant associations of variants in genes encoding drug targets model the effect of modifying the same targets pharmacologically. To delineate drug development (including repurposing) opportunities arising from this paradigm, we connected complex disease- and biomarker-associated loci from genome-wide association studies to an updated set of genes encoding druggable human proteins, to agents with bioactivity against these targets, and, where there were licensed drugs, to clinical indications. We used this set of genes to inform the design of a new genotyping array, which will enable association studies of druggable genes for drug target selection and validation in human disease. Copyright © 2017, American Association for the Advancement of Science.

Automatic and Controlled Response Inhibition: Associative Learning in the Go/No-Go and Stop-Signal Paradigms

ERIC Educational Resources Information Center

Verbruggen, Frederick; Logan, Gordon D.

2008-01-01

In 5 experiments, the authors examined the development of automatic response inhibition in the go/no-go paradigm and a modified version of the stop-signal paradigm. They hypothesized that automatic response inhibition may develop over practice when stimuli are consistently associated with stopping. All 5 experiments consisted of a training phase…

The safety of sacubitril-valsartan for the treatment of chronic heart failure.

PubMed

Tyler, Jeffrey M; Teerlink, John R

2017-02-01

Sacubitril-valsartan is a combination drug that contains the neprilysin inhibitor sacubitril and angiotensin II receptor blocker valsartan. In 2015, the US Food and Drug Administration approved sacubitril-valsartan for treatment of heart failure patients with reduced ejection fraction and New York Heart Association class II-IV symptoms following a large, Phase III clinical trial (PARADIGM-HF) that demonstrated a 20% reduction in the combined primary end-point of death from cardiovascular cause or hospitalization for heart failure compared to enalapril. Areas covered: This review discusses the clinical efficacy and safety of angiotensin receptor neprilysin inhibitor sacubitril-valsartan in heart failure with reduced ejection fraction. Expert opinion: Based on the PARADIGM-HF trial, sacubitril-valsartan offers compelling reductions in meaningful clinical endpoints, independent of age or severity of disease. The rate of adverse events was comparable between the enalapril and sacubitril-valsartan groups, although the absolute rates are likely underestimated due to the entry criteria and run-in period. Future trials and post-market surveillance are critical to better understand the risk of angioedema in high risk populations, particularly African-Americans, as well as long-term theoretical risks including the potential for increased cerebral amyloid plaque deposition with possible development of neurocognitive disease. Current trials are underway to evaluate potential benefit in patients with heart failure with preserved ejection fraction.

Stress-based animal models of depression: Do we actually know what we are doing?

PubMed

Yin, Xin; Guven, Nuri; Dietis, Nikolas

2016-12-01

Depression is one of the leading causes of disability and a significant health-concern worldwide. Much of our current understanding on the pathogenesis of depression and the pharmacology of antidepressant drugs is based on pre-clinical models. Three of the most popular stress-based rodent models are the forced swimming test, the chronic mild stress paradigm and the learned helplessness model. Despite their recognizable advantages and limitations, they are associated with an immense variability due to the high number of design parameters that define them. Only few studies have reported how minor modifications of these parameters affect the model phenotype. Thus, the existing variability in how these models are used has been a strong barrier for drug development as well as benchmark and evaluation of these pre-clinical models of depression. It also has been the source of confusing variability in the experimental outcomes between research groups using the same models. In this review, we summarize the known variability in the experimental protocols, identify the main and relevant parameters for each model and describe the variable values using characteristic examples. Our view of depression and our efforts to discover novel and effective antidepressants is largely based on our detailed knowledge of these testing paradigms, and requires a sound understanding around the importance of individual parameters to optimize and improve these pre-clinical models. Copyright © 2016 Elsevier B.V. All rights reserved.

Adapting Social Neuroscience Measures for Schizophrenia Clinical Trials, Part 1: Ferrying Paradigms Across Perilous Waters

PubMed Central

Green, Michael F.

2013-01-01

Social cognitive impairment is prominent in schizophrenia, and it is closely related to functional outcome. Partly for these reasons, it has rapidly become a target for both training and psychopharmacological interventions. However, there is a paucity of reliable and valid social cognitive endpoints that can be used to evaluate treatment response in clinical trials. Also, clinical studies in schizophrenia have benefited rather little from the surge of activity and knowledge in nonclinical social neuroscience. The National Institute of Mental Health-sponsored study, “Social Cognition and Functioning in Schizophrenia” (SCAF), attempted to address this translational challenge by selecting paradigms from social neuroscience that could be adapted for use in schizophrenia. The project also evaluated the psychometric properties and external validity of the tasks to determine their suitability for multisite clinical trials. This first article in the theme section presents the goals, conceptual background, and rationale for the SCAF project. PMID:24072811

Translating genomic information into clinical medicine: lung cancer as a paradigm.

PubMed

Levy, Mia A; Lovly, Christine M; Pao, William

2012-11-01

We are currently in an era of rapidly expanding knowledge about the genetic landscape and architectural blueprints of various cancers. These discoveries have led to a new taxonomy of malignant diseases based upon clinically relevant molecular alterations in addition to histology or tissue of origin. The new molecularly based classification holds the promise of rational rather than empiric approaches for the treatment of cancer patients. However, the accelerated pace of discovery and the expanding number of targeted anti-cancer therapies present a significant challenge for healthcare practitioners to remain informed and up-to-date on how to apply cutting-edge discoveries into daily clinical practice. In this Perspective, we use lung cancer as a paradigm to discuss challenges related to translating genomic information into the clinic, and we present one approach we took at Vanderbilt-Ingram Cancer Center to address these challenges.

UROLOGIC ROBOTS AND FUTURE DIRECTIONS

PubMed Central

Mozer, Pierre; Troccaz, Jocelyne; Stoianovici, Dan

2009-01-01

Purpose of review Robot-assisted laparoscopic surgery in urology has gained immense popularity with the Da Vinci system but a lot of research teams are working on new robots. The purpose of this paper is to review current urologic robots and present future developments directions. Recent findings Future systems are expected to advance in two directions: improvements of remote manipulation robots and developments of image-guided robots. Summary The final goal of robots is to allow safer and more homogeneous outcomes with less variability of surgeon performance, as well as new tools to perform tasks based on medical transcutaneous imaging, in a less invasive way, at lower costs. It is expected that improvements for remote system could be augmented reality, haptic feed back, size reduction and development of new tools for NOTES surgery. The paradigm of image-guided robots is close to a clinical availability and the most advanced robots are presented with end-user technical assessments. It is also notable that the potential of robots lies much further ahead than the accomplishments of the daVinci system. The integration of imaging with robotics holds a substantial promise, because this can accomplish tasks otherwise impossible. Image guided robots have the potential to offer a paradigm shift. PMID:19057227

Urologic robots and future directions.

PubMed

Mozer, Pierre; Troccaz, Jocelyne; Stoianovici, Dan

2009-01-01

Robot-assisted laparoscopic surgery in urology has gained immense popularity with the daVinci system, but a lot of research teams are working on new robots. The purpose of this study is to review current urologic robots and present future development directions. Future systems are expected to advance in two directions: improvements of remote manipulation robots and developments of image-guided robots. The final goal of robots is to allow safer and more homogeneous outcomes with less variability of surgeon performance, as well as new tools to perform tasks on the basis of medical transcutaneous imaging, in a less invasive way, at lower costs. It is expected that improvements for a remote system could be augmented in reality, with haptic feedback, size reduction, and development of new tools for natural orifice translumenal endoscopic surgery. The paradigm of image-guided robots is close to clinical availability and the most advanced robots are presented with end-user technical assessments. It is also notable that the potential of robots lies much further ahead than the accomplishments of the daVinci system. The integration of imaging with robotics holds a substantial promise, because this can accomplish tasks otherwise impossible. Image-guided robots have the potential to offer a paradigm shift.

Reliability of Task-Based fMRI for Preoperative Planning: A Test-Retest Study in Brain Tumor Patients and Healthy Controls

PubMed Central

Morrison, Melanie A.; Churchill, Nathan W.; Cusimano, Michael D.; Schweizer, Tom A.; Das, Sunit; Graham, Simon J.

2016-01-01

Background Functional magnetic resonance imaging (fMRI) continues to develop as a clinical tool for patients with brain cancer, offering data that may directly influence surgical decisions. Unfortunately, routine integration of preoperative fMRI has been limited by concerns about reliability. Many pertinent studies have been undertaken involving healthy controls, but work involving brain tumor patients has been limited. To develop fMRI fully as a clinical tool, it will be critical to examine these reliability issues among patients with brain tumors. The present work is the first to extensively characterize differences in activation map quality between brain tumor patients and healthy controls, including the effects of tumor grade and the chosen behavioral testing paradigm on reliability outcomes. Method Test-retest data were collected for a group of low-grade (n = 6) and high-grade glioma (n = 6) patients, and for matched healthy controls (n = 12), who performed motor and language tasks during a single fMRI session. Reliability was characterized by the spatial overlap and displacement of brain activity clusters, BOLD signal stability, and the laterality index. Significance testing was performed to assess differences in reliability between the patients and controls, and low-grade and high-grade patients; as well as between different fMRI testing paradigms. Results There were few significant differences in fMRI reliability measures between patients and controls. Reliability was significantly lower when comparing high-grade tumor patients to controls, or to low-grade tumor patients. The motor task produced more reliable activation patterns than the language tasks, as did the rhyming task in comparison to the phonemic fluency task. Conclusion In low-grade glioma patients, fMRI data are as reliable as healthy control subjects. For high-grade glioma patients, further investigation is required to determine the underlying causes of reduced reliability. To maximize reliability outcomes, testing paradigms should be carefully selected to generate robust activation patterns. PMID:26894279

Advances Afoot in Microbiology

PubMed Central

Karon, Brad S.

2017-01-01

ABSTRACT In 2016, the American Academy of Microbiology convened a colloquium to examine point-of-care (POC) microbiology testing and to evaluate its effects on clinical microbiology. Colloquium participants included representatives from clinical microbiology laboratories, industry, and the government, who together made recommendations regarding the implementation, oversight, and evaluation of POC microbiology testing. The colloquium report is timely and well written (V. Dolen et al., Changing Diagnostic Paradigms for Microbiology, 2017, https://www.asm.org/index.php/colloquium-reports/item/6421-changing-diagnostic-paradigms-for-microbiology?utm_source=Commentary&utm_medium=referral&utm_campaign=diagnostics). Emerging POC microbiology tests, especially nucleic acid amplification tests, have the potential to advance medical care. PMID:28539341

It shouldn't happen to a dog … or a veterinarian: clinical paradigms for canine vector-borne diseases.

PubMed

Irwin, Peter J

2014-02-01

Canine vector-borne diseases (CVBDs) comprise a diverse group of viral, bacterial, protozoal, and helminth pathogens, transmitted predominantly by ticks and fleas, and cause significant health problems for dogs worldwide. Growing numbers of reports indicate that CVBDs are emerging in regions where they previously did not exist and this, combined with pathogens that are inherently difficult to detect, is providing companion animal veterinarians with some significant diagnostic challenges. This review discusses six paradigms concerning the diagnosis, treatment, prevention, and zoonotic implications of CVBDs from a veterinary clinical perspective. Copyright © 2013 Elsevier Ltd. All rights reserved.

Method of injection of onabotulinumtoxinA for chronic migraine: a safe, well-tolerated, and effective treatment paradigm based on the PREEMPT clinical program.

PubMed

Blumenfeld, Andrew; Silberstein, Stephen D; Dodick, David W; Aurora, Sheena K; Turkel, Catherine C; Binder, William J

2010-10-01

Chronic migraine (CM) is a prevalent and disabling neurological disorder. Few prophylactic treatments for CM have been investigated. OnabotulinumtoxinA, which inhibits the release of nociceptive mediators, such as glutamate, substance P, and calcitonin gene-related peptide, has been evaluated in randomized, placebo-controlled studies for the preventive treatment of a variety of headache disorders, including CM. These studies have yielded insight into appropriate patient selection, injection sites, dosages, and technique. Initial approaches used a set of fixed sites for the pericranial injections. However, the treatment approach evolved to include other sites that corresponded to the location of pain and tenderness in the individual patient in addition to the fixed sites. The Phase III REsearch Evaluating Migraine Prophylaxis Therapy (PREEMPT) injection paradigm uses both fixed and follow-the-pain sites, with additional specific follow-the-pain sites considered depending on individual symptoms. The PREEMPT paradigm for injecting onabotulinumtoxinA has been shown to be safe, well-tolerated, and effective in well-designed, controlled clinical trials and is the evidence-based approach recommended to optimize clinical outcomes for patients with CM. © 2010 American Headache Society.

Across the consciousness continuum—from unresponsive wakefulness to sleep

PubMed Central

Blume, Christine; del Giudice, Renata; Wislowska, Malgorzata; Lechinger, Julia; Schabus, Manuel

2015-01-01

Advances in the development of new paradigms as well as in neuroimaging techniques nowadays enable us to make inferences about the level of consciousness patients with disorders of consciousness (DOC) retain. They, moreover, allow to predict their probable development. Today, we know that certain brain responses (e.g., event-related potentials or oscillatory changes) to stimulation, circadian rhythmicity, the presence or absence of sleep patterns as well as measures of resting state brain activity can serve the diagnostic and prognostic evaluation process. Still, the paradigms we are using nowadays do not allow to disentangle VS/UWS and minimally conscious state (MCS) patients with the desired reliability and validity. Furthermore, even rather well-established methods have, unfortunately, not found their way into clinical routine yet. We here review current literature as well as recent findings from our group and discuss how neuroimaging methods (fMRI, PET) and particularly electroencephalography (EEG) can be used to investigate cognition in DOC or even to assess the degree of residual awareness. We, moreover, propose that circadian rhythmicity and sleep in brain-injured patients are promising fields of research in this context. PMID:25805982

The Translation of Cognitive Paradigms for Patient Research

PubMed Central

Luck, Steven J.; Gold, James M.

2008-01-01

Many cognitive tasks have been developed by basic scientists to isolate and measure specific cognitive processes in healthy young adults, and these tasks have the potential to provide important information about cognitive dysfunction in psychiatric disorders, both in psychopathology research and in clinical trials. However, several practical and conceptual challenges arise in translating these tasks for patient research. Here we outline a paradigm development strategy—which involves iteratively testing modifications of the tasks in college students, in older healthy adults, and in patients—that we have used to successfully translate a large number of cognitive tasks for use in schizophrenia patients. This strategy makes it possible to make the tasks patient friendly while maintaining their cognitive precision. We also outline several measurement issues that arise in these tasks, including differences in baseline performance levels and speed-accuracy trade-offs, and we provide suggestions for addressing these issues. Finally, we present examples of 2 experiments, one of which exemplifies our recommendations regarding measurement issues and was a success and one of which was a painful but informative failure. PMID:18487226

Selecting Paradigms From Cognitive Neuroscience for Translation into Use in Clinical Trials: Proceedings of the Third CNTRICS Meeting

PubMed Central

Barch, Deanna M.; Carter, Cameron S.; Arnsten, Amy; Buchanan, Robert W.; Cohen, Jonathan D.; Geyer, Mark; Green, Michael F.; Krystal, John H.; Nuechterlein, Keith; Robbins, Trevor; Silverstein, Steven; Smith, Edward E.; Strauss, Milton; Wykes, Til; Heinssen, Robert

2009-01-01

This overview describes the goals and objectives of the third conference conducted as part of the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS) initiative. This third conference was focused on selecting specific paradigms from cognitive neuroscience that measured the constructs identified in the first CNTRICS meeting, with the goal of facilitating the translation of these paradigms into use in clinical trials contexts. To identify such paradigms, we had an open nomination process in which the field was asked to nominate potentially relevant paradigms and to provide information on several domains relevant to selecting the most promising tasks for each construct (eg, construct validity, neural bases, psychometrics, availability of animal models). Our goal was to identify 1–2 promising tasks for each of the 11 constructs identified at the first CNTRICS meeting. In this overview article, we describe the on-line survey used to generate nominations for promising tasks, the criteria that were used to select the tasks, the rationale behind the criteria, and the ways in which breakout groups worked together to identify the most promising tasks from among those nominated. This article serves as an introduction to the set of 6 articles included in this special issue that provide information about the specific tasks discussed and selected for the constructs from each of 6 broad domains (working memory, executive control, attention, long-term memory, perception, and social cognition). PMID:19023126

Syndromic Panel-Based Testing in Clinical Microbiology.

PubMed

Ramanan, Poornima; Bryson, Alexandra L; Binnicker, Matthew J; Pritt, Bobbi S; Patel, Robin

2018-01-01

The recent development of commercial panel-based molecular diagnostics for the rapid detection of pathogens in positive blood culture bottles, respiratory specimens, stool, and cerebrospinal fluid has resulted in a paradigm shift in clinical microbiology and clinical practice. This review focuses on U.S. Food and Drug Administration (FDA)-approved/cleared multiplex molecular panels with more than five targets designed to assist in the diagnosis of bloodstream, respiratory tract, gastrointestinal, or central nervous system infections. While these panel-based assays have the clear advantages of a rapid turnaround time and the detection of a large number of microorganisms and promise to improve health care, they present certain challenges, including cost and the definition of ideal test utilization strategies (i.e., optimal ordering) and test interpretation. Copyright © 2017 American Society for Microbiology.

Molecular genetics and genomics progress in urothelial bladder cancer.

PubMed

Netto, George J

2013-11-01

The clinical management of solid tumor patients has recently undergone a paradigm shift as the result of the accelerated advances in cancer genetics and genomics. Molecular diagnostics is now an integral part of routine clinical management in lung, colon, and breast cancer patients. In a disappointing contrast, molecular biomarkers remain largely excluded from current management algorithms of urologic malignancies. The need for new treatment alternatives and validated prognostic molecular biomarkers that can help clinicians identify patients in need of early aggressive management is pressing. Identifying robust predictive biomarkers that can stratify response to newly introduced targeted therapeutics is another crucially needed development. The following is a brief discussion of some promising candidate biomarkers that may soon become a part of clinical management of bladder cancers. © 2013 Published by Elsevier Inc.

The First Expert CAI System

PubMed Central

Feurzeig, Wallace

1984-01-01

The first expert instructional system, the Socratic System, was developed in 1964. One of the earliest applications of this system was in the area of differential diagnosis in clinical medicine. The power of the underlying instructional paradigm was demonstrated and the potential of the approach for valuably supplementing medical instruction was recognized. Twenty years later, despite further educationally significant advances in expert systems technology and enormous reductions in the cost of computers, expert instructional methods have found very little application in medical schools.

Novel Androgen Deprivation Therapy (ADT) in the Treatment of Advanced Prostate Cancer

PubMed Central

Aragon-Ching, Jeanny B.; Dahut, William L.

2011-01-01

Androgen deprivation therapy has been the mainstay of treatment for advanced and metastatic prostate cancer. The use of novel agents targeting the androgen receptor and its signaling pathways offers a promising approach that is both safe and effective. We describe the rationale behind the use of these compounds in clinical development and the existing challenges as to how best to incorporate these new and emerging therapies in the changing treatment paradigm of metastatic prostate cancer. PMID:21922023

[Evidence based medicine. A new paradigm for medical practice].

PubMed

Carneiro, A V

1998-01-01

Modern medical practice is an ever-changing process, and the doctor's need for information has been partially met by continuous medical education (CME) activities. It has been shown that CME activities have not prevented clinical knowledge, as well as medical practice, from deteriorating with time. When faced with the need to get the most recent and relevant information possible, the busy clinician has two major problems: most of the published medical literature is either irrelevant or not useful; and there is little time to read it. Evidence-based medicine constitutes a new paradigm for medical practice in the sense that it tries to transform clinical problems into well formulated clinical questions, selecting and critically appraising scientific evidence with predefined and rigorous rules. It combines the expertise of the individual clinician with the best external evidence from clinical research for rational, ethical and efficacious practice. Evidence-based medicine can be taught and practiced by physicians with different degrees of autonomy, with several subspecialties, working in the hospital or in outpatient clinics, alone or in groups.

How modeling and simulation have enhanced decision making in new drug development.

PubMed

Miller, Raymond; Ewy, Wayne; Corrigan, Brian W; Ouellet, Daniele; Hermann, David; Kowalski, Kenneth G; Lockwood, Peter; Koup, Jeffrey R; Donevan, Sean; El-Kattan, Ayman; Li, Cheryl S W; Werth, John L; Feltner, Douglas E; Lalonde, Richard L

2005-04-01

The idea of model-based drug development championed by Lewis Sheiner, in which pharmacostatistical models of drug efficacy and safety are developed from preclinical and available clinical data, offers a quantitative approach to improving drug development and development decision-making. Examples are presented that support this paradigm. The first example describes a preclinical model of behavioral activity to predict potency and time-course of response in humans and assess the potential for differentiation between compounds. This example illustrates how modeling procedures expounded by Lewis Sheiner provided the means to differentiate potency and the lag time between drug exposure and response and allow for rapid decision making and dose selection. The second example involves planning a Phase 2a dose-ranging and proof of concept trial in Alzheimer's disease (AD). The issue was how to proceed with the study and what criteria to use for a go/no go decision. The combined knowledge of AD disease progression, and preclinical and clinical information about the drug were used to simulate various clinical trial scenarios to identify an efficient and effective Phase 2 study. A design was selected and carried out resulting in a number of important learning experiences as well as extensive financial savings. The motivation for this case in point was the "Learn-Confirm" paradigm described by Lewis Sheiner. The final example describes the use of Pharmacokinetic and Pharmacodynamic (PK/PD) modeling and simulation to confirm efficacy across doses. In the New Drug Application for gabapentin, data from two adequate and well-controlled clinical trials was submitted to the Food and Drug Administration (FDA) in support of the approval of the indication for the treatment of post-herpetic neuralgia. The clinical trial data was not replicated for each of the sought dose levels in the drug application presenting a regulatory dilemma. Exposure response analysis submitted in the New Drug Application was applied to confirm the evidence of efficacy across these dose levels. Modeling and simulation analyses showed that the two studies corroborate each other with respect to the pain relief profiles. The use of PK/PD information confirmed evidence of efficacy across the three studied doses, eliminating the need for additional clinical trials and thus supporting the approval of the product. It can be speculated that the work by Lewis Sheiner reflected in the FDA document titled "Innovation or Stagnation: Challenge and Opportunity on the Critical Path to New Medical Products" made this scientific approach to the drug approval process possible.

Geographic Object-Based Image Analysis - Towards a new paradigm.

PubMed

Blaschke, Thomas; Hay, Geoffrey J; Kelly, Maggi; Lang, Stefan; Hofmann, Peter; Addink, Elisabeth; Queiroz Feitosa, Raul; van der Meer, Freek; van der Werff, Harald; van Coillie, Frieke; Tiede, Dirk

2014-01-01

The amount of scientific literature on (Geographic) Object-based Image Analysis - GEOBIA has been and still is sharply increasing. These approaches to analysing imagery have antecedents in earlier research on image segmentation and use GIS-like spatial analysis within classification and feature extraction approaches. This article investigates these development and its implications and asks whether or not this is a new paradigm in remote sensing and Geographic Information Science (GIScience). We first discuss several limitations of prevailing per-pixel methods when applied to high resolution images. Then we explore the paradigm concept developed by Kuhn (1962) and discuss whether GEOBIA can be regarded as a paradigm according to this definition. We crystallize core concepts of GEOBIA, including the role of objects, of ontologies and the multiplicity of scales and we discuss how these conceptual developments support important methods in remote sensing such as change detection and accuracy assessment. The ramifications of the different theoretical foundations between the ' per-pixel paradigm ' and GEOBIA are analysed, as are some of the challenges along this path from pixels, to objects, to geo-intelligence. Based on several paradigm indications as defined by Kuhn and based on an analysis of peer-reviewed scientific literature we conclude that GEOBIA is a new and evolving paradigm.

Clinical considerations in the management of inflammatory periodontal diseases in children and adolescents.

PubMed

Cabanilla, Leyvee; Molinari, Gail

2009-01-01

Periodontal diseases and conditions, as defined by The 1999 International Workshop for Classification of Periodontal Diseases and Conditions presented some significant paradigm shifts based on evidence that the transition from plaque-associated reversible gingival diseases to periodontitis can occur in children and adolescents with characteristics which were previously thought to be typical of adult periodontitis. The purposes of this paper are to present the periodontal diseases and conditions described in the 1999 workshop sponsored by the American Academy of Periodontology, review the risk factors for the development of periodontal diseases in the pediatric and adolescent populations, and present appropriate clinical periodontal assessment and management for these age groups.

Mesenchymal Stem/Stromal Cells: A New "Cells as Drugs" Paradigm. Efficacy and Critical Aspects in Cell Therapy

PubMed Central

de Girolamo, Laura; Lucarelli, Enrico; Alessandri, Giulio; Avanzini, Maria Antonietta; Bernardo, Maria Ester; Biagi, Ettore; Brini, Anna Teresa; D’Amico, Giovanna; Fagioli, Franca; Ferrero, Ivana; Locatelli, Franco; Maccario, Rita; Marazzi, Mario; Parolini, Ornella; Pessina, Augusto; Torre, Maria Luisa

2013-01-01

Mesenchymal stem cells (MSCs) were first isolated more than 50 years ago from the bone marrow. Currently MSCs may also be isolated from several alternative sources and they have been used in more than a hundred clinical trials worldwide to treat a wide variety of diseases. The MSCs mechanism of action is undefined and currently under investigation. For in vivo purposes MSCs must be produced in compliance with good manufacturing practices and this has stimulated research on MSCs characterization and safety. The objective of this review is to describe recent developments regarding MSCs properties, physiological effects, delivery, clinical applications and possible side effects. PMID:23278600

Management of Anterior Cruciate Ligament Injury: What's In and What's Out?

PubMed Central

Raines, Benjamin Todd; Naclerio, Emily; Sherman, Seth L

2017-01-01

Sports medicine physicians have a keen clinical and research interest in the anterior cruciate ligament (ACL). The biomechanical, biologic, and clinical data researchers generate, help drive injury management and prevention practices globally. The current concepts in ACL injury and surgery are being shaped by technological advances, expansion in basic science research, resurging interest in ACL preservation, and expanding efforts regarding injury prevention. As new methods are being developed in this field, the primary goal of safely improving patient outcomes will be a unifying principle. With this review, we provide an overview of topics currently in controversy or debate, and we identify paradigm shifts in the understanding, management, and prevention of ACL tears. PMID:28966380

Regenerative endodontics: a true paradigm shift or a bandwagon about to be derailed?

PubMed

Nazzal, H; Duggal, M S

2017-02-01

Regenerative endodontic techniques (RETs) have been hailed as a paradigm shift for the management of traumatised non-vital immature permanent anterior teeth. In this article the aim was to critically appraise the literature with regards to the outcome of regenerative endodontics on root development. Critical review of the literature where regenerative endodontic techniques have been used in the management of immature non-vital teeth with continuation of root development as the main outcome reported. Most studies published were in the form of case reports and series with very few randomised controlled trials with a high risk of bias. Continuation of root development following the use of RET has been shown to be unpredictable at best with lower success in those teeth losing vitality as a result of dental trauma. Despite the high success of regenerative endodontics in terms of periodontal healing including resolution of clinical and radiographic signs and symptoms of infection, continuation of root development remains an unpredictable outcome. The use of a blood clot as a scaffold in regenerative endodontics should be reviewed carefully as that might offer an environment for repair rather than regeneration. In addition, preservation of structures, such as Hertwig's epithelial root sheath, may have an important bearing on the success of this approach and should be further investigated.

Mutations in Either TUBB or MAPRE2 Cause Circumferential Skin Creases Kunze Type

PubMed Central

Isrie, Mala; Breuss, Martin; Tian, Guoling; Hansen, Andi Harley; Cristofoli, Francesca; Morandell, Jasmin; Kupchinsky, Zachari A.; Sifrim, Alejandro; Rodriguez-Rodriguez, Celia Maria; Dapena, Elena Porta; Doonanco, Kurston; Leonard, Norma; Tinsa, Faten; Moortgat, Stéphanie; Ulucan, Hakan; Koparir, Erkan; Karaca, Ender; Katsanis, Nicholas; Marton, Valeria; Vermeesch, Joris Robert; Davis, Erica E.; Cowan, Nicholas J.; Keays, David Anthony; Van Esch, Hilde

2015-01-01

Circumferential skin creases Kunze type (CSC-KT) is a specific congenital entity with an unknown genetic cause. The disease phenotype comprises characteristic circumferential skin creases accompanied by intellectual disability, a cleft palate, short stature, and dysmorphic features. Here, we report that mutations in either MAPRE2 or TUBB underlie the genetic origin of this syndrome. MAPRE2 encodes a member of the microtubule end-binding family of proteins that bind to the guanosine triphosphate cap at growing microtubule plus ends, and TUBB encodes a β-tubulin isotype that is expressed abundantly in the developing brain. Functional analyses of the TUBB mutants show multiple defects in the chaperone-dependent tubulin heterodimer folding and assembly pathway that leads to a compromised yield of native heterodimers. The TUBB mutations also have an impact on microtubule dynamics. For MAPRE2, we show that the mutations result in enhanced MAPRE2 binding to microtubules, implying an increased dwell time at microtubule plus ends. Further, in vivo analysis of MAPRE2 mutations in a zebrafish model of craniofacial development shows that the variants most likely perturb the patterning of branchial arches, either through excessive activity (under a recessive paradigm) or through haploinsufficiency (dominant de novo paradigm). Taken together, our data add CSC-KT to the growing list of tubulinopathies and highlight how multiple inheritance paradigms can affect dosage-sensitive biological systems so as to result in the same clinical defect. PMID:26637975

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.

Update on the Medical Management of Crohn's Disease.

PubMed

Deepak, Parakkal; Bruining, David H

2015-11-01

The medical management of Crohn's disease is a rapidly evolving field with expanding therapeutic drug options and treatment strategies. In addition to corticosteroids, immunomodulators, and anti-tumor necrosis (anti-TNF) agents, a new anti-adhesion medication (vedolizumab) has been approved. Individualized patient-based dosing of immunomodulators and biologic agents is now possible with therapeutic drug monitoring (TDM). There is a changing paradigm in treatment goals to achieve deeper remission identified by composite clinical and endoscopic endpoints. More aggressive treatment strategies in the postoperative setting have been proposed due to emerging data on medication efficacy in this setting. Management algorithms that stratify CD patients into risk groups to balance treatment benefit against adverse events and costs are being developed to translate research into clinical practice. This review provides an update on these new developments for practicing gastroenterologists.

Recruitment and Retention Strategies for Minority or Poor Clinical Research Participants: Lessons From the Healthy Aging in Neighborhoods of Diversity Across the Life Span Study

PubMed Central

Ejiogu, Ngozi; Norbeck, Jennifer H.; Mason, Marc A.; Cromwell, Bridget C.; Zonderman, Alan B.; Evans, Michele K.

2011-01-01

Purpose of the study: Investigating health disparities requires studies designed to recruit and retain racially and socioeconomically diverse cohorts. It is critical to address the barriers that disproportionately affect participation in clinical research by minorities and the socioeconomically disadvantaged. This study sought to identify and rectify these barriers to recruit and retain a biracial (African American and non-Hispanic White) and socioeconomically diverse cohort for a longitudinal study. Design and Method: The Healthy Aging in Neighborhoods of Diversity across the Life Span study is a 20-year longitudinal examination of how race and socioeconomic status influence the development of age-related health disparities. One goal was to create a multifactorial recruitment and retention strategy. The recruitment paradigm targeted known barriers and identified those unique to the study's urban environment. The retention paradigm mirrored the recruitment plan but was based on specifically developed approaches. Results: This cohort recruitment required attention to developing community partnerships, designing the research study to meet the study hypotheses and to provide benefit to participants, providing a safe community-based site for the research and creating didactics to develop staff cultural proficiency. These efforts facilitated study implementation and enhanced recruitment resulting in accrual of a biracial and socioeconomically diverse cohort of 3,722 participants. Implications: Recruiting and retaining minority or poor research participants is challenging but possible. The essential facets include clear communication of the research hypothesis, focus on providing a direct benefit for participants, and selection of a hypothesis that is directly relevant to the community studied PMID:21565817

Biomarkers for the clinical evaluation of the cognitively impaired elderly: amyloid is not enough

PubMed Central

McEvoy, Linda K; Brewer, James B

2012-01-01

The number of elderly patients seeking clinical treatment for memory problems will rise sharply in coming years as our population ages. These patients present a challenge for diagnosis and prognosis since cognitive problems in older patients can arise from many etiologies, some of which are curable. With the development of clinically available biomarkers for detecting Alzheimer’s disease pathology in living patients, evaluation of cognitively impaired elderly patients is about to undergo a major paradigm shift. This article describes the two classes of biomarkers available for assessing Alzheimer’s disease risk: those that indicate presence of amyloid pathology and those that provide evidence of neuronal injury and neurodegeneration. We argue that, currently, incorporation of biomarkers of neurodegeneration can help in patient prognosis whereas tests for amyloid, if used in isolation, have potential for harm. Amyloid tests are clinically useful only when evidence suggests progressive cognitive decline or neurodegeneration. PMID:23420460

A framework to link international clinical research to the promotion of justice in global health.

PubMed

Pratt, Bridget; Loff, Bebe

2014-10-01

How international research might contribute to justice in global health has not been substantively addressed by bioethics. Theories of justice from political philosophy establish obligations for parties from high-income countries owed to parties from low and middle-income countries. We have developed a new framework that is based on Jennifer Ruger's health capability paradigm to strengthen the link between international clinical research and justice in global health. The 'research for health justice' framework provides direction on three aspects of international clinical research: the research target, research capacity strengthening, and post-trial benefits. It identifies the obligations of justice owed by national governments, research funders, research sponsors, and investigators to trial participants and host communities. These obligations vary from those currently articulated in international research ethics guidelines. Ethical requirements of a different kind are needed if international clinical research is to advance global health equity. © 2012 John Wiley & Sons Ltd.

A Road Map to Commercialization of Cartilage Therapy in the United States of America.

PubMed

Sridharan, BanuPriya; Sharma, Blanka; Detamore, Michael S

2015-11-05

Despite numerous efforts in cartilage regeneration, few products see the light of clinical translation as the commercialization process is opaque, financially demanding, and requires collaboration with people of varied skill sets. The aim of this review is to introduce, to an academic audience, the different paradigms involved in the commercialization of cartilage regeneration technology, elucidate the different hurdles associated with the use of cells and materials in developing new technologies, discuss potential commercialization strategies, and inform the reader about the current trends observed in both the clinical and laboratory setting for establishing clinical trials. Although there are review articles on articular cartilage tissue engineering, independent reports provided by the Food and Drug Administration, and separate review articles on animal models, this is the first review that encompasses all of these facets and is presented in a format favorable to the academic investigator interested in clinical translation from bench to bedside.

A Road Map to Commercialization of Cartilage Therapy in the United States of America

PubMed Central

Sridharan, BanuPriya; Sharma, Blanka

2016-01-01

Despite numerous efforts in cartilage regeneration, few products see the light of clinical translation as the commercialization process is opaque, financially demanding, and requires collaboration with people of varied skill sets. The aim of this review is to introduce, to an academic audience, the different paradigms involved in the commercialization of cartilage regeneration technology, elucidate the different hurdles associated with the use of cells and materials in developing new technologies, discuss potential commercialization strategies, and inform the reader about the current trends observed in both the clinical and laboratory setting for establishing clinical trials. Although there are review articles on articular cartilage tissue engineering, independent reports provided by the Food and Drug Administration, and separate review articles on animal models, this is the first review that encompasses all of these facets and is presented in a format favorable to the academic investigator interested in clinical translation from bench to bedside. PMID:26192161

Guillain–Barré syndrome and anti-ganglioside antibodies: a clinician-scientist’s journey

PubMed Central

YUKI, Nobuhiro

2012-01-01

Guillain–Barré syndrome (GBS) is the most frequent cause of acute flaccid paralysis. Having seen my first GBS patient in 1989, I have since then dedicated my time in research towards understanding the pathogenesis of GBS. Along with several colleagues, we identified IgG autoantibodies against ganglioside GM1 in two patients with GBS subsequent to Campylobacter jejuni enteritis. We proceeded to demonstrate molecular mimicry between GM1 and bacterial lipo-oligosaccharide of C. jejuni isolated from a patient with GBS. Our group then established a disease model for GBS by sensitization with GM1 or GM1-like lipo-oligosaccharide. With this, a new paradigm that carbohydrate mimicry can cause autoimmune disorders was demonstrated, making GBS the first proof of molecular mimicry in autoimmune disease. Patients with Fisher syndrome, characterized by ophthalmoplegia and ataxia, can develop the disease after an infection by C. jejuni. We showed that the genetic polymorphism of C. jejuni sialyltransferase, an enzyme essential to the biosynthesis of ganglioside-like lipo-oligosaccharides determines whether patients develop GBS or Fisher syndrome. This introduces another paradigm that microbial genetic polymorphism can determine the clinical phenotype of human autoimmune diseases. Similarities between the clinical presentation of Fisher syndrome and Bickerstaff brainstem encephalitis have caused debate as to whether they are in fact the same disease. We demonstrated that IgG anti-GQ1b antibodies were common to both, suggesting that they are part of the same disease spectrum. We followed this work by clarifying the nosological relationship between the various clinical presentations within the anti-GQ1b antibody syndrome. In this review, I wanted to share my journey from being a clinician to a clinician-scientist in the hopes of inspiring younger clinicians to follow a similar path. PMID:22850724

Cross-sector sponsorship of research in eosinophilic esophagitis: a collaborative model for rational drug development in rare diseases.

PubMed

Fiorentino, Robert; Liu, Gumei; Pariser, Anne R; Mulberg, Andrew E

2012-09-01

Like many rare diseases, eosinophilic esophagitis (EoE) is a poorly understood disorder, and assessment tools to accurately determine disease activity, remission, and natural history have long been inadequate. Clinical outcome end points able to assess the effectiveness of candidate therapeutic agents in clinical trials have been a particular deficiency and are urgently needed. With no approved therapy available to patients and with the prevalence of EoE on the increase, collaborative approaches to drug development are becoming ever more important. We describe a collaborative effort mobilized across institutions, including both the public and private sectors, that was initiated within the past 18 months expressly to address the need for further clinical research into the cause and treatment of EoE. Collaborators include the North American Society of Pediatric Gastroenterology, Hepatology and Nutrition; the International Gastrointestinal Eosinophilic Researchers; and the US Food and Drug Administration. This effort has resulted in the elucidation of several parameters essential for effective EoE registration trials, including the need for clinically meaningful end points that measure changes in clinical symptoms in addition to the assessment of intraepithelial mucosal eosinophilia. The development and use of biomarkers, particularly in early-phase drug development, have become an important focus for investigations that might reduce clinical reliance on serial invasive monitoring. The concerted efforts described here to develop rational therapeutics and drug development paradigms in EoE also appear to provide a model for effective collaboration in the context of drug development for rare diseases and perhaps more generally for public health initiatives. Published by Mosby, Inc.

Stressor paradigms in developmental studies: what does and does not work to produce mean increases in salivary cortisol.

PubMed

Gunnar, Megan R; Talge, Nicole M; Herrera, Adriana

2009-08-01

The stress response system is comprised of an intricate interconnected network that includes the hypothalamic-pituitary-adrenocortical (HPA) axis. The HPA axis maintains the organism's capacity to respond to acute and prolonged stressors and is a focus of research on the sequelae of stress. Human studies of the HPA system have been facilitated enormously by the development of salivary assays which measure cortisol, the steroid end-product of the HPA axis. The use of salivary cortisol is prevalent in child development stress research. However, in order to measure children's acute cortisol reactivity to circumscribed stressors, researchers must put children in stressful situations which produce elevated levels of cortisol. Unfortunately, many studies on the cortisol stress response in children use paradigms that fail to produce mean elevations in cortisol. This paper reviews stressor paradigms used with infants, children, and adolescents to guide researchers in selecting effective stressor tasks. A number of different types of stressor paradigms were examined, including: public speaking, negative emotion, relationship disruption/threatening, novelty, handling, and mild pain paradigms. With development, marked changes are evident in the effectiveness of the same stressor paradigm to provoke elevations in cortisol. Several factors appear to be critical in determining whether a stressor paradigm is successful, including the availability of coping resources and the extent to which, in older children, the task threatens the social self. A consideration of these issues is needed to promote the implementation of more effective stressor paradigms in human developmental psychoendocrine research.

AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY PROTOCOL FOR STANDARDIZED PRODUCTION OF CLINICAL PRACTICE GUIDELINES, ALGORITHMS, AND CHECKLISTS - 2017 UPDATE.

PubMed

Mechanick, Jeffrey I; Pessah-Pollack, Rachel; Camacho, Pauline; Correa, Ricardo; Figaro, M Kathleen; Garber, Jeffrey R; Jasim, Sina; Pantalone, Kevin M; Trence, Dace; Upala, Sikarin

2017-08-01

Clinical practice guideline (CPG), clinical practice algorithm (CPA), and clinical checklist (CC, collectively CPGAC) development is a high priority of the American Association of Clinical Endocrinologists (AACE) and American College of Endocrinology (ACE). This 2017 update in CPG development consists of (1) a paradigm change wherein first, environmental scans identify important clinical issues and needs, second, CPA construction focuses on these clinical issues and needs, and third, CPG provide CPA node/edge-specific scientific substantiation and appended CC; (2) inclusion of new technical semantic and numerical descriptors for evidence types, subjective factors, and qualifiers; and (3) incorporation of patient-centered care components such as economics and transcultural adaptations, as well as implementation, validation, and evaluation strategies. This third point highlights the dominating factors of personal finances, governmental influences, and third-party payer dictates on CPGAC implementation, which ultimately impact CPGAC development. The AACE/ACE guidelines for the CPGAC program is a successful and ongoing iterative exercise to optimize endocrine care in a changing and challenging healthcare environment. AACE = American Association of Clinical Endocrinologists ACC = American College of Cardiology ACE = American College of Endocrinology ASeRT = ACE Scientific Referencing Team BEL = best evidence level CC = clinical checklist CPA = clinical practice algorithm CPG = clinical practice guideline CPGAC = clinical practice guideline, algorithm, and checklist EBM = evidence-based medicine EHR = electronic health record EL = evidence level G4GAC = Guidelines for Guidelines, Algorithms, and Checklists GAC = guidelines, algorithms, and checklists HCP = healthcare professional(s) POEMS = patient-oriented evidence that matters PRCT = prospective randomized controlled trial.

Faith Development in Older Adults.

ERIC Educational Resources Information Center

Shulik, Richard N.

1988-01-01

Introduces the faith development paradigm of James Fowler, describing six stages of faith development: intuitive-projective faith, mythic-literal faith, synthetic-conventional faith, individuating-reflective faith, conjunctive faith, and universalizing faith. Reviews one research project in which Fowler's paradigm was applied to older adults.…

From Microscale Devices to 3D Printing: Advances in Fabrication of 3D Cardiovascular Tissues

PubMed Central

Borovjagin, Anton V.; Ogle, Brenda; Berry, Joel; Zhang, Jianyi

2016-01-01

Current strategies for engineering cardiovascular cells and tissues have yielded a variety of sophisticated tools for studying disease mechanisms, for development of drug therapies, and for fabrication of tissue equivalents that may have application in future clinical use. These efforts are motivated by the need to extend traditional two-dimensional (2D) cell culture systems into 3D to more accurately replicate in vivo cell and tissue function of cardiovascular structures. Developments in microscale devices and bioprinted 3D tissues are beginning to supplant traditional 2D cell cultures and pre-clinical animal studies that have historically been the standard for drug and tissue development. These new approaches lend themselves to patient-specific diagnostics, therapeutics, and tissue regeneration. The emergence of these technologies also carries technical challenges to be met before traditional cell culture and animal testing become obsolete. Successful development and validation of 3D human tissue constructs will provide powerful new paradigms for more cost effective and timely translation of cardiovascular tissue equivalents. PMID:28057791

Preserved consciousness in vegetative and minimal conscious states: systematic review and meta-analysis.

PubMed

Kondziella, Daniel; Friberg, Christian K; Frokjaer, Vibe G; Fabricius, Martin; Møller, Kirsten

2016-05-01

Active, passive and resting state paradigms using functional MRI (fMRI) or EEG may reveal consciousness in the vegetative (VS) and the minimal conscious state (MCS). A meta-analysis was performed to assess the prevalence of preserved consciousness in VS and MCS as revealed by fMRI and EEG, including command following (active paradigms), cortical functional connectivity elicited by external stimuli (passive paradigms) and default mode networks (resting state). Studies were selected from multiple indexing databases until February 2015 and evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2. 37 studies were identified, including 1041 patients (mean age 43 years, range 16-89; male/female 2.1:1; 39.5% traumatic brain injuries). MCS patients were more likely than VS patients to follow commands during active paradigms (32% vs 14%; OR 2.85 (95% CI 1.90 to 4.27; p<0.0001)) and to show preserved functional cortical connectivity during passive paradigms (55% vs 26%; OR 3.53 (95% CI 2.49 to 4.99; p<0.0001)). Passive paradigms suggested preserved consciousness more often than active paradigms (38% vs 24%; OR 1.98 (95% CI 1.54 to 2.54; p<0.0001)). Data on resting state paradigms were insufficient for statistical evaluation. In conclusion, active paradigms may underestimate the degree of consciousness as compared to passive paradigms. While MCS patients show signs of preserved consciousness more frequently in both paradigms, roughly 15% of patients with a clinical diagnosis of VS are able to follow commands by modifying their brain activity. However, there remain important limitations at the single-subject level; for example, patients from both categories may show command following despite negative passive paradigms. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Benefits and challenges of a QSP approach through case study: Evaluation of a hypothetical GLP-1/GIP dual agonist therapy.

PubMed

Rieger, Theodore R; Musante, Cynthia J

2016-10-30

Quantitative Systems Pharmacology (QSP) is an emerging science with increasing application to pharmaceutical research and development paradigms. Through case study we provide an overview of the benefits and challenges of applying QSP approaches to inform program decisions in the early stages of drug discovery and development. Specifically, we describe the use of a type 2 diabetes systems model to inform a No-Go decision prior to lead development for a potential GLP-1/GIP dual agonist program, enabling prioritization of exploratory programs with higher probability of clinical success. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Managing Innovation to Maximize Value Along the Discovery-Translation-Application Continuum.

PubMed

Waldman, S A; Terzic, A

2017-01-01

Success in pharmaceutical development led to a record 51 drugs approved in the past year, surpassing every previous year since 1950. Technology innovation enabled identification and exploitation of increasingly precise disease targets ensuring next generation diagnostic and therapeutic products for patient management. The expanding biopharmaceutical portfolio stands, however, in contradistinction to the unsustainable costs that reflect remarkable challenges of clinical development programs. This annual Therapeutic Innovations issue juxtaposes advances in translating molecular breakthroughs into transformative therapies with essential considerations for lowering attrition and improving the cost-effectiveness of the drug-development paradigm. Realizing the discovery-translation-application continuum mandates a congruent approval, adoption, and access triad. © 2016 ASCPT.

Managing Innovation to Maximize Value Along the Discovery-Translation-Application Continuum

PubMed Central

Waldman, SA; Terzic, A

2017-01-01

Success in pharmaceutical development led to a record 51 drug approved in the past year, surpassing every previous year since 1950. Technology innovation enabled identification and exploitation of increasingly precise disease targets ensuring a next generation diagnostic and therapeutic products for patient management. The expanding biopharmaceutical portfolio stands however in contradistinction to the unsustainable costs that reflect remarkable challenges of clinical development programs. This annual Therapeutic Innovations issue juxtaposes advances in translating molecular breakthroughs into transformative therapies with essential considerations for lowering attrition and improving the cost-effectiveness of the drug development paradigm. Realizing the discovery-translation-application continuum mandates a congruent approval, adoption and access triad. PMID:27869291

Postdoctoral Fellow | Center for Cancer Research

Cancer.gov

The Laboratory of Tumor Immunology and Biology (LTIB) functions as a multidisciplinary and interdisciplinary translational research programmatic effort with the goal of developing novel immunotherapies for cancer. The LTIB strategic plan focuses on the development of novel immunotherapeutics for human cancer, not only as monotherapies, but more importantly, in combination with other immune-mediating modalities, and other conventional or experimental therapies, as part of an immuno-oncology programmatic effort. Within this effort are several research groups, a clinical trials group, and multiple collaborations with intramural and extramural scientific and clinical investigators and with investigators in the private sector. The program takes advantage of the uniqueness of the NCI intramural program in that it spans high-risk basic discovery research in immunology, genomics and tumor biology, through preclinical translational research, to paradigm-shifting clinical trials. Focus is placed on the design and development of novel "off-the-shelf" recombinant immunotherapeutics that can be used in clinical studies at numerous institutions. A major strength of the program is the rapid translation of preclinical studies to hypothesis-generating clinical trials. We are looking for postdoctoral fellows interested in learning immunology and immunotherapy, as well as those postdoctoral fellows with a background and/or interest in experimental pathology.  The position is available immediately. The appointment duration is up to 5 years. Stipends are commensurate with education and experience.

The Failure of Progressive Paradigm Reversal

ERIC Educational Resources Information Center

Guthrie, Gerard

2017-01-01

The student-centred, progressive paradigm has not had sustained success in changing teacher-centred, formalistic practices in "developing" country classrooms. Does "Gestalt-switch" and paradigm reversal demonstrate that progressive theory has realigned with formalistic reality, or has it remained axiomatic in the research and…

Advances Afoot in Microbiology.

PubMed

Patel, Robin; Karon, Brad S

2017-07-01

In 2016, the American Academy of Microbiology convened a colloquium to examine point-of-care (POC) microbiology testing and to evaluate its effects on clinical microbiology. Colloquium participants included representatives from clinical microbiology laboratories, industry, and the government, who together made recommendations regarding the implementation, oversight, and evaluation of POC microbiology testing. The colloquium report is timely and well written (V. Dolen et al., Changing Diagnostic Paradigms for Microbiology , 2017, https://www.asm.org/index.php/colloquium-reports/item/6421-changing-diagnostic-paradigms-for-microbiology?utm_source=Commentary&utm_medium=referral&utm_campaign=diagnostics). Emerging POC microbiology tests, especially nucleic acid amplification tests, have the potential to advance medical care. Copyright © 2017 American Society for Microbiology.

A task-based support architecture for developing point-of-care clinical decision support systems for the emergency department.

PubMed

Wilk, S; Michalowski, W; O'Sullivan, D; Farion, K; Sayyad-Shirabad, J; Kuziemsky, C; Kukawka, B

2013-01-01

The purpose of this study was to create a task-based support architecture for developing clinical decision support systems (CDSSs) that assist physicians in making decisions at the point-of-care in the emergency department (ED). The backbone of the proposed architecture was established by a task-based emergency workflow model for a patient-physician encounter. The architecture was designed according to an agent-oriented paradigm. Specifically, we used the O-MaSE (Organization-based Multi-agent System Engineering) method that allows for iterative translation of functional requirements into architectural components (e.g., agents). The agent-oriented paradigm was extended with ontology-driven design to implement ontological models representing knowledge required by specific agents to operate. The task-based architecture allows for the creation of a CDSS that is aligned with the task-based emergency workflow model. It facilitates decoupling of executable components (agents) from embedded domain knowledge (ontological models), thus supporting their interoperability, sharing, and reuse. The generic architecture was implemented as a pilot system, MET3-AE--a CDSS to help with the management of pediatric asthma exacerbation in the ED. The system was evaluated in a hospital ED. The architecture allows for the creation of a CDSS that integrates support for all tasks from the task-based emergency workflow model, and interacts with hospital information systems. Proposed architecture also allows for reusing and sharing system components and knowledge across disease-specific CDSSs.

Ferenczi and Groddeck: simpatico. Roots of a paradigm shift in psychoanalysis.

PubMed

Poster, Mark F

2009-09-01

Sigmund Freud introduced Sandor Ferenczi to Georg Groddeck in 1917. The warm personal friendship that these two men shared for the rest of their lives was a breeding ground for many of their respective theoretical and clinical contributions. 1923 was a schismatic year in the history of psychoanalysis. Freud's appropriation of Groddeck's Das Es and its adaptation to Heinroth's tri-partite model (Freud, 1923; Poster, 1997) marked the beginning of Ego psychology. Almost simultaneously there appeared Groddeck's Book of the It (Groddeck, 1923), together with Rank and Ferenczi's The Development of Psychoanalysis (Rank and Ferenczi, 1924), and Ferenczi's Thalassa (Ferenczi, 1924). These three seminal publications set the stage for a paradigm shift (Hoffer, 2008; Rudnytsky, 2002). They were the forerunner of later developments in object relations, self-psychology, interpersonal and relational psychoanalysis. Taken together, the contributions of Groddeck and Ferenczi and Rank reinvigorated psychoanalysis, Freud's baby, with "the constructive aspect" that Groddeck told Freud had been lost in Freud's re-definition of Das Es (Groddeck, 1977, p. 13). Each of these pioneers stimulated the thinking of the others. Always an independent thinker, Groddeck was welcomed into the psychoanalytic circle by both Freud and Ferenczi. Suffering under the "crushing paternal(ism)" of Freud, Ferenczi was supported by Groddeck to carry out his own clinical experiments. Preoccupied with his own legacy and intolerant of dissent, Freud was able to maintain cordial contact with these two creative spirits and allow them to modify his own ideas.

Drug development and nonclinical to clinical translational databases: past and current efforts.

PubMed

Monticello, Thomas M

2015-01-01

The International Consortium for Innovation and Quality (IQ) in Pharmaceutical Development is a science-focused organization of pharmaceutical and biotechnology companies. The mission of the Preclinical Safety Leadership Group (DruSafe) of the IQ is to advance science-based standards for nonclinical development of pharmaceutical products and to promote high-quality and effective nonclinical safety testing that can enable human risk assessment. DruSafe is creating an industry-wide database to determine the accuracy with which the interpretation of nonclinical safety assessments in animal models correctly predicts human risk in the early clinical development of biopharmaceuticals. This initiative aligns with the 2011 Food and Drug Administration strategic plan to advance regulatory science and modernize toxicology to enhance product safety. Although similar in concept to the initial industry-wide concordance data set conducted by International Life Sciences Institute's Health and Environmental Sciences Institute (HESI/ILSI), the DruSafe database will proactively track concordance, include exposure data and large and small molecules, and will continue to expand with longer duration nonclinical and clinical study comparisons. The output from this work will help identify actual human and animal adverse event data to define both the reliability and the potential limitations of nonclinical data and testing paradigms in predicting human safety in phase 1 clinical trials. © 2014 by The Author(s).

[New paradigm for soil and water conservation: a method based on watershed process modeling and scenario analysis].

PubMed

Zhu, A-Xing; Chen, La-Jiao; Qin, Cheng-Zhi; Wang, Ping; Liu, Jun-Zhi; Li, Run-Kui; Cai, Qiang-Guo

2012-07-01

With the increase of severe soil erosion problem, soil and water conservation has become an urgent concern for sustainable development. Small watershed experimental observation is the traditional paradigm for soil and water control. However, the establishment of experimental watershed usually takes long time, and has the limitations of poor repeatability and high cost. Moreover, the popularization of the results from the experimental watershed is limited for other areas due to the differences in watershed conditions. Therefore, it is not sufficient to completely rely on this old paradigm for soil and water loss control. Recently, scenario analysis based on watershed modeling has been introduced into watershed management, which can provide information about the effectiveness of different management practices based on the quantitative simulation of watershed processes. Because of its merits such as low cost, short period, and high repeatability, scenario analysis shows great potential in aiding the development of watershed management strategy. This paper elaborated a new paradigm using watershed modeling and scenario analysis for soil and water conservation, illustrated this new paradigm through two cases for practical watershed management, and explored the future development of this new soil and water conservation paradigm.

Changing the culture of assessment: the dominance of the summative assessment paradigm.

PubMed

Harrison, Christopher J; Könings, Karen D; Schuwirth, Lambert W T; Wass, Valerie; van der Vleuten, Cees P M

2017-04-28

Despite growing evidence of the benefits of including assessment for learning strategies within programmes of assessment, practical implementation of these approaches is often problematical. Organisational culture change is often hindered by personal and collective beliefs which encourage adherence to the existing organisational paradigm. We aimed to explore how these beliefs influenced proposals to redesign a summative assessment culture in order to improve students' use of assessment-related feedback. Using the principles of participatory design, a mixed group comprising medical students, clinical teachers and senior faculty members was challenged to develop radical solutions to improve the use of post-assessment feedback. Follow-up interviews were conducted with individual members of the group to explore their personal beliefs about the proposed redesign. Data were analysed using a socio-cultural lens. Proposed changes were dominated by a shared belief in the primacy of the summative assessment paradigm, which prevented radical redesign solutions from being accepted by group members. Participants' prior assessment experiences strongly influenced proposals for change. As participants had largely only experienced a summative assessment culture, they found it difficult to conceptualise radical change in the assessment culture. Although all group members participated, students were less successful at persuading the group to adopt their ideas. Faculty members and clinical teachers often used indirect techniques to close down discussions. The strength of individual beliefs became more apparent in the follow-up interviews. Naïve epistemologies and prior personal experiences were influential in the assessment redesign but were usually not expressed explicitly in a group setting, perhaps because of cultural conventions of politeness. In order to successfully implement a change in assessment culture, firmly-held intuitive beliefs about summative assessment will need to be clearly understood as a first step.

Comparison of a row-column speller vs. a novel lateral single-character speller: assessment of BCI for severe motor disabled patients.

PubMed

Pires, Gabriel; Nunes, Urbano; Castelo-Branco, Miguel

2012-06-01

Non-invasive brain-computer interface (BCI) based on electroencephalography (EEG) offers a new communication channel for people suffering from severe motor disorders. This paper presents a novel P300-based speller called lateral single-character (LSC). The LSC performance is compared to that of the standard row-column (RC) speller. We developed LSC, a single-character paradigm comprising all letters of the alphabet following an event strategy that significantly reduces the time for symbol selection, and explores the intrinsic hemispheric asymmetries in visual perception to improve the performance of the BCI. RC and LSC paradigms were tested by 10 able-bodied participants, seven participants with amyotrophic lateral sclerosis (ALS), five participants with cerebral palsy (CP), one participant with Duchenne muscular dystrophy (DMD), and one participant with spinal cord injury (SCI). The averaged results, taking into account all participants who were able to control the BCI online, were significantly higher for LSC, 26.11 bit/min and 89.90% accuracy, than for RC, 21.91 bit/min and 88.36% accuracy. The two paradigms produced different waveforms and the signal-to-noise ratio was significantly higher for LSC. Finally, the novel LSC also showed new discriminative features. The results suggest that LSC is an effective alternative to RC, and that LSC still has a margin for potential improvement in bit rate and accuracy. The high bit rates and accuracy of LSC are a step forward for the effective use of BCI in clinical applications. Copyright © 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

WE-E-12A-01: Medical Physics 1.0 to 2.0: MRI, Displays, Informatics

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

Pickens, D; Flynn, M; Peck, D

Medical Physics 2.0 is a bold vision for an existential transition of clinical imaging physics in face of the new realities of value-based and evidence-based medicine, comparative effectiveness, and meaningful use. It speaks to how clinical imaging physics can expand beyond traditional insular models of inspection and acceptance testing, oriented toward compliance, towards team-based models of operational engagement, prospective definition and assurance of effective use, and retrospective evaluation of clinical performance. Organized into four sessions of the AAPM, this particular session focuses on three specific modalities as outlined below. MRI 2.0: This presentation will look into the future of clinicalmore » MR imaging and what the clinical medical physicist will need to be doing as the technology of MR imaging evolves. Many of the measurement techniques used today will need to be expanded to address the advent of higher field imaging systems and dedicated imagers for specialty applications. Included will be the need to address quality assurance and testing metrics for multi-channel MR imagers and hybrid devices such as MR/PET systems. New pulse sequences and acquisition methods, increasing use of MR spectroscopy, and real-time guidance procedures will place the burden on the medical physicist to define and use new tools to properly evaluate these systems, but the clinical applications must be understood so that these tools are use correctly. Finally, new rules, clinical requirements, and regulations will mean that the medical physicist must actively work to keep her/his sites compliant and must work closely with physicians to ensure best performance of these systems. Informatics Display 1.0 to 2.0: Medical displays are an integral part of medical imaging operation. The DICOM and AAPM (TG18) efforts have led to clear definitions of performance requirements of monochrome medical displays that can be followed by medical physicists to ensure proper performance. However, effective implementation of that oversight has been challenging due to the number and extend of medical displays in use at a facility. The advent of color display and mobile displays has added additional challenges to the task of the medical physicist. This informatics display lecture first addresses the current display guidelines (the 1.0 paradigm) and further outlines the initiatives and prospects for color and mobile displays (the 2.0 paradigm). Informatics Management 1.0 to 2.0: Imaging informatics is part of every radiology practice today. Imaging informatics covers everything from the ordering of a study, through the data acquisition and processing, display and archiving, reporting of findings and the billing for the services performed. The standardization of the processes used to manage the information and methodologies to integrate these standards is being developed and advanced continuously. These developments are done in an open forum and imaging organizations and professionals all have a part in the process. In the Informatics Management presentation, the flow of information and the integration of the standards used in the processes will be reviewed. The role of radiologists and physicists in the process will be discussed. Current methods (the 1.0 paradigm) and evolving methods (the 2.0 paradigm) for validation of informatics systems function will also be discussed. Learning Objectives: Identify requirements for improving quality assurance and compliance tools for advanced and hybrid MRI systems. Identify the need for new quality assurance metrics and testing procedures for advanced systems. Identify new hardware systems and new procedures needed to evaluate MRI systems. Understand the components of current medical physics expectation for medical displays. Understand the role and prospect fo medical physics for color and mobile display devices. Understand different areas of imaging informatics and the methodology for developing informatics standards. Understand the current status of informatics standards and the role of physicists and radiologists in the process, and the current technology for validating the function of these systems.« less

Paradigms for Assessing Hedonic Processing and Motivation in Humans: Relevance to Understanding Negative Symptoms in Psychopathology.

PubMed

Barch, Deanna M; Gold, James M; Kring, Ann M

2017-07-01

Clinicians and researchers have long known that one of the debilitating aspects of psychotic disorders is the presence of "negative symptoms," which involve impairments in hedonic and motivational function, and/or alterations in expressive affect. We have a number of excellent clinical tools available for assessing the presence and severity of negative symptoms. However, to better understand the mechanisms that may give rise to negative symptoms, we need tools and methods that can help distinguish among different potential contributing causes, as a means to develop more targeted intervention pathways. Using such paradigms is particularly important if we wish to understand whether the causes are the same or different across disorders that may share surface features of negative symptoms. This approach is in line with the goals of the Research Diagnostic Criteria Initiative, which advocates understanding the nature of core dimensions of brain-behavior relationships transdiagnostically. Here we highlight some of the emerging measures and paradigms that may help us to parse the nature and causes of negative symptoms, illustrating both the research approaches from which they emerge and the types of constructs that they can help elucidate. © The Author 2017. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

[Application of portfolio in teaching dermatology clinic: an experience in teaching of medicine].

PubMed

de Cabalier, M E; Chalub, D M

2009-01-01

We present a learning experience conducted in the Chair of Dermatology Clinic of the Faculty of Medical Sciences, National University of Cordoba in the context of curriculum change. For comprehension,present a theoretical framework and practical from the conceptualization of the "portfolio" teaching and its role teaching and learning paradigms sustained constructivist medical education. The portfolio Teach-ing is not a collection of papers, but a coherent set of experiences led thoughtful learning between teachers and students. This resource allows to account for the "qualitative achievements" of students from their work produced, sorted and evaluated in a carefully planned sequence of experiences and case Dermatology Clinic. To introduce the teaching portfolio, the planned new student grouping shapes and a sequence of learning experiences for the construction of this resource, namely: "The development of theoretical material iconographic resources and working guidelines for students. "The clinical reasoning on a case or laboratory experience-Clinical case Discussion and bibliography. -The development of records to from observation of patients. "The study of clinical cases: diagnosis and evolution of clinical cases. Interconsultations-Registration and referrals. "The magazine room and sharing experiences. In each of these, production, tutorial feedback Team teaching and assessment tasks allowed assessment approach to learning and improving he achievements of the students to the approval of the subject.

An Integrative Paradigm

ERIC Educational Resources Information Center

Hammack, Phillip L.

2005-01-01

Through the application of life course theory to the study of sexual orientation, this paper specifies a new paradigm for research on human sexual orientation that seeks to reconcile divisions among biological, social science, and humanistic paradigms. Recognizing the historical, social, and cultural relativity of human development, this paradigm…

Paradigms, Citations, and Maps of Science: A Personal History.

ERIC Educational Resources Information Center

Small, Henry

2003-01-01

Discusses mapping science and Kuhn's theories of paradigms and scientific development. Highlights include cocitation clustering; bibliometric definition of a paradigm; specialty dynamics; pathways through science; a new Web tool called Essential Science Indicators (ESI) for studying the structure of science; and microrevolutions. (Author/LRW)

A communication model to integrate the Request-Response and the Publish-Subscribe paradigms into ubiquitous systems.

PubMed

Rodríguez-Domínguez, Carlos; Benghazi, Kawtar; Noguera, Manuel; Garrido, José Luis; Rodríguez, María Luisa; Ruiz-López, Tomás

2012-01-01

The Request-Response (RR) paradigm is widely used in ubiquitous systems to exchange information in a secure, reliable and timely manner. Nonetheless, there is also an emerging need for adopting the Publish-Subscribe (PubSub) paradigm in this kind of systems, due to the advantages that this paradigm offers in supporting mobility by means of asynchronous, non-blocking and one-to-many message distribution semantics for event notification. This paper analyzes the strengths and weaknesses of both the RR and PubSub paradigms to support communications in ubiquitous systems and proposes an abstract communication model in order to enable their seamless integration. Thus, developers will be focused on communication semantics and the required quality properties, rather than be concerned about specific communication mechanisms. The aim is to provide developers with abstractions intended to decrease the complexity of integrating different communication paradigms commonly needed in ubiquitous systems. The proposal has been applied to implement a middleware and a real home automation system to show its applicability and benefits.

Emerging treatment paradigms of ocular surface disease: proceedings of the Ocular Surface Workshop.

PubMed

Rolando, M; Geerling, G; Dua, H S; Benítez-del-Castillo, J M; Creuzot-Garcher, C

2010-01-01

The objective of the Ocular Surface Workshop in Rome, Italy, on 6 February 2009, was to enhance the understanding of ocular surface disease (OSD) through an exploration of the nature of its complexities and current treatment paradigms across Europe. It was hoped that the peer-to-peer discussions and updates regarding common knowledge, clinical practices and shared experiences at this workshop would subsequently shape future treatment approaches to OSD.

An online hybrid brain-computer interface combining multiple physiological signals for webpage browse.

PubMed

Long Chen; Zhongpeng Wang; Feng He; Jiajia Yang; Hongzhi Qi; Peng Zhou; Baikun Wan; Dong Ming

2015-08-01

The hybrid brain computer interface (hBCI) could provide higher information transfer rate than did the classical BCIs. It included more than one brain-computer or human-machine interact paradigms, such as the combination of the P300 and SSVEP paradigms. Research firstly constructed independent subsystems of three different paradigms and tested each of them with online experiments. Then we constructed a serial hybrid BCI system which combined these paradigms to achieve the functions of typing letters, moving and clicking cursor, and switching among them for the purpose of browsing webpages. Five subjects were involved in this study. They all successfully realized these functions in the online tests. The subjects could achieve an accuracy above 90% after training, which met the requirement in operating the system efficiently. The results demonstrated that it was an efficient system capable of robustness, which provided an approach for the clinic application.

Toward a patient-based paradigm for blood transfusion.

PubMed

Farrugia, Albert; Vamvakas, Eleftherios

2014-01-01

The current "manufacturing paradigm" of transfusion practice has detached transfusion from the clinical environment. As an example, fresh whole blood in large-volume hemorrhage may be superior to whole blood reconstituted from multiple components. Multicomponent apheresis can overcome logistical difficulties in matching patient needs with fresh component availability and can deliver the benefits of fresh whole blood. Because of the different transfusion needs of patients in emerging economies and the vulnerability of these blood systems to emerging infections, fresh whole blood and multicomponent apheresis can better meet patient needs when compared with transplants of the "manufacturing paradigm". We propose that patient blood management, along with panels of repeat, paid, accredited apheresis and fresh whole-blood donors can be used in emerging economies to support decentralized blood services. This alternative transfusion-medicine paradigm could eventually also be adopted by established economies to focus transfusion medicine on local patient needs and to alleviate the problem of the aging volunteer donor base.

Integration, Telecommunication, and Development: Power in the Paradigms.

ERIC Educational Resources Information Center

Samarajiva, Rohan; Shields, Peter

1990-01-01

Notes that much research in telecommunication and development continues to treat technology as neutral and neglects its impact on the powerless. Argues that the view of development as desirable often goes uncontested. Calls for a paradigm which places power in the center of the analysis. (SG)

Stream computing for biomedical signal processing: A QRS complex detection case-study.

PubMed

Murphy, B M; O'Driscoll, C; Boylan, G B; Lightbody, G; Marnane, W P

2015-01-01

Recent developments in "Big Data" have brought significant gains in the ability to process large amounts of data on commodity server hardware. Stream computing is a relatively new paradigm in this area, addressing the need to process data in real time with very low latency. While this approach has been developed for dealing with large scale data from the world of business, security and finance, there is a natural overlap with clinical needs for physiological signal processing. In this work we present a case study of streams processing applied to a typical physiological signal processing problem: QRS detection from ECG data.

Novel Cognitive Paradigms for the Detection of Memory Impairment in Preclinical Alzheimer’s Disease

PubMed Central

Loewenstein, David A.; Curiel, Rosie E.; Duara, Ranjan; Buschke, Herman

2017-01-01

In spite of advances in neuroimaging and other brain biomarkers to assess preclinical Alzheimer’s disease (AD), cognitive assessment has relied on traditional memory paradigms developed well over six decades ago. This has led to a growing concern about their effectiveness in the early diagnosis of AD which is essential to develop preventive and early targeted interventions before the occurrence of multisystem brain degeneration. We describe the development of novel tests that are more cognitively challenging, minimize variability in learning strategies, enhance initial acquisition and retrieval using cues, and exploit vulnerabilities in persons with incipient AD such as the susceptibility to proactive semantic interference, and failure to recover from proactive semantic interference. The advantages of various novel memory assessment paradigms are examined as well as how they compare with traditional neuropsychological assessments of memory. Finally, future directions for the development of more effective assessment paradigms are suggested. PMID:29214859

The revolution of personalized psychiatry: will technology make it happen sooner?

PubMed

Perna, G; Grassi, M; Caldirola, D; Nemeroff, C B

2018-04-01

Personalized medicine (PM) aims to establish a new approach in clinical decision-making, based upon a patient's individual profile in order to tailor treatment to each patient's characteristics. Although this has become a focus of the discussion also in the psychiatric field, with evidence of its high potential coming from several proof-of-concept studies, nearly no tools have been developed by now that are ready to be applied in clinical practice. In this paper, we discuss recent technological advances that can make a shift toward a clinical application of the PM paradigm. We focus specifically on those technologies that allow both the collection of massive as much as real-time data, i.e., electronic medical records and smart wearable devices, and to achieve relevant predictions using these data, i.e. the application of machine learning techniques.

The words we work with that work on us: clinical paradigm and cumulative relational trauma.

PubMed

Heuer, Birgit

2017-11-01

This paper addresses a gap between analytic clinical theory and practice which emerges when examining the words we work with via textual and narrative research of case histories. Both subject matter and methodology fit with the remit of conceptual research in psychoanalysis, currently ranging from inductive to nomothetical approaches. Research of clinical language reveals an implicit account of human nature and the world which undergirds clinical practice. Based in the critical philosophy of the previous century, this is termed clinical paradigm. Such implicit views are induced rather than explicitly taught during analytic training, and need to be spelled out in order to become available to discourse and difference of opinion. Textual research shows these implicit pre-clinical attitudes to be inherently pessimistic and thus too similar to the views of self and others found in cumulative relational trauma. Moreover, clinical accounts tend to normalize subtly antagonistic forms of relating, recently recognised as micro-trauma. Importantly, this contravenes the agapic orientation of our theories and ethics. Paradigmatic reflection as a form of professional individuation addresses this gap. This includes a more optimistic outlook which can be traced through the philosophical implications of quantum theory. © 2017, The Society of Analytical Psychology.

The "hospital central laboratory": automation, integration and clinical usefulness.

PubMed

Zaninotto, Martina; Plebani, Mario

2010-07-01

Recent technological developments in laboratory medicine have led to a major challenge, maintaining a close connection between the search of efficiency through automation and consolidation and the assurance of effectiveness. The adoption of systems that automate most of the manual tasks characterizing routine activities has significantly improved the quality of laboratory performance; total laboratory automation being the paradigm of the idea that "human-less" robotic laboratories may allow for better operation and insuring less human errors. Furthermore, even if ongoing technological developments have considerably improved the productivity of clinical laboratories as well as reducing the turnaround time of the entire process, the value of qualified personnel remains a significant issue. Recent evidence confirms that automation allows clinical laboratories to improve analytical performances only if trained staff operate in accordance with well-defined standard operative procedures, thus assuring continuous monitoring of the analytical quality. In addition, laboratory automation may improve the appropriateness of test requests through the use of algorithms and reflex testing. This should allow the adoption of clinical and biochemical guidelines. In conclusion, in laboratory medicine, technology represents a tool for improving clinical effectiveness and patient outcomes, but it has to be managed by qualified laboratory professionals.

Investigational Notch and Hedgehog Inhibitors – Therapies for Cardiovascular disease

PubMed Central

Redmond, EM; Guha, S; Walls, D; Cahill, PA

2011-01-01

Importance to the field During the past decade a variety of Notch and Hedgehog pathway inhibitors have been developed for the treatment of several cancers. An emerging paradigm suggests that these same gene regulatory networks are often recapitulated in the context of cardiovascular disease and may now offer an attractive target for therapeutic intervention. Areas Covered This article briefly reviews the profile of Notch and Hedgehog inhibitors that have reached the pre-clinic and clinic for cancer treatment and discusses the clinical issues surrounding targeted use of these inhibitors in the treatment of vascular disorders. Expert Opinion Pre-clinical and clinical data using pan-Notch inhibitors (γ-secretase inhibitors) and selective antibodies to preferentially target notch receptors and ligands has proven successful but concerns remain over normal organ homeostasis and significant pathology in multiple organs. In contrast, the Hedgehog based drug pipeline is rich with more than a dozen Smoothened (SMO) inhibitors at various stages of development. Overall, refined strategies will be necessary to harness these pathways safely as a powerful tool to disrupt angiogenesis and vascular proliferative phenomena without causing prohibitive side effects already seen with cancer models and patients. PMID:22007748

Drugs for solid cancer: the productivity crisis prompts a rethink

PubMed Central

Rösel, Daniel; Brábek, Jan; Veselý, Pavel; Fernandes, Michael

2013-01-01

Despite remarkable progress in cancer-drug discovery, the delivery of novel, safe, and sustainably effective products to the clinic has stalled. Using Src as a model, we examine key steps in drug development. The preclinical evidence on the relationship between Src and solid cancer is in sharp contrast with the modest anticancer effect noted in conventional clinical trials. Here, we consider Src inhibitors as an example of a promising drug class directed to invasion and metastasis and identify roadblocks in translation. We question the assumption that a drug-induced tumor shrinkage in preclinical and clinical studies predicts a successful outcome. Our analysis indicates that the key areas requiring attention are related, and include preclinical models (in vitro and mouse models), meaningful clinical trial end points, and an appreciation of the role of metastasis in morbidity and mortality. Current regulations do not reflect the natural history of the disease, and may be unrelated to the key complications: local invasion, metastasis, and the development of resistance. Alignment of preclinical and clinical studies and regulations based on mechanistic trial end points and platforms may help in overcoming these roadblocks. Viewed kaleidoscopically, most elements necessary and sufficient for a novel translational paradigm are in place. PMID:23836990

A new system for quantitative evaluation of infant gaze capabilities in a wide visual field.

PubMed

Pratesi, Andrea; Cecchi, Francesca; Beani, Elena; Sgandurra, Giuseppina; Cioni, Giovanni; Laschi, Cecilia; Dario, Paolo

2015-09-07

The visual assessment of infants poses specific challenges: many techniques that are used on adults are based on the patient's response, and are not suitable for infants. Significant advances in the eye-tracking have made this assessment of infant visual capabilities easier, however, eye-tracking still requires the subject's collaboration, in most cases and thus limiting the application in infant research. Moreover, there is a lack of transferability to clinical practice, and thus it emerges the need for a new tool to measure the paradigms and explore the most common visual competences in a wide visual field. This work presents the design, development and preliminary testing of a new system for measuring infant's gaze in the wide visual field called CareToy C: CareToy for Clinics. The system is based on a commercial eye tracker (SmartEye) with six cameras running at 60 Hz, suitable for measuring an infant's gaze. In order to stimulate the infant visually and audibly, a mechanical structure has been designed to support five speakers and five screens at a specific distance (60 cm) and angle: one in the centre, two on the right-hand side and two on the left (at 30° and 60° respectively). Different tasks have been designed in order to evaluate the system capability to assess the infant's gaze movements during different conditions (such as gap, overlap or audio-visual paradigms). Nine healthy infants aged 4-10 months were assessed as they performed the visual tasks at random. We developed a system able to measure infant's gaze in a wide visual field covering a total visual range of ±60° from the centre with an intermediate evaluation at ±30°. Moreover, the same system, thanks to different integrated software, was able to provide different visual paradigms (as gap, overlap and audio-visual) assessing and comparing different visual and multisensory sub-competencies. The proposed system endowed the integration of a commercial eye-tracker into a purposive setup in a smart and innovative way. The proposed system is suitable for measuring and evaluating infant's gaze capabilities in a wide visual field, in order to provide quantitative data that can enrich the clinical assessment.

At the Crossroads of Clinical Practice and Teacher Leadership: A Changing Paradigm for Professional Practice

ERIC Educational Resources Information Center

Sawyer, Richard D.; Neel, Michael; Coulter, Matthew

2016-01-01

This paper examines the endemic separation between K-12 schools and colleges of education in teacher preparation. Specifically, we examine a new approach related to the promise of clinical practice--a clinical practice program that overlaps a public high school, a graduate-level teacher preparation program, and a professional practice doctoral…

Foundation-industry relationships--a new business model joint-venture philanthropy in therapy development.

PubMed

Bartek, Ronald J

2014-01-01

The business model for medical therapy development has changed drastically. Large companies that once conducted their own Research and Development (R&D) and funded all the preclinical studies, all phases of clinical development and marketing of the products are increasingly turning to others for more and more of the earlier work in hopes of being able to in-license a de-risked program well downstream, take it through the final phases of clinical development and into the marketplace. This new paradigm has required patient-advocacy foundations, especially in the rare-disease space, to become far more effective in building relationships with all the players along the therapy-development pathway -- academic scientists, government agencies, other foundations with overlapping interests, biotechs, small biopharmaceutical entities and even the larger industry companies. From the perspective of the patient-advocacy community, these increasingly essential public-private partnerships have taken on the nature of what could be called joint-venture philanthropy and involve a broad spectrum of collaborations and financial relationships between foundations and industry partners that are not without concerns about potential conflicts of interest.

Design Recommendations for Pharmacogenomics Clinical Decision Support Systems

PubMed Central

Khelifi, Maher; Tarczy-Hornoch, Peter; Devine, Emily B.; Pratt, Wanda

2017-01-01

The use of pharmacogenomics (PGx) in clinical practice still faces challenges to fully adopt genetic information in targeting drug therapy. To incorporate genetics into clinical practice, many support the use of Pharmacogenomics Clinical Decision Support Systems (PGx-CDS) for medication prescriptions. This support was fueled by new guidelines to incorporate genetics for optimizing drug dosage and reducing adverse events. In addition, the complexity of PGx led to exploring CDS outside the paradigm of the basic CDS tools embedded in commercial electronic health records. Therefore, designing the right CDS is key to unleashing the full potential of pharmacogenomics and making it a part of clinicians’ daily workflow. In this work, we 1) identify challenges and barriers of the implementation of PGx-CDS in clinical settings, 2) develop a new design approach to CDS with functional characteristics that can improve the adoption of pharmacogenomics guidelines and thus patient safety, and 3) create design guidelines and recommendations for such PGx-CDS tools. PMID:28815136

Translating Life Course Theory to Clinical Practice to Address Health Disparities

PubMed Central

Solomon, Barry S.

2013-01-01

Life Course Theory (LCT) is a framework that explains health and disease across populations and over time and in a powerful way, conceptualizes health and health disparities to guide improvements. It suggests a need to change priorities and paradigms in our healthcare delivery system. In “Rethinking Maternal and Child Health: The Life Course Model as an Organizing Framework,” Fine and Kotelchuck identify three areas of rethinking that have relevance to clinical care: (1) recognition of context and the “whole-person, whole-family, whole-community systems approach;” (2) longitudinal approach with “greater emphasis on early (“upstream”) determinants of health”; and (3) need for integration and “developing integrated, multi-sector service systems that become lifelong “pipelines” for healthy development”. This paper discusses promising clinical practice innovations in these three areas: addressing social influences on health in clinical practice, longitudinal and vertical integration of clinical services and horizontal integration with community services and resources. In addition, barriers and facilitators to implementation are reviewed. PMID:23677685

Transforming Psychological Practice and Society: Policies that Reflect the New Paradigm.

ERIC Educational Resources Information Center

Gill, Carol J.; Kewman, Donald G.; Brannon, Ruth W.

2003-01-01

Understanding disability through a social paradigm offers opportunities to reframe the way psychologists define problems related to disability, develop more collaborative relationships between psychologists and people with disabilities, and adopt new professional responsibilities. Addresses the impact of the social paradigm on policies within…

Towards a New Paradigm of Moral Personhood

ERIC Educational Resources Information Center

Frimer, Jeremy A.; Walker, Lawrence J.

2008-01-01

Moral psychology is between paradigms. Kohlberg's model of moral rationality has proved inadequate in explaining action; yet its augmentation--moral personality--awaits empirical embodiment. This article addresses some critical issues in developing a comprehensive empirical paradigm of moral personhood. Is a first-person or a third-person…

Stressor paradigms in developmental studies: What does and does not work to produce mean increases in salivary cortisol

PubMed Central

Gunnar, Megan R.; Talge, Nicole M.; Herrera, Adriana

2009-01-01

Summary The stress response system is comprised of an intricate interconnected network that includes the hypothalamic–pituitary–adrenocortical (HPA) axis. The HPA axis maintains the organism’s capacity to respond to acute and prolonged stressors and is a focus of research on the sequelae of stress. Human studies of the HPA system have been facilitated enormously by the development of salivary assays which measure cortisol, the steroid end-product of the HPA axis. The use of salivary cortisol is prevalent in child development stress research. However, in order to measure children’s acute cortisol reactivity to circumscribed stressors, researchers must put children in stressful situations which produce elevated levels of cortisol. Unfortunately, many studies on the cortisol stress response in children use paradigms that fail to produce mean elevations in cortisol. This paper reviews stressor paradigms used with infants, children, and adolescents to guide researchers in selecting effective stressor tasks. A number of different types of stressor paradigms were examined, including: public speaking, negative emotion, relationship disruption/threatening, novelty, handling, and mild pain paradigms. With development, marked changes are evident in the effectiveness of the same stressor paradigm to provoke elevations in cortisol. Several factors appear to be critical in determining whether a stressor paradigm is successful, including the availability of coping resources and the extent to which, in older children, the task threatens the social self. A consideration of these issues is needed to promote the implementation of more effective stressor paradigms in human developmental psychoendocrine research. PMID:19321267

Neurocounseling: Brain-Based Clinical Approaches

ERIC Educational Resources Information Center

Field, Thomas A., Ed.; Jones, Laura K., Ed.; Russell-Chapin, Lori A.

2017-01-01

This text presents current, accessible information on enhancing the counseling process using a brain-based paradigm. Leading experts provide guidelines and insights for becoming a skillful neuroscience-informed counselor, making direct connections between the material covered and clinical practice. In this much-needed resource-the first to address…

Influence of emotional states on inhibitory gating: Animals models to clinical neurophysiology

PubMed Central

Cromwell, Howard C.; Atchley, Rachel M.

2014-01-01

Integrating research efforts using a cross-domain approach could redefine traditional constructs used in behavioral and clinical neuroscience by demonstrating that behavior and mental processes arise not from functional isolation but from integration. Our research group has been examining the interface between cognitive and emotional processes by studying inhibitory gating. Inhibitory gating can be measured via changes in behavior or neural signal processing. Sensorimotor gating of the startle response is a well-used measure. To study how emotion and cognition interact during startle modulation in the animal model, we examined ultrasonic vocalization (USV) emissions during acoustic startle and prepulse inhibition. We found high rates of USV emission during the sensorimotor gating paradigm and revealed links between prepulse inhibition (PPI) and USV emission that could reflect emotional and cognitive influences. Measuring inhibitory gating as P50 event-related potential suppression has also revealed possible connections between emotional states and cognitive processes. We have examined the single unit responses during the traditional gating paradigm and found that acute and chronic stress can alter gating of neural signals in regions such as amygdala, striatum and medial prefrontal cortex. Our findings point to the need for more cross-domain research on how shifting states of emotion can impact basic mechanisms of information processing. Results could inform clinical work with the development of tools that depend upon cross-domain communication, and enable a better understanding and evaluation of psychological impairment. PMID:24861710

Potential hormonal mechanisms of attention-deficit/hyperactivity disorder and major depressive disorder: a new perspective.

PubMed

Martel, Michelle M; Klump, Kelly; Nigg, Joel T; Breedlove, S Marc; Sisk, Cheryl L

2009-04-01

Hormonal influences on the organization of behavior are apparent to neuroendocrinologists but under-examined in relation to childhood and adolescent mental disorders. A central mystery in the field of developmental psychopathology is the preferential male vulnerability to behavior disorders in childhood and female vulnerability to emotional disorders in adolescence. Relative neglect of a hormonal explanation may be due to lack of simple or unifying conceptual paradigms to guide studies. This paper seeks to stimulate research in this area by drawing upon clinical psychology and neuroscience literatures to offer a heuristic paradigm for clinical research. Two syndromes are selected here for illustration: Attention-Deficit/Hyperactivity Disorder (ADHD) and Major Depressive Disorder (MDD), because they have opposite gender risk profiles. Two guiding theories are evaluated. First, prenatal organizational effects of testosterone may modulate striatally-based dopaminergic circuits in such a way as to place boys at greater risk for early developing inattention and disruptive behavioral disorders. Second, activational effects of estradiol at puberty may modulate amygdalar and other circuitry, with particular effects on serotonergic pathways, in such a way as to place girls at greater risk for internalizing and mood disorders. Hypotheses from these theories are evaluated based on the current available literature, and limitations of, and future directions for, this literature are discussed.

Potential Hormonal Mechanisms of Attention-Deficit/Hyperactivity Disorder and Major Depressive Disorder: A New Perspective

PubMed Central

Martel, Michelle M.; Klump, Kelly; Nigg, Joel T.; Breedlove, S. Marc; Sisk, Cheryl L.

2013-01-01

Hormonal influences on the organization of behavior are apparent to neuroendocrinologists but under-examined in relation to childhood and adolescent mental disorders. A central mystery in the field of developmental psychopathology is the preferential male vulnerability to behavior disorders in childhood and female vulnerability to emotional disorders in adolescence. Relative neglect of a hormonal explanation may be due to lack of simple or unifying conceptual paradigms to guide studies. This paper seeks to stimulate research in this area by drawing upon clinical psychology and neuroscience literatures to offer a heuristic paradigm for clinical research. Two syndromes are selected here for illustration: Attention-Deficit/Hyperactivity Disorder (ADHD) and Major Depressive Disorder (MDD), because they have opposite gender risk profiles. Two guiding theories are evaluated. First, prenatal organizational effects of testosterone may modulate striatally-based dopaminergic circuits in such a way as to place boys at greater risk for early developing inattention and disruptive behavioral disorders. Second, activational effects of estradiol at puberty may modulate amygdalar and other circuitry, with particular effects on serotoninergic pathways, in such a way as to place girls at greater risk for internalizing and mood disorders. Hypotheses from these theories are evaluated based on the current available literature, and limitations of, and future directions for, this literature are discussed. PMID:19265696

PARADIGM - HF: The Rise of the Arnis.

PubMed

Guha, Kaushik; Varkey, Sneha; Sharma, Rakesh

2016-01-01

Heart failure remains a widespread commonly encountered clinical condition. It is responsible for increased healthcare expenditure, driven by frequent and often prolonged hospital admissions associated with an increased mortality. A clinically useful classification of the syndrome is, patients with left ventricular systolic impairment (Heart Failure and reduced ejection fraction, HFREF) and patients with preserved left ventricular systolic function (HFPEF). The pharmacological treatment for patients with HFREF has evolved over the last twenty five years, focusing on modulation of the neurohormonal activation which represents a hallmark of this condition. This has led to the development of a stepwise treatment algorithm predominately based on inhibition of the renin angiotensin aldosterone pathway and counteracting sympathetic over-activation. In particular since the early trials in chronic heart failure (CHF) demonstrated a significant mortality benefit with ACE-inhibitors, subsequent studies have been conducted in conjunction with these drugs. The rationale being that it would be unethical to trial any new agent without the concomitant use of ACE-inhibitors. The recent publication of the PARADIGM -HF study has challenged this convention by trialling a novel pharmacological agent against an ACE-inhibitor in a landmark trial. The review sets out the current pharmacological treatment for patients with heart failure and discusses the recent findings with this novel class of medication.

Primary repair of the anterior cruciate ligament: A paradigm shift.

PubMed

van der List, Jelle P; DiFelice, Gregory S

2017-06-01

Over the last century, many surgical treatments have been developed in the orthopedic field, including treatments of anterior cruciate ligament (ACL) injuries. These treatments ideally evolve in a process of trial and error with prospective comparison of new treatments to the current treatment standard. However, these evolutions are sometimes not linear and periodically undergo paradigm shifts. In this article, we review the evolution of ACL treatment and explain how it underwent a paradigm shift. Open primary ACL repair was the most common treatment in the 1970s and 1980s, but because multiple studies noted deterioration of outcomes at mid-term follow-up, in addition to several randomized clinical trials (RCTs) that noted better outcomes following ACL reconstruction, the open primary repair technique was abandoned. At the end of the primary repair era, however, several studies showed that outcomes of open primary repair were good to excellent and did not deteriorate when this technique was selectively performed in patients with proximal ACL tears, whereas primary repair led to disappointing and unpredictable results in patients with mid-substance tears. Unfortunately, enrollment of patients in the aforementioned RCTs was already finished, ultimately leading to abandoning of open primary repair, despite the advantages of ligament preservation. In this review, we discuss (I) why the evolution of ACL treatment underwent a paradigm shift, (II) which factors may have played a role in this and (III) what the future role of arthroscopic primary ACL repair is in the evolution of ACL treatments. Copyright © 2016. Published by Elsevier Ltd.

A Novel Analog Reasoning Paradigm: New Insights in Intellectually Disabled Patients.

PubMed

Curie, Aurore; Brun, Amandine; Cheylus, Anne; Reboul, Anne; Nazir, Tatjana; Bussy, Gérald; Delange, Karine; Paulignan, Yves; Mercier, Sandra; David, Albert; Marignier, Stéphanie; Merle, Lydie; de Fréminville, Bénédicte; Prieur, Fabienne; Till, Michel; Mortemousque, Isabelle; Toutain, Annick; Bieth, Eric; Touraine, Renaud; Sanlaville, Damien; Chelly, Jamel; Kong, Jian; Ott, Daniel; Kassai, Behrouz; Hadjikhani, Nouchine; Gollub, Randy L; des Portes, Vincent

2016-01-01

Intellectual Disability (ID) is characterized by deficits in intellectual functions such as reasoning, problem-solving, planning, abstract thinking, judgment, and learning. As new avenues are emerging for treatment of genetically determined ID (such as Down's syndrome or Fragile X syndrome), it is necessary to identify objective reliable and sensitive outcome measures for use in clinical trials. We developed a novel visual analogical reasoning paradigm, inspired by the Progressive Raven's Matrices, but appropriate for Intellectually Disabled patients. This new paradigm assesses reasoning and inhibition abilities in ID patients. We performed behavioural analyses for this task (with a reaction time and error rate analysis, Study 1) in 96 healthy controls (adults and typically developed children older than 4) and 41 genetically determined ID patients (Fragile X syndrome, Down syndrome and ARX mutated patients). In order to establish and quantify the cognitive strategies used to solve the task, we also performed an eye-tracking analysis (Study 2). Down syndrome, ARX and Fragile X patients were significantly slower and made significantly more errors than chronological age-matched healthy controls. The effect of inhibition on error rate was greater than the matrix complexity effect in ID patients, opposite to findings in adult healthy controls. Interestingly, ID patients were more impaired by inhibition than mental age-matched healthy controls, but not by the matrix complexity. Eye-tracking analysis made it possible to identify the strategy used by the participants to solve the task. Adult healthy controls used a matrix-based strategy, whereas ID patients used a response-based strategy. Furthermore, etiologic-specific reasoning differences were evidenced between ID patients groups. We suggest that this paradigm, appropriate for ID patients and developmental populations as well as adult healthy controls, provides an objective and quantitative assessment of visual analogical reasoning and cognitive inhibition, enabling testing for the effect of pharmacological or behavioural intervention in these specific populations.

Neurobehavioral, neuropathological and biochemical profiles in a novel mouse model of co-morbid post-traumatic stress disorder and mild traumatic brain injury

PubMed Central

Ojo, Joseph O.; Greenberg, M. Banks; Leary, Paige; Mouzon, Benoit; Bachmeier, Corbin; Mullan, Michael; Diamond, David M.; Crawford, Fiona

2014-01-01

Co-morbid mild traumatic brain injury (mTBI) and post-traumatic stress disorder (PTSD) has become the signature disorder for returning combat veterans. The clinical heterogeneity and overlapping symptomatology of mTBI and PTSD underscore the need to develop a preclinical model that will enable the characterization of unique and overlapping features and allow discrimination between both disorders. This study details the development and implementation of a novel experimental paradigm for PTSD and combined PTSD-mTBI. The PTSD paradigm involved exposure to a danger-related predator odor under repeated restraint over a 21 day period and a physical trauma (inescapable footshock). We administered this paradigm alone, or in combination with a previously established mTBI model. We report outcomes of behavioral, pathological and biochemical profiles at an acute timepoint. PTSD animals demonstrated recall of traumatic memories, anxiety and an impaired social behavior. In both mTBI and combination groups there was a pattern of disinhibitory like behavior. mTBI abrogated both contextual fear and impairments in social behavior seen in PTSD animals. No major impairment in spatial memory was observed in any group. Examination of neuroendocrine and neuroimmune responses in plasma revealed a trend toward increase in corticosterone in PTSD and combination groups, and an apparent increase in Th1 and Th17 proinflammatory cytokine(s) in the PTSD only and mTBI only groups respectively. In the brain there were no gross neuropathological changes in any groups. We observed that mTBI on a background of repeated trauma exposure resulted in an augmentation of axonal injury and inflammatory markers, neurofilament L and ICAM-1 respectively. Our observations thus far suggest that this novel stress-trauma-related paradigm may be a useful model for investigating further the overlapping and distinct spatio-temporal and behavioral/biochemical relationship between mTBI and PTSD experienced by combat veterans. PMID:25002839

Beyond the “at risk mental state” concept: transitioning to transdiagnostic psychiatry

PubMed Central

McGorry, Patrick D.; Hartmann, Jessica A.; Spooner, Rachael; Nelson, Barnaby

2018-01-01

The “at risk mental state” for psychosis approach has been a catalytic, highly productive research paradigm over the last 25 years. In this paper we review that paradigm and summarize its key lessons, which include the valence of this phenotype for future psychosis outcomes, but also for comorbid, persistent or incident non‐psychotic disorders; and the evidence that onset of psychotic disorder can at least be delayed in ultra high risk (UHR) patients, and that some full‐threshold psychotic disorder may emerge from risk states not captured by UHR criteria. The paradigm has also illuminated risk factors and mechanisms involved in psychosis onset. However, findings from this and related paradigms indicate the need to develop new identification and diagnostic strategies. These findings include the high prevalence and impact of mental disorders in young people, the limitations of current diagnostic systems and risk identification approaches, the diffuse and unstable symptom patterns in early stages, and their pluripotent, transdiagnostic trajectories. The approach we have recently adopted has been guided by the clinical staging model and adapts the original “at risk mental state” approach to encompass a broader range of inputs and output target syndromes. This approach is supported by a number of novel modelling and prediction strategies that acknowledge and reflect the dynamic nature of psychopathology, such as dynamical systems theory, network theory, and joint modelling. Importantly, a broader transdiagnostic approach and enhancing specific prediction (profiling or increasing precision) can be achieved concurrently. A holistic strategy can be developed that applies these new prediction approaches, as well as machine learning and iterative probabilistic multimodal models, to a blend of subjective psychological data, physical disturbances (e.g., EEG measures) and biomarkers (e.g., neuroinflammation, neural network abnormalities) acquired through fine‐grained sequential or longitudinal assessments. This strategy could ultimately enhance our understanding and ability to predict the onset, early course and evolution of mental ill health, further opening pathways for preventive interventions. PMID:29856558

Information processing as a paradigm for decision making.

PubMed

Oppenheimer, Daniel M; Kelso, Evan

2015-01-03

For decades, the dominant paradigm for studying decision making--the expected utility framework--has been burdened by an increasing number of empirical findings that question its validity as a model of human cognition and behavior. However, as Kuhn (1962) argued in his seminal discussion of paradigm shifts, an old paradigm cannot be abandoned until a new paradigm emerges to replace it. In this article, we argue that the recent shift in researcher attention toward basic cognitive processes that give rise to decision phenomena constitutes the beginning of that replacement paradigm. Models grounded in basic perceptual, attentional, memory, and aggregation processes have begun to proliferate. The development of this new approach closely aligns with Kuhn's notion of paradigm shift, suggesting that this is a particularly generative and revolutionary time to be studying decision science.

Adapting clinical paradigms to the challenges of cancer clonal evolution.

PubMed

Murugaesu, Nirupa; Chew, Su Kit; Swanton, Charles

2013-06-01

Emerging evidence suggests that cancer branched evolution may affect biomarker validation, clinical outcome, and emergence of drug resistance. The changing spatial and temporal nature of cancer subclonal architecture during the disease course suggests the need for longitudinal prospective studies of cancer evolution and robust and clinically implementable pathologic definitions of intratumor heterogeneity, genetic diversity, and chromosomal instability. Furthermore, subclonal heterogeneous events in tumors may evade detection through conventional biomarker strategies and influence clinical outcome. Minimally invasive methods for the study of cancer evolution and new approaches to clinical study design, incorporating understanding of the dynamics of tumor clonal architectures through treatment and during acquisition of drug resistance, have been suggested as important areas for development. Coordinated efforts will be required by the scientific and clinical trial communities to adapt to the challenges of detecting infrequently occurring somatic events that may influence clinical outcome and to understand the dynamics of cancer evolution and the waxing and waning of tumor subclones over time in advanced metastatic epithelial malignancies. Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Co-"Lab"oration: A New Paradigm for Building a Management Information Systems Course

ERIC Educational Resources Information Center

Breimer, Eric; Cotler, Jami; Yoder, Robert

2010-01-01

We propose a new paradigm for building a Management Information Systems course that focuses on laboratory activities developed collaboratively using Computer-Mediated Communication and Collaboration tools. A highlight of our paradigm is the "practice what you preach" concept where the computer communication tools and collaboration…

Toward a Quality-of-Life Paradigm for Sustainable Communities.

ERIC Educational Resources Information Center

Hyman, Drew

This paper suggests that current paradigms and world views guiding research for social action are inadequate for directing rural community change in a high-tech, global community. For several generations, the agrarian and industrial paradigms have been accepted as appropriate for guiding social change and development. However, there are problems…

The Use of Narrative Paradigm Theory in Assessing Audience Value Conflict in Image Advertising.

ERIC Educational Resources Information Center

Stutts, Nancy B.; Barker, Randolph T.

1999-01-01

Presents an analysis of image advertisement developed from Narrative Paradigm Theory. Suggests that the nature of postmodern culture makes image advertising an appropriate external communication strategy for generating stake holder loyalty. Suggests that Narrative Paradigm Theory can identify potential sources of audience conflict by illuminating…

Illustrating a Model-Game-Model Paradigm for Using Human Wargames in Analysis

DTIC Science & Technology

2017-02-01

Working Paper Illustrating a Model- Game -Model Paradigm for Using Human Wargames in Analysis Paul K. Davis RAND National Security Research...paper proposes and illustrates an analysis-centric paradigm (model- game -model or what might be better called model-exercise-model in some cases) for...to involve stakehold- ers in model development from the outset. The model- game -model paradigm was illustrated in an application to crisis planning

Using Epigenetic Therapy to Overcome Chemotherapy Resistance.

PubMed

Strauss, Julius; Figg, William D

2016-01-01

It has been known for decades that as cancer progresses, tumors develop genetic alterations, making them highly prone to developing resistance to therapies. Classically, it has been thought that these acquired genetic changes are fixed. This has led to the paradigm of moving from one cancer therapy to the next while avoiding past therapies. However, emerging data on epigenetic changes during tumor progression and use of epigenetic therapies have shown that epigenetic modifications leading to chemotherapy resistance have the potential to be reversible with epigenetic therapy. In fact, promising clinical data exist that treatment with epigenetic agents can diminish chemotherapy resistance in a number of tumor types including chronic myelogenous leukemia, colorectal, ovarian, lung and breast cancer. The potential for epigenetic-modifying drugs to allow for treatment of resistant disease is exciting and clinical trials have just begun to evaluate this area. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Overcoming the four toughest management challenges. Increase your effectiveness by using situational leadership.

PubMed

Ketchum, S M

1991-01-01

The high-pressure work environment of the clinical laboratory presents significant challenges for managers. Often thrust into supervisory roles without formal management training, laboratory managers must find ways to delegate tasks, mediate conflict, minimize office politics, and build effective teams out of employees who may be quite diverse in their experience levels, motivation levels, and cultural backgrounds. This article explores the concept of situational leadership, which was developed by Ken Blanchard and Paul Hersey, and its applicability within the clinical laboratory. This practical paradigm involves matching one of four distinct management styles to the four development levels of employees. Each leadership style is explained, along with guidelines for giving performance feedback to employees, so that managers can evaluate their own supervisory styles. Finally, step-by-step recommendations for coping with the four management roles of delegator, referee, influencer, and team builder are presented.

Empowered to Contest the Terms of Empowerment? Empowerment and Development in a Transnational Women's Education Projec

ERIC Educational Resources Information Center

Khurshid, Ayesha

2016-01-01

The contemporary paradigm of international development invests in individuals and communities as the main agents of development. In this paradigm, education is presented as the central avenue for individuals and communities to generate resources and networks to empower themselves. Some development and feminist scholars have critiqued this intense…

Developing sustainability: a new metaphor for progress.

PubMed

Bensimon, Cécile M; Benatar, Solomon R

2006-01-01

In this paper, we propose a new model for development, one that transcends the North-South dichotomy and goes beyond a narrow conception of development as an economic process. This model requires a paradigm shift toward a new metaphor that develops sustainability, rather than sustains development. We conclude by defending a 'report card on development' as a means for evaluating how countries perform within this new paradigm.

Negative pressure darwinism: survival of the fittest paradigm.

PubMed

Miller, Michael; Bybordi, Farhad

2009-07-01

The use of negative pressure for wound healing has been based on a set of parameters and devices that until recently were combined into a single paradigm. Despite historical and more recent evidence providing viable alternative considerations, it is only recently that this paradigm and its tenets have come into question. As the understanding of the limits of the current paradigm and specific instances of its benefits and drawbacks are identified, shifts in the paradigm must take place if the therapy is to evolve, develop, and continue to be efficacious. The pertinence of the concept of survival of the fittest is used to explore the need for a paradigm shift in negative pressure wound therapy.

Ancient Ethical Practices of Dualism and Ethical Implications for Future Paradigms in Nursing.

PubMed

Milton, Constance L

2016-07-01

Paradigms contain theoretical structures to guide scientific disciplines. Since ancient times, Cartesian dualism has been a prominent philosophy incorporated in the practice of medicine. The discipline of nursing has continued the body-mind emphasis with similar paradigmatic thinking and theories of nursing that separate body and mind. Future trends for paradigm and nursing theory development are harkening to former ways of thinking. In this article the author discusses the origins of Cartesian dualism and implications for its current usage. The author shall illuminate what it potentially means to engage in dualism in nursing and discuss possible ethical implications for future paradigm and theory development in nursing. © The Author(s) 2016.

The ethics of disclosing genetic diagnosis for Alzheimer's disease: do we need a new paradigm?

PubMed

Arribas-Ayllon, Michael

2011-01-01

Genetic testing for rare Mendelian disorders represents the dominant ethical paradigm in clinical and professional practice. Predictive testing for Huntington's disease is the model against which other kinds of genetic testing are evaluated, including testing for Alzheimer's disease. This paper retraces the historical development of ethical reasoning in relation to predictive genetic testing and reviews a range of ethical, sociological and psychological literature from the 1970s to the present. In the past, ethical reasoning has embodied a distinct style whereby normative principles are developed from a dominant disease exemplar. This reductionist approach to formulating ethical frameworks breaks down in the case of disease susceptibility. Recent developments in the genetics of Alzheimer's disease present a significant case for reconsidering the ethics of disclosing risk for common complex diseases. Disclosing the results of susceptibility testing for Alzheimer's disease has different social, psychological and behavioural consequences. Furthermore, what genetic susceptibility means to individuals and their families is diffuse and often mitigated by other factors and concerns. The ethics of disclosing a genetic diagnosis of susceptibility is contingent on whether professionals accept that probabilistic risk information is in fact 'diagnostic' and it will rely substantially on empirical evidence of how people actually perceive, recall and communicate complex risk information.

Disrupted latent inhibition in individuals at ultra high-risk for developing psychosis.

PubMed

Kraus, Michael; Rapisarda, Attilio; Lam, Max; Thong, Jamie Y J; Lee, Jimmy; Subramaniam, Mythily; Collinson, Simon L; Chong, Siow Ann; Keefe, Richard S E

2016-12-01

The addition of off-the-shelf cognitive measures to established prodromal criteria has resulted in limited improvement in the prediction of conversion to psychosis. Tests that assess cognitive processes central to schizophrenia might better identify those at highest risk. The latent inhibition paradigm assesses a subject's tendency to ignore irrelevant stimuli, a process integral to healthy perceptual and cognitive function that has been hypothesized to be a key deficit underlying the development of schizophrenia. In this study, 142 young people at ultra high-risk for developing psychosis and 105 controls were tested on a within-subject latent inhibition paradigm. Additionally, we later inquired about the strategy that each subject employed to complete the test, and further investigated the relationship between reported strategy and the extent of latent inhibition exhibited. Unlike controls, ultra high-risk subjects did not demonstrate a significant latent inhibition effect. This difference between groups became greater when controlling for strategy. The lack of latent inhibition effect in our ultra high-risk sample suggests that individuals at ultra high-risk for psychosis are impaired in their allocation of attentional resources based on past predictive value of repeated stimuli. This fundamental deficit in the allocation of attention may contribute to the broader array of cognitive impairments and clinical symptoms displayed by individuals at ultra high-risk for psychosis.

Paradigm Shift or Annoying Distraction

PubMed Central

Spallek, H.; O’Donnell, J.; Clayton, M.; Anderson, P.; Krueger, A.

2010-01-01

Web 2.0 technologies, known as social media, social technologies or Web 2.0, have emerged into the mainstream. As they grow, these new technologies have the opportunity to influence the methods and procedures of many fields. This paper focuses on the clinical implications of the growing Web 2.0 technologies. Five developing trends are explored: information channels, augmented reality, location-based mobile social computing, virtual worlds and serious gaming, and collaborative research networks. Each trend is discussed based on their utilization and pattern of use by healthcare providers or healthcare organizations. In addition to explorative research for each trend, a vignette is presented which provides a future example of adoption. Lastly each trend lists several research challenge questions for applied clinical informatics. PMID:23616830

Endoscopic Endonasal Management of Craniopharyngioma.

PubMed

Zacharia, Brad E; Amine, Muhamad; Anand, Vijay; Schwartz, Theodore H

2016-02-01

Craniopharyngioma is a rare clinical entity that poses a significant management challenge given their location and propensity to recur. As part of a minimally disruptive treatment paradigm, the expanded endonasal approach has the potential to improve rates of resection, improve postoperative visual recovery, and minimize surgical morbidity. This article updates the otolaryngologic community on the basic principles and techniques regarding the incorporation of the endoscopic, endonasal approach in the management paradigm of craniopharyngioma. Copyright © 2016 Elsevier Inc. All rights reserved.

Serotonergic hallucinogens and emerging targets for addiction pharmacotherapies.

PubMed

Ross, Stephen

2012-06-01

Only time will tell if serotonergic hallucinogen-assisted psychotherapy treatment paradigms for SUDs will prove to be safe and effective in double-blind, placebo-controlled clinical trials. If they are, they would truly constitute a novel psychopharmacologic-psychosocial treatment paradigm to treat addictive disorders, although the risk of adverse psychological events would have to be controlled through a careful screening process and the risk of misuse of the substances or developing use syndromes would have to be considered, although the overall risk would be low because, as mentioned, SHs are unlike all other drugs of abuse in that they do not appear to produce dependence syndromes. There effects on the NA and DA range from inhibition to slight activation, all this without producing addiction. The ability of these medicinal tools to treat a range of addictive, psychiatric, and existential disorders is remarkable in scope and possibility. They truly represent a potential paradigmatic shift within the field of psychiatry, too interesting to not explore further.

A feasibility study of using biodegradable magnesium alloy in glaucoma drainage device

PubMed Central

Li, Xiang-Ji; Xie, Lin; Pan, Fu-Sheng; Wang, Yong; Liu, Hong; Tang, Yu-Rong; Hutnik, Cindy ML

2018-01-01

Technological advances in glaucoma have challenged the traditional treatment paradigm. Historically incisional surgery has been used in cases of advanced disease and/or uncontrolled intraocular pressures resistant to medical or laser interventions. More recently, perhaps due to advancements in imaging, surgery has been suggested to be beneficial earlier in the treatment paradigm. Despite these trends, surgical manipulation of the tissues and unpredictability of wound healing continue to result in surgical failure. Magnesium is an essential element for human body and plays a critically important role in maintaining the functional and structural integrity of several tissues, including the eye. Due to several of its advantageous properties such as non-toxicity, biodegradability, and high biological compatibility, magnesium alloy has attracted great attention as a novel biomaterial. Biodegradable cardiovascular stents made of magnesium alloy have already been introduced into clinical practice. The purpose of this review is to determine if bioabsorbable magnesium alloys can be utilized as a promising candidate for the development of a new generation of glaucoma surgical assistive devices. PMID:29376002

Diverticular Disease: Traditional and Evolving Paradigms.

PubMed

Lamanna, Lenore; Moran, Patricia E

Diverticular disease includes diverticulosis, which are sac protrusions of the intestinal mucosa, and diverticulitis, inflammation of the diverticula. Diverticular disease is listed as one of the top 10 leading physician diagnoses for gastrointestinal disorders in outpatient clinic visits in the United States. There are several classifications of diverticular disease ranging from asymptomatic diverticulosis to diverticulitis with complications. Several theories are linked to the development of diverticula which includes the physiology of the colon itself, collagen cross-linking, and recently challenged, low-fiber intake. The differential diagnoses of lower abdominal pain in addition to diverticular disease have overlapping signs and symptoms, which can make a diagnosis challenging. Identification of the distinct signs and symptoms of each classification will assist the practitioner in making the correct diagnosis and lead to appropriate management. The findings from recent studies have changed the paradigm of diverticular disease. The purpose of this article is to discuss traditional dogma and evolving concepts in the pathophysiology, prevention, and management of diverticular disease. Practitioners must be knowledgeable about diverticular disease for improved outcomes.

Clinical trials update from the European Society of Cardiology meeting 2014: PARADIGM-HF, CONFIRM-HF, SIGNIFY, atrial fibrillation, beta-blockers and heart failure, and vagal stimulation in heart failure.

PubMed

Clark, Andrew L; Pellicori, Pierpaolo

2014-12-01

This article provides an overview of trials relevant to the pathophysiology, prevention, and treatment of heart failure, presented at the European Society of Cardiology meeting held in Barcelona in autumn 2014. Trials reported here include PARADIGM-HF (LCZ696 versus enalapril in heart failure), CONFIRM-HF (treatment of iron deficiency in heart failure), and SIGNIFY (ivabradine in patients with stable coronary artery disease). In addition, we discuss recent developments in the treatment of atrial fibrillation and the lack of benefit with the use of beta-blockers in these patients. Finally, the article describes recent advances in the use of vagal stimulation in patients with heart failure. © 2014 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology. © 2014 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

Tumor-associated macrophages as a paradigm of macrophage plasticity, diversity, and polarization: lessons and open questions.

PubMed

Mantovani, Alberto; Locati, Massimo

2013-07-01

Macrophages are present in all body compartments, including cancerous tissues, and their functions are profoundly affected by signals from the microenvironment under homeostatic and pathological conditions. Tumor-associated macrophages are a major cellular component of cancer-related inflammation and have served as a paradigm for the plasticity and functional polarization of mononuclear phagocytes. Tumor-associated macrophages can exert dual influence of cancer depending on the activation state, with classically activated (M1) and alternatively activated (M2) cells generally exerting antitumoral and protumoral functions, respectively. These are extremes in a continuum of polarization states in a universe of diversity. Tumor-associated macrophages affect virtually all aspects of tumor tissues, including stem cells, metabolism, angiogenesis, invasion, and metastasis. Progress has been made in defining signaling molecules, transcription factors, epigenetic changes, and repertoire of microRNAs underlying macrophage polarization. Preclinical and early clinical data suggest that macrophages may serve as tools for the development of innovative diagnostic and therapeutic strategies in cancer and chronic nonresolving inflammatory diseases.

Racism: A Symptom of the Narcissistic Personality

PubMed Central

Bell, Carl C.

1980-01-01

Despite the criticism that psychoanalytic models are not applicable to social phenomena, knowledge of the dynamics of narcissistic development aids in understanding a particular kind of racist individual. Specifically, racist attitudes may be indicative of a narcissistic personality disorder or of a regression to primitive narcissistic functioning secondary to environmental forces. The differentiation between the narcissistic racist, the stress-induced racist, and the socially misinformed racist is discussed utilizing clinical paradigms discovered in psychotherapy. Life experiences and religion are discussed as possible aids in the transformation of primary narcissism into secondary narcissism. PMID:7392083

Development of a novel visuomotor integration paradigm by integrating a virtual environment with mobile eye-tracking and motion-capture systems

PubMed Central

Miller, Haylie L.; Bugnariu, Nicoleta; Patterson, Rita M.; Wijayasinghe, Indika; Popa, Dan O.

2018-01-01

Visuomotor integration (VMI), the use of visual information to guide motor planning, execution, and modification, is necessary for a wide range of functional tasks. To comprehensively, quantitatively assess VMI, we developed a paradigm integrating virtual environments, motion-capture, and mobile eye-tracking. Virtual environments enable tasks to be repeatable, naturalistic, and varied in complexity. Mobile eye-tracking and minimally-restricted movement enable observation of natural strategies for interacting with the environment. This paradigm yields a rich dataset that may inform our understanding of VMI in typical and atypical development. PMID:29876370

Using Hermeneutic Phenomenology to Investigate How Experienced Practitioners Learn to Communicate Clinical Reasoning

ERIC Educational Resources Information Center

Ajjawi, Rola; Higgs, Joy

2007-01-01

This paper is primarily targeted at doctoral students and other researchers considering using hermeneutic phenomenology as a research strategy. We present interpretive paradigm research designed to investigate how experienced practitioners learn to communicate their clinical reasoning in professional practice. Twelve experienced physiotherapy…

Memory bias for threatening information in anxiety and anxiety disorders: a meta-analytic review.

PubMed

Mitte, Kristin

2008-11-01

Although some theories suggest that anxious individuals selectively remember threatening stimuli, findings remain contradictory despite a considerable amount of research. A quantitative integration of 165 studies with 9,046 participants (clinical and nonclinical samples) examined whether a memory bias exists and which moderator variables influence its magnitude. Implicit memory bias was investigated in lexical decision/stimulus identification and word-stem completion paradigms; explicit memory bias was investigated in recognition and recall paradigms. Overall, effect sizes showed no significant impact of anxiety on implicit memory and recognition. Analyses indicated a memory bias for recall, whose magnitude depended on experimental study procedures like the encoding procedure or retention interval. Anxiety influenced recollection of previous experiences; anxious individuals favored threat-related information. Across all paradigms, clinical status was not significantly linked to effect sizes, indicating no qualitative difference in information processing between anxiety patients and high-anxious persons. The large discrepancy between study effects in recall and recognition indicates that future research is needed to identify moderator variables for avoidant and preferred remembering.

An Object-Oriented Approach to Writing Computational Electromagnetics Codes

NASA Technical Reports Server (NTRS)

Zimmerman, Martin; Mallasch, Paul G.

1996-01-01

Presently, most computer software development in the Computational Electromagnetics (CEM) community employs the structured programming paradigm, particularly using the Fortran language. Other segments of the software community began switching to an Object-Oriented Programming (OOP) paradigm in recent years to help ease design and development of highly complex codes. This paper examines design of a time-domain numerical analysis CEM code using the OOP paradigm, comparing OOP code and structured programming code in terms of software maintenance, portability, flexibility, and speed.

Integrating medical informatics into the medical undergraduate curriculum.

PubMed

Khonsari, L S; Fabri, P J

1997-01-01

The advent of healthcare reform and the rapid application of new technologies have resulted in a paradigm shift in medical practice. Integrating medical Informatics into the full spectrum of medical education is a viral step toward implementing this new instructional model, a step required for the understanding and practice of modern medicine. We have developed an informatics curriculum, a new educational paradigm, and an intranet-based teaching module which are designed to enhance adult-learning principles, life-long self education, and evidence-based critical thinking. Thirty two, fourth year medical students have participated in a one month, full time, independent study focused on but not limited to four topics: mastering the windows-based environment, understanding hospital based information management systems, developing competence in using the internet/intranet and world wide web/HTML, and experiencing distance communication and TeleVideo networks. Each student has completed a clinically relevant independent study project utilizing technology mastered during the course. This initial curriculum offering was developed in conjunction with faculty from the College of Medicine, College of Engineering, College of Education, College of Business, College of Public Health. Florida Center of Instructional Technology, James A. Haley Veterans Hospital, Moffitt Cancer Center, Tampa General Hospital, GTE, Westshore Walk-in Clinic (paperless office), and the Florida Engineering Education Delivery System. Our second step toward the distributive integration process was the introduction of Medical Informatics to first, second and third year medical students. To date, these efforts have focused on undergraduate medical education. Our next step is to offer workshops in Informatics to college of medicine faculty, to residents in post graduate training programs (GME), and ultimately as a method of distance learning in continuing medical education (CME).

Experience with an online prospective database on adolescent idiopathic scoliosis: development and implementation.

PubMed

Arlet, Vincent; Shilt, Jeffrey; Bersusky, Ernesto; Abel, Mark; Ouellet, Jean Albert; Evans, Davis; Menon, K V; Kandziora, Frank; Shen, Frank; Lamartina, Claudio; Adams, Marc; Reddi, Vasantha

2008-11-01

Considerable variability exists in the surgical treatment and outcomes of adolescent idiopathic scoliosis (AIS). This is due to the lack of evidence-based treatment guidelines and outcome measures. Although clinical trials have been extolled as the highest form of evidence for evaluating treatment efficacy, the disadvantage of cost, time, lack of feasibility, and ethical considerations indicate a need for a new paradigm for evidence based research in this spinal deformity. High quality clinical databases offer an alternative approach for evidence-based research in medicine. So, we developed and established Scolisoft, an international, multidimensional and relational database designed to be a repository of surgical cases for AIS, and an active vehicle for standardized surgical information in a format that would permit qualitative and quantitative research and analysis. Here, we describe and discuss the utility of Scolisoft as a new paradigm for evidence-based research on AIS. Scolisoft was developed using dot.net platform and SQL server from Microsoft. All data is deidentified to protect patient privacy. Scolisoft can be accessed at (www.scolisoft.org). Collection of high quality data on surgical cases of AIS is a priority and processes continue to improve the database quality. The database currently has 67 registered users from 21 countries. To date, Scolisoft has 200 detailed surgical cases with pre, post, and follow up data. Scolisoft provides a structured process and practical information for surgeons to benchmark their treatment methods against other like treatments. Scolisoft is multifaceted and its use extends to education of health care providers in training, patients, ability to mine important data to stimulate research and quality improvement initiatives of healthcare organizations.

Collaborative Approach in the Development of High‐Performance Brain–Computer Interfaces for a Neuroprosthetic Arm: Translation from Animal Models to Human Control

PubMed Central

Collinger, Jennifer L.; Kryger, Michael A.; Barbara, Richard; Betler, Timothy; Bowsher, Kristen; Brown, Elke H. P.; Clanton, Samuel T.; Degenhart, Alan D.; Foldes, Stephen T.; Gaunt, Robert A.; Gyulai, Ferenc E.; Harchick, Elizabeth A.; Harrington, Deborah; Helder, John B.; Hemmes, Timothy; Johannes, Matthew S.; Katyal, Kapil D.; Ling, Geoffrey S. F.; McMorland, Angus J. C.; Palko, Karina; Para, Matthew P.; Scheuermann, Janet; Schwartz, Andrew B.; Skidmore, Elizabeth R.; Solzbacher, Florian; Srikameswaran, Anita V.; Swanson, Dennis P.; Swetz, Scott; Tyler‐Kabara, Elizabeth C.; Velliste, Meel; Wang, Wei; Weber, Douglas J.; Wodlinger, Brian

2013-01-01

Abstract Our research group recently demonstrated that a person with tetraplegia could use a brain–computer interface (BCI) to control a sophisticated anthropomorphic robotic arm with skill and speed approaching that of an able‐bodied person. This multiyear study exemplifies important principles in translating research from foundational theory and animal experiments into a clinical study. We present a roadmap that may serve as an example for other areas of clinical device research as well as an update on study results. Prior to conducting a multiyear clinical trial, years of animal research preceded BCI testing in an epilepsy monitoring unit, and then in a short‐term (28 days) clinical investigation. Scientists and engineers developed the necessary robotic and surgical hardware, software environment, data analysis techniques, and training paradigms. Coordination among researchers, funding institutes, and regulatory bodies ensured that the study would provide valuable scientific information in a safe environment for the study participant. Finally, clinicians from neurosurgery, anesthesiology, physiatry, psychology, and occupational therapy all worked in a multidisciplinary team along with the other researchers to conduct a multiyear BCI clinical study. This teamwork and coordination can be used as a model for others attempting to translate basic science into real‐world clinical situations. PMID:24528900

Geographic Object-Based Image Analysis – Towards a new paradigm

PubMed Central

Blaschke, Thomas; Hay, Geoffrey J.; Kelly, Maggi; Lang, Stefan; Hofmann, Peter; Addink, Elisabeth; Queiroz Feitosa, Raul; van der Meer, Freek; van der Werff, Harald; van Coillie, Frieke; Tiede, Dirk

2014-01-01

The amount of scientific literature on (Geographic) Object-based Image Analysis – GEOBIA has been and still is sharply increasing. These approaches to analysing imagery have antecedents in earlier research on image segmentation and use GIS-like spatial analysis within classification and feature extraction approaches. This article investigates these development and its implications and asks whether or not this is a new paradigm in remote sensing and Geographic Information Science (GIScience). We first discuss several limitations of prevailing per-pixel methods when applied to high resolution images. Then we explore the paradigm concept developed by Kuhn (1962) and discuss whether GEOBIA can be regarded as a paradigm according to this definition. We crystallize core concepts of GEOBIA, including the role of objects, of ontologies and the multiplicity of scales and we discuss how these conceptual developments support important methods in remote sensing such as change detection and accuracy assessment. The ramifications of the different theoretical foundations between the ‘per-pixel paradigm’ and GEOBIA are analysed, as are some of the challenges along this path from pixels, to objects, to geo-intelligence. Based on several paradigm indications as defined by Kuhn and based on an analysis of peer-reviewed scientific literature we conclude that GEOBIA is a new and evolving paradigm. PMID:24623958

Towards precision prevention: Technologies for identifying healthy individuals with high risk of disease.

PubMed

Nagel, Zachary D; Engelward, Bevin P; Brenner, David J; Begley, Thomas J; Sobol, Robert W; Bielas, Jason H; Stambrook, Peter J; Wei, Qingyi; Hu, Jennifer J; Terry, Mary Beth; Dilworth, Caroline; McAllister, Kimberly A; Reinlib, Les; Worth, Leroy; Shaughnessy, Daniel T

2017-08-01

The rise of advanced technologies for characterizing human populations at the molecular level, from sequence to function, is shifting disease prevention paradigms toward personalized strategies. Because minimization of adverse outcomes is a key driver for treatment decisions for diseased populations, developing personalized therapy strategies represent an important dimension of both precision medicine and personalized prevention. In this commentary, we highlight recently developed enabling technologies in the field of DNA damage, DNA repair, and mutagenesis. We propose that omics approaches and functional assays can be integrated into population studies that fuse basic, translational and clinical research with commercial expertise in order to accelerate personalized prevention and treatment of cancer and other diseases linked to aberrant responses to DNA damage. This collaborative approach is generally applicable to efforts to develop data-driven, individualized prevention and treatment strategies for other diseases. We also recommend strategies for maximizing the use of biological samples for epidemiological studies, and for applying emerging technologies to clinical applications. Copyright © 2017 Elsevier B.V. All rights reserved.

Towards precision prevention: Technologies for identifying healthy individuals with high risk of disease

PubMed Central

Nagel, Zachary D.; Engelward, Bevin P.; Brenner, David J.; Begley, Thomas J.; Sobol, Robert W.; Bielas, Jason H.; Stambrook, Peter J.; Wei, Qingyi; Hu, Jennifer J.; Terry, Mary Beth; Dilworth, Caroline; McAllister, Kimberly A.; Reinlib, Les; Worth, Leroy; Shaughnessy, Daniel T.

2018-01-01

The rise of advanced technologies for characterizing human populations at the molecular level, from sequence to function, is shifting disease prevention paradigms toward personalized strategies. Because minimization of adverse outcomes is a key driver for treatment decisions for diseased populations, developing personalized therapy strategies represent an important dimension of both precision medicine and personalized prevention. In this commentary, we highlight recently developed enabling technologies in the field of DNA damage, DNA repair, and mutagenesis. We propose that omics approaches and functional assays can be integrated into population studies that fuse basic, translational and clinical research with commercial expertise in order to accelerate personalized prevention and treatment of cancer and other diseases linked to aberrant responses to DNA damage. This collaborative approach is generally applicable to efforts to develop data-driven, individualized prevention and treatment strategies for other diseases. We also recommend strategies for maximizing the use of biological samples for epidemiological studies, and for applying emerging technologies to clinical applications. PMID:28458064

Laboratory management of cervical intraepithelial neoplasia: proposing a new paradigm.

PubMed

Herfs, Michael; Crum, Christopher P

2013-03-01

Since the discovery of human papillomavirus (HPV) type 16 in early 80s, the link between HPV and cervical cancer has been established with certainty, a function of the discovery and cloning of a range of HPV types associated with both cancer precursors (cervical intraepithelial neoplasia or CIN) and carcinomas and extensive epidemiologic, clinical, pathologic, and experimental data. These accumulated results have culminated in new paradigms of cancer prevention through screening and triage. Despite this, the management of women with CIN is still suboptimal and the overtreatment of these conditions still occurs, largely due to the lack of clarity regarding which precancerous lesions are most likely to progress in grade. Recently, a discrete population of cuboidal cells was discovered at the cervical squamocolumnar junction, the anatomic site where the large majority of HPV-related (pre)neoplastic lesions develop. These cells seem to be embryonic in nature and participate both in benign metaplasias and the initial phase of precancer development. This review summarizes the historical evolution of precursor management, assesses the potential role of this and other discoveries in segregating lower from higher-risk precursors, and examines their potential impact on the management of women with real or potential cervical cancer precursors.

Cue-induced craving for marijuana in cannabis-dependent adults.

PubMed

Lundahl, Leslie H; Johanson, Chris-Ellyn

2011-06-01

Recent interest in the development of medications for treatment of cannabis-use disorders indicates the need for laboratory models to evaluate potential compounds prior to undertaking clinical trials. To investigate whether a cue-reactivity paradigm could induce marijuana craving in cannabis-dependent adults, 16 (eight female) cannabis-dependent and 16 (eight female) cannabis-naïve participants were exposed to neutral and marijuana-related cues, and subsequent changes in mood, self-reported craving, and physiologic function were assessed. Significant Group X cue interactions were found on all three VAS craving indices as well as on the Compulsivity scale of the Marijuana Craving Questionnaire-Brief Form (MCQ-BF). Cannabis-dependent individuals responded to marijuana-related cues with significantly increased reports of marijuana craving compared to neutral cue exposure, although there were no cue-induced changes in any of the physiological measures. There were no significant gender differences on any of the measures. These results indicate that marijuana craving can be induced and assessed in cannabis-dependent, healthy adults within a laboratory setting, and support the need for further research of the cue reactivity paradigm in the development of medications to treat cannabis-use disorders. (PsycINFO Database Record (c) 2011 APA, all rights reserved).

Cue-induced Craving for Marijuana in Cannabis Dependent Adults

PubMed Central

Lundahl, Leslie H.; Johanson, Chris-Ellyn

2016-01-01

Recent interest in the development of medications for treatment of cannabis-use disorders indicates the need for laboratory models to evaluate potential compounds prior to undertaking clinical trials. To investigate whether a cue-reactivity paradigm could induce marijuana craving in cannabis dependent adults, 16 (eight female) cannabis dependent and 16 (eight female) cannabis-naïve participants were exposed to neutral and marijuana-related cues, and subsequent changes in mood, self-reported craving, and physiologic function were assessed. Significant group X cue interactions were found on all three VAS craving indices as well as on the Compulsivity scale of the Marijuana Craving Questionnaire-Brief Form (MCQ-BF). Cannabis dependent individuals responded to marijuana-related cues with significantly increased reports of marijuana craving compared to neutral cue exposure, although there were no cue-induced changes in any of the physiological measures. There were no significant gender differences on any of the measures. These results indicate that marijuana craving can be induced and assessed in cannabis dependent, healthy adults within a laboratory setting, and support the need for further research of the cue reactivity paradigm in the development of medications to treat cannabis-use disorders. PMID:21480734

A Framework for Safe Composition of Heterogeneous SOA Services in a Pervasive Computing Environment with Resource Constraints

ERIC Educational Resources Information Center

Reyes Alamo, Jose M.

2010-01-01

The Service Oriented Computing (SOC) paradigm, defines services as software artifacts whose implementations are separated from their specifications. Application developers rely on services to simplify the design, reduce the development time and cost. Within the SOC paradigm, different Service Oriented Architectures (SOAs) have been developed.…

Clinical Competencies and the Basic Sciences: An Online Case Tutorial Paradigm for Delivery of Integrated Clinical and Basic Science Content

ERIC Educational Resources Information Center

DiLullo, Camille; Morris, Harry J.; Kriebel, Richard M.

2009-01-01

Understanding the relevance of basic science knowledge in the determination of patient assessment, diagnosis, and treatment is critical to good medical practice. One method often used to direct students in the fundamental process of integrating basic science and clinical information is problem-based learning (PBL). The faculty facilitated small…

Advancing Clinical Proteomics via Analysis Based on Biological Complexes: A Tale of Five Paradigms.

PubMed

Goh, Wilson Wen Bin; Wong, Limsoon

2016-09-02

Despite advances in proteomic technologies, idiosyncratic data issues, for example, incomplete coverage and inconsistency, resulting in large data holes, persist. Moreover, because of naïve reliance on statistical testing and its accompanying p values, differential protein signatures identified from such proteomics data have little diagnostic power. Thus, deploying conventional analytics on proteomics data is insufficient for identifying novel drug targets or precise yet sensitive biomarkers. Complex-based analysis is a new analytical approach that has potential to resolve these issues but requires formalization. We categorize complex-based analysis into five method classes or paradigms and propose an even-handed yet comprehensive evaluation rubric based on both simulated and real data. The first four paradigms are well represented in the literature. The fifth and newest paradigm, the network-paired (NP) paradigm, represented by a method called Extremely Small SubNET (ESSNET), dominates in precision-recall and reproducibility, maintains strong performance in small sample sizes, and sensitively detects low-abundance complexes. In contrast, the commonly used over-representation analysis (ORA) and direct-group (DG) test paradigms maintain good overall precision but have severe reproducibility issues. The other two paradigms considered here are the hit-rate and rank-based network analysis paradigms; both of these have good precision-recall and reproducibility, but they do not consider low-abundance complexes. Therefore, given its strong performance, NP/ESSNET may prove to be a useful approach for improving the analytical resolution of proteomics data. Additionally, given its stability, it may also be a powerful new approach toward functional enrichment tests, much like its ORA and DG counterparts.

Aristeia Leadership: A Catalyst for the i[superscript 2]Flex Methodology

ERIC Educational Resources Information Center

Gialamas, Stefanos; Avgerinou, Maria D.

2015-01-01

In response to the global educational reform we have developed a new education paradigm, the Global Morfosis paradigm which has been implemented at the American Community Schools of Athens (ACS Athens) Greece for the past decade. This dynamic paradigm consists of three inseparable, interconnected, and interrelated components: the Educational…

The Development of the Foundations of Modern Pedagogy: Paradigmal and Methodological Aspects of Research

ERIC Educational Resources Information Center

Dmitrenko, ?amara ?.; Lavryk, Tatjana V.; Yaresko, Ekaterina V.

2015-01-01

Changes in the various fields of knowledge influenced the pedagogical science. The article explains the structure of the foundations of modern pedagogy through paradigmal and methodological aspects. Bases of modern pedagogy include complex of paradigms, object and subject of science, general and specific principles, methods and technologies.…

The Question of Work: Adolescent Literature and the Eriksonian Paradigm.

ERIC Educational Resources Information Center

Burgan, Mary

1988-01-01

Suggests that focusing on paradigms of work--the way it is described, together with the thematic implications it embodies--can be useful in teaching literature to young adults. Examines how examples from literature illustrate Erik H. Erikson's paradigm of the psychosocial stages of development in late childhood and adolescence. (MM)

Treatment of Children with Speech Oral Placement Disorders (OPDs): A Paradigm Emerges

ERIC Educational Resources Information Center

Bahr, Diane; Rosenfeld-Johnson, Sara

2010-01-01

Epidemiological research was used to develop the Speech Disorders Classification System (SDCS). The SDCS is an important speech diagnostic paradigm in the field of speech-language pathology. This paradigm could be expanded and refined to also address treatment while meeting the standards of evidence-based practice. The article assists that process…

A Communication Model to Integrate the Request-Response and the Publish-Subscribe Paradigms into Ubiquitous Systems

PubMed Central

Rodríguez-Domínguez, Carlos; Benghazi, Kawtar; Noguera, Manuel; Garrido, José Luis; Rodríguez, María Luisa; Ruiz-López, Tomás

2012-01-01

The Request-Response (RR) paradigm is widely used in ubiquitous systems to exchange information in a secure, reliable and timely manner. Nonetheless, there is also an emerging need for adopting the Publish-Subscribe (PubSub) paradigm in this kind of systems, due to the advantages that this paradigm offers in supporting mobility by means of asynchronous, non-blocking and one-to-many message distribution semantics for event notification. This paper analyzes the strengths and weaknesses of both the RR and PubSub paradigms to support communications in ubiquitous systems and proposes an abstract communication model in order to enable their seamless integration. Thus, developers will be focused on communication semantics and the required quality properties, rather than be concerned about specific communication mechanisms. The aim is to provide developers with abstractions intended to decrease the complexity of integrating different communication paradigms commonly needed in ubiquitous systems. The proposal has been applied to implement a middleware and a real home automation system to show its applicability and benefits. PMID:22969366

Vaccines for emerging infectious diseases: Lessons from MERS coronavirus and Zika virus.

PubMed

Maslow, Joel N

2017-12-02

The past decade and a half has been characterized by numerous emerging infectious diseases. With each new threat, there has been a call for rapid vaccine development. Pathogens such as the Middle East Respiratory Syndrome coronavirus (MERS-CoV) and the Zika virus represent either new viral entities or viruses emergent in new geographic locales and characterized by novel complications. Both serve as paradigms for the global spread that can accompany new pathogens. In this paper, we review the epidemiology and pathogenesis of MERS-CoV and Zika virus with respect to vaccine development. The challenges in vaccine development and the approach to clinical trial design to test vaccine candidates for disease entities with a changing epidemiology are discussed.

Vaccines for emerging infectious diseases: Lessons from MERS coronavirus and Zika virus

PubMed Central

Maslow, Joel N.

2017-01-01

ABSTRACT The past decade and a half has been characterized by numerous emerging infectious diseases. With each new threat, there has been a call for rapid vaccine development. Pathogens such as the Middle East Respiratory Syndrome coronavirus (MERS-CoV) and the Zika virus represent either new viral entities or viruses emergent in new geographic locales and characterized by novel complications. Both serve as paradigms for the global spread that can accompany new pathogens. In this paper, we review the epidemiology and pathogenesis of MERS-CoV and Zika virus with respect to vaccine development. The challenges in vaccine development and the approach to clinical trial design to test vaccine candidates for disease entities with a changing epidemiology are discussed. PMID:28846484

Pharmacological Treatment Effects on Eye Movement Control

ERIC Educational Resources Information Center

Reilly, James L.; Lencer, Rebekka; Bishop, Jeffrey R.; Keedy, Sarah; Sweeney, John A.

2008-01-01

The increasing use of eye movement paradigms to assess the functional integrity of brain systems involved in sensorimotor and cognitive processing in clinical disorders requires greater attention to effects of pharmacological treatments on these systems. This is needed to better differentiate disease and medication effects in clinical samples, to…

Narratives of neoliberalism: 'clinical labour' in context.

PubMed

Parry, Bronwyn

2015-06-01

Cross-border reproductive care has been thrust under the international spotlight by a series of recent scandals. These have prompted calls to develop more robust means of assessing the exploitative potential of such practices and the need for overarching and normative forms of national and international regulation. Allied theorisations of the emergence of forms of clinical labour have cast the outsourcing of reproductive services such as gamete donation and gestational surrogacy as artefacts of a wider neoliberalisation of service provision. These accounts share with many other narratives of neoliberalism a number of key assertions that relate to the presumed organisation of labour relations within this paradigm. This article critically engages with four assumptions implicit in these accounts: that clinical labourers constitute a largely homogeneous underclass of workers; that reproductive labour has been contractualised in ways that disembed it from wider social and communal relations; that contractualisation can provide protection for clinical labour lessening the need for formal regulatory oversight; and that the transnationalisation of reproductive service labour is largely unidirectional and characterised by a dynamic of provision in which 'the rest' services 'the West'. Drawing on the first findings of a large-scale ethnographic research project into assisted reproduction in India I provide evidence to refute these assertions. In so doing the article demonstrates that while the outsourcing and contractualisation of reproductive labour may be embedded in a wider neoliberal paradigm these practices cannot be understood nor their impacts be fully assessed in isolation from their social and cultural contexts. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

fMRI paradigm designing and post-processing tools

PubMed Central

James, Jija S; Rajesh, PG; Chandran, Anuvitha VS; Kesavadas, Chandrasekharan

2014-01-01

In this article, we first review some aspects of functional magnetic resonance imaging (fMRI) paradigm designing for major cognitive functions by using stimulus delivery systems like Cogent, E-Prime, Presentation, etc., along with their technical aspects. We also review the stimulus presentation possibilities (block, event-related) for visual or auditory paradigms and their advantage in both clinical and research setting. The second part mainly focus on various fMRI data post-processing tools such as Statistical Parametric Mapping (SPM) and Brain Voyager, and discuss the particulars of various preprocessing steps involved (realignment, co-registration, normalization, smoothing) in these software and also the statistical analysis principles of General Linear Modeling for final interpretation of a functional activation result. PMID:24851001

Multiscale Modeling in the Clinic: Drug Design and Development

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

Clancy, Colleen E.; An, Gary; Cannon, William R.

A wide range of length and time scales are relevant to pharmacology, especially in drug development, drug design and drug delivery. Therefore, multi-scale computational modeling and simulation methods and paradigms that advance the linkage of phenomena occurring at these multiple scales have become increasingly important. Multi-scale approaches present in silico opportunities to advance laboratory research to bedside clinical applications in pharmaceuticals research. This is achievable through the capability of modeling to reveal phenomena occurring across multiple spatial and temporal scales, which are not otherwise readily accessible to experimentation. The resultant models, when validated, are capable of making testable predictions tomore » guide drug design and delivery. In this review we describe the goals, methods, and opportunities of multi-scale modeling in drug design and development. We demonstrate the impact of multiple scales of modeling in this field. We indicate the common mathematical techniques employed for multi-scale modeling approaches used in pharmacology and present several examples illustrating the current state-of-the-art regarding drug development for: Excitable Systems (Heart); Cancer (Metastasis and Differentiation); Cancer (Angiogenesis and Drug Targeting); Metabolic Disorders; and Inflammation and Sepsis. We conclude with a focus on barriers to successful clinical translation of drug development, drug design and drug delivery multi-scale models.« less

Phytochemicals as Prototypes for Pharmaceutical Leads Towards Drug Development Against Diabetic Cardiomyopathy.

PubMed

Ojha, Shreesh; Kurdi, Amani; Sadek, Bassem; Kaleem, M; Cai, Lu; Kamal, M A; Rajesh, Mohanraj

2016-01-01

Globally diabetes mellitus (DM) is swiftly reaching epidemic proportions and impose major health care and socio-economic challenges that are associated with its complications. DM is considered as the major risk factor for the development of debilitating micro & macro vascular complications. Clinical studies have revealed that development of diabetic cardiomyopathy (DCM) in subjects with diabetes can occur both- dependent and independent of pre-existing increased risk factors such as poor glycemic control, hyperlipidemia, and or hypertension. Therefore, DCM represents as a major challenge for the clinical community for the prompt diagnosis and devising the treatment paradigm to combat the diabetes induced cardiac dysfunction. In Chinese traditional medical practice, heart ailments have been coped with herbal extracts. Phytochemicals bioavailability and pharmacokinetic properties are to yet be established completely in human subjects. However, tremendous progress has been made to isolate, purify the phytochemicals and characterize their effects on mitigating the development of DCM in pre-clinical models. Currently there are no approved drugs available for the treatment of DCM. In this review, we have discussed the progress made in understanding the mechanisms for the phytochemicals cardio-protective actions in the diabetic milieu and their caveats and provide future perspectives for proposing these agents to serve as prototypes in the development of drugs for the management of DCM.

Mapping of Technological Opportunities-Labyrinth Seal Example

NASA Technical Reports Server (NTRS)

Clarke, Dana W., Sr.

2006-01-01

All technological systems evolve based on evolutionary sequences that have repeated throughout history and can be abstracted from the history of technology and patents. These evolutionary sequences represent objective patterns and provide considerable insights that can be used to proactively model future seal concepts. This presentation provides an overview of how to map seal technology into the future using a labyrinth seal example. The mapping process delivers functional descriptions of sequential changes in market/consumer demand, from today s current paradigm to the next major paradigm shift. The future paradigm is developed according to a simple formula: the future paradigm is free of all flaws associated with the current paradigm; it is as far into the future as we can see. Although revolutionary, the vision of the future paradigm is typically not immediately or completely realizable nor is it normally seen as practical. There are several reasons that prevent immediate and complete practical application, such as: 1) Some of the required technological or business resources and knowledge not being available; 2) Availability of other technological or business resources are limited; and/or 3) Some necessary knowledge has not been completely developed. These factors tend to drive the Total Cost of Ownership or Utilization out of an acceptable range and revealing the reasons for the high Total Cost of Ownership or Utilization which provides a clear understanding of research opportunities essential for future developments and defines the current limits of the immediately achievable improvements. The typical roots of high Total Cost of Ownership or Utilization lie in the limited availability or even the absence of essential resources and knowledge necessary for its realization. In order to overcome this obstacle, step-by-step modification of the current paradigm is pursued to evolve from the current situation toward the ideal future, i.e., evolution rather than revolution. A key point is that evolutionary stages are mapped to show step-by-step evolution from the current paradigm to the next major paradigm.

Organizational Dimensions of Innovative Practice: A Qualitative Investigation of the Processes Supporting Innovation Adoption in Outpatient Physical Therapy Practice.

PubMed

Sabus, Carla; Spake, Ellen

2018-01-01

The ability to innovate and adapt practice is a requirement of the progressive healthcare provider. Innovative practice by rehabilitation providers has largely been approached as personal professional development; this study extends that perspective by examining innovation uptake from the organizational level. The varied professions can be expected to have distinct qualities of innovation adoption that reflect professional norms, values, and expectations. The purpose of this qualitative study was to describe the organizational processes of innovation uptake in outpatient physical therapy practice. Through nomination, two outpatient, privately owned physical therapy clinics were identified as innovation practices. Eighteen physical therapists, three owners, and a manager participated in the study. The two clinics served as case studies within a grounded theory approach. Data were collected through observation, unstructured questioning, work flow analysis, focus group sessions, and artifact analysis. Data were analyzed and coded among the investigators. A theoretical model of the innovation adoption process in outpatient physical therapy practice was developed. Elements of the model included (1) change grounded in relationship-centered care, (2) clinic readiness to accept change, and (3) clinic adaptability and resilience. A social paradigm of innovation adoption informed through this research complements the concentration on personal professional development.

A Growing Consensus for Change in Interpretation of Clinical Research Evidence.

PubMed

Wilkerson, Gary B; Denegar, Craig R

2018-03-01

  The paradigm of evidence-based practice (EBP) is well established among the health care professions, but perspectives on the best methods for acquiring, analyzing, appraising, and using research evidence are evolving.   The EBP paradigm has shifted away from a hierarchy of research-evidence quality to recognize that multiple research methods can yield evidence to guide clinicians and patients through a decision-making process. Whereas the "frequentist" approach to data interpretation through hypothesis testing has been the dominant analytical method used by and taught to athletic training students and scholars, this approach is not optimal for integrating evidence into routine clinical practice. Moreover, the dichotomy of rejecting, or failing to reject, a null hypothesis is inconsistent with the Bayesian-like clinical decision-making process that skilled health care providers intuitively use. We propose that data derived from multiple research methods can be best interpreted by reporting a credible lower limit that represents the smallest treatment effect at a specified level of certainty, which should be judged in relation to the smallest effect considered to be clinically meaningful. Such an approach can provide a quantifiable estimate of certainty that an individual patient needs follow-up attention to prevent an adverse outcome or that a meaningful level of therapeutic benefit will be derived from a given intervention.   The practice of athletic training will be influenced by the evolution of the EBP paradigm. Contemporary practice will require clinicians to expand their critical-appraisal skills to effectively integrate the results derived from clinical research into the care of individual patients. Proper interpretation of a credible lower limit value for a magnitude ratio has the potential to increase the likelihood of favorable patient outcomes, thereby advancing the practice of evidence-based athletic training.

Professional Identity Formation and the Clinician-Scientist: A Paradigm for a Clinical Career Combining Two Distinct Disciplines.

PubMed

Rosenblum, Norman D; Kluijtmans, Manon; Ten Cate, Olle

2016-12-01

The clinician-scientist role is critical to the future of health care, and in 2010, the Carnegie Report on Educating Physicians focused attention on the professional identity of practicing clinicians. Although limited in number, published studies on the topic suggest that professional identity is likely a critical factor that determines career sustainability. In contrast to clinicians with a singular focus on clinical practice, clinician-scientists combine two major disciplines, clinical medicine and scientific research, to bridge discovery and clinical care. Despite its importance to advancing medical practice, the clinician-scientist career faced a variety of threats, which have been identified recently by the 2014 National Institutes of Health Physician Scientist Workforce. Yet, professional identity development in this career pathway is poorly understood. This Perspective focuses on the challenges to the clinician-scientist's professional identity and its development. First, the authors identify the particular challenges that arise from the different cultures of clinical care and science and the implications for clinician-scientist professional identity formation. Next, the authors synthesize insights about professional identity development within a dual-discipline career and apply their analysis to a discussion about the implications for clinician-scientist identity formation. Although not purposely developed to address identity formation, the authors highlight those elements within clinician-scientist training and career development programs that may implicitly support identity development. Finally, the authors highlight a need to identify empirically the elements that compose and determine clinician-scientist professional identity and the processes that shape its formation and sustainability.

Why Physics in Medicine?

PubMed

Samei, Ehsan; Grist, Thomas M

2018-05-18

Despite its crucial role in the development of new medical imaging technologies, in clinical practice, physics has primarily been involved in the technical evaluation of technologies. However, this narrow role is no longer adequate. New trajectories in medicine call for a stronger role for physics in the clinic. The movement toward evidence-based, quantitative, and value-based medicine requires physicists to play a more integral role in delivering innovative precision care through the intentional clinical application of physical sciences. There are three aspects of this clinical role: technology assessment based on metrics as they relate to expected clinical performance, optimized use of technologies for patient-centered clinical outcomes, and retrospective analysis of imaging operations to ensure attainment of expectations in terms of quality and variability. These tasks fuel the drive toward high-quality, consistent practice of medical imaging that is patient centered, evidence based, and safe. While this particular article focuses on imaging, this trajectory and paradigm is equally applicable to the multitudes of the applications of physics in medicine. Copyright © 2018 American College of Radiology. Published by Elsevier Inc. All rights reserved.

Ethical and Clinical Considerations at the Intersection of Functional Neuroimaging and Disorders of Consciousness.

PubMed

Byram, Adrian C; Lee, Grace; Owen, Adrian M; Ribary, Urs; Stoessl, A Jon; Townson, Andrea; Illes, Judy

2016-10-01

Recent neuroimaging research on disorders of consciousness provides direct evidence of covert consciousness otherwise not detected clinically in a subset of severely brain-injured patients. These findings have motivated strategic development of binary communication paradigms, from which researchers interpret voluntary modulations in brain activity to glean information about patients' residual cognitive functions and emotions. The discovery of such responsiveness raises ethical and legal issues concerning the exercise of autonomy and capacity for decisionmaking on matters such as healthcare, involvement in research, and end of life. These advances have generated demands for access to the technology against a complex background of continued scientific advancement, questions about just allocation of healthcare resources, and unresolved legal issues. Interviews with professionals whose work is relevant to patients with disorders of consciousness reveal priorities concerning further basic research, legal and policy issues, and clinical considerations.

Commercial landscape of noninvasive prenatal testing in the United States.

PubMed

Agarwal, Ashwin; Sayres, Lauren C; Cho, Mildred K; Cook-Deegan, Robert; Chandrasekharan, Subhashini

2013-06-01

Cell-free fetal DNA-based noninvasive prenatal testing (NIPT) could significantly change the paradigm of prenatal testing and screening. Intellectual property (IP) and commercialization promise to be important components of the emerging debate about clinical implementation of these technologies. We have assembled information about types of testing, prices, turnaround times, and reimbursement of recently launched commercial tests in the United States from the trade press, news articles, and scientific, legal, and business publications. We also describe the patenting and licensing landscape of technologies underlying these tests and ongoing patent litigation in the United States. Finally, we discuss how IP issues may affect clinical translation of NIPT and their potential implications for stakeholders. Fetal medicine professionals (clinicians and researchers), genetic counselors, insurers, regulators, test developers, and patients may be able to use this information to make informed decisions about clinical implementation of current and emerging noninvasive prenatal tests. © 2013 John Wiley & Sons, Ltd.

Commercial Landscape of noninvasive prenatal testing in the United States

PubMed Central

Agarwal, Ashwin; Sayres, Lauren C.; Cho, Mildred K.; Cook-Deegan, Robert; Chandrasekharan, Subhashini

2014-01-01

Cell-free fetal DNA-based noninvasive prenatal testing (NIPT) could significantly change the paradigm of prenatal testing and screening. Intellectual property (IP) and commercialization promise to be important components of the emerging debate about clinical implementation of these technologies. We have assembled information about types of testing, prices, turnaround times and reimbursement of recently launched commercial tests in the United States from the trade press, news articles, and scientific, legal, and business publications. We also describe the patenting and licensing landscape of technologies underlying these tests and ongoing patent litigation in the United States. Finally, we discuss how IP issues may affect clinical translation of NIPT and their potential implications for stakeholders. Fetal medicine professionals (clinicians and researchers), genetic counselors, insurers, regulators, test developers and patients may be able to use this information to make informed decisions about clinical implementation of current and emerging noninvasive prenatal tests. PMID:23686656

Fuzzy Hybrid Deliberative/Reactive Paradigm (FHDRP)

NASA Technical Reports Server (NTRS)

Sarmadi, Hengameth

2004-01-01

This work aims to introduce a new concept for incorporating fuzzy sets in hybrid deliberative/reactive paradigm. After a brief review on basic issues of hybrid paradigm the definition of agent-based fuzzy hybrid paradigm, which enables the agents to proceed and extract their behavior through quantitative numerical and qualitative knowledge and to impose their decision making procedure via fuzzy rule bank, is discussed. Next an example performs a more applied platform for the developed approach and finally an overview of the corresponding agents architecture enhances agents logical framework.

Information processing psychology: A promising paradigm for research in science teaching

NASA Astrophysics Data System (ADS)

Stewart, James H.; Atkin, Julia A.

Three research paradigms, those of Ausubel, Gagné and Piaget, have received a great deal of attention in the literature of science education. In this article a fourth paradigm is presented - an information processing psychology paradigm. The article is composed of two sections. The first section describes a model of memory developed by information processing psychologists. The second section describes how such a model could be used to guide science education research on learning and problem solving.Received: 19 October 1981

Developing critical practice: a South African's perspective.

PubMed

Pillay, M

1998-01-01

The manner in which speech and language therapy (SLT) considers communicating evidence of practice with a multicultural clientele is considered in context of cultural imperialism. A conceptual framework (i.e., the curriculum of practice) developed from a South African study (Pillay 1997), is highlighted for use in understanding, evaluating and communicating evidence of practice with the clientele in focus. The lens (or paradigm) used by SLT to view its curriculum of practice may reveal different stories about the same subject. Given this, the critical paradigm is proffered over that of the empirical-analytical (or 'scientific') and hermeneutic-interpretive types of paradigms. Finally, suggestions regarding the development of critical SLT are discussed.

Translational neuropathic pain research: A clinical perspective.

PubMed

Bouhassira, D; Attal, N

2016-12-03

Neuropathic pain encompasses a broad range of conditions associated with a lesion or disease of the peripheral or central somatosensory system and its prevalence in the general population may be as high as 7-8%. The interest in the pathophysiology of neuropathic pain has increased over the last two decades with an exponential increase in the number of experimental studies. However, despite the hopes raised by scientific discoveries, there has been no rational development of a truly new class of drugs. This situation revealing the limitations of certain experimental models, also results of limitations in clinical research. One of the reasons for the therapeutic difficulties in these patients is probably due to the fact that treatments are used in a uniform fashion whatever the clinical picture, while these syndromes are in fact highly heterogeneous. Clinical advances have recently been made in this field, following the validation of new specific clinical tools and the standardization of quantitative sensory testing paradigms facilitating improvements in the clinical characterization of these syndromes. It has been clearly demonstrated that neuropathic pain is a consistent clinical entity, but it is multidimensional in terms of its clinical expression, with different sensory profiles, potentially reflecting specific pathophysiological mechanisms. This new conceptualization of neuropathic pain should improve the characterization of the responder profiles in clinical trials and provide valuable information for the development of new and more clinically sound translational approaches in experimental models in animals. Copyright © 2016. Published by Elsevier Ltd.

A new learning paradigm: learning using privileged information.

PubMed

Vapnik, Vladimir; Vashist, Akshay

2009-01-01

In the Afterword to the second edition of the book "Estimation of Dependences Based on Empirical Data" by V. Vapnik, an advanced learning paradigm called Learning Using Hidden Information (LUHI) was introduced. This Afterword also suggested an extension of the SVM method (the so called SVM(gamma)+ method) to implement algorithms which address the LUHI paradigm (Vapnik, 1982-2006, Sections 2.4.2 and 2.5.3 of the Afterword). See also (Vapnik, Vashist, & Pavlovitch, 2008, 2009) for further development of the algorithms. In contrast to the existing machine learning paradigm where a teacher does not play an important role, the advanced learning paradigm considers some elements of human teaching. In the new paradigm along with examples, a teacher can provide students with hidden information that exists in explanations, comments, comparisons, and so on. This paper discusses details of the new paradigm and corresponding algorithms, introduces some new algorithms, considers several specific forms of privileged information, demonstrates superiority of the new learning paradigm over the classical learning paradigm when solving practical problems, and discusses general questions related to the new ideas.

Horizon Mission Methodology - A tool for the study of technology innovation and new paradigms

NASA Technical Reports Server (NTRS)

Anderson, John L.

1993-01-01

The Horizon Mission (HM) methodology was developed to provide a means of identifying and evaluating highly innovative, breakthrough technology concepts (BTCs) and for assessing their potential impact on advanced space missions. The methodology is based on identifying new capabilities needed by hypothetical 'horizon' space missions having performance requirements that cannot be met even by extrapolating known space technologies. Normal human evaluation of new ideas such as BTCs appears to be governed (and limited) by 'inner models of reality' defined as paradigms. Thus, new ideas are evaluated by old models. This paper describes the use of the HM Methodology to define possible future paradigms that would provide alternatives to evaluation by current paradigms. The approach is to represent a future paradigm by a set of new BTC-based capabilities - called a paradigm abstract. The paper describes methods of constructing and using the abstracts for evaluating BTCs for space applications and for exploring the concept of paradigms and paradigm shifts as a representation of technology innovation.

Competency-Based Medical Education in the Internal Medicine Clerkship: A Report From the Alliance for Academic Internal Medicine Undergraduate Medical Education Task Force.

PubMed

Fazio, Sara B; Ledford, Cynthia H; Aronowitz, Paul B; Chheda, Shobhina G; Choe, John H; Call, Stephanie A; Gitlin, Scott D; Muntz, Marty; Nixon, L James; Pereira, Anne G; Ragsdale, John W; Stewart, Emily A; Hauer, Karen E

2018-03-01

As medical educators continue to redefine learning and assessment across the continuum, implementation of competency-based medical education in the undergraduate setting has become a focus of many medical schools. While standards of competency have been defined for the graduating student, there is no uniform approach for defining competency expectations for students during their core clerkship year. The authors describe the process by which an Alliance for Academic Internal Medicine task force developed a paradigm for competency-based assessment of students during their inpatient internal medicine (IM) clerkship. Building on work at the resident and fellowship levels, the task force focused on the development of key learning outcomes as defined by entrustable professional activities (EPAs) that were specific to educational experiences on the IM clerkship, as well as identification of high-priority assessment domains. The work was informed by a national survey of clerkship directors.Six key EPAs emerged: generating a differential diagnosis, obtaining a complete and accurate history and physical exam, obtaining focused histories and clinically relevant physical exams, preparing an oral presentation, interpreting the results of basic diagnostic studies, and providing well-organized clinical documentation. A model for assessment was proposed, with descriptors aligned to the scale of supervision and mapped to Accreditation Council for Graduate Medical Education domains of competence. The proposed paradigm offers a standardized template that may be used across IM clerkships, and which would effectively bridge competency evaluation in the clerkship to fourth-year assessment as well as eventual postgraduate training.

Urgent Need for Improved Mental Health Care and a More Collaborative Model of Care

PubMed Central

Lake, James; Turner, Mason Spain

2017-01-01

Current treatments and the dominant model of mental health care do not adequately address the complex challenges of mental illness, which accounts for roughly one-third of adult disability globally. These circumstances call for radical change in the paradigm and practices of mental health care, including improving standards of clinician training, developing new research methods, and re-envisioning current models of mental health care delivery. Because of its dominant position in the US health care marketplace and its commitment to research and innovation, Kaiser Permanente (KP) is strategically positioned to make important contributions that will shape the future of mental health care nationally and globally. This article reviews challenges facing mental health care and proposes an agenda for developing a collaborative care model in primary care settings that incorporates conventional biomedical therapies and complementary and alternative medicine approaches. By moving beyond treatment delivery via telephone and secure video and providing earlier interventions through primary care clinics, KP is shifting the paradigm of mental health care to a collaborative care model focusing on prevention. Recommendations are to expand current practices to include integrative treatment strategies incorporating evidence-based biomedical and complementary and alternative medicine modalities that can be provided to patients using a collaborative care model. Recommendations also are made for an internal research program aimed at investigating the efficacy and cost-effectiveness of promising complementary and alternative medicine and integrative treatments addressing the complex needs of patients with severe psychiatric disorders, many of whom respond poorly to treatments available in KP mental health clinics. PMID:28898197

Assessing Selective Sustained Attention in 3- to 5-Year-Old Children: Evidence from a New Paradigm

ERIC Educational Resources Information Center

Fisher, Anna; Thiessen, Erik; Godwin, Karrie; Kloos, Heidi; Dickerson, John

2013-01-01

Selective sustained attention (SSA) is crucial for higher order cognition. Factors promoting SSA are described as exogenous or endogenous. However, there is little research specifying how these factors interact during development, due largely to the paucity of developmentally appropriate paradigms. We report findings from a novel paradigm designed…

The Global Imperatives for an Education Paradigm Shift.

ERIC Educational Resources Information Center

Bright, Larry K.; And Others

The future role of education is covered in a discussion concerning the shifting of the dominant social paradigm of the United States. It is noted that the paradigm is changing from one that requires social institutions to seek and develop human resources to maintain a position of competitive dominance, to an emerging view of world interdependence.…

Communities of Practice: A Research Paradigm for the Mixed Methods Approach

ERIC Educational Resources Information Center

Denscombe, Martyn

2008-01-01

The mixed methods approach has emerged as a "third paradigm" for social research. It has developed a platform of ideas and practices that are credible and distinctive and that mark the approach out as a viable alternative to quantitative and qualitative paradigms. However, there are also a number of variations and inconsistencies within the mixed…

What's Past Is Prologue: The Evolving Paradigms of Student Affairs

ERIC Educational Resources Information Center

Taylor, Simone Himbeault

2008-01-01

The purpose of this article is to frame--and reframe--the work of student affairs. Evolving paradigms have defined and advanced this work, which is dedicated to total student development and the betterment of society. The article promotes integrative learning as a new framework for student affairs. This paradigm, grounded in theory, research, and…

Rising to the challenges of evidence-based medicine: a way forward for acupuncture.

PubMed

Godwin, Jacob

2014-11-01

Evidence-based medicine offers important opportunities and poses critical challenges to the acupuncture profession. Having a clear understanding of what evidence-based medicine is and what it is not is necessary to understanding how the acupuncture field might benefit by adopting evidence-based medicine as its paradigm. This article discusses the need for the acupuncture field to retool its professional, academic, and clinical apparatuses to produce, critically appraise, and use high-quality scientific evidence in order to develop acupuncture as an evidence-based procedure. Development of evidence-based acupuncture procedures, practice guidelines, and research directives may help acupuncture become a standard therapeutic procedure rather than a complement or alternative to conventional medicine.

Alliance for NanoHealth (ANH) Training Program for the development of future generations of interdisciplinary scientists and collaborative research focused upon the advancement of nanomedicine

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

Gorenstein, David

The objectives of this program are to promote the mission of the Department of Energy (DOE) Science, Technology, Engineering, Math (STEM) Program by recruiting students to science and engineering disciplines with the intent of mentoring and supporting the next generation of scientists; to foster interdisciplinary and collaborative research under the sponsorship of ANH for the discovery and design of nano-based materials and devices with novel structures, functions, and properties; and to prepare a diverse work force of scientists, engineers, and clinicians by utilizing the unique intellectual and physical resources to develop novel nanotechnology paradigms for clinical application.

Object-oriented design of medical imaging software.

PubMed

Ligier, Y; Ratib, O; Logean, M; Girard, C; Perrier, R; Scherrer, J R

1994-01-01

A special software package for interactive display and manipulation of medical images was developed at the University Hospital of Geneva, as part of a hospital wide Picture Archiving and Communication System (PACS). This software package, called Osiris, was especially designed to be easily usable and adaptable to the needs of noncomputer-oriented physicians. The Osiris software has been developed to allow the visualization of medical images obtained from any imaging modality. It provides generic manipulation tools, processing tools, and analysis tools more specific to clinical applications. This software, based on an object-oriented paradigm, is portable and extensible. Osiris is available on two different operating systems: the Unix X-11/OSF-Motif based workstations, and the Macintosh family.

What mental health teams want in their leaders.

PubMed

Corrigan, P W; Garman, A N; Lam, C; Leary, M

1998-11-01

The authors present the findings of the first phase of a 3-year study developing a skills training curriculum for mental health team leaders. A factor model empirically generated from clinical team members was compared to Bass' (1990) Multifactor Model of Leadership. Members of mental health teams generated individual responses to questions about effective leaders. Results from this survey were subsequently administered to a sample of mental health team members. Analysis of these data yielded six factors: Autocratic Leadership, Clear Roles and Goals, Reluctant Leadership, Vision, Diversity Issues, and Supervision. Additional analyses suggest Bass' Multifactor Model offers a useful paradigm for developing a curriculum specific to the needs of mental health team leaders.

The interpersonal relationship in clinical practice. The Barrett-Lennard Relationship Inventory as an assessment instrument.

PubMed

Simmons, J; Roberge, L; Kendrick, S B; Richards, B

1995-03-01

The biomedical model that has long been central to medical practice is gradually being expanded to a broader biopsychosocial model. Relationship-building skills commensurate with the new paradigm need to be understood by educators and taught to medical practitioners. The person-centered, or humanistic, model of psychologist Carl Rogers provides a theoretical approach for the development of effective biopsychosocial relationships. The Barrett-Lennard Relationship Inventory (BLRI) was developed in 1962 as an assessment instrument for the person-centered model. In this article, the person-centered model and the use of the BLRI as an assessment instrument of this model are discussed. Current and potential uses of the BLRI are explored.

Targeted Therapies for Brain Metastases from Breast Cancer.

PubMed

Venur, Vyshak Alva; Leone, José Pablo

2016-09-13

The discovery of various driver pathways and targeted small molecule agents/antibodies have revolutionized the management of metastatic breast cancer. Currently, the major targets of clinical utility in breast cancer include the human epidermal growth factor receptor 2 (HER2) and epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF) receptor, mechanistic target of rapamycin (mTOR) pathway, and the cyclin-dependent kinase 4/6 (CDK-4/6) pathway. Brain metastasis, however, remains a thorn in the flesh, leading to morbidity, neuro-cognitive decline, and interruptions in the management of systemic disease. Approximately 20%-30% of patients with metastatic breast cancer develop brain metastases. Surgery, whole brain radiation therapy, and stereotactic radiosurgery are the traditional treatment options for patients with brain metastases. The therapeutic paradigm is changing due to better understanding of the blood brain barrier and the advent of tyrosine kinase inhibitors and monoclonal antibodies. Several of these agents are in clinical practice and several others are in early stage clinical trials. In this article, we will review the common targetable pathways in the management of breast cancer patients with brain metastases, and the current state of the clinical development of drugs against these pathways.

Discovering Drugs with DNA-Encoded Library Technology: From Concept to Clinic with an Inhibitor of Soluble Epoxide Hydrolase.

PubMed

Belyanskaya, Svetlana L; Ding, Yun; Callahan, James F; Lazaar, Aili L; Israel, David I

2017-05-04

DNA-encoded chemical library technology was developed with the vision of its becoming a transformational platform for drug discovery. The hope was that a new paradigm for the discovery of low-molecular-weight drugs would be enabled by combining the vast molecular diversity achievable with combinatorial chemistry, the information-encoding attributes of DNA, the power of molecular biology, and a streamlined selection-based discovery process. Here, we describe the discovery and early clinical development of GSK2256294, an inhibitor of soluble epoxide hydrolase (sEH, EPHX2), by using encoded-library technology (ELT). GSK2256294 is an orally bioavailable, potent and selective inhibitor of sEH that has a long half life and produced no serious adverse events in a first-time-in-human clinical study. To our knowledge, GSK2256294 is the first molecule discovered from this technology to enter human clinical testing and represents a realization of the vision that DNA-encoded chemical library technology can efficiently yield molecules with favorable properties that can be readily progressed into high-quality drugs. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Precision medicine based on epigenomics: the paradigm of carcinoma of unknown primary.

PubMed

Moran, Sebastián; Martinez-Cardús, Anna; Boussios, Stergios; Esteller, Manel

2017-11-01

Epigenetic alterations are a common hallmark of human cancer. Single epigenetic markers are starting to be incorporated into clinical practice; however, the translational use of these biomarkers has not been validated at the 'omics' level. The identification of the tissue of origin in patients with cancer of unknown primary (CUP) is an example of how epigenomics can be incorporated in clinical settings, addressing an unmet need in the diagnostic and clinical management of these patients. Despite the great diagnostic advances made in the past decade, the use of traditional diagnostic procedures only enables the tissue of origin to be determined in ∼30% of patients with CUP. Thus, development of molecularly guided diagnostic strategies has emerged to complement traditional procedures, thereby improving the clinical management of patients with CUP. In this Review, we present the latest data on strategies using epigenetics and other molecular biomarkers to guide therapeutic decisions involving patients with CUP, and we highlight areas warranting further research to engage the medical community in this unmet need.

Fibromyalgia: harmonizing science with clinical practice considerations.

PubMed

Perrot, Serge; Dickenson, Anthony H; Bennett, Robert M

2008-01-01

This review summarizes the present and emerging knowledge base on the pathophysiology, diagnosis, and management of fibromyalgia. Fibromyalgia is the most common chronic pain syndrome encountered in general medicine and rheumatology. Historically, contemporary concepts of fibromyalgia have evolved in terms of its clinical description and parallel advances in the understanding of its pathophysiology. A generally accepted paradigm postulates that fibromyalgia is the clinical expression of a rheumatologic disorder in which the associated pain is driven primarily by central sensitization and possibly through changes in several neuronal systems but not necessarily reliant on peripheral processes. Several agents, including serotonin-norepinephrine reuptake inhibitors (ie, duloxetine and milnacipran), opioids (ie, tramadol), and the alpha2-delta ligand pregabalin, which recently received U.S. regulatory approval for the treatment of fibromyalgia, have been evaluated in clinical trials, demonstrating benefit in terms of pain reduction and improvement in core symptoms (ie, fatigue and sleep disturbance). The European League Against Rheumatism has developed updated guidelines for the management of fibromyalgia.

The Experiment Factory: Standardizing Behavioral Experiments.

PubMed

Sochat, Vanessa V; Eisenberg, Ian W; Enkavi, A Zeynep; Li, Jamie; Bissett, Patrick G; Poldrack, Russell A

2016-01-01

The administration of behavioral and experimental paradigms for psychology research is hindered by lack of a coordinated effort to develop and deploy standardized paradigms. While several frameworks (Mason and Suri, 2011; McDonnell et al., 2012; de Leeuw, 2015; Lange et al., 2015) have provided infrastructure and methods for individual research groups to develop paradigms, missing is a coordinated effort to develop paradigms linked with a system to easily deploy them. This disorganization leads to redundancy in development, divergent implementations of conceptually identical tasks, disorganized and error-prone code lacking documentation, and difficulty in replication. The ongoing reproducibility crisis in psychology and neuroscience research (Baker, 2015; Open Science Collaboration, 2015) highlights the urgency of this challenge: reproducible research in behavioral psychology is conditional on deployment of equivalent experiments. A large, accessible repository of experiments for researchers to develop collaboratively is most efficiently accomplished through an open source framework. Here we present the Experiment Factory, an open source framework for the development and deployment of web-based experiments. The modular infrastructure includes experiments, virtual machines for local or cloud deployment, and an application to drive these components and provide developers with functions and tools for further extension. We release this infrastructure with a deployment (http://www.expfactory.org) that researchers are currently using to run a set of over 80 standardized web-based experiments on Amazon Mechanical Turk. By providing open source tools for both deployment and development, this novel infrastructure holds promise to bring reproducibility to the administration of experiments, and accelerate scientific progress by providing a shared community resource of psychological paradigms.

The Experiment Factory: Standardizing Behavioral Experiments

PubMed Central

Sochat, Vanessa V.; Eisenberg, Ian W.; Enkavi, A. Zeynep; Li, Jamie; Bissett, Patrick G.; Poldrack, Russell A.

2016-01-01

The administration of behavioral and experimental paradigms for psychology research is hindered by lack of a coordinated effort to develop and deploy standardized paradigms. While several frameworks (Mason and Suri, 2011; McDonnell et al., 2012; de Leeuw, 2015; Lange et al., 2015) have provided infrastructure and methods for individual research groups to develop paradigms, missing is a coordinated effort to develop paradigms linked with a system to easily deploy them. This disorganization leads to redundancy in development, divergent implementations of conceptually identical tasks, disorganized and error-prone code lacking documentation, and difficulty in replication. The ongoing reproducibility crisis in psychology and neuroscience research (Baker, 2015; Open Science Collaboration, 2015) highlights the urgency of this challenge: reproducible research in behavioral psychology is conditional on deployment of equivalent experiments. A large, accessible repository of experiments for researchers to develop collaboratively is most efficiently accomplished through an open source framework. Here we present the Experiment Factory, an open source framework for the development and deployment of web-based experiments. The modular infrastructure includes experiments, virtual machines for local or cloud deployment, and an application to drive these components and provide developers with functions and tools for further extension. We release this infrastructure with a deployment (http://www.expfactory.org) that researchers are currently using to run a set of over 80 standardized web-based experiments on Amazon Mechanical Turk. By providing open source tools for both deployment and development, this novel infrastructure holds promise to bring reproducibility to the administration of experiments, and accelerate scientific progress by providing a shared community resource of psychological paradigms. PMID:27199843

Time for paradigmatic substitution in psychology. What are the alternatives?

PubMed

Kolstad, Arnulf

2010-03-01

This article focuses on the "machine paradigm" in psychology and its consequences for (mis)understanding of human beings. It discusses causes of the mainstream epistemology in Western societies, referring to philosophical traditions, the prestige of some natural sciences and mathematical statistics. It emphasizes how the higher psychological functions develop dialectically from a biological basis and how the brain due to its plasticity changes with mental and physical activity. This makes a causal machine paradigm unfit to describe and explain human psychology and human development. Some concepts for an alternative paradigm are suggested.

Precision Oncology Medicine: The Clinical Relevance of Patient-Specific Biomarkers Used to Optimize Cancer Treatment.

PubMed

Schmidt, Keith T; Chau, Cindy H; Price, Douglas K; Figg, William D

2016-12-01

Precision medicine in oncology is the result of an increasing awareness of patient-specific clinical features coupled with the development of genomic-based diagnostics and targeted therapeutics. Companion diagnostics designed for specific drug-target pairs were the first to widely utilize clinically applicable tumor biomarkers (eg, HER2, EGFR), directing treatment for patients whose tumors exhibit a mutation susceptible to an FDA-approved targeted therapy (eg, trastuzumab, erlotinib). Clinically relevant germline mutations in drug-metabolizing enzymes and transporters (eg, TPMT, DPYD) have been shown to impact drug response, providing a rationale for individualized dosing to optimize treatment. The use of multigene expression-based assays to analyze an array of prognostic biomarkers has been shown to help direct treatment decisions, especially in breast cancer (eg, Oncotype DX). More recently, the use of next-generation sequencing to detect many potential "actionable" cancer molecular alterations is further shifting the 1 gene-1 drug paradigm toward a more comprehensive, multigene approach. Currently, many clinical trials (eg, NCI-MATCH, NCI-MPACT) are assessing novel diagnostic tools with a combination of different targeted therapeutics while also examining tumor biomarkers that were previously unexplored in a variety of cancer histologies. Results from ongoing trials such as the NCI-MATCH will help determine the clinical utility and future development of the precision-medicine approach. © 2016, The American College of Clinical Pharmacology.

Transforming the Activation of Clinical Trials.

PubMed

Watters, Julie T; Pitzen, Jason H; Sanders, Linda J; Bruce, Virginia Nickie M; Cornell, Alissa R; Cseko, Gary C; Grace, Janice S; Kwon, Pamela S; Kukla, Andrea K; Lee, Michael S; Monosmith, Michelle D; Myren, John D; Kottschade, Rebecca S; Shaft, Marc N; Weis, Jennifer Jenny A; Welter, Jane C; Bharucha, Adil E

2018-01-01

The Institute of Medicine and US Food and Drug Administration (FDA) recognize that activating clinical trials in the United States is lengthy and inefficient. Downstream consequences include increased expense, suboptimal accrual, move of clinical trials overseas, and delayed availability of treatments for patients. An in-tandem processing initiative is here highlighted that transformed the activation of clinical trials (TACT), reduced the activation time by 70%, and offers a paradigm for enhanced translational readiness. © 2017 American Society for Clinical Pharmacology and Therapeutics.

Gaze-independent BCI-spelling using rapid serial visual presentation (RSVP).

PubMed

Acqualagna, Laura; Blankertz, Benjamin

2013-05-01

A Brain Computer Interface (BCI) speller is a communication device, which can be used by patients suffering from neurodegenerative diseases to select symbols in a computer application. For patients unable to overtly fixate the target symbol, it is crucial to develop a speller independent of gaze shifts. In the present online study, we investigated rapid serial visual presentation (RSVP) as a paradigm for mental typewriting. We investigated the RSVP speller in three conditions, regarding the Stimulus Onset Asynchrony (SOA) and the use of color features. A vocabulary of 30 symbols was presented one-by-one in a pseudo random sequence at the same location of display. All twelve participants were able to successfully operate the RSVP speller. The results show a mean online spelling rate of 1.43 symb/min and a mean symbol selection accuracy of 94.8% in the best condition. We conclude that the RSVP is a promising paradigm for BCI spelling and its performance is competitive with the fastest gaze-independent spellers in literature. The RSVP speller does not require gaze shifts towards different target locations and can be operated by non-spatial visual attention, therefore it can be considered as a valid paradigm in applications with patients for impaired oculo-motor control. Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Something old, something new and something borrowed: emerging paradigm of insulin-like growth factor type 1 receptor (IGF-1R) signaling regulation.

PubMed

Girnita, Leonard; Worrall, Claire; Takahashi, Shin-Ichiro; Seregard, Stefan; Girnita, Ada

2014-07-01

The insulin-like growth factor type 1 receptor (IGF-1R) plays a key role in the development and progression of cancer; however, therapeutics targeting it have had disappointing results in the clinic. As a receptor tyrosine kinase (RTK), IGF-1R is traditionally described as an ON/OFF system, with ligand stabilizing the ON state and exclusive kinase-dependent signaling activation. Newly added to the traditional model, ubiquitin-mediated receptor downregulation and degradation was originally described as a response to ligand/receptor interaction and thus inseparable from kinase signaling activation. Yet, the classical model has proven over-simplified and insufficient to explain experimental evidence accumulated over the last decade, including kinase-independent signaling, unbalanced signaling, or dissociation between signaling and receptor downregulation. Based on the recent findings that IGF-1R "borrows" components of G-protein coupled receptor (GPCR) signaling, including β-arrestins and G-protein-related kinases, we discuss the emerging paradigm for the IGF-1R as a functional RTK/GPCR hybrid, which integrates the kinase signaling with the IGF-1R canonical GPCR characteristics. The contradictions to the classical IGF-1R signaling concept as well as the design of anti-IGF-1R therapeutics treatment are considered in the light of this paradigm shift and we advocate recognition of IGF-1R as a valid target for cancer treatment.

Δ9-tetrahydrocannabinol (Δ9-THC) administration after neonatal exposure to phencyclidine potentiates schizophrenia-related behavioral phenotypes in mice.

PubMed

Rodríguez, Guadalupe; Neugebauer, Nichole M; Yao, Katherine Lan; Meltzer, Herbert Y; Csernansky, John G; Dong, Hongxin

2017-08-01

The clinical onset of schizophrenia often coincides with cannabis use in adolescents and young adults. However, the neurobiological consequences of this co-morbidity are not well understood. In this study, we examined the effects of Δ9-THC exposure during early adulthood on schizophrenia-related behaviors using a developmental mouse model of schizophrenia. Phencyclidine (PCP) or saline was administered once in neonatal mice (at P7; 10mg/kg). In turn, Δ9-THC or saline was administered sub-acutely later in life to cohorts of animals who had received either PCP or saline (P55-80, 5mg/kg). Mice who were administered PCP alone displayed behavioral changes in the Morris water waze (MWM) and pre-pulse inhibition (PPI) task paradigm that were consistent with schizophrenia-related phenotypes, but not in the locomotor activity or novel object recognition (NOR) task paradigms. Mice who were administered PCP and then received Δ9-THC later in life displayed behavioral changes in the locomotor activity paradigm (p<0.001) that was consistent with a schizophrenia-related phenotype, as well as potentiated changes in the NOR (p<0.01) and MWM (p<0.05) paradigms as compared to mice that received PCP alone. Decreased cortical receptor expression of NMDA receptor 1 subunit (NR1) was observed in mice that received PCP and PCP+Δ9-THC, while mice that received Δ9-THC and PCP+Δ9-THC displayed decreases in CB1 receptor expression. These findings suggest that administration of Δ9-THC during the early adulthood can potentiate the development of schizophrenia-related behavioral phenotypes induced by neonatal exposure to PCP in mice. Copyright © 2017 Elsevier Inc. All rights reserved.

A novel Brain Computer Interface for classification of social joint attention in autism and comparison of 3 experimental setups: A feasibility study.

PubMed

Amaral, Carlos P; Simões, Marco A; Mouga, Susana; Andrade, João; Castelo-Branco, Miguel

2017-10-01

We present a novel virtual-reality P300-based Brain Computer Interface (BCI) paradigm using social cues to direct the focus of attention. We combined interactive immersive virtual-reality (VR) technology with the properties of P300 signals in a training tool which can be used in social attention disorders such as autism spectrum disorder (ASD). We tested the novel social attention training paradigm (P300-based BCI paradigm for rehabilitation of joint-attention skills) in 13 healthy participants, in 3 EEG systems. The more suitable setup was tested online with 4 ASD subjects. Statistical accuracy was assessed based on the detection of P300, using spatial filtering and a Naïve-Bayes classifier. We compared: 1 - g.Mobilab+ (active dry-electrodes, wireless transmission); 2 - g.Nautilus (active electrodes, wireless transmission); 3 - V-Amp with actiCAP Xpress dry-electrodes. Significant statistical classification was achieved in all systems. g.Nautilus proved to be the best performing system in terms of accuracy in the detection of P300, preparation time, speed and reported comfort. Proof of concept tests in ASD participants proved that this setup is feasible for training joint attention skills in ASD. This work provides a unique combination of 'easy-to-use' BCI systems with new technologies such as VR to train joint-attention skills in autism. Our P300 BCI paradigm is feasible for future Phase I/II clinical trials to train joint-attention skills, with successful classification within few trials, online in ASD participants. The g.Nautilus system is the best performing one to use with the developed BCI setup. Copyright © 2017 Elsevier B.V. All rights reserved.

Finding a Way out of the Ethnographic Paradigm Jungle

ERIC Educational Resources Information Center

Roy, Subhadip; Banerjee, Pratyush

2012-01-01

In this paper, an attempt has been made to develop a hybrid ethnographic paradigm, taking the best points from the different approaches of ethnographic research. The pioneering proponents of ethnography differed in their conceptualization of the method, resulting in the development of three distinct schools of thought-holistic, semiotic and…

Staff Development: A Gestalt Paradigm.

ERIC Educational Resources Information Center

Parsons, Michael H.

Hagerstown Junior College, Maryland, has had a staff development program for the past five years. The major components have been evaluated, revised, and integrated into a gestalt paradigm--a total institutional thrust designed to insure that the goals of the college meet the challenges presented by the service area. Each component exists to foster…

Necessary and Irreconcilable Differences: Paradigms within the Field of Reading

ERIC Educational Resources Information Center

Gill, Sharon Ruth

2005-01-01

Thomas Kuhn's ideas of paradigm are discussed and their role in the development of science and their application to the issue of disagreements in the field of reading is examined. Disagreements in the field of reading occur and new theories keep on developing, but they should not be abandoned.

A Technical/Strategic Paradigm for Online Executive Education

ERIC Educational Resources Information Center

Smith, Marlene A.; Keaveney, Susan M.

2017-01-01

This article discusses the development and delivery of online courses for the executive education audience. The goal is to introduce a new framework, the technical/strategic paradigm, that will help educators to identify the pedagogical needs of disparate executive groups and adjust their online course development plans accordingly. We describe…

The state of the art in organizational cognitive neuroscience: the therapeutic gap and possible implications for clinical practice

PubMed Central

Senior, Carl; Lee, Nick

2013-01-01

In the last decade, researchers in the social sciences have increasingly adopted neuroscientific techniques, with the consequent rise of research inspired by neuroscience in disciplines such as economics, marketing, decision sciences, and leadership. In 2007, we introduced the term organizational cognitive neuroscience (OCN), in an attempt to clearly demarcate research carried out in these many areas, and provide an overarching paradigm for research utilizing cognitive neuroscientific methods, theories, and concepts, within the organizational and business research fields. Here we will revisit and further refine the OCN paradigm, and define an approach where we feel the marriage of organizational theory and neuroscience will return even greater dividends in the future and that is within the field of clinical practice. PMID:24367310

Introduction: Science, Sexuality, and Psychotherapy: Shifting Paradigms.

PubMed

Cerbone, Armand R

2017-08-01

This introduction presents an overview of the current issue (73, 8) of Journal of Clinical Psychology: In Session. This issue features a series of articles, with clinical cases, each presented to illustrate the challenges faced by individuals and couples whose sexual and gender identities and expressions do not comport with traditional and cultural norms. These articles also document the challenges to the therapists who treat them. Considered individually, each article underscores the need to recognize the importance of evidence in guiding psychotherapy in cases involving sexuality. The discussions in each article offer recommendations meant to help and guide psychotherapists. Considered collectively, they raise important questions and considerations about shifting paradigms of human sexuality. Implications for assessment and treatment of cases involving sexuality and gender identity are discussed and recommended. © 2017 Wiley Periodicals, Inc.

The state of the art in organizational cognitive neuroscience: the therapeutic gap and possible implications for clinical practice.

PubMed

Senior, Carl; Lee, Nick

2013-01-01

In the last decade, researchers in the social sciences have increasingly adopted neuroscientific techniques, with the consequent rise of research inspired by neuroscience in disciplines such as economics, marketing, decision sciences, and leadership. In 2007, we introduced the term organizational cognitive neuroscience (OCN), in an attempt to clearly demarcate research carried out in these many areas, and provide an overarching paradigm for research utilizing cognitive neuroscientific methods, theories, and concepts, within the organizational and business research fields. Here we will revisit and further refine the OCN paradigm, and define an approach where we feel the marriage of organizational theory and neuroscience will return even greater dividends in the future and that is within the field of clinical practice.

Using the Constructivist Tridimensional Design Model for Online Continuing Education for Health Care Clinical Faculty

ERIC Educational Resources Information Center

Seo, Kay Kyeong-Ju; Engelhard, Chalee

2014-01-01

This article presents a new paradigm for continuing education of Clinical Instructors (CIs): the Constructivist Tridimensional (CTD) model for the design of an online curriculum. Based on problem-based learning, self-regulated learning, and adult learning theory, the CTD model was designed to facilitate interactive, collaborative, and authentic…

Clinical knowledge management: an overview of current understanding.

PubMed

Bali, Rajeev K; Dwivedi, Ashish

2005-01-01

This chapter outlines contributions to a workshop for ICMCC 2005. We details some of the central issues surrounding the incorporation of the Knowledge Management (KM) paradigm for the healthcare and clinical sectors. The complex nature of KM is discussed, together with some essential theories and some contemporary applications of the tools and techniques are presented.

Collaborating across organizational boundaries to improve the quality of care.

PubMed

Plsek, P E

1997-04-01

The paradigm of modern quality management is in wide use in health care. Although much of the initial effort in health care has focused on improving service, administrative, and support processes, many organizations are also using these concepts to improve clinical care. The analysis of data on clinical outcomes has undoubtedly led to many local improvements, but such analysis is inevitably limited by three issues: small samples, lack of detailed knowledge of what others are doing, and paradigm paralysis. These issues can be partially overcome when multiple health care organizations work together on focused clinical quality improvement efforts. Through the use of multiorganizational collaborative groups, literature reviews, expert panels, best-practice conferences, multiorganizational databases, and bench-marking groups, organizations can effectively pool data and learn from the many natural experiments constantly underway in the health care community. This article outlines the key concepts behind such collaborative improvement efforts and describes pioneering work in the application of these techniques in health care. A better understanding and wider use of collaborative improvement efforts may lead to dramatic breakthroughs in clinical outcomes in the coming years.

Redefining cancer: a new paradigm for better and faster treatment innovation.

PubMed

Stewart, David J; Batist, Gerald

2014-01-01

Common cancers may arise from several different mutations, and each causative mutation may require different treatment approaches. There are also several mechanisms by which malignancies may become resistant to therapy, and each mechanism will also require a different therapeutic strategy. Hence, the paradigm of devising therapies based on tumor type is suboptimal. Each common malignancy may now be regarded as a collection of morphologically similar but molecularly distinct orphan diseases, each requiring unique approaches. Current strategies that employ randomized clinical trials (RCTs) in unselected patients carry a high risk of misleading results. Available data suggest that it is reasonable to grant marketing approval for new anticancer agents based solely on high single-agent response rates in small phase I-II studies involving molecularly-defined patient groups where benefit from other therapies is unlikely. This could markedly speed patient access to important therapies while reducing health care costs by slashing drug development costs. Feasible post-approval surveillance procedures could provide ongoing monitoring of drug safety. While assessment of drug combinations would be more complex due to variable contributions of each component, new strategies have been proposed. In addition to savings from more efficient clinical trials methods, it is essential that we also markedly reduce costs of complying with clinical research regulations. Compliance is too cumbersome and expensive, and current regulatory inflexibility markedly slows progress while escalating health care costs. This requires urgent attention. Regulatory approaches intended to enhance safety may instead potentially cost far more life-years than they save by delaying approval of effective therapies. 

Nonalcoholic fatty liver disease: Evolving paradigms

PubMed Central

Lonardo, Amedeo; Nascimbeni, Fabio; Maurantonio, Mauro; Marrazzo, Alessandra; Rinaldi, Luca; Adinolfi, Luigi Elio

2017-01-01

In the last years new evidence has accumulated on nonalcoholic fatty liver disease (NAFLD) challenging the paradigms that had been holding the scene over the previous 30 years. NAFLD has such an epidemic prevalence as to make it impossible to screen general population looking for NAFLD cases. Conversely, focusing on those cohorts of individuals exposed to the highest risk of NAFLD could be a more rational approach. NAFLD, which can be diagnosed with either non-invasive strategies or through liver biopsy, is a pathogenically complex and clinically heterogeneous disease. The existence of metabolic as opposed to genetic-associated disease, notably including ”lean NAFLD” has recently been recognized. Moreover, NAFLD is a systemic condition, featuring metabolic, cardiovascular and (hepatic/extra-hepatic) cancer risk. Among the clinico-laboratory features of NAFLD we discuss hyperuricemia, insulin resistance, atherosclerosis, gallstones, psoriasis and selected endocrine derangements. NAFLD is a precursor of type 2 diabetes (T2D) and metabolic syndrome and progressive liver disease develops in T2D patients in whom the course of disease is worsened by NAFLD. Finally, lifestyle changes and drug treatment options to be implemented in the individual patient are also critically discussed. In conclusion, this review emphasizes the new concepts on clinical and pathogenic heterogeneity of NAFLD, a systemic disorder with a multifactorial pathogenesis and protean clinical manifestations. It is highly prevalent in certain cohorts of individuals who are thus potentially amenable to selective screening strategies, intensive follow-up schedules for early identification of liver-related and extrahepatic complications and in whom earlier and more aggressive treatment schedules should be carried out whenever possible. PMID:29085206

Test-retest reliability of functional connectivity networks during naturalistic fMRI paradigms.

PubMed

Wang, Jiahui; Ren, Yudan; Hu, Xintao; Nguyen, Vinh Thai; Guo, Lei; Han, Junwei; Guo, Christine Cong

2017-04-01

Functional connectivity analysis has become a powerful tool for probing the human brain function and its breakdown in neuropsychiatry disorders. So far, most studies adopted resting-state paradigm to examine functional connectivity networks in the brain, thanks to its low demand and high tolerance that are essential for clinical studies. However, the test-retest reliability of resting-state connectivity measures is moderate, potentially due to its low behavioral constraint. On the other hand, naturalistic neuroimaging paradigms, an emerging approach for cognitive neuroscience with high ecological validity, could potentially improve the reliability of functional connectivity measures. To test this hypothesis, we characterized the test-retest reliability of functional connectivity measures during a natural viewing condition, and benchmarked it against resting-state connectivity measures acquired within the same functional magnetic resonance imaging (fMRI) session. We found that the reliability of connectivity and graph theoretical measures of brain networks is significantly improved during natural viewing conditions over resting-state conditions, with an average increase of almost 50% across various connectivity measures. Not only sensory networks for audio-visual processing become more reliable, higher order brain networks, such as default mode and attention networks, but also appear to show higher reliability during natural viewing. Our results support the use of natural viewing paradigms in estimating functional connectivity of brain networks, and have important implications for clinical application of fMRI. Hum Brain Mapp 38:2226-2241, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

[Treatment of testicular cancer].

PubMed

Droz, Jean-Pierre; Boyle, Helen; Culine, Stéphane; Fizazi, Karim; Fléchon, Aude; Massard, Christophe

2013-12-01

Germ-cell tumours (GCTs) are the most common type of cancer in young men. Since the late 1970s, disseminated GCT have been a paradigm for curable metastatic cancer and metastatic GCTs are highly curable with cisplatin-based chemotherapy followed by surgical resection of residual masses. Patients' prognosis is currently assessed using the International Germ-Cell Consensus Classification (IGCCC) and used to adapt the burden of chemotherapy. Approximately 20% of patients still do not achieve cure after first-line cisplatin-based chemotherapy, and need salvage chemotherapy (high dose or standard dose chemotherapy). Clinical stage I testicular cancer is the most common presentation and different strategies are proposed: adjuvant therapies, surgery or surveillance. During the last three decades, clinical trials and strong international collaborations lead to the development of a consensus in the management of GCTs.

Shared decision making in mental health: the importance for current clinical practice.

PubMed

Alguera-Lara, Victoria; Dowsey, Michelle M; Ride, Jemimah; Kinder, Skye; Castle, David

2017-12-01

We reviewed the literature on shared decision making (regarding treatments in psychiatry), with a view to informing our understanding of the decision making process and the barriers that exist in clinical practice. Narrative review of published English-language articles. After culling, 18 relevant articles were included. Themes identified included models of psychiatric care, benefits for patients, and barriers. There is a paucity of published studies specifically related to antipsychotic medications. Shared decision making is a central part of the recovery paradigm and is of increasing importance in mental health service delivery. The field needs to better understand the basis on which decisions are reached regarding psychiatric treatments. Discrete choice experiments might be useful to inform the development of tools to assist shared decision making in psychiatry.

Perspectives on Emerging/Novel Computing Paradigms and Future Aerospace Workforce Environments

NASA Technical Reports Server (NTRS)

Noor, Ahmed K.

2003-01-01

The accelerating pace of the computing technology development shows no signs of abating. Computing power reaching 100 Tflop/s is likely to be reached by 2004 and Pflop/s (10(exp 15) Flop/s) by 2007. The fundamental physical limits of computation, including information storage limits, communication limits and computation rate limits will likely be reached by the middle of the present millennium. To overcome these limits, novel technologies and new computing paradigms will be developed. An attempt is made in this overview to put the diverse activities related to new computing-paradigms in perspective and to set the stage for the succeeding presentations. The presentation is divided into five parts. In the first part, a brief historical account is given of development of computer and networking technologies. The second part provides brief overviews of the three emerging computing paradigms grid, ubiquitous and autonomic computing. The third part lists future computing alternatives and the characteristics of future computing environment. The fourth part describes future aerospace workforce research, learning and design environments. The fifth part lists the objectives of the workshop and some of the sources of information on future computing paradigms.

Cancer Vaccines: Moving Beyond Current Paradigms

PubMed Central

Schlom, Jeffrey; Arlen, Philip M.; Gulley, James L.

2008-01-01

The field of cancer vaccines is currently in an active state of preclinical and clinical investigations. While no therapeutic cancer vaccine has to date been approved by the FDA, several new paradigms are emerging from recent clinical findings in both the use of combination therapy approaches and, perhaps more importantly, in clinical trial design and endpoint analyses. This paper will review recent clinical trials involving several different cancer vaccines from which data are emerging contrasting classical “tumor response” (RECIST) criteria with “patient response” in the manifestation of increased patient survival post-vaccine therapy. Also described are several strategies in which cancer vaccines can be exploited in combination with other agents and therapeutic modalities that are quite unique when compared with “conventional” combination therapies. This is most likely due to the phenomena that (a) cancer vaccines initiate a dynamic immune process that can be exploited in subsequent therapies, and (b) both radiation and certain chemotherapeutic agents have been shown to alter the phenotype of tumor cells as to render them more susceptible to T-cell–mediated killing. Consequently, evidence is emerging from several studies in which patient cohorts who first receive a cancer vaccine (as contrasted with control cohorts) benefit clinically from subsequent therapies. PMID:17606707

Automatic and Controlled Response Inhibition: Associative Learning in the Go/No-Go and Stop-Signal Paradigms

PubMed Central

Verbruggen, Frederick; Logan, Gordon D.

2008-01-01

In five experiments, the authors examined the development of automatic response inhibition in the go/no-go paradigm and a modified version of the stop-signal paradigm. They hypothesized that automatic response inhibition may develop over practice when stimuli are consistently associated with stopping. All five experiments consisted of a training phase and a test phase in which the stimulus mapping was reversed for a subset of the stimuli. Consistent with the automatic-inhibition hypothesis, the authors found that responding in the test phase was slowed when the stimulus had been consistently associated with stopping in the training phase. In addition, they found that response inhibition benefited from consistent stimulus-stop associations. These findings suggest that response inhibition may rely on the retrieval of stimulus-stop associations after practice with consistent stimulus-stop mappings. Stimulus-stop mapping is typically consistent in the go/no-go paradigm, so automatic inhibition is likely to occur. However, stimulus-stop mapping is typically inconsistent in the stop-signal paradigm, so automatic inhibition is unlikely to occur. Thus, the results suggest that the two paradigms are not equivalent because they allow different kinds of response inhibition. PMID:18999358

A Precision Medicine Initiative for Alzheimer's disease: the road ahead to biomarker-guided integrative disease modeling.

PubMed

Hampel, H; O'Bryant, S E; Durrleman, S; Younesi, E; Rojkova, K; Escott-Price, V; Corvol, J-C; Broich, K; Dubois, B; Lista, S

2017-04-01

After intense scientific exploration and more than a decade of failed trials, Alzheimer's disease (AD) remains a fatal global epidemic. A traditional research and drug development paradigm continues to target heterogeneous late-stage clinically phenotyped patients with single 'magic bullet' drugs. Here, we propose that it is time for a paradigm shift towards the implementation of precision medicine (PM) for enhanced risk screening, detection, treatment, and prevention of AD. The overarching structure of how PM for AD can be achieved will be provided through the convergence of breakthrough technological advances, including big data science, systems biology, genomic sequencing, blood-based biomarkers, integrated disease modeling and P4 medicine. It is hypothesized that deconstructing AD into multiple genetic and biological subsets existing within this heterogeneous target population will provide an effective PM strategy for treating individual patients with the specific agent(s) that are likely to work best based on the specific individual biological make-up. The Alzheimer's Precision Medicine Initiative (APMI) is an international collaboration of leading interdisciplinary clinicians and scientists devoted towards the implementation of PM in Neurology, Psychiatry and Neuroscience. It is hypothesized that successful realization of PM in AD and other neurodegenerative diseases will result in breakthrough therapies, such as in oncology, with optimized safety profiles, better responder rates and treatment responses, particularly through biomarker-guided early preclinical disease-stage clinical trials.

Digital technology in respiratory diseases: Promises, (no) panacea and time for a new paradigm.

PubMed

Pinnock, Hilary; McKinstry, Brian

2016-05-01

In a world where digital technology has revolutionized the way we work, shop and manage our finances it is unsurprising that digital systems are suggested as potential solutions to delivering clinically and cost-effective care for an aging population with one or more long-term conditions. However, recent evidence suggesting that telehealth may not be quite the panacea that was promised, has led to discussions on the mechanisms and role of digital technology in respiratory care. Implementation in rural and remote settings offers significant benefits in terms of convenient access to care, but is contingent on technical and organizational infrastructure. Telemonitoring systems rely on algorithms to detect deterioration and trigger alerts; machine learning may enable telemonitoring of the future to develop personalized systems that are sensitive to clinical status whilst reducing false alerts. By providing access to information, offering convenient and flexible modes of communication and enabling the transfer of monitoring data to support professional assessment, telehealth can support self-management. At present, all too often, expensive 'off the shelf' systems are purchased and given to clinicians to use. It is time for the paradigm to shift. As clinicians we should identify the specific challenges we face in delivering care, and expect flexible systems that can be customized to individual patients' requirements and adapted to our diverse healthcare contexts. © The Author(s) 2016.

An evolving paradigm for the secretory pathway?

PubMed Central

Lippincott-Schwartz, Jennifer

2011-01-01

The paradigm that the secretory pathway consists of a stable endoplasmic reticulum and Golgi apparatus, using discrete transport vesicles to exchange their contents, gained important support from groundbreaking biochemical and genetic studies during the 1980s. However, the subsequent development of new imaging technologies with green fluorescent protein introduced data on dynamic processes not fully accounted for by the paradigm. As a result, we may be seeing an example of how a paradigm is evolving to account for the results of new technologies and their new ways of describing cellular processes. PMID:22039065

The placebo puzzle: examining the discordant space between biomedical science and illness/healing.

PubMed

Pohlman, Shawn; Cibulka, Nancy J; Palmer, Janice L; Lorenz, Rebecca A; SmithBattle, Lee

2013-03-01

The placebo response presents an enigma to biomedical science: how can 'inert' or 'sham' procedures reduce symptoms and produce physiological changes that are comparable to prescribed treatments? In this study, we examine this puzzle by explicating the discordant space between the prevailing biomedical paradigm, which focuses on a technical understanding of diagnosis and treatment, and a broader understanding of illness and healing as relational and embodied. Although biomedical achievements are impressive, the knowledge resulting from this paradigm is limited by its ontological and epistemological assumptions. When the body and world are objectified, illness meanings, therapeutic relationships, and healing practices are dismissed or distorted. In spite of a robust critique of the tenets of biomedicine for guiding practice, the biomedical paradigm retains a tenacious hold on evidence-based medicine and nursing, downplaying our clinical understanding of the sentient body, patients' life-worlds, and illness and healing. In reality, skilled nurses rely on multiple forms of knowledge in providing high-quality care to particular patients. Clinically wise nurses integrate their experience and knowledge of patients' priorities, fears, and illness trajectories along with biomedical findings to make astute judgments and promote health and healing. © 2012 Blackwell Publishing Ltd.

A paradigm for the study of paranoia in the general population: the Prisoner's Dilemma Game.

PubMed

Ellett, Lyn; Allen-Crooks, Rhani; Stevens, Adele; Wildschut, Tim; Chadwick, Paul

2013-01-01

A growing body of research shows that paranoia is common in the general population. We report three studies that examined the Prisoner's Dilemma Game (PDG) as a paradigm for evaluation of non-clinical paranoia. The PDG captures three key qualities that are at the heart of paranoia--it is interpersonal, it concerns threat, and it concerns the perception of others' intentions towards the self. Study 1 (n=175) found that state paranoia was positively associated with selection of the competitive PDG choice. Study 2 (n=111) found that this association was significant only when participants believed they were playing the PDG against another person, and not when playing against a computer. This finding underscores the interpersonal nature of paranoia and the concomitant necessity of studying paranoia in interpersonal context. In Study 3 (n=152), we assessed both trait and state paranoia, and differentiated between distrust- and greed-based competition. Both trait and state paranoia were positively associated with distrust-based competition (but not with greed-based competition). Crucially, we found that the association between trait paranoia and distrust-based competition was fully mediated by state paranoia. The PDG is a promising paradigm for the study of non-clinical paranoia.

Re-reading "Little Hans": Freud's case study and the question of competing paradigms in psychoanalysis.

PubMed

Midgley, Nicholas

2006-01-01

Psychoanalysts have long recognized the complex interaction between clinical data and formal psychoanalytic theories. While clinical data are often used to provide "evidence" for psychoanalytic paradigms, the theoretical model used by the analyst also structures what can and cannot be seen in the data. This delicate interaction between theory and clinical data can be seen in the history of interpretations of Freud's "Analysis of a Phobia in a Five-Year-Old Boy" ("Little Hans"). Freud's himself revised his reading of the case in 1926, after which a number of psychoanalysts--including Melanie Klein, Jacques Lacan, and John Bowlby--reinterpreted the case in the light of their particular models of the mind. These analysts each found "evidence" for their theoretical model within this classic case study, and in doing so they illuminated aspects of the case that had previously been obscured, while also revealing a great deal about the shifting preoccupations of psychoanalysis as a field.

Evolving paradigms in multifocal breast cancer.

PubMed

Salgado, Roberto; Aftimos, Philippe; Sotiriou, Christos; Desmedt, Christine

2015-04-01

The 7th edition of the TNM defines multifocal breast cancer as multiple simultaneous ipsilateral and synchronous breast cancer lesions, provided they are macroscopically distinct and measurable using current traditional pathological and clinical tools. According to the College of American Pathologists (CAP), the characterization of only the largest lesion is considered sufficient, unless the grade and/or histology are different between the lesions. Here, we review three potentially clinically relevant aspects of multifocal breast cancers: first, the importance of a different intrinsic breast cancer subtype of the various lesions; second, the emerging awareness of inter-lesion heterogeneity; and last but not least, the potential introduction of bias in clinical trials due to the unrecognized biological diversity of these cancers. Although the current strategy to assess the lesion with the largest diameter has clearly its advantages in terms of costs and feasibility, this recommendation may not be sustainable in time and might need to be adapted to be compliant with new evolving paradigms in breast cancer. Copyright © 2014 Elsevier Ltd. All rights reserved.

Improving Health Care Workers for Seasonal Influenza Vaccination at University Health System: A Paradigm for Closing the Quality Chasm

PubMed Central

Patterson, Jan E.; Cadena, Jose; Prigmore, Teresa; Bowling, Jason; Ayala, Beth Ann; Kirkman, Leni; Parekh, Amruta; Scepanski, Theresa

2011-01-01

Significant gaps in quality and patient safety in the US health-care system have been identified and were reported in the past decade by the Institute of Medicine. Despite recognition of these gaps in “knowing versus doing,” change in health care is slow and difficult. The quality improvement and clinical safety movement is increasing among US medical centers. Our health science center implemented the UT System Clinical Safety and Effectiveness course, providing project-based teaching of quality-improvement tools and principles of patient safety. A quality-improvement project that increased healthcare workers' influenza vaccination rate by 17.8% from that in 2008 to a rate of 76.6% in 2009 serves as a paradigm of how physicians can lead quality-improvement project teams to narrow the quality chasm (1). Local efforts to narrow the chasm are discussed in the present paper, including inter-professional education in quality improvement and clinical safety. PMID:21686222

The mathematics of cancer: integrating quantitative models.

PubMed

Altrock, Philipp M; Liu, Lin L; Michor, Franziska

2015-12-01

Mathematical modelling approaches have become increasingly abundant in cancer research. The complexity of cancer is well suited to quantitative approaches as it provides challenges and opportunities for new developments. In turn, mathematical modelling contributes to cancer research by helping to elucidate mechanisms and by providing quantitative predictions that can be validated. The recent expansion of quantitative models addresses many questions regarding tumour initiation, progression and metastases as well as intra-tumour heterogeneity, treatment responses and resistance. Mathematical models can complement experimental and clinical studies, but also challenge current paradigms, redefine our understanding of mechanisms driving tumorigenesis and shape future research in cancer biology.

Quest for quality care and patient safety: the case of Singapore

PubMed Central

Lim, M

2004-01-01



 Quality of care in Singapore has seen a paradigm shift from a traditional focus on structural approaches to a broader multidimensional concept which includes the monitoring of clinical indicators and medical errors. Strong political commitment and institutional capacities have been important factors for making the transition. What is still lacking, however, is a culture of rigorous programme evaluation, public involvement, and patient empowerment. Despite these imperfections, Singapore has made considerable strides and its experience may hold lessons for other small developing countries in the common quest for quality care and patient safety. PMID:14757804

Retrograde ejaculation, painful ejaculation and hematospermia

PubMed Central

Parnham, Arie

2016-01-01

Although there has been an increased interest on premature ejaculation in the recent years, our understanding regarding the disorders of retrograde ejaculation, painful ejaculation and hematospermia remain limited. All three of these conditions require a keen clinical acumen and willingness to engage in thinking outside of the standard established treatment paradigm. The development of novel investigational techniques and treatments has led to progress in the management of these conditions symptoms; however, the literature almost uniformly is limited to small series and rare randomised trials. Further investigation and randomised controlled trials are needed for progress in these often challenging cases. PMID:27652230

Adaptation: paradigm for the gut and an academic career.

PubMed

Warner, Brad W

2013-01-01

Adaptation is an important compensatory response to environmental cues resulting in enhanced survival. In the gut, the abrupt loss of intestinal length is characterized by increased rates of enterocyte proliferation and apoptosis and culminates in adaptive villus and crypt growth. In the development of an academic pediatric surgical career, adaptation is also an important compensatory response to survive the ever changing research, clinical, and economic environment. The ability to adapt in both situations is critical for patients and a legacy of pediatric surgical contributions to advance our knowledge of multiple conditions and diseases. Copyright © 2013 Elsevier Inc. All rights reserved.

New Developments in Insomnia Medications of Relevance to Mental Health Disorders.

PubMed

Krystal, Andrew D

2015-12-01

Many insomnia medications with high specificity have become available recently. They provide a window into the clinical effects of modulating specific brain systems and establish a new guiding principal for conceptualizing insomnia medications: "mechanism matters." A new paradigm for insomnia therapy in which specific drugs are selected to target the specific type of sleep difficulty for each patient includes administering specific treatments for patients with insomnia comorbid with particular psychiatric disorders. This article reviews insomnia medications and discusses the implications for optimizing the treatment of insomnia occurring comorbid with psychiatric conditions. Copyright © 2015 Elsevier Inc. All rights reserved.

Interocular suppression in amblyopia for global orientation processing.

PubMed

Zhou, Jiawei; Huang, Pi-Chun; Hess, Robert F

2013-04-22

We developed a dichoptic global orientation coherence paradigm to quantify interocular suppression in amblyopia. This task is biased towards ventral processing and allows comparison with two other techniques-global motion processing, which is more dorsally biased, and binocular phase combination, which most likely reflects striate function. We found a similar pattern for the relationship between coherence threshold and interocular contrast curves (thresholds vs. interocular contrast ratios or TvRs) in our new paradigm compared with those of the previous dichoptic global motion coherence paradigm. The effective contrast ratios at balance point (where the signals from the two eyes have equal weighting) in our new paradigm were larger than those of the dichoptic global motion coherence paradigm but less than those of the binocular phase combination paradigm. The measured effective contrast ratios in the three paradigms were also positively correlated with each other, with the two global coherence paradigms having the highest correlation. We concluded that: (a) The dichoptic global orientation coherence paradigm is effective in quantifying interocular suppression in amblyopia; and (b) Interocular suppression, while sharing a common suppression mechanism at the early stage in the pathway (e.g., striate cortex), may have additional extra-striate contributions that affect both dorsal and ventral streams differentially.

[Background and practical use of the assessment of identity development in adolescence (AIDA)].

PubMed

Birkhölzer, Marc; Goth, Kirstin; Schrobildgen, Christian; Schmeck, Klaus; Schlüter-Müller, Susanne

2015-01-01

A paradigm shift towards early detection and intervention of personality disorders in adolescence to prevent persistent and chronic suffering is currently taking place. Aside further distinct areas of impaired psychosocial integrity, disturbed identity development is seen as one core component of personality disorders. Thus, the detection of early antecedents of impaired identity development is an important step to allow for early intervention. The self-report questionnaire Assessment of Identity Development in Adolescence (AIDA) is a reliable and valid diagnostic instrument to detect disturbed identity development. This questionnaire allows for global assessment of identity and a differentiation in fundamental subdomains as well and distinguishes between identity diffusion on one side and consolidated and stable identity on the other. In clinical practice, it supports the differentiation between severely disturbed identity as the core component of personality disorders and identity crisis or stable identity development that can be found in other mental disorders.

Introduction to the special issue: toward implementing physiological measures in clinical child and adolescent assessments.

PubMed

De Los Reyes, Andres; Aldao, Amelia

2015-01-01

The National Institute of Mental Health recently launched the Research Domain Criteria (RDoC). The RDoC is an initiative to improve classification of mental health concerns by promoting research on the brain mechanisms underlying these concerns, with the ultimate goal of developing interventions that target these brain mechanisms. A key focus of RDoC involves opening new lines of research examining patients' responses on biological measures. The RDoC presents unique challenges to mental health professionals who work with children and adolescents. Indeed, mental health professionals rarely integrate biological measures into clinical assessments. Thus, RDoC's ability to improve patient care rests, in part, on the development of strategies for implementing biological measures within mental health assessments. Further, mental health professionals already carry out comprehensive assessments that frequently yield inconsistent findings. These inconsistencies have historically posed challenges to interpreting research findings as well as assessment outcomes in practice settings. In this introductory article, we review key issues that informed the development of a special issue of articles demonstrating methods for implementing low-cost measures of physiological functioning in clinical child and adolescent assessments. We also outline a conceptual framework, informed by theoretical work on using and interpreting multiple informants' clinical reports (De Los Reyes, Thomas, Goodman, & Kundey, 2013 ), to guide hypothesis testing when using physiological measures within clinical child and adolescent assessments. This special issue and the conceptual model described in this article may open up new lines of research testing paradigms for implementing clinically feasible physiological measures in clinical child and adolescent assessments.

SHAPING A NEW GENERATION OF HISPANIC CLINICAL AND TRANSLATIONAL RESEARCHERS ADDRESSING MINORITY HEALTH AND HEALTH DISPARITIES

PubMed Central

Estape, Estela S.; Segarra, Barbara; Baez, Adriana; Huertas, Aracelis; Diaz, Clemente; Frontera, Walter

2012-01-01

In 2011, research educators face significant challenges. Training programs in Clinical and Translational Research need to develop or enhance their curriculum to comply with new scientific trends and government policies. Curricula must impart the skills and competencies needed to help facilitate the dissemination and transfer of scientific advances at a faster pace than current health policy and practice. Clinical and translational researchers are facing also the need of new paradigms for effective collaboration, and resource sharing while using the best educational models. Both government and public policy makers emphasize addressing the goals of improving health quality and elimination of health disparities. To help achieve this goal, our academic institution is taking an active role and striving to develop an environment that fosters the career development of clinical and translational researchers. Consonant with this vision, in 2002 the University of Puerto Rico, Medical Sciences Campus School of Health Professions and School of Medicine initiated a multidisciplinary post-doctoral Master of Science in Clinical Research focused in training Hispanics who will address minority health and health disparities research. Recently, we proposed a curriculum revision to enhance this commitment in promoting competency-based curricula for clinician-scientists in clinical and translational sciences. The revised program will be a post-doctoral Master of Science in Clinical and Translational Research (MCTR), expanding its outreach by actively engaging in establishing new collaborations and partnerships that will increase our capability to diversify our educational efforts and make significant contributions to help reduce and eliminate the gap in health disparities. PMID:22263296

Developing Competency-Based Advising Practices in Response to Paradigm Shifts in Higher Education

ERIC Educational Resources Information Center

Walters, Giovanna

2016-01-01

Competency-based programs have gained prominence in recent years for two primary reasons. First, more students are seeking ways to apply nonclassroom learning experiences toward a degree. Second, a paradigm shift in higher education encourages postsecondary curriculum developers to accept nonclassroom experiences as demonstrations of skills and…

Developing Cultural Understanding: The Culture Triangle Paradigm in FCS

ERIC Educational Resources Information Center

Sullivan, Deborah A.; Schmidt-Rinehart, Barbara C.; Morris, Nancy A.

2011-01-01

Academic institutions as well as professional organizations are faced with providing their constituents with the knowledge and tools that will enable them to interact with people of other cultures--to be global citizens in both their personal and professional lives. The foreign language profession developed a paradigm that has been effectively…

Toward patient-centered, personalized and personal decision support and knowledge management: a survey.

PubMed

Leong, T-Y

2012-01-01

This paper summarizes the recent trends and highlights the challenges and opportunities in decision support and knowledge management for patient-centered, personalized, and personal health care. The discussions are based on a broad survey of related references, focusing on the most recent publications. Major advances are examined in the areas of i) shared decision making paradigms, ii) continuity of care infrastructures and architectures, iii) human factors and system design approaches, iv) knowledge management innovations, and v) practical deployment and change considerations. Many important initiatives, projects, and plans with promising results have been identified. The common themes focus on supporting the individual patients who are playing an increasing central role in their own care decision processes. New collaborative decision making paradigms and information infrastructures are required to ensure effective continuity of care. Human factors and usability are crucial for the successful development and deployment of the relevant systems, tools, and aids. Advances in personalized medicine can be achieved through integrating genomic, phenotypic and other biological, individual, and population level information, and gaining useful insights from building and analyzing biological and other models at multiple levels of abstraction. Therefore, new Information and Communication Technologies and evaluation approaches are needed to effectively manage the scale and complexity of biomedical and health information, and adapt to the changing nature of clinical decision support. Recent research in decision support and knowledge management combines heterogeneous information and personal data to provide cost-effective, calibrated, personalized support in shared decision making at the point of care. Current and emerging efforts concentrate on developing or extending conventional paradigms, techniques, systems, and architectures for the new predictive, preemptive, and participatory health care model for patient-centered, personalized medicine. There is also an increasing emphasis on managing complexity with changing care models, processes, and settings.

An Economic Evaluation of Sacubitril/Valsartan for Heart Failure Patients in the Netherlands.

PubMed

van der Pol, Simon; Degener, Fabian; Postma, Maarten J; Vemer, Pepijn

2017-03-01

In September 2014, the PARADIGM-HF trial showed the heart failure drug combination sacubitril/valsartan to be superior to enalapril for patients with a reduced ejection fraction. To determine the incremental cost-effectiveness of sacubitril/valsartan compared with enalapril in the Netherlands using the clinical data from the PARADIGM-HF trial. To compare sacubitril/valsartan and enalapril in a cost-effectiveness study, a Markov model was developed using the effectiveness data from the PARADIGM-HF trial. A health care payer's perspective was applied in the economic evaluation. The developed model was used to evaluate the cost-effectiveness for sacubitril/valsartan at different per diem prices. The base-case analysis showed that sacubitril/valsartan can be cost-effective at maximum daily costs of €5.50 and €14.14 considering willingness-to-pay thresholds of €20,000 and €50,000 per quality-adjusted life-year (QALY), respectively. Sensitivity analysis demonstrated the robustness of the model, identifying only the price of sacubitril/valsartan and the mortality within the sacubitril/valsartan group as significant drivers of the cost-effectiveness ratio. Sacubitril/valsartan was cost-effective at a willingness-to-pay threshold of €20,000 per QALY (€50,000 per QALY) in more than 80% of the replications with certainty at the price point of €3 (€10). Sacubitril/valsartan can be considered a cost-effective treatment at a daily price of €5.25. Unless priced lower than enalapril (<€0.045 per day), sacubitril/valsartan is very unlikely to be cost-saving/dominant. Copyright © 2017 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Developing Implantable Neuroprosthetics: a New Model in Pig

PubMed Central

Yin, Ming; Aceros, Juan; Agha, Naubahar; Minxha, Juri; Komar, Jacob; Patterson, William; Bull, Christopher; Nurmikko, Arto

2014-01-01

A new model has been established in the domestic pig for neural prosthetic device development and testing. To this end, we report on a complete neural prosthetic developmental system using a wireless sensor as the implant, a pig as the animal model, and a novel data acquisition paradigm for actuator control. A new type of stereotactic frame with clinically-inspired fixations pins that place the pig brain in standard surgical plane was developed and tested with success during the implantation of the microsystem. The microsystem implanted was an ultralow power (12.5mW) 16-channel intracortical/epicranial device transmitting broadband (40kS/s) data over a wireless infrared telemetric link. Pigs were implanted and neural data was collected over a period of 5 weeks, clearly showing single unit spiking activity. PMID:22254977

Developing implantable neuroprosthetics: a new model in pig.

PubMed

Borton, David; Yin, Ming; Aceros, Juan; Agha, Naubahar; Minxha, Juri; Komar, Jacob; Patterson, William; Bull, Christopher; Nurmikko, Arto

2011-01-01

A new model has been established in the domestic pig for neural prosthetic device development and testing. To this end, we report on a complete neural prosthetic developmental system using a wireless sensor as the implant, a pig as the animal model, and a novel data acquisition paradigm for actuator control. A new type of stereotactic frame with clinically-inspired fixations pins that place the pig brain in standard surgical plane was developed and tested with success during the implantation of the microsystem. The microsystem implanted was an ultra-low power (12.5 mW) 16-channel intracortical/epicranial device transmitting broadband (40 kS/s) data over a wireless infrared telemetric link. Pigs were implanted and neural data was collected over a period of 5 weeks, clearly showing single unit spiking activity.

Developing sustainable software solutions for bioinformatics by the “ Butterfly” paradigm

PubMed Central

Ahmed, Zeeshan; Zeeshan, Saman; Dandekar, Thomas

2014-01-01

Software design and sustainable software engineering are essential for the long-term development of bioinformatics software. Typical challenges in an academic environment are short-term contracts, island solutions, pragmatic approaches and loose documentation. Upcoming new challenges are big data, complex data sets, software compatibility and rapid changes in data representation. Our approach to cope with these challenges consists of iterative intertwined cycles of development (“ Butterfly” paradigm) for key steps in scientific software engineering. User feedback is valued as well as software planning in a sustainable and interoperable way. Tool usage should be easy and intuitive. A middleware supports a user-friendly Graphical User Interface (GUI) as well as a database/tool development independently. We validated the approach of our own software development and compared the different design paradigms in various software solutions. PMID:25383181

Ensuring the Enduring Viability of the Space Science Enterprise: New Questions, New Thinking, New Paradigms

NASA Astrophysics Data System (ADS)

Arenberg, Jonathan; Conti, Alberto; Atkinson, Charles

2017-01-01

Pursuing ground breaking science in a highly cost and funding constrained environment presents new challenges to the development of future space astrophysics missions. Within the conventional cost models for large observatories, executing a flagship “mission after next” appears to be unstainable. To achieve our nation’s space astrophysics ambitions requires new paradigms in system design, development and manufacture. Implementation of this new paradigm requires that the space astrophysics community adopt new answers to a new set of questions. This paper will discuss the origins of these new questions and the steps to their answers.

Building a Common Pediatric Research Terminology for Accelerating Child Health Research

PubMed Central

Bailey, L. Charles; Forrest, Christopher B.; Padula, Michael A.; Hirschfeld, Steven

2014-01-01

Longitudinal observational clinical data on pediatric patients in electronic format is becoming widely available. A new era of multi-institutional data networks that study pediatric diseases and outcomes across disparate health delivery models and care settings are also enabling an innovative collaborative rapid improvement paradigm called the Learning Health System. However, the potential alignment of routine clinical care, observational clinical research, pragmatic clinical trials, and health systems improvement requires a data infrastructure capable of combining information from systems and workflows that historically have been isolated from each other. Removing barriers to integrating and reusing data collected in different settings will permit new opportunities to develop a more complete picture of a patient’s care and to leverage data from related research studies. One key barrier is the lack of a common terminology that provides uniform definitions and descriptions of clinical observations and data. A well-characterized terminology ensures a common meaning and supports data reuse and integration. A common terminology allows studies to build upon previous findings and to reuse data collection tools and data management processes. We present the current state of terminology harmonization and describe a governance structure and mechanism for coordinating the development of a common pediatric research terminology that links to clinical terminologies and can be used to align existing terminologies. By reducing the barriers between clinical care and clinical research, a Learning Health System can leverage and reuse not only its own data resources but also broader extant data resources. PMID:24534404

How Adolescents with Autism Spectrum Disorder (ASD) Spontaneously Attend to Real-World Scenes: Use of a Change Blindness Paradigm

ERIC Educational Resources Information Center

Hochhauser, Michal; Aran, Adi; Grynszpan, Ouriel

2018-01-01

Visual attention of adolescents with autism spectrum disorder (ASD) was assessed using a change blindness paradigm. Twenty-five adolescents with ASD aged 12-18 years and 25 matched typically developing (TD) adolescents viewed 36 pairs of digitized real-world images. Each pair of images was displayed in a "flicker paradigm" whereby a…

The Neurological Basis and Potential Modification of Emotional Intelligence through Affective/Behavioral Training

DTIC Science & Technology

2010-10-01

facial trustworthiness; facial displays of anger) presented subliminally . Furthermore, the responsiveness of these regions to subliminal stimulation ...develop, or program the computerized stimulation paradigms for use during functional neuroimaging (i.e., MJT; BMAT; EFAT). These paradigms will be...programming began on the computerized functional MRI stimulation paradigms using e-prime software. • Quarter #2: Programming of all computerized functional

Towards sustainable traumatic brain injury care systems: healthcare leadership imperatives in Canada.

PubMed

Caro, Denis

2011-01-01

Traumatic brain injuries pose strategic population health challenges in the face of burgeoning clinical demands that continue to tax capital, financial, and social resource capacities. The sustainability of traumatic brain injury care systems depends on paradigmatic shifts in healthcare leadership thinking. In quest for high-performance care and sustained quality of life for traumatic brain injury patients, this article presents a unique paradigm of seven care performance layers and seven health leadership imperatives that together form the paradigm for the systemic sustainability of TBI care systems of the future.

The Primacy of Standards for Paradigm Evaluation: A Rejoinder.

ERIC Educational Resources Information Center

Rowland, Robert C.

1982-01-01

Considers the positions developed by Lichtman and Rohrer and by Ulrich, and then focuses on Zarefsky's indictment of the proposed standards for evaluating debate paradigms. (See CS 705 841-705 844). (PD)

The impact and determinants of the energy paradigm on economic growth in European Union.

PubMed

Andrei, Jean Vasile; Mieila, Mihai; Panait, Mirela

2017-01-01

Contemporary economies are strongly reliant on energy and analyzing the determining factors that trigger the changes in energy paradigm and their impact upon economic growth is a topical research subject. Our contention is that energy paradigm plays a major role in achieving the sustainable development of contemporary economies. In order to prove this the panel data methodology of research was employed, namely four panel unit root tests (LLC, IPS, F-ADF and F-PP) aiming to reveal the connections and relevance among 17 variables denoting energy influence on economic development. Moreover, it was introduced a specific indicator to express energy consumption per capita. Our findings extend the classical approach of the changes in energy paradigm and their impact upon economic growth and offer a comprehensive analysis which surpasses the practices and policy decisions in the field.

Biomarkers and Surrogate Endpoints in Uveitis: The Impact of Quantitative Imaging.

PubMed

Denniston, Alastair K; Keane, Pearse A; Srivastava, Sunil K

2017-05-01

Uveitis is a major cause of sight loss across the world. The reliable assessment of intraocular inflammation in uveitis ('disease activity') is essential in order to score disease severity and response to treatment. In this review, we describe how 'quantitative imaging', the approach of using automated analysis and measurement algorithms across both standard and emerging imaging modalities, can develop objective instrument-based measures of disease activity. This is a narrative review based on searches of the current world literature using terms related to quantitative imaging techniques in uveitis, supplemented by clinical trial registry data, and expert knowledge of surrogate endpoints and outcome measures in ophthalmology. Current measures of disease activity are largely based on subjective clinical estimation, and are relatively insensitive, with poor discrimination and reliability. The development of quantitative imaging in uveitis is most established in the use of optical coherence tomographic (OCT) measurement of central macular thickness (CMT) to measure severity of macular edema (ME). The transformative effect of CMT in clinical assessment of patients with ME provides a paradigm for the development and impact of other forms of quantitative imaging. Quantitative imaging approaches are now being developed and validated for other key inflammatory parameters such as anterior chamber cells, vitreous haze, retinovascular leakage, and chorioretinal infiltrates. As new forms of quantitative imaging in uveitis are proposed, the uveitis community will need to evaluate these tools against the current subjective clinical estimates and reach a new consensus for how disease activity in uveitis should be measured. The development, validation, and adoption of sensitive and discriminatory measures of disease activity is an unmet need that has the potential to transform both drug development and routine clinical care for the patient with uveitis.

The Influence of Context on Residents' Evaluations: Effects of Priming on Clinical Judgment and Affect

ERIC Educational Resources Information Center

Teunissen, P. W.; Stapel, D. A.; Scheele, F.; Scherpbier, A. J. J. A.; Boor, K.; van Diemen-Steenvoorde, J. A. A. M.; van der Vleuten, C. P. M.

2009-01-01

Different lines of research have suggested that context is important in acting and learning in the clinical workplace. It is not clear how contextual information influences residents' constructions of the situations in which they participate. The category accessibility paradigm from social psychology appears to offer an interesting perspective for…

Pharma Success in Product Development—Does Biotechnology Change the Paradigm in Product Development and Attrition.

PubMed

Evens, Ronald P

2016-01-01

The biotechnology segment of the overall biopharma industry has existed for only about 40–45 years, as a driver of new product development. This driving force was initiated with the FDA approval of recombinant human insulin in 1982, originating from the Genentech company. The pharma industry in the early years of 1970s and 1980s engaged with biotechnology companies only to a small extent with their in-licensing of a few recombinant molecules, led by Roche, Eli Lilly, and Johnson and Johnson. However, subsequently and dramatically over the last 25 years, biotechnology has become a primary driver of product and technology innovation and has become a cornerstone in new product development by all biopharma companies. This review demonstrates these evolutionary changes regarding approved products, product pipelines, novelty of the products, FDA approval rates, product sales, financial R&D investments in biotechnology, partnerships, mergers and acquisitions, and patent issues. We now have about 300 biotechnology products approved in USA covering 16 medical disciplines and about 250 indications, with the engagement of 25 pharma companies, along with their biotechnology company innovators and partners. The biotechnology pipeline involves over 1000 molecules in clinical trials, including over 300 molecules associated with the top 10 pharma companies. Product approval rates by the FDA for biotechnology products are over double the rate for drugs. Yes, the R&D paradigm has changed with biotechnology now as one of the major focuses for new product development with novel molecules by the whole biopharma industry.

An Overview of Biofield Devices

PubMed Central

Muehsam, David; Chevalier, Gaétan; Barsotti, Tiffany

2015-01-01

Advances in biophysics, biology, functional genomics, neuroscience, psychology, psychoneuroimmunology, and other fields suggest the existence of a subtle system of “biofield” interactions that organize biological processes from the subatomic, atomic, molecular, cellular, and organismic to the interpersonal and cosmic levels. Biofield interactions may bring about regulation of biochemical, cellular, and neurological processes through means related to electromagnetism, quantum fields, and perhaps other means of modulating biological activity and information flow. The biofield paradigm, in contrast to a reductionist, chemistry-centered viewpoint, emphasizes the informational content of biological processes; biofield interactions are thought to operate in part via low-energy or “subtle” processes such as weak, nonthermal electromagnetic fields (EMFs) or processes potentially related to consciousness and nonlocality. Biofield interactions may also operate through or be reflected in more well-understood informational processes found in electroencephalographic (EEG) and electrocardiographic (ECG) data. Recent advances have led to the development of a wide variety of therapeutic and diagnostic biofield devices, defined as physical instruments best understood from the viewpoint of a biofield paradigm. Here, we provide a broad overview of biofield devices, with emphasis on those devices for which solid, peer-reviewed evidence exists. A subset of these devices, such as those based upon EEG- and ECG-based heart rate variability, function via mechanisms that are well understood and are widely employed in clinical settings. Other device modalities, such a gas discharge visualization and biophoton emission, appear to operate through incompletely understood mechanisms and have unclear clinical significance. Device modes of operation include EMF-light, EMF-heat, EMF-nonthermal, electrical current, vibration and sound, physical and mechanical, intentionality and nonlocality, gas and plasma, and other (mode of operation not well-understood). Methodological issues in device development and interfaces for future interdisciplinary research are discussed. Devices play prominent cultural and scientific roles in our society, and it is likely that device technologies will be one of the most influential access points for the furthering of biofield research and the dissemination of biofield concepts. This developing field of study presents new areas of research that have many important implications for both basic science and clinical medicine. PMID:26665041

An Overview of Biofield Devices.

PubMed

Muehsam, David; Chevalier, Gaétan; Barsotti, Tiffany; Gurfein, Blake T

2015-11-01

Advances in biophysics, biology, functional genomics, neuroscience, psychology, psychoneuroimmunology, and other fields suggest the existence of a subtle system of "biofield" interactions that organize biological processes from the subatomic, atomic, molecular, cellular, and organismic to the interpersonal and cosmic levels. Biofield interactions may bring about regulation of biochemical, cellular, and neurological processes through means related to electromagnetism, quantum fields, and perhaps other means of modulating biological activity and information flow. The biofield paradigm, in contrast to a reductionist, chemistry-centered viewpoint, emphasizes the informational content of biological processes; biofield interactions are thought to operate in part via low-energy or "subtle" processes such as weak, nonthermal electromagnetic fields (EMFs) or processes potentially related to consciousness and nonlocality. Biofield interactions may also operate through or be reflected in more well-understood informational processes found in electroencephalographic (EEG) and electrocardiographic (ECG) data. Recent advances have led to the development of a wide variety of therapeutic and diagnostic biofield devices, defined as physical instruments best understood from the viewpoint of a biofield paradigm. Here, we provide a broad overview of biofield devices, with emphasis on those devices for which solid, peer-reviewed evidence exists. A subset of these devices, such as those based upon EEG- and ECG-based heart rate variability, function via mechanisms that are well understood and are widely employed in clinical settings. Other device modalities, such a gas discharge visualization and biophoton emission, appear to operate through incompletely understood mechanisms and have unclear clinical significance. Device modes of operation include EMF-light, EMF-heat, EMF-nonthermal, electrical current, vibration and sound, physical and mechanical, intentionality and nonlocality, gas and plasma, and other (mode of operation not well-understood). Methodological issues in device development and interfaces for future interdisciplinary research are discussed. Devices play prominent cultural and scientific roles in our society, and it is likely that device technologies will be one of the most influential access points for the furthering of biofield research and the dissemination of biofield concepts. This developing field of study presents new areas of research that have many important implications for both basic science and clinical medicine.

Checkpoint inhibitors in advanced melanoma: effect on the field of immunotherapy.

PubMed

O'reilly, Aine; Larkin, James

2017-07-01

The success of the immune checkpoint inhibitors in melanoma has reinvigorated the field of immunotherapy. Immune checkpoint inhibitors are now the standard of care in multiple cancer types including lung cancer, head and neck cancer, urothelial cancer and renal cell cancer. The field of immunotherapy is currently expanding rapidly and will be a focus of research and development for decades to come. Areas covered: This review covers the early development of immune checkpoint inhibitors and the changes that occurred in the drug development paradigm to facilitate the development of immunotherapy. The review will summarise the areas into which immune checkpoint inhibitors have been adopted and will review the data that supported this. Furthermore, we will discuss future developments in immunotherapy and the current landscape regarding maximising the potential of immunotherapy in clinical practice. Expert commentary: In the author's opinion, the potential of immunotherapy is vast. To date immune checkpoint inhibition has already delivered durable responses in a proportion of patients with cancer types which were previously universally lethal. The future of immunotherapy will rely upon the intelligent application of translational research to clinical practice, such that immunotherapy can be effective for a wider population and maintain its current growth.

Challenges in Developing Novel Treatments for Childhood Disorders: Lessons from Research on Anxiety

PubMed Central

Pine, Daniel S; Helfinstein, Sarah M; Bar-Haim, Yair; Nelson, Eric; Fox, Nathan A

2009-01-01

Alterations in brain development may contribute to chronic mental disorders. Novel treatments targeted toward the early-childhood manifestations of such chronic disorders may provide unique therapeutic opportunities. However, attempts to develop and deliver novel treatments face many challenges. Work on pediatric anxiety disorders illustrates both the inherent challenges as well as the unusual opportunities for therapeutic advances. The present review summarizes three aspects of translational research on pediatric anxiety disorders as the work informs efforts to develop novel interventions. First, the review summarizes data on developmental conceptualizations of anxiety from both basic neuroscience and clinical perspectives. This summary is integrated with a discussion of the two best-established treatments, cognitive behavioral therapy and selective serotonin reuptake inhibitors. Second, the review summarizes work on attention bias to threat, considering implications for both novel treatments and translational research on neural circuitry functional development. This illustrates the manner in which clinical findings inform basic systems neuroscience research. Finally, the review summarizes work in basic science on fear learning, as studied in fear conditioning, consolidation, and extinction paradigms. This summary ends by describing potential novel treatments, illustrating the manner in which basic neuroscience informs therapeutics. PMID:18754004

Translational systems biology using an agent-based approach for dynamic knowledge representation: An evolutionary paradigm for biomedical research.

PubMed

An, Gary C

2010-01-01

The greatest challenge facing the biomedical research community is the effective translation of basic mechanistic knowledge into clinically effective therapeutics. This challenge is most evident in attempts to understand and modulate "systems" processes/disorders, such as sepsis, cancer, and wound healing. Formulating an investigatory strategy for these issues requires the recognition that these are dynamic processes. Representation of the dynamic behavior of biological systems can aid in the investigation of complex pathophysiological processes by augmenting existing discovery procedures by integrating disparate information sources and knowledge. This approach is termed Translational Systems Biology. Focusing on the development of computational models capturing the behavior of mechanistic hypotheses provides a tool that bridges gaps in the understanding of a disease process by visualizing "thought experiments" to fill those gaps. Agent-based modeling is a computational method particularly well suited to the translation of mechanistic knowledge into a computational framework. Utilizing agent-based models as a means of dynamic hypothesis representation will be a vital means of describing, communicating, and integrating community-wide knowledge. The transparent representation of hypotheses in this dynamic fashion can form the basis of "knowledge ecologies," where selection between competing hypotheses will apply an evolutionary paradigm to the development of community knowledge.

Lessons from Toxicology: Developing a 21st-Century Paradigm for Medical Research

PubMed Central

Austin, Christopher P.; Balapure, Anil K.; Birnbaum, Linda S.; Bucher, John R.; Fentem, Julia; Fitzpatrick, Suzanne C.; Fowle, John R.; Kavlock, Robert J.; Kitano, Hiroaki; Lidbury, Brett A.; Muotri, Alysson R.; Peng, Shuang-Qing; Sakharov, Dmitry; Seidle, Troy; Trez, Thales; Tonevitsky, Alexander; van de Stolpe, Anja; Whelan, Maurice; Willett, Catherine

2015-01-01

Summary Biomedical developments in the 21st century provide an unprecedented opportunity to gain a dynamic systems-level and human-specific understanding of the causes and pathophysiologies of disease. This understanding is a vital need, in view of continuing failures in health research, drug discovery, and clinical translation. The full potential of advanced approaches may not be achieved within a 20th-century conceptual framework dominated by animal models. Novel technologies are being integrated into environmental health research and are also applicable to disease research, but these advances need a new medical research and drug discovery paradigm to gain maximal benefits. We suggest a new conceptual framework that repurposes the 21st-century transition underway in toxicology. Human disease should be conceived as resulting from integrated extrinsic and intrinsic causes, with research focused on modern human-specific models to understand disease pathways at multiple biological levels that are analogous to adverse outcome pathways in toxicology. Systems biology tools should be used to integrate and interpret data about disease causation and pathophysiology. Such an approach promises progress in overcoming the current roadblocks to understanding human disease and successful drug discovery and translation. A discourse should begin now to identify and consider the many challenges and questions that need to be solved. PMID:26523530

Auditory perception and attention as reflected by the brain event-related potentials in children with Asperger syndrome.

PubMed

Lepistö, T; Silokallio, S; Nieminen-von Wendt, T; Alku, P; Näätänen, R; Kujala, T

2006-10-01

Language development is delayed and deviant in individuals with autism, but proceeds quite normally in those with Asperger syndrome (AS). We investigated auditory-discrimination and orienting in children with AS using an event-related potential (ERP) paradigm that was previously applied to children with autism. ERPs were measured to pitch, duration, and phonetic changes in vowels and to corresponding changes in non-speech sounds. Active sound discrimination was evaluated with a sound-identification task. The mismatch negativity (MMN), indexing sound-discrimination accuracy, showed right-hemisphere dominance in the AS group, but not in the controls. Furthermore, the children with AS had diminished MMN-amplitudes and decreased hit rates for duration changes. In contrast, their MMN to speech pitch changes was parietally enhanced. The P3a, reflecting involuntary orienting to changes, was diminished in the children with AS for speech pitch and phoneme changes, but not for the corresponding non-speech changes. The children with AS differ from controls with respect to their sound-discrimination and orienting abilities. The results of the children with AS are relatively similar to those earlier obtained from children with autism using the same paradigm, although these clinical groups differ markedly in their language development.

Effects of buspirone and the dopamine D3 receptor compound PG619 on cocaine and methamphetamine self-administration in rhesus monkeys using a food-drug choice paradigm.

PubMed

John, William S; Banala, Ashwini K; Newman, Amy H; Nader, Michael A

2015-04-01

The dopamine (DA) D2 and D3 receptors have been associated with cocaine abuse. A recent study with the D3 receptor (D3R) partial agonist PG619 found that it attenuated cocaine-induced reinstatement and the D2-like receptor antagonist buspirone has shown positive outcomes in two studies of cocaine abuse in monkeys. However, a recent clinical trial indicated that buspirone did not improve abstinence in treatment-seeking cocaine abusers. The objective of the study was to examine PG619 and buspirone under a food-drug choice paradigm in order to better model the clinical findings. In addition, we extended the characterization of both compounds to include methamphetamine (MA) self-administration (SA). Six adult male rhesus monkeys were trained to respond under a concurrent food (1.0-g pellets) and drug (0.01-0.3 mg/kg/injection cocaine or MA) choice paradigm in which complete SA dose-response curves were determined each session (N = 3/group). Monkeys received 5 days of treatment with either PG619 (0.1-3.0 mg/kg, i.v.) or buspirone (0.01-1.0 mg/kg, i.m.). In a follow-up study, the SA doses were reduced (0.003-0.1 mg/kg/injection) to increase reinforcement frequency and buspirone was retested. PG619 did not affect cocaine or MA choice, while buspirone increased low-dose cocaine choice. Changing the SA doses increased the number of reinforcers received each session, but buspirone did not decrease drug choice. Consistent with clinical findings, these results do not support the use of buspirone for psychostimulant abuse and suggest that food-drug choice paradigms may have greater predictive validity than the use of other schedules of reinforcement.

[The nurse answers for health in social inequalities: the development of the nursing critical paradigm.].

PubMed

Rocco, Gennaro; Stievano, Alessandro

2007-01-01

Until the early Eighties, critical social theory as a philosophical orientation informing nursing science, theory development and practice did not exist. Interest on this topic began to arise only after the mid-Eighties. In fact, nursing scholars questioned the validity of empiricism as the historical foundation for nursing science and the limitations of interpretivism in strengthening nursing knowledge, and thus started to focus on the lack of epistemological perspectives in nursing, giving particular prominence to the peculiar social, political, historical and economic conditions involving those who needed nursing care. The theoretical reflection began to develop, like the empirical paradigm, the post-positivist paradigm and, later, the interpretative paradigm, expanded thanks to the early works by Martha Rogers and Rosemarie Rizzo Parse, were seen as unable to address issues related to power inequities, structural constraints and oppression suffered by vulnerable groups such as the homeless, mental health individuals, people affected by HIV+ and other infectious diseases, unemployed, etc.. Empiricism and interpretative paradigms did not manage to bridge the gap between theory and praxis, and a new theoretical and philosophical approach gradually gained ground. This paradigm, based on critical social theory, was developed by distinguished scholars and intellectuals, such as Max Horkheimer, Theodor Adorno, Herbert Marcuse of the Frankfurt School in the Thirties, and, in recent years, by Giddens, Bourdieu, Foucault, Habermas. On this social field the first works of Allen, Thompson, Stevens, Campbell and Bunting, Kendall, allowed to work out a new paradigmatic nursing approach that would have predicted the employment of the critical theory for particular nursing aspects, as a conceptual framework for nursing education, as a paradigm to carry out participatory action-research and for the development of the discipline. The purpose of this article was to describe this new paradigmatic nursing approach. In this way, we hope to give emphasis to the epistemological debate that should characterize a discipline that has undertaken by now, also in Italy, the characteristics of a scientific and a fully epistemological validity.

The Senses of Agency and Ownership: A Review.

PubMed

Braun, Niclas; Debener, Stefan; Spychala, Nadine; Bongartz, Edith; Sörös, Peter; Müller, Helge H O; Philipsen, Alexandra

2018-01-01

Usually, we do not question that we possess a body and act upon the world. This pre-reflective awareness of being a bodily and agentive self can, however, be disrupted by different clinical conditions. Whereas sense of ownership (SoO) describes the feeling of mineness toward one's own body parts, feelings or thoughts, sense of agency (SoA) refers to the experience of initiating and controlling an action. Although SoA and SoO naturally coincide, both experiences can also be made in isolation. By using many different experimental paradigms, both experiences have been extensively studied over the last years. This review introduces both concepts, with a special focus also onto their interplay. First, current experimental paradigms, results and neurocognitive theories about both concepts will be presented and then their clinical and therapeutic relevance is discussed.

The Senses of Agency and Ownership: A Review

PubMed Central

Braun, Niclas; Debener, Stefan; Spychala, Nadine; Bongartz, Edith; Sörös, Peter; Müller, Helge H. O.; Philipsen, Alexandra

2018-01-01

Usually, we do not question that we possess a body and act upon the world. This pre-reflective awareness of being a bodily and agentive self can, however, be disrupted by different clinical conditions. Whereas sense of ownership (SoO) describes the feeling of mineness toward one’s own body parts, feelings or thoughts, sense of agency (SoA) refers to the experience of initiating and controlling an action. Although SoA and SoO naturally coincide, both experiences can also be made in isolation. By using many different experimental paradigms, both experiences have been extensively studied over the last years. This review introduces both concepts, with a special focus also onto their interplay. First, current experimental paradigms, results and neurocognitive theories about both concepts will be presented and then their clinical and therapeutic relevance is discussed. PMID:29713301