How Stuttering Develops: The Multifactorial Dynamic Pathways Theory.

PubMed

Smith, Anne; Weber, Christine

2017-09-18

We advanced a multifactorial, dynamic account of the complex, nonlinear interactions of motor, linguistic, and emotional factors contributing to the development of stuttering. Our purpose here is to update our account as the multifactorial dynamic pathways theory. We review evidence related to how stuttering develops, including genetic/epigenetic factors; motor, linguistic, and emotional features; and advances in neuroimaging studies. We update evidence for our earlier claim: Although stuttering ultimately reflects impairment in speech sensorimotor processes, its course over the life span is strongly conditioned by linguistic and emotional factors. Our current account places primary emphasis on the dynamic developmental context in which stuttering emerges and follows its course during the preschool years. Rapid changes in many neurobehavioral systems are ongoing, and critical interactions among these systems likely play a major role in determining persistence of or recovery from stuttering. Stuttering, or childhood onset fluency disorder (Diagnostic and Statistical Manual of Mental Disorders, 5th edition; American Psychiatric Association [APA], 2013), is a neurodevelopmental disorder that begins when neural networks supporting speech, language, and emotional functions are rapidly developing. The multifactorial dynamic pathways theory motivates experimental and clinical work to determine the specific factors that contribute to each child's pathway to the diagnosis of stuttering and those most likely to promote recovery.

What factors influence community-dwelling older people’s intent to undertake multifactorial fall prevention programs?

PubMed Central

Hill, Keith D; Day, Lesley; Haines, Terry P

2014-01-01

Purpose To investigate previous, current, or planned participation in, and perceptions toward, multifactorial fall prevention programs such as those delivered through a falls clinic in the community setting, and to identify factors influencing older people’s intent to undertake these interventions. Design and methods Community-dwelling people aged >70 years completed a telephone survey. Participants were randomly selected from an electronic residential telephone listing, but purposeful sampling was used to include equal numbers with and without common chronic health conditions associated with fall-related hospitalization. The survey included scenarios for fall prevention interventions, including assessment/multifactorial interventions, such as those delivered through a falls clinic. Participants were asked about previous exposure to, or intent to participate in, the interventions. A path model analysis was used to identify factors associated with intent to participate in assessment/multifactorial interventions. Results Thirty of 376 participants (8.0%) reported exposure to a multifactorial falls clinic-type intervention in the past 5 years, and 16.0% expressed intention to undertake this intervention. Of the 132 participants who reported one or more falls in the past 12 months, over one-third were undecided or disagreed that a falls clinic type of intervention would be of benefit to them. Four elements from the theoretical model positively influenced intention to participate in the intervention: personal perception of intervention effectiveness, self-perceived risk of falls, self-perceived risk of injury, and inability to walk up/down steps without a handrail (P<0.05). Conclusion Multifactorial falls clinic-type interventions are not commonly accessed or considered as intended fall prevention approaches among community-dwelling older people, even among those with falls in the past 12 months. Factors identified as influencing intention to undertake these interventions may be useful in promoting or targeting these interventions. PMID:25473276

Effectiveness of a new health care organization model in primary care for chronic cardiovascular disease patients based on a multifactorial intervention: the PROPRESE randomized controlled trial.

PubMed

Orozco-Beltran, Domingo; Ruescas-Escolano, Esther; Navarro-Palazón, Ana Isabel; Cordero, Alberto; Gaubert-Tortosa, María; Navarro-Perez, Jorge; Carratalá-Munuera, Concepción; Pertusa-Martínez, Salvador; Soler-Bahilo, Enrique; Brotons-Muntó, Francisco; Bort-Cubero, Jose; Nuñez-Martinez, Miguel Angel; Bertomeu-Martinez, Vicente; Gil-Guillen, Vicente Francisco

2013-08-02

To evaluate the effectiveness of a new multifactorial intervention to improve health care for chronic ischemic heart disease patients in primary care. The strategy has two components: a) organizational for the patient/professional relationship and b) training for professionals. Experimental study. Randomized clinical trial. Follow-up period: one year. primary care, multicenter (15 health centers). For the intervention group 15 health centers are selected from those participating in ESCARVAL study. Once the center agreed to participate patients are randomly selected from the total amount of patients with ischemic heart disease registered in the electronic health records. For the control group a random sample of patients with ischemic heart disease is selected from all 72 health centers electronic records. This study aims to evaluate the efficacy of a multifactorial intervention strategy involving patients with ischemic heart disease for the improvement of the degree of control of the cardiovascular risk factors and of the quality of life, number of visits, and number of hospitalizations. NCT01826929.

Coadjuvants in the Diabetic Complications: Nutraceuticals and Drugs with Pleiotropic Effects

PubMed Central

Pereira, Thiago Melo Costa; Pimenta, Fabio Silva; Porto, Marcella Lima; Baldo, Marcelo Perim; Campagnaro, Bianca Prandi; Gava, Agata Lages; Meyrelles, Silvana Santos; Vasquez, Elisardo Corral

2016-01-01

Because diabetes mellitus (DM) is a multifactorial metabolic disease, its prevention and treatment has been a constant challenge for basic and clinical investigators focused on translating their discoveries into clinical treatment of this complex disorder. In this review, we highlight recent experimental and clinical evidences of potential coadjuvants in the management of DM, such as polyphenols (quercetin, resveratrol and silymarin), cultured probiotic microorganisms and drugs acting through direct/indirect or pleiotropic effects on glycemic control in DM. Among several options, we highlight new promising therapeutic coadjuvants, including chemical scavengers, the probiotic kefir and the phosphodiesterase 5 inhibitors, which besides the reduction of hyperglycemia and ameliorate insulin resistance, they reduce oxidative stress and improve endothelial dysfunction in the systemic vascular circulation. In the near future, experimental studies are expected to clear the intracellular pathways involving coadjuvants. The design of clinical trials may also contribute to new strategies with coadjuvants against the harmful effects of diabetic complications. PMID:27527163

The effects of multifactorial fall prevention on depressive symptoms among the aged at increased risk of falling.

PubMed

Sjösten, Noora M; Vahlberg, Tero J; Kivelä, Sirkka-Liisa

2008-05-01

The aim was to determine the effects of multifactorial fall prevention on depressive symptoms among aged Finns at increased risk of falling. This study is part of a multifactorial fall prevention trial with a randomised controlled design implemented in the town of Pori, western Finland. The study population consisted of ambulatory, 65-year-old or older Finns, with moderate or high cognitive and physical abilities who had fallen at least once during the previous 12 months. The participants (n=591) were randomised into a risk-based multifactorial fall prevention programme (intervention group, IG) or into a one-time counselling group (control group, CG). The 1-year intervention included individual geriatric assessment followed by treatment recommendations, individual guidance regarding fall prevention, physical exercise in small groups twice a month, psychosocial group activities and lectures once a month, home-exercises and home hazard assessment. The outcome, depressive symptoms, was measured by the 30-item Geriatric Depression Scale (GDS). The full GDS data with no missing items were available for 464 persons. A significant decrease in depressive symptoms during the 12-month intervention was found both in IG and in CG, but the difference in change was not significant (p=0.110). However, a significant difference in change between the groups was found among men and older subjects (>or=75) in favour of the IG. Multifactorial fall prevention had no effects on depressive symptoms among the community-dwelling aged. However, men and older participants benefited from the intervention.

Geometric Model of Induction Heating Process of Iron-Based Sintered Materials

NASA Astrophysics Data System (ADS)

Semagina, Yu V.; Egorova, M. A.

2018-03-01

The article studies the issue of building multivariable dependences based on the experimental data. A constructive method for solving the issue is presented in the form of equations of (n-1) – surface compartments of the extended Euclidean space E+n. The dimension of space is taken to be equal to the sum of the number of parameters and factors of the model of the system being studied. The basis for building multivariable dependencies is the generalized approach to n-space used for the surface compartments of 3D space. The surface is designed on the basis of the kinematic method, moving one geometric object along a certain trajectory. The proposed approach simplifies the process aimed at building the multifactorial empirical dependencies which describe the process being investigated.

Effectiveness of a new health care organization model in primary care for chronic cardiovascular disease patients based on a multifactorial intervention: the PROPRESE randomized controlled trial

PubMed Central

2013-01-01

Background To evaluate the effectiveness of a new multifactorial intervention to improve health care for chronic ischemic heart disease patients in primary care. The strategy has two components: a) organizational for the patient/professional relationship and b) training for professionals. Methods/design Experimental study. Randomized clinical trial. Follow-up period: one year. Study setting: primary care, multicenter (15 health centers). For the intervention group 15 health centers are selected from those participating in ESCARVAL study. Once the center agreed to participate patients are randomly selected from the total amount of patients with ischemic heart disease registered in the electronic health records. For the control group a random sample of patients with ischemic heart disease is selected from all 72 health centers electronic records. Intervention components: a) Organizational intervention on the patient/professional relationship. Centered on the Chronic Care Model, the Stanford Expert Patient Program and the Kaiser Permanente model: Teamwork, informed and active patient, decision making shared with the patient, recommendations based on clinical guidelines, single electronic medical history per patient that allows the use of indicators for risk monitoring and stratification. b) Formative strategy for professionals: 4 face-to-face training workshops (one every 3 months), monthly update clinical sessions, online tutorial by a cardiologist, availability through the intranet of the action protocol and related documents. Measurements: Blood pressure, blood glucose, HbA1c, lipid profile and smoking. Frequent health care visits. Number of hospitalizations related to vascular disease. Therapeutic compliance. Drug use. Discussion This study aims to evaluate the efficacy of a multifactorial intervention strategy involving patients with ischemic heart disease for the improvement of the degree of control of the cardiovascular risk factors and of the quality of life, number of visits, and number of hospitalizations. Trial registration NCT01826929 PMID:23915267

The effect of infectious bursal disease virus induced immunosuppression on vaccination against highly pathogenic avian influenza virus

USDA-ARS?s Scientific Manuscript database

Poor efficacy of avian influenza virus (AIV) vaccines in chickens has been documented in the field in spite of good results in experimental settings. Although the causes are multi-factorial and complex, one contributing factor may be prior infection with immunosuppressive viruses. In an effort to ...

Aspects of the "Design Space" in high pressure liquid chromatography method development.

PubMed

Molnár, I; Rieger, H-J; Monks, K E

2010-05-07

The present paper describes a multifactorial optimization of 4 critical HPLC method parameters, i.e. gradient time (t(G)), temperature (T), pH and ternary composition (B(1):B(2)) based on 36 experiments. The effect of these experimental variables on critical resolution and selectivity was carried out in such a way as to systematically vary all four factors simultaneously. The basic element is a gradient time-temperature (t(G)-T) plane, which is repeated at three different pH's of the eluent A and at three different ternary compositions of eluent B between methanol and acetonitrile. The so-defined volume enables the investigation of the critical resolution for a part of the Design Space of a given sample. Further improvement of the analysis time, with conservation of the previously optimized selectivity, was possible by reducing the gradient time and increasing the flow rate. Multidimensional robust regions were successfully defined and graphically depicted. Copyright (c) 2010 Elsevier B.V. All rights reserved.

Defining a procedure for predicting the duration of the approximately isothermal segments within the proposed drying regime as a function of the drying air parameters

NASA Astrophysics Data System (ADS)

Vasić, M.; Radojević, Z.

2017-08-01

One of the main disadvantages of the recently reported method, for setting up the drying regime based on the theory of moisture migration during drying, lies in a fact that it is based on a large number of isothermal experiments. In addition each isothermal experiment requires the use of different drying air parameters. The main goal of this paper was to find a way how to reduce the number of isothermal experiments without affecting the quality of the previously proposed calculation method. The first task was to define the lower and upper inputs as well as the output of the “black box” which will be used in the Box-Wilkinson’s orthogonal multi-factorial experimental design. Three inputs (drying air temperature, humidity and velocity) were used within the experimental design. The output parameter of the model represents the time interval between any two chosen characteristic points presented on the Deff - t. The second task was to calculate the output parameter for each planed experiments. The final output of the model is the equation which can predict the time interval between any two chosen characteristic points as a function of the drying air parameters. This equation is valid for any value of the drying air parameters which are within the defined area designated with lower and upper limiting values.

Smile: A review

PubMed Central

Manjula, W. S.; Sukumar, M. R.; Kishorekumar, S.; Gnanashanmugam, K.; Mahalakshmi, K.

2015-01-01

“Beauty is in the mind of the beholder, each mind perceives a different beauty” famously said by writer Margeret Wolfe Hungerford. A beautiful smile is a gateway to the world. The aim of this article was to identify the criteria for designing the perfect smile. It was determined, smile design is a multifactorial process and various steps are involved in designing a radiant smile. PMID:26015730

Application of multi-factorial design of experiments to successfully optimize immunoassays for robust measurements of therapeutic proteins.

PubMed

Ray, Chad A; Patel, Vimal; Shih, Judy; Macaraeg, Chris; Wu, Yuling; Thway, Theingi; Ma, Mark; Lee, Jean W; Desilva, Binodh

2009-02-20

Developing a process that generates robust immunoassays that can be used to support studies with tight timelines is a common challenge for bioanalytical laboratories. Design of experiments (DOEs) is a tool that has been used by many industries for the purpose of optimizing processes. The approach is capable of identifying critical factors and their interactions with a minimal number of experiments. The challenge for implementing this tool in the bioanalytical laboratory is to develop a user-friendly approach that scientists can understand and apply. We have successfully addressed these challenges by eliminating the screening design, introducing automation, and applying a simple mathematical approach for the output parameter. A modified central composite design (CCD) was applied to three ligand binding assays. The intra-plate factors selected were coating, detection antibody concentration, and streptavidin-HRP concentrations. The inter-plate factors included incubation times for each step. The objective was to maximize the logS/B (S/B) of the low standard to the blank. The maximum desirable conditions were determined using JMP 7.0. To verify the validity of the predictions, the logS/B prediction was compared against the observed logS/B during pre-study validation experiments. The three assays were optimized using the multi-factorial DOE. The total error for all three methods was less than 20% which indicated method robustness. DOE identified interactions in one of the methods. The model predictions for logS/B were within 25% of the observed pre-study validation values for all methods tested. The comparison between the CCD and hybrid screening design yielded comparable parameter estimates. The user-friendly design enables effective application of multi-factorial DOE to optimize ligand binding assays for therapeutic proteins. The approach allows for identification of interactions between factors, consistency in optimal parameter determination, and reduced method development time.

Quality by design approach for developing chitosan-Ca-alginate microspheres for colon delivery of celecoxib-hydroxypropyl-β-cyclodextrin-PVP complex.

PubMed

Mennini, N; Furlanetto, S; Cirri, M; Mura, P

2012-01-01

The aim of the present work was to develop a new multiparticulate system, designed for colon-specific delivery of celecoxib for both systemic (in chronotherapic treatment of arthritis) and local (in prophylaxis of colon carcinogenesis) therapy. The system simultaneously benefits from ternary complexation with hydroxypropyl-β-cyclodextrin and PVP (polyvinylpyrrolidone), to increase drug solubility, and vectorization in chitosan-Ca-alginate microspheres, to exploit the colon-specific carrier properties of these polymers. Statistical experimental design was employed to investigate the combined effect of four formulation variables, i.e., % of alginate, CaCl₂, and chitosan and time of cross-linking on microsphere entrapment efficiency (EE%) and drug amount released after 4h in colonic medium, considered as the responses to be optimized. Design of experiment was used in the context of Quality by Design, which requires a multivariate approach for understanding the multifactorial relationships among formulation parameters. Doehlert design allowed for defining a design space, which revealed that variations of the considered factors had in most cases an opposite influence on the responses. Desirability function was used to attain simultaneous optimization of both responses. The desired goals were achieved for both systemic and local use of celecoxib. Experimental values obtained from the optimized formulations were in both cases very close to the predicted values, thus confirming the validity of the generated mathematical model. These results demonstrated the effectiveness of the proposed jointed use of drug cyclodextrin complexation and chitosan-Ca-alginate microsphere vectorization, as well as the usefulness of the multivariate approach for the preparation of colon-targeted celecoxib microspheres with optimized properties. Copyright © 2011 Elsevier B.V. All rights reserved.

Clinical and cost outcomes of multifactorial, cardiovascular risk management interventions in worksites: a comprehensive review and analysis.

PubMed

Pelletier, K R

1997-12-01

This paper is a critical review of the clinical and cost outcome evaluation studies of multifactorial, comprehensive, cardiovascular risk management programs in worksites. A comprehensive international literature search conducted under the auspices of the National Heart, Lung and Blood Institute identified 17 articles based on 12 studies that examined the clinical outcomes of multifactorial, comprehensive programs. These articles were identified through MEDLINE, manual searches of recent journals, and through direct inquiries to worksite health promotion researchers. All studies were conducted between 1978 and 1995, with 1978 being the date of the first citation of a methodologically rigorous evaluation. Of the 12 research studies, only 8 utilized the worksite as both the unit of assignment and as the unit of analysis. None of the studies analyzed adequately for cost effectiveness. Given this limitation, this review briefly considers the relevant worksite research that has demonstrated cost outcomes. Worksite-based, multifactorial cardiovascular intervention programs reviewed for this article varied widely in the comprehensiveness, intensity, and duration of both the interventions and evaluations. Results from randomized trials suggest that providing opportunities for individualized, cardiovascular risk reduction counseling for high-risk employees within the context of comprehensive programming may be the critical component of an effective worksite intervention. Despite the many limitations of the current methodologies of the 12 studies, the majority of the research to date indicates the following: (1) favorable clinical and cost outcomes; (2) that more recent and more rigorously designed research tends to support rather than refute earlier and less rigorously designed studies; and (3) that rather than interpreting the methodological flaws and diversity as inherently negative, one may consider it as indicative of a robust phenomena evident in many types of worksites, with diverse employees, differing interventions, and varying degrees of methodological sophistication. Results of these studies reviewed provide both cautious optimism about the effectiveness of these worksite programs and insights regarding the essential components and characteristics of successful programs.

Treatment of automotive industry oily wastewater by electrocoagulation: statistical optimization of the operational parameters.

PubMed

GilPavas, Edison; Molina-Tirado, Kevin; Gómez-García, Miguel Angel

2009-01-01

An electrocoagulation process was used for the treatment of oily wastewater generated from an automotive industry in Medellín (Colombia). An electrochemical cell consisting of four parallel electrodes (Fe and Al) in bipolar configuration was implemented. A multifactorial experimental design was used for evaluating the influence of several parameters including: type and arrangement of electrodes, pH, and current density. Oil and grease removal was defined as the response variable for the statistical analysis. Additionally, the BOD(5), COD, and TOC were monitored during the treatment process. According to the results, at the optimum parameter values (current density = 4.3 mA/cm(2), distance between electrodes = 1.5 cm, Fe as anode, and pH = 12) it was possible to reach a c.a. 95% oils removal, COD and mineralization of 87.4% and 70.6%, respectively. A final biodegradability (BOD(5)/COD) of 0.54 was reached.

Does disinfection of environmental surfaces influence nosocomial infection rates? A systematic review.

PubMed

Dettenkofer, Markus; Wenzler, Sibylle; Amthor, Susanne; Antes, Gerd; Motschall, Edith; Daschner, Franz D

2004-04-01

To review the evidence on the effects of disinfection of environmental surfaces in hospitals (as compared with cleaning without use of disinfectants) on the occurrence of nosocomial infections. Systematic review of experimental and nonexperimental intervention studies dealing with environmental disinfection or cleaning in different health care settings. A total of 236 scientific articles were identified. None described a meta-analysis, systematic review, or randomized controlled trial. Only 4 articles described completed cohort studies matching the inclusion criteria. None of these studies showed lower infection rates associated with routine disinfection of surfaces (mainly floors) versus cleaning with detergent only. Disinfectants may pose a danger to staff, patients, and the environment and require special safety precautions. However, targeted disinfection of certain environmental surfaces is in certain instances an established component of hospital infection control. Given the complex, multifactorial nature of nosocomial infections, well-designed studies that systematically investigate the role of surface disinfection are required.

The quality estimation of exterior wall’s and window filling’s construction design

NASA Astrophysics Data System (ADS)

Saltykov, Ivan; Bovsunovskaya, Maria

2017-10-01

The article reveals the term of “artificial envelope” in dwelling building. Authors offer a complex multifactorial approach to the design quality estimation of external fencing structures, which is based on various parameters impact. These referred parameters are: functional, exploitation, cost, and also, the environmental index is among them. The quality design index Qк is inputting for the complex characteristic of observed above parameters. The mathematical relation of this index from these parameters is the target function for the quality design estimation. For instance, the article shows the search of optimal variant for wall and window designs in small, middle and large square dwelling premises of economic class buildings. The graphs of target function single parameters are expressed for the three types of residual chamber’s dimensions. As a result of the showing example, there is a choice of window opening’s dimensions, which make the wall’s and window’s constructions properly correspondent to the producible complex requirements. The authors reveal the comparison of recommended window filling’s square in accordance with the building standards, and the square, due to the finding of the optimal variant of the design quality index. The multifactorial approach for optimal design searching, which is mentioned in this article, can be used in consideration of various construction elements of dwelling buildings in accounting of suitable climate, social and economic construction area features.

Multifactorial screening for fall risk in community-dwelling older adults in the primary care office: development of the fall risk assessment & screening tool.

PubMed

Renfro, Mindy Oxman; Fehrer, Steven

2011-01-01

Unintentional falls is an increasing public health problem as incidence of falls rises and the population ages. The Centers for Disease Control and Prevention reports that 1 in 3 adults aged 65 years and older will experience a fall this year; 20% to 30% of those who fall will sustain a moderate to severe injury. Physical therapists caring for older adults are usually engaged with these patients after the first injury fall and may have little opportunity to abate fall risk before the injuries occur. This article describes the content selection and development of a simple-to-administer, multifactorial, Fall Risk Assessment & Screening Tool (FRAST), designed specifically for use in primary care settings to identify those older adults with high fall risk. Fall Risk Assessment & Screening Tool incorporates previously validated measures within a new multifactorial tool and includes targeted recommendations for intervention. Development of the multifactorial FRAST used a 5-part process: identification of significant fall risk factors, review of best evidence, selection of items, creation of the scoring grid, and development of a recommended action plan. Fall Risk Assessment & Screening Tool has been developed to assess fall risk in the target population of older adults (older than 65 years) living and ambulating independently in the community. Many fall risk factors have been considered and 15 items selected for inclusion. Fall Risk Assessment & Screening Tool includes 4 previously validated measures to assess balance, depression, falls efficacy, and home safety. Reliability and validity studies of FRAST are under way. Fall risk for community-dwelling older adults is an urgent, multifactorial, public health problem. Providing primary care practitioners (PCPs) with a very simple screening tool is imperative. Fall Risk Assessment & Screening Tool was created to allow for safe, quick, and low-cost administration by minimally trained office staff with interpretation and follow-up provided by the PCP.

MECHANISTIC INDICATORS OF CHILDHOOD ASTHMA (MICA): A SYSTEMS BIOLOGY APPROACH FOR THE INTEGRATION OF MULTIFACTORIAL EXPOSURE AND ENVIRONMENTAL HEALTH DATA

EPA Science Inventory

Modem methods in molecular biology and advanced computational tools show promise in elucidating complex interactions that occur between genes and environmental factors in diseases such as asthma. However, appropriately designed studies are critical for these methods to reach the...

How Stuttering Develops: The Multifactorial Dynamic Pathways Theory

ERIC Educational Resources Information Center

Smith, Anne; Weber, Christine

2017-01-01

Purpose: We advanced a multifactorial, dynamic account of the complex, nonlinear interactions of motor, linguistic, and emotional factors contributing to the development of stuttering. Our purpose here is to update our account as the multifactorial dynamic pathways theory. Method: We review evidence related to how stuttering develops, including…

Optimisation of colour stability of cured ham during packaging and retail display by a multifactorial design.

PubMed

Møller, Jens K S; Jakobsen, Marianne; Weber, Claus J; Martinussen, Torben; Skibsted, Leif H; Bertelsen, Grete

2003-02-01

A multifactorial design, including (1) percent residual oxygen, (2) oxygen transmission rate of packaging film (OTR), (3) product to headspace volume ratio, (4) illuminance level and (5) nitrite level during curing, was established to investigate factors affecting light-induced oxidative discoloration of cured ham (packaged in modified atmosphere of 20% carbon dioxide and balanced with nitrogen) during 14 days of chill storage. Univariate statistical analysis found significant effects of all main factors on the redness (tristimulus a-value) of the ham. Subsequently, Response Surface Modelling of the data further proved that the interactions between packaging and storage conditions are important when optimising colour stability. The measured content of oxygen in the headspace was incorporated in the model and the interaction between measured oxygen content in the headspace and the product to headspace volume ratio was found to be crucial. Thus, it is not enough to keep the headspace oxygen level low, if the headspace volume at the same time is large, there will still be sufficient oxygen for colour deteriorating processes to take place.

Speed over efficiency: locusts select body temperatures that favour growth rate over efficient nutrient utilization

PubMed Central

Miller, Gabriel A.; Clissold, Fiona J.; Mayntz, David; Simpson, Stephen J.

2009-01-01

Ectotherms have evolved preferences for particular body temperatures, but the nutritional and life-history consequences of such temperature preferences are not well understood. We measured thermal preferences in Locusta migratoria (migratory locusts) and used a multi-factorial experimental design to investigate relationships between growth/development and macronutrient utilization (conversion of ingesta to body mass) as a function of temperature. A range of macronutrient intake values for insects at 26, 32 and 38°C was achieved by offering individuals high-protein diets, high-carbohydrate diets or a choice between both. Locusts placed in a thermal gradient selected temperatures near 38°C, maximizing rates of weight gain; however, this enhanced growth rate came at the cost of poor protein and carbohydrate utilization. Protein and carbohydrate were equally digested across temperature treatments, but once digested both macronutrients were converted to growth most efficiently at the intermediate temperature (32°C). Body temperature preference thus yielded maximal growth rates at the expense of efficient nutrient utilization. PMID:19625322

An evaluation of musician earplugs with college music students.

PubMed

Chesky, Kris; Pair, Marla; Yoshimura, Eri; Landford, Scott

2009-01-01

Musician earplugs are marketed and recommended for use in music settings but no studies have evaluated these products with musicians. This study evaluated the influences of earplugs on college students' perception and abilities to communicate in a musical environment, attitudes of earplugs, comfort over time, and the influence of earplugs on ability to play music. College students (N = 323) were provided with earplugs for use during and following an experimental condition designed to mimic a night club. Results underline the challenges of earplugs in environments that are both loud and require verbal interaction. Responses to comfort questions were variable and suggest a multi-factorial set of influences that may include intrinsic variables. Despite these limitations, subjects in this study generally liked the earplugs and believed that they are valuable. However, the earplugs were not viewed favorably by musicians willing to use the earplugs while playing music. This study supports the view that earplugs are subject to many problems and should be considered as a last resort.

Reduced risk of heart failure with intensified multifactorial intervention in individuals with type 2 diabetes and microalbuminuria: 21 years of follow-up in the randomised Steno-2 study.

PubMed

Oellgaard, Jens; Gæde, Peter; Rossing, Peter; Rørth, Rasmus; Køber, Lars; Parving, Hans-Henrik; Pedersen, Oluf

2018-05-30

In type 2 diabetes mellitus, heart failure is a frequent, potentially fatal and often forgotten complication. Glucose-lowering agents and adjuvant therapies modify the risk of heart failure. We recently reported that 7.8 years of intensified compared with conventional multifactorial intervention in individuals with type 2 diabetes and microalbuminuria in the Steno-2 study reduced the risk of cardiovascular disease and prolonged life over 21.2 years of follow-up. In this post hoc analysis, we examine the impact of intensified multifactorial intervention on the risk of hospitalisation for heart failure. One hundred and sixty individuals were randomised to conventional or intensified multifactorial intervention, using sealed envelopes. The trial was conducted using the Prospective, Randomised, Open, Blinded Endpoints (PROBE) design. After 7.8 years, all individuals were offered intensified therapy and the study continued as an observational follow-up study for an additional 13.4 years. Heart-failure hospitalisations were adjudicated from patient records by an external expert committee blinded for treatment allocation. Event rates were compared using a Cox regression model adjusted for age and sex. Eighty patients were assigned to each treatment group. Ten patients undergoing intensive therapy vs 24 undergoing conventional therapy were hospitalised for heart failure during follow-up. The HR (95% CI) was 0.30 (0.14, 0.64), p = 0.002 in the intensive-therapy group compared with the conventional-therapy group. Including death in the endpoint did not lead to an alternate overall outcome; HR 0.51 (0.34, 0.76), p = 0.001. In a pooled cohort analysis, an increase in plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) during the first two years of the trial was associated with incident heart failure. Intensified, multifactorial intervention for 7.8 years in type 2 diabetic individuals with microalbuminuria reduced the risk of hospitalisation for heart failure by 70% during a total of 21.2 years of observation. ClinicalTrials.gov NCT00320008.

Decreasing Uncorrected Refractive Error in the Classroom through a Multifactorial Pilot Intervention

ERIC Educational Resources Information Center

Kodjebacheva, Gergana; Maliski, Sally; Yu, Fei; Oelrich, Faye; Coleman, Anne L.

2014-01-01

The study assessed the effectiveness of a pilot intervention to promote the use of eyeglasses in one school in California. The intervention used a one-group pretest, posttest design. Between January and June 2011, during the intervention, all first- and second-grade children received eye evaluations and the children with refractive error received…

The impact of home care nurses' numeracy and graph literacy on comprehension of visual display information: implications for dashboard design.

PubMed

Dowding, Dawn; Merrill, Jacqueline A; Onorato, Nicole; Barrón, Yolanda; Rosati, Robert J; Russell, David

2018-02-01

To explore home care nurses' numeracy and graph literacy and their relationship to comprehension of visualized data. A multifactorial experimental design using online survey software. Nurses were recruited from 2 Medicare-certified home health agencies. Numeracy and graph literacy were measured using validated scales. Nurses were randomized to 1 of 4 experimental conditions. Each condition displayed data for 1 of 4 quality indicators, in 1 of 4 different visualized formats (bar graph, line graph, spider graph, table). A mixed linear model measured the impact of numeracy, graph literacy, and display format on data understanding. In all, 195 nurses took part in the study. They were slightly more numerate and graph literate than the general population. Overall, nurses understood information presented in bar graphs most easily (88% correct), followed by tables (81% correct), line graphs (77% correct), and spider graphs (41% correct). Individuals with low numeracy and low graph literacy had poorer comprehension of information displayed across all formats. High graph literacy appeared to enhance comprehension of data regardless of numeracy capabilities. Clinical dashboards are increasingly used to provide information to clinicians in visualized format, under the assumption that visual display reduces cognitive workload. Results of this study suggest that nurses' comprehension of visualized information is influenced by their numeracy, graph literacy, and the display format of the data. Individual differences in numeracy and graph literacy skills need to be taken into account when designing dashboard technology. © The Author 2017. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Multi-Response Optimization of Granaticinic Acid Production by Endophytic Streptomyces thermoviolaceus NT1, Using Response Surface Methodology

PubMed Central

Roy, Sudipta; Halder, Suman Kumar; Banerjee, Debdulal

2016-01-01

Streptomyces thermoviolaceus NT1, an endophytic isolate, was studied for optimization of granaticinic acid production. It is an antimicrobial metabolite active against even drug resistant bacteria. Different media, optimum glucose concentration, initial media pH, incubation temperature, incubation period, and inoculum size were among the selected parameters optimized in the one-variable-at-a-time (OVAT) approach, where glucose concentration, pH, and temperature were found to play a critical role in antibiotic production by this strain. Finally, the Box–Behnken experimental design (BBD) was employed with three key factors (selected after OVAT studies) for response surface methodological (RSM) analysis of this optimization study.RSM analysis revealed a multifactorial combination; glucose 0.38%, pH 7.02, and temperature 36.53 °C as the optimum conditions for maximum antimicrobial yield. Experimental verification of model analysis led to 3.30-fold (61.35 mg/L as compared to 18.64 mg/L produced in un-optimized condition) enhanced granaticinic acid production in ISP2 medium with 5% inoculum and a suitable incubation period of 10 days. So, the conjugated optimization study for maximum antibiotic production from Streptomyces thermoviolaceus NT1 was found to result in significantly higher yield, which might be exploited in industrial applications. PMID:28952581

Benzimidazoles: an ideal privileged drug scaffold for the design of multitargeted anti-inflammatory ligands.

PubMed

Kaur, Gaganpreet; Kaur, Maninder; Silakari, Om

2014-01-01

The recent research area endeavors to discover ultimate multi-target ligands, an increasingly feasible and attractive alternative to existing mono-targeted drugs for treatment of complex, multi-factorial inflammation process which underlays plethora of debilitated health conditions. In order to improvise this option, exploration of relevant chemical core scaffold will be an utmost need. Privileged benzimidazole scaffold being historically versatile structural motif could offer a viable starting point in the search for novel multi-target ligands against multi-factorial inflammation process since, when appropriately substituted, it can selectively modulate diverse receptors, pathways and enzymes associated with the pathogenesis of inflammation. Despite this remarkable capability, the multi-target capacity of the benzimidazole scaffold remains largely unexploited. With this in focus, the present review article attempts to provide synopsis of published research to exemplify the valuable use of benzimidazole nucleus and focus on their suitability as starting scaffold to develop multi-targeted anti-inflammatory ligands.

Simultaneous virtual prediction of anti-Escherichia coli activities and ADMET profiles: A chemoinformatic complementary approach for high-throughput screening.

PubMed

Speck-Planche, Alejandro; Cordeiro, M N D S

2014-02-10

Escherichia coli remains one of the principal pathogens that cause nosocomial infections, medical conditions that are increasingly common in healthcare facilities. E. coli is intrinsically resistant to many antibiotics, and multidrug-resistant strains have emerged recently. Chemoinformatics has been a great ally of experimental methodologies such as high-throughput screening, playing an important role in the discovery of effective antibacterial agents. However, there is no approach that can design safer anti-E. coli agents, because of the multifactorial nature and complexity of bacterial diseases and the lack of desirable ADMET (absorption, distribution, metabolism, elimination, and toxicity) profiles as a major cause of disapproval of drugs. In this work, we introduce the first multitasking model based on quantitative-structure biological effect relationships (mtk-QSBER) for simultaneous virtual prediction of anti-E. coli activities and ADMET properties of drugs and/or chemicals under many experimental conditions. The mtk-QSBER model was developed from a large and heterogeneous data set of more than 37800 cases, exhibiting overall accuracies of >95% in both training and prediction (validation) sets. The utility of our mtk-QSBER model was demonstrated by performing virtual prediction of properties for the investigational drug avarofloxacin (AVX) under 260 different experimental conditions. Results converged with the experimental evidence, confirming the remarkable anti-E. coli activities and safety of AVX. Predictions also showed that our mtk-QSBER model can be a promising computational tool for virtual screening of desirable anti-E. coli agents, and this chemoinformatic approach could be extended to the search for safer drugs with defined pharmacological activities.

Systems Biology Methods for Alzheimer's Disease Research Toward Molecular Signatures, Subtypes, and Stages and Precision Medicine: Application in Cohort Studies and Trials.

PubMed

Castrillo, Juan I; Lista, Simone; Hampel, Harald; Ritchie, Craig W

2018-01-01

Alzheimer's disease (AD) is a complex multifactorial disease, involving a combination of genomic, interactome, and environmental factors, with essential participation of (a) intrinsic genomic susceptibility and (b) a constant dynamic interplay between impaired pathways and central homeostatic networks of nerve cells. The proper investigation of the complexity of AD requires new holistic systems-level approaches, at both the experimental and computational level. Systems biology methods offer the potential to unveil new fundamental insights, basic mechanisms, and networks and their interplay. These may lead to the characterization of mechanism-based molecular signatures, and AD hallmarks at the earliest molecular and cellular levels (and beyond), for characterization of AD subtypes and stages, toward targeted interventions according to the evolving precision medicine paradigm. In this work, an update on advanced systems biology methods and strategies for holistic studies of multifactorial diseases-particularly AD-is presented. This includes next-generation genomics, neuroimaging and multi-omics methods, experimental and computational approaches, relevant disease models, and latest genome editing and single-cell technologies. Their progressive incorporation into basic research, cohort studies, and trials is beginning to provide novel insights into AD essential mechanisms, molecular signatures, and markers toward mechanism-based classification and staging, and tailored interventions. Selected methods which can be applied in cohort studies and trials, with the European Prevention of Alzheimer's Dementia (EPAD) project as a reference example, are presented and discussed.

Is appendectomy a causative factor in ulcerative colitis?

PubMed

Russel, M G; Stockbrügger, R W

1998-06-01

There are strong indicators that the aetiology of inflammatory bowel disease should be regarded as multifactorial, involving an interaction between genetic and environmental factors which give rise to an inadequate immunological response. During the past decade at least seven case-control studies have shown an inverse association between appendectomy and ulcerative colitis. Conclusions have been that either ulcerative colitis protects against appendicitis, or appendectomy protects against ulcerative colitis. The immunological function of the appendix is not well known, but experimental studies suggest that the appendix is possibly an important site for priming of the cells involved in the development of inflammatory bowel disease. Experimental and prospective cohort studies are needed to provide more insight in a possible relation between ulcerative colitis and the appendix.

[Contribution of endogenous potentials to the study of cognitive development in children: review of the literature].

PubMed

Robaey, P

1987-09-01

A review of the studies concerning age-related changes of the cognitive event-related potentials is presented. Graded changes (with little or no difference in waveform morphology but shifts in component latency or amplitude) draw to continuous developmental models, but morphological waveform differences are assumed to reflect fundamental differences in modes of cognitive processing. The authors equally present an experimental paradigm indicating that a multifactorial model of amplitude variations is able to reflect the passing from one cognitive stage to the next one, according to Piaget's theory.

The Effect of Ovariectomy and Orchiectomy on Orthodontic Tooth Movement and Root Resorption in Wistar Rats.

PubMed

Seifi, Massoud; Ezzati, Baharak; Saedi, Sara; Hedayati, Mehdi

2015-12-01

Root resorption (RR) after orthodontic tooth movement (OTM) is known as a multifactorial complication of orthodontic treatments. Hormonal deficiencies and their effect on bone turnover are reported to have influences on the rate of tooth movement and root resorption. This study was designed to evaluate the effect of female and male steroid sex hormones on tooth movement and root resorption. Orthodontic appliances were placed on the right maxillary first molars of 10 ovariectomized female and 10 orchiectomized male Wistar rats as experimental groups and 10 female and 10 male healthy Wistar rats as control groups. NiTi closed-coil springs (9mm, Medium, 011"×.030", Ortho Technology(®); Tampa, Florida) were placed between the right incisors and the first right maxillary molars to induce tipping movement in the first molars with the application of a 60g force. After 21 days, the rats were sacrificed and tooth movement was measured by using a digital caliper (Guanglu, China). Orthodontic induced root resorption (OIRR) was assessed by histomorphometric analysis after hematoxylin and eosin staining of sections of the mesial root. The rate of tooth movement was significantly higher in all female rats, with the root resorption being lower in the experimental group. The rate of tooth movement in experimental male rats was significantly higher than the control group (p= 0.001) and the rate of root resorption was significantly lower in the experimental group (p= 0.001). It seems that alterations in plasma levels of estrogen, progesterone, and testosterone hormones can influence the rate of OTM and RR. The acceleration in tooth movement increased OTM and decreased RR.

The impact of intensive multifactorial treatment on perceptions of chronic care among individuals with screen-detected diabetes: results from the ADDITION-Denmark trial.

PubMed

Kuznetsov, L; Simmons, R K; Sandbaek, A; Maindal, H T

2015-04-01

To describe perceptions of chronic care among diabetes patients 6 years after diagnosis by screening and to examine the impact of intensive treatment on patients' perceptions of chronic care. The ADDITION-Denmark (2001-2006) trial compared the effects of intensive multifactorial therapy (IT) with routine care (RC) among individuals with screen-detected diabetes. Perceptions of chronic care were assessed using the Patient Assessment of Chronic Illness Care (PACIC) measure after 6-year follow-up (n = 937). Analysis was by intention-to-treat, accounting for clustering by general practice. The mean (SD) summary PACIC score was 2.4 (0.79) in the RC and 2.4 (0.82) in the IT group. The highest mean (SD) PACIC subscale score was for Delivery System Design/Decision Support [RC: 3.2 (0.95), IT: 3.3 (0.91)] and the lowest was for Follow-up/Coordination [RC: 2.1 (0.84), IT: 2.1 (0.87)]. Perceptions of chronic care did not differ between trial groups. Compared to RC, an intensive multifactorial intervention was not associated with differences in perceptions of chronic care among patients with screen-detected diabetes after 6 years. Intensive treatment does not adversely affect perceptions of chronic care early in the course of the disease. However, there is potentially room for improvement in some aspects of chronic care. © 2014 The Authors. International Journal of Clinical Practice Published by John Wiley & Sons Ltd.

Strategies to Reduce Injuries and Develop Confidence in Elders (STRIDE): A Cluster-Randomized Pragmatic Trial of a Multifactorial Fall Injury Prevention Strategy: Design and Methods.

PubMed

Bhasin, Shalender; Gill, Thomas M; Reuben, David B; Latham, Nancy K; Gurwitz, Jerry H; Dykes, Patricia; McMahon, Siobhan; Storer, Thomas W; Duncan, Pamela W; Ganz, David A; Basaria, Shehzad; Miller, Michael E; Travison, Thomas G; Greene, Erich J; Dziura, James; Esserman, Denise; Allore, Heather; Carnie, Martha B; Fagan, Maureen; Hanson, Catherine; Baker, Dorothy; Greenspan, Susan L; Alexander, Neil; Ko, Fred; Siu, Albert L; Volpi, Elena; Wu, Albert W; Rich, Jeremy; Waring, Stephen C; Wallace, Robert; Casteel, Carri; Magaziner, Jay; Charpentier, Peter; Lu, Charles; Araujo, Katy; Rajeevan, Haseena; Margolis, Scott; Eder, Richard; McGloin, Joanne M; Skokos, Eleni; Wiggins, Jocelyn; Garber, Lawrence; Clauser, Steven B; Correa-De-Araujo, Rosaly; Peduzzi, Peter

2017-10-14

Fall injuries are a major cause of morbidity and mortality among older adults. We describe the design of a pragmatic trial to compare the effectiveness of an evidence-based, patient-centered multifactorial fall injury prevention strategy to an enhanced usual care. Strategies to Reduce Injuries and Develop Confidence in Elders (STRIDE) is a 40-month cluster-randomized, parallel-group, superiority, pragmatic trial being conducted at 86 primary care practices in 10 healthcare systems across USA. The 86 practices were randomized to intervention or control group using covariate-based constrained randomization, stratified by healthcare system. Participants are community-living persons, ≥70 years, at increased risk for serious fall injuries. The intervention is a co-management model in which a nurse Falls Care Manager performs multifactorial risk assessments, develops individualized care plans, which include surveillance, follow-up evaluation, and intervention strategies. Control group receives enhanced usual care, with clinicians and patients receiving evidence-based information on falls prevention. Primary outcome is serious fall injuries, operationalized as those leading to medical attention (non-vertebral fractures, joint dislocation, head injury, lacerations, and other major sequelae). Secondary outcomes include all fall injuries, all falls, and well-being (concern for falling; anxiety and depressive symptoms; physical function and disability). Target sample size was 5,322 participants to provide 90% power to detect 20% reduction in primary outcome rate relative to control. Trial enrolled 5451 subjects in 20 months. Intervention and follow-up are ongoing. The findings of the STRIDE study will have important clinical and policy implications for the prevention of fall injuries in older adults. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Effect of Autoclave Cycles on Surface Characteristics of S-File Evaluated by Scanning Electron Microscopy.

PubMed

Razavian, Hamid; Iranmanesh, Pedram; Mojtahedi, Hamid; Nazeri, Rahman

2016-01-01

Presence of surface defects in endodontic instruments can lead to unwanted complications such as instrument fracture and incomplete preparation of the canal. The current study was conducted to evaluate the effect of autoclave cycles on surface characteristics of S-File by scanning electron microscopy (SEM). In this experimental study, 17 brand new S-Files (#30) were used. The surface characteristics of the files were examined in four steps (without autoclave, 1 autoclave cycle, 5 autoclave cycles and 10 autoclave cycles) by SEM under 200× and 1000× magnifications. Data were analyzed using the SPSS software and the paired sample t-test, independent sample t-test and multifactorial repeated measures ANOVA. The level of significance was set at 0.05. New files had debris and pitting on their surfaces. When the autoclave cycles were increased, the mean of surface roughness also increased at both magnifications (P<0.05). Moreover, under 1000× magnification the multifactorial repeated measures ANOVA showed more surface roughness (P<0.001). Sterilization by autoclave increased the surface roughness of the files and this had was directly related to the number of autoclave cycles.

Effect of Autoclave Cycles on Surface Characteristics of S-File Evaluated by Scanning Electron Microscopy

PubMed Central

Razavian, Hamid; Iranmanesh, Pedram; Mojtahedi, Hamid; Nazeri, Rahman

2016-01-01

Introduction: Presence of surface defects in endodontic instruments can lead to unwanted complications such as instrument fracture and incomplete preparation of the canal. The current study was conducted to evaluate the effect of autoclave cycles on surface characteristics of S-File by scanning electron microscopy (SEM). Methods and Materials: In this experimental study, 17 brand new S-Files (#30) were used. The surface characteristics of the files were examined in four steps (without autoclave, 1 autoclave cycle, 5 autoclave cycles and 10 autoclave cycles) by SEM under 200× and 1000× magnifications. Data were analyzed using the SPSS software and the paired sample t-test, independent sample t-test and multifactorial repeated measures ANOVA. The level of significance was set at 0.05. Results: New files had debris and pitting on their surfaces. When the autoclave cycles were increased, the mean of surface roughness also increased at both magnifications (P<0.05). Moreover, under 1000× magnification the multifactorial repeated measures ANOVA showed more surface roughness (P<0.001). Conclusion: Sterilization by autoclave increased the surface roughness of the files and this had was directly related to the number of autoclave cycles. PMID:26843874

Universal etiology, multifactorial diseases and the constitutive model of disease classification.

PubMed

Fuller, Jonathan

2018-02-01

Infectious diseases are often said to have a universal etiology, while chronic and noncommunicable diseases are said to be multifactorial in their etiology. It has been argued that the universal etiology of an infectious disease results from its classification using a monocausal disease model. In this article, I will reconstruct the monocausal model and argue that modern 'multifactorial diseases' are not monocausal by definition. 'Multifactorial diseases' are instead defined according to a constitutive disease model. On closer analysis, infectious diseases are also defined using the constitutive model rather than the monocausal model. As a result, our classification models alone cannot explain why infectious diseases have a universal etiology while chronic and noncommunicable diseases lack one. The explanation is instead provided by the Nineteenth Century germ theorists. Copyright © 2017 Elsevier Ltd. All rights reserved.

Technologies for participatory medicine and health promotion in the elderly population.

PubMed

Nieto-Riveiro, Laura; Groba, Betania; Miranda, M Carmen; Concheiro, Patricia; Pazos, Alejandro; Pousada, Thais; Pereira, Javier

2018-05-01

The progressive aging of the population is a socio-demographic phenomenon experienced by most countries in the world in recent decades, especially in Japan and in many European Union countries. During this process, so-called "geriatric syndromes" frequently occur. The focus of this study is the quality of life of the elderly in relation to these 3 factors: risk of falls, urinary incontinence, and insomnia. The main purpose is to determine the impact of a multifactorial intervention program implemented with institutionalized elderly people. The program is focused on the treatment of the aforementioned factors. The study will be carried out with elderly people living in three residences for the elderly in A Coruña Province (Galicia, Spain).It is a prospective and longitudinal study, with a temporary series design of a "quasi-experimental" type that evaluates the effect of an intervention in 1 given population by doing assessments pre- and post-intervention, but there is no comparison with a control group.The intervention will be based on a multifactorial program, including the following phases: the use of wearable devices (wearable fitness trackers to register physical activity and sleep), the use of an App on a Tablet to record the participants' occupations and activities, counseling about performance in activities of daily living, the implementation of a physical activity program, and the treatment of the pelvic floor (according to each research line). The Quality of Life (QoL) will be assessed before and after the intervention, with the use of the questionnaire EuroQol-5D-5L. Data analysis will be applied with all registered variables through a quantitative perspective. The protocol has been approved by the host institution's ethics committee (Research Ethics Committee of Galicia) under the number 2017/106. Results will be disseminated via peer-reviewed journal articles and conferences. This clinical trial is registered at ClinicalTrials.gov identifier: NCT03504813.

Restoration Enhances Wetland Biodiversity and Ecosystem Service Supply, but Results Are Context-Dependent: A Meta-Analysis

PubMed Central

Meli, Paula; Rey Benayas, José María; Balvanera, Patricia; Martínez Ramos, Miguel

2014-01-01

Wetlands are valuable ecosystems because they harbor a huge biodiversity and provide key services to societies. When natural or human factors degrade wetlands, ecological restoration is often carried out to recover biodiversity and ecosystem services (ES). Although such restorations are routinely performed, we lack systematic, evidence-based assessments of their effectiveness on the recovery of biodiversity and ES. Here we performed a meta-analysis of 70 experimental studies in order to assess the effectiveness of ecological restoration and identify what factors affect it. We compared selected ecosystem performance variables between degraded and restored wetlands and between restored and natural wetlands using response ratios and random-effects categorical modeling. We assessed how context factors such as ecosystem type, main agent of degradation, restoration action, experimental design, and restoration age influenced post-restoration biodiversity and ES. Biodiversity showed excellent recovery, though the precise recovery depended strongly on the type of organisms involved. Restored wetlands showed 36% higher levels of provisioning, regulating and supporting ES than did degraded wetlands. In fact, wetlands showed levels of provisioning and cultural ES similar to those of natural wetlands; however, their levels of supporting and regulating ES were, respectively, 16% and 22% lower than in natural wetlands. Recovery of biodiversity and of ES were positively correlated, indicating a win-win restoration outcome. The extent to which restoration increased biodiversity and ES in degraded wetlands depended primarily on the main agent of degradation, restoration actions, experimental design, and ecosystem type. In contrast, the choice of specific restoration actions alone explained most differences between restored and natural wetlands. These results highlight the importance of comprehensive, multi-factorial assessment to determine the ecological status of degraded, restored and natural wetlands and thereby evaluate the effectiveness of ecological restorations. Future research on wetland restoration should also seek to identify which restoration actions work best for specific habitats. PMID:24743348

Rationale and design of the ADDITION-Leicester study, a systematic screening programme and Randomised Controlled Trial of multi-factorial cardiovascular risk intervention in people with Type 2 Diabetes Mellitus detected by screening

PubMed Central

2010-01-01

Background Earlier diagnosis followed by multi-factorial cardiovascular risk intervention may improve outcomes in Type 2 Diabetes Mellitus (T2DM). Latent phase identification through screening requires structured, appropriately targeted population-based approaches. Providers responsible for implementing screening policy await evidence of clinical and cost effectiveness from randomised intervention trials in screen-detected T2DM cases. UK South Asians are at particularly high risk of abnormal glucose tolerance and T2DM. To be effective national screening programmes must achieve good coverage across the population by identifying barriers to the detection of disease and adapting to the delivery of earlier care. Here we describe the rationale and methods of a systematic community screening programme and randomised controlled trial of cardiovascular risk management within a UK multiethnic setting (ADDITION-Leicester). Design A single-blind cluster randomised, parallel group trial among people with screen-detected T2DM comparing a protocol driven intensive multi-factorial treatment with conventional care. Methods ADDITION-Leicester consists of community-based screening and intervention phases within 20 general practices coordinated from a single academic research centre. Screening adopts a universal diagnostic approach via repeated 75g-Oral Glucose Tolerance Tests within an eligible non-diabetic population of 66,320 individuals aged 40-75 years (25-75 years South Asian). Volunteers also provide detailed medical and family histories; complete health questionnaires, undergo anthropometric measures, lipid profiling and a proteinuria assessment. Primary outcome is reduction in modelled Coronary Heart Disease (UKPDS CHD) risk at five years. Seven thousand (30% of South Asian ethnic origin) volunteers over three years will be recruited to identify a screen-detected T2DM cohort (n = 285) powered to detected a 6% relative difference (80% power, alpha 0.05) between treatment groups at one year. Randomisation will occur at practice-level with newly diagnosed T2DM cases receiving either conventional (according to current national guidelines) or intensive (algorithmic target-driven multi-factorial cardiovascular risk intervention) treatments. Discussion ADDITION-Leicester is the largest multiethnic (targeting >30% South Asian recruitment) community T2DM and vascular risk screening programme in the UK. By assessing feasibility and efficacy of T2DM screening, it will inform national disease prevention policy and contribute significantly to our understanding of the health care needs of UK South Asians. Trial registration Clinicaltrial.gov (NCT00318032). PMID:20170482

Comparison of energy expenditure, body composition, metabolic disorders, and energy intake between obese children with a history of craniopharyngioma and children with multifactorial obesity.

PubMed

Bomer, Ilanit; Saure, Carola; Caminiti, Carolina; Ramos, Javier Gonzales; Zuccaro, Graciela; Brea, Mercedes; Bravo, Mónica; Maza, Carmen

2015-11-01

Craniopharyngioma is a histologically benign brain malformation with a fundamental role in satiety modulation, causing obesity in up to 52% of patients. To evaluate cardiovascular risk factors, body composition, resting energy expenditure (REE), and energy intake in craniopharyngioma patients and to compare the data with those from children with multifactorial obesity. All obese children and adolescents who underwent craniopharyngioma resection and a control group of children with multifactorial obesity in follow-up between May 2012 and April 2013. Anthropometric measurements, bioelectrical impedance, indirect calorimetry, energy intake, homeostatic model assessment insulin resistance (HOMA-IR), and dyslipidemia were evaluated. Twenty-three patients with craniopharyngioma and 43 controls were included. Children with craniopharyngioma-related obesity had a lower fat-free mass percentage (62.4 vs. 67.5; p=0.01) and a higher fat mass percentage (37.5 vs. 32.5; p=0.01) compared to those with multifactorial obesity. A positive association was found between %REE and %fat-free mass in subjects with multifactorial obesity (68±1% in normal REE vs. 62.6±1% in low REE; p=0.04), but not in craniopharyngioma patients (62±2.7 in normal REE vs. 61.2±1.8% in low REE; p=0.8). No differences were found in metabolic involvement or energy intake. REE was lower in craniopharyngioma patients compared to children with multifactorial obesity regardless of the amount of fat-free mass, suggesting that other factors may be responsible for the lower REE.

puma: a Bioconductor package for propagating uncertainty in microarray analysis.

PubMed

Pearson, Richard D; Liu, Xuejun; Sanguinetti, Guido; Milo, Marta; Lawrence, Neil D; Rattray, Magnus

2009-07-09

Most analyses of microarray data are based on point estimates of expression levels and ignore the uncertainty of such estimates. By determining uncertainties from Affymetrix GeneChip data and propagating these uncertainties to downstream analyses it has been shown that we can improve results of differential expression detection, principal component analysis and clustering. Previously, implementations of these uncertainty propagation methods have only been available as separate packages, written in different languages. Previous implementations have also suffered from being very costly to compute, and in the case of differential expression detection, have been limited in the experimental designs to which they can be applied. puma is a Bioconductor package incorporating a suite of analysis methods for use on Affymetrix GeneChip data. puma extends the differential expression detection methods of previous work from the 2-class case to the multi-factorial case. puma can be used to automatically create design and contrast matrices for typical experimental designs, which can be used both within the package itself but also in other Bioconductor packages. The implementation of differential expression detection methods has been parallelised leading to significant decreases in processing time on a range of computer architectures. puma incorporates the first R implementation of an uncertainty propagation version of principal component analysis, and an implementation of a clustering method based on uncertainty propagation. All of these techniques are brought together in a single, easy-to-use package with clear, task-based documentation. For the first time, the puma package makes a suite of uncertainty propagation methods available to a general audience. These methods can be used to improve results from more traditional analyses of microarray data. puma also offers improvements in terms of scope and speed of execution over previously available methods. puma is recommended for anyone working with the Affymetrix GeneChip platform for gene expression analysis and can also be applied more generally.

Clinical trials with multiple endpoints can establish a correlation, but not (yet) causality, between dietary supplementation with omega-3 fatty acids and keratoconjunctivitis sicca.

PubMed

Mendoza, Roger Lee

2018-06-13

We review clinical evidence of therapeutic efficacy and effectiveness of omega-3 fatty acids (omega-3s) in keratoconjunctivitis sicca, colloquially known as dry eye disease. In doing so, we identify relevant literature to address the following questions: (1) What definitive guidance can clinical evidence offer eye physicians and their patients? (2) What aspects of omega-3 supplementation lack definitive evidence, and how might economic assessments help? A targeted and systematic search strategy based on PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) was designed in this study for refereed clinical trials of omega-3s in dry eye treatment. Four key databases were accessed. Records were filtered through a three-step process using predetermined inclusion criteria. Data was extracted for experimental design, sample population characteristics, content of test and control groups, symptoms and associated opthalmologic conditions, diagnostic measures, patient health outcomes, adverse events, and model time horizon. A total of 219 records were initially identified, of which 21 prospective clinical trials, with a total of 2,973 participants, were admitted for review. Clinical evidence indicates that daily oral supplementation with omega-3s statistically correlates with dry eye treatment in the general symptomatic population as well as induced sub-populations. Reported adverse events are minimal. These trials nonetheless exhibit considerable heterogeneity in clinical endpoints, particularly as a result of the multi-factorial character of dry eye as well as continuous advances in scientific knowledge and technology. Their findings and recommendations appear to be of limited external validity. And causal inferences are needed, but difficult to establish. These have encouraged and sustained wide variations in ophthalmologic practice and normative decision-making. Comparability of omega-3 therapeutic efficacy and effectiveness remains a major challenge in dry eye disease management. Notwithstanding its multi-factorial character, addressing prevailing methodological and empirical issues in clinical trials will help reduce knowledge gaps and normative choices among eye physicians and patients alike. In this regard, pharmacoeconomics offers a useful and robust toolset through which analysis of cost-minimization, cost-effectiveness, and cost-utility as well as meta-analysis can be comparatively pursued. Blending measures of costs and outcomes puts in perspective the heterogeneity of clinical endpoints in keratoconjunctivitis sicca.

Multifactorial intervention for children with asthma and overweight (Mikado): study design of a randomised controlled trial.

PubMed

Willeboordse, Maartje; van de Kant, Kim D G; de Laat, Maroeska N; van Schayck, Onno C P; Mulkens, Sandra; Dompeling, Edward

2013-05-21

In children, the prevalence's of both obesity and asthma are disconcertingly high. Asthmatic children with obesity are characterised by less asthma control and a high need for asthma medication. As the obese asthmatic child is becoming more common in the clinical setting and the disease burden of the asthma-obesity phenotype is high, there is an increasing need for effective treatment in these children. In adults, weight reduction resulted in improved lung function, better asthma control and less need for asthma medication. In children this is hardly studied. The Mikado study aims to evaluate the effectiveness of a long term multifactorial weight reduction intervention, on asthma characteristics in children with asthma and a high body weight. The Mikado study is a two-armed, randomised controlled trial. In total, 104 participants will be recruited via online questionnaires, pulmonary paediatricians, the youth department of the Municipal Health Services and cohorts of existing studies. All participants will be aged 6-16 years, will have current asthma, a Body Mass Index in the overweight or obesity range, and no serious comorbidities (such as diabetes, heart diseases). Participants in the intervention arm will receive a multifactorial intervention of 18 months consisting of sessions concerning sports, parental involvement, individual counselling and lifestyle advices including dietary advices and cognitive behavioural therapy. The control group will receive usual care. The primary outcome variables will include Forced Expiratory Volume in one second and Body Mass Index - Standard Deviation Score. Secondary outcomes will include other lung function parameters (including dynamic and static lung function parameters), asthma control, asthma-specific quality of life, use of asthma medication and markers of systemic inflammation and airway inflammation. In this randomised controlled trial we will study the potential of a multifactorial weight reduction intervention to improve asthma-related outcome measures in asthmatic children with overweight. Moreover, it will provide information about the underlying mechanisms in the relationship between asthma and a high body weight in children. These findings can contribute to optimal management programs and better clinical guidelines for children with asthma and overweight. Clinicaltrial.gov NCT00998413.

Combination of uniform design with artificial neural network coupling genetic algorithm: an effective way to obtain high yield of biomass and algicidal compound of a novel HABs control actinomycete

PubMed Central

2014-01-01

Controlling harmful algae blooms (HABs) using microbial algicides is cheap, efficient and environmental-friendly. However, obtaining high yield of algicidal microbes to meet the need of field test is still a big challenge since qualitative and quantitative analysis of algicidal compounds is difficult. In this study, we developed a protocol to increase the yield of both biomass and algicidal compound present in a novel algicidal actinomycete Streptomyces alboflavus RPS, which kills Phaeocystis globosa. To overcome the problem in algicidal compound quantification, we chose algicidal ratio as the index and used artificial neural network to fit the data, which was appropriate for this nonlinear situation. In this protocol, we firstly determined five main influencing factors through single factor experiments and generated the multifactorial experimental groups with a U15(155) uniform-design-table. Then, we used the traditional quadratic polynomial stepwise regression model and an accurate, fully optimized BP-neural network to simulate the fermentation. Optimized with genetic algorithm and verified using experiments, we successfully increased the algicidal ratio of the fermentation broth by 16.90% and the dry mycelial weight by 69.27%. These results suggested that this newly developed approach is a viable and easy way to optimize the fermentation conditions for algicidal microorganisms. PMID:24886410

Combination of uniform design with artificial neural network coupling genetic algorithm: an effective way to obtain high yield of biomass and algicidal compound of a novel HABs control actinomycete.

PubMed

Cai, Guanjing; Zheng, Wei; Yang, Xujun; Zhang, Bangzhou; Zheng, Tianling

2014-05-24

Controlling harmful algae blooms (HABs) using microbial algicides is cheap, efficient and environmental-friendly. However, obtaining high yield of algicidal microbes to meet the need of field test is still a big challenge since qualitative and quantitative analysis of algicidal compounds is difficult. In this study, we developed a protocol to increase the yield of both biomass and algicidal compound present in a novel algicidal actinomycete Streptomyces alboflavus RPS, which kills Phaeocystis globosa. To overcome the problem in algicidal compound quantification, we chose algicidal ratio as the index and used artificial neural network to fit the data, which was appropriate for this nonlinear situation. In this protocol, we firstly determined five main influencing factors through single factor experiments and generated the multifactorial experimental groups with a U15(155) uniform-design-table. Then, we used the traditional quadratic polynomial stepwise regression model and an accurate, fully optimized BP-neural network to simulate the fermentation. Optimized with genetic algorithm and verified using experiments, we successfully increased the algicidal ratio of the fermentation broth by 16.90% and the dry mycelial weight by 69.27%. These results suggested that this newly developed approach is a viable and easy way to optimize the fermentation conditions for algicidal microorganisms.

Does the Use of Multifactorial Training Methods Increase Practitioners' Competence?

ERIC Educational Resources Information Center

Pittman, Corinthus Omari; Lawdis, Katina

2017-01-01

Skilled therapy practitioners are required by their governing associations to seek professional development per licensure requirements. These requirements facilitate clinical reasoning and confidence during patient care. There are limited online professional development workshops, especially ones that offer multifactorial training as an…

Production of polycaprolactone nanoparticles with low polydispersity index in a tubular recirculating system by using a multifactorial design of experiments

NASA Astrophysics Data System (ADS)

Colmenares Roldán, Gabriel Jaime; Agudelo Gomez, Liliana María; Carlos Cornelio, Jesús Antonio; Rodriguez, Luis Fernando; Pinal, Rodolfo; Hoyos Palacio, Lina Marcela

2018-03-01

Encapsulation and controlled release of substances using polymeric nanoparticles require that these have a high reproducibility, homogeneity, and control over their properties (diameter and polydispersity), especially when they are to be used in medical, pharmaceutical, or nutritional applications among others. In conventional production systems, it is tough to ensure these characteristics; hence, the cost increases when we try to control these properties. This paper shows a comparison between a recirculating system and the standard nanoprecipitation technique for producing polymeric nanoparticles. In previous investigations, we evaluate the effect of recirculating flow and the ratio between the organic and aqueous phase. For this paper, we evaluated the effect of polymer and surfactant concentrations using a multifactorial design of experiments on the recirculating system and on the standard nanoprecipitation system. The response of the design was the average diameter of the nanoparticles and polydispersity index. Finally, we found that the polymer and surfactant concentrations could change the average diameter and polydispersity index of the nanoparticles obtained. On the other hand, it was found that the effect of the polymer concentration was stronger than the surfactant concentration to reduce the average diameter of the nanoparticles. The results of the present study show that the proposed recirculation system presents a high potential to produce polymer nanoparticles with good morphological characteristics, particle size distributions in the nano range, and with a low polydispersity. The average mean size of nanoparticles of polycaprolactone for the design using the recirculating system was of 61 to 140 nm and the values of polydispersity index PDI for this design were between 0.097 and 0.22, while for the design using the standard nanoprecipitation technique, the obtained diameters were 74 to 176 nm and the polydispersity was between 0.26 and 0.41.

Current State and Future Perspectives in QSAR Models to Predict Blood- Brain Barrier Penetration in Central Nervous System Drug R&D.

PubMed

Morales, Juan F; Montoto, Sebastian Scioli; Fagiolino, Pietro; Ruiz, Maria E

2017-01-01

The Blood-Brain Barrier (BBB) is a physical and biochemical barrier that restricts the entry of certain drugs to the Central Nervous System (CNS), while allowing the passage of others. The ability to predict the permeability of a given molecule through the BBB is a key aspect in CNS drug discovery and development, since neurotherapeutic agents with molecular targets in the CNS should be able to cross the BBB, whereas peripherally acting agents should not, to minimize the risk of CNS adverse effects. In this review we examine and discuss QSAR approaches and current availability of experimental data for the construction of BBB permeability predictive models, focusing on the modeling of the biorelevant parameter unbound partitioning coefficient (Kp,uu). Emphasis is made on two possible strategies to overcome the current limitations of in silico models: considering the prediction of brain penetration as a multifactorial problem, and increasing experimental datasets through accurate and standardized experimental techniques.

The effectiveness of a multidisciplinary QI activity for accidental fall prevention: Staff compliance is critical

PubMed Central

2012-01-01

Background Accidental falls among inpatients are a substantial cause of hospital injury. A number of successful experimental studies on fall prevention have shown the importance and efficacy of multifactorial intervention, though success rates vary. However, the importance of staff compliance with these effective, but often time-consuming, multifactorial interventions has not been fully investigated in a routine clinical setting. The purpose of this observational study was to describe the effectiveness of a multidisciplinary quality improvement (QI) activity for accidental fall prevention, with particular focus on staff compliance in a non-experimental clinical setting. Methods This observational study was conducted from July 2004 through December 2010 at St. Luke’s International Hospital in Tokyo, Japan. The QI activity for in-patient falls prevention consisted of: 1) the fall risk assessment tool, 2) an intervention protocol to prevent in-patient falls, 3) specific environmental safety interventions, 4) staff education, and 5) multidisciplinary healthcare staff compliance monitoring and feedback mechanisms. Results The overall fall rate was 2.13 falls per 1000 patient days (350/164331) in 2004 versus 1.53 falls per 1000 patient days (263/172325) in 2010, representing a significant decrease (p = 0.039). In the first 6 months, compliance with use of the falling risk assessment tool at admission was 91.5% in 2007 (3998/4368), increasing to 97.6% in 2010 (10564/10828). The staff compliance rate of implementing an appropriate intervention plan was 85.9% in 2007, increasing to 95.3% in 2010. Conclusion In our study we observed a substantial decrease in patient fall rates and an increase of staff compliance with a newly implemented falls prevention program. A systematized QI approach that closely involves, encourages, and educates healthcare staff at multiple levels is effective. PMID:22788785

RNAi control of aflatoxins in peanut plants, a multifactorial system

USDA-ARS?s Scientific Manuscript database

RNA-interference (RNAi)-mediated control of aflatoxin contamination in peanut plants is a multifactorial and hyper variable system. The use of RNAi biotechnology to silence single genes in plants has inherently high-variability among transgenic events. Also the level of expression of small interfe...

How are information seeking, scanning, and processing related to beliefs about the roles of genetics and behavior in cancer causation?

PubMed Central

Waters, Erika A.; Wheeler, Courtney; Hamilton, Jada G.

2016-01-01

Background Understanding that cancer is caused by both genetic and behavioral risk factors is an important component of genomic literacy. However, a considerable percentage of people in the U.S. do not endorse such multifactorial beliefs. Methods Using nationally representative cross-sectional data from the U.S. Health Information National Trends Survey (N=2,529), we examined how information seeking, information scanning, and key information processing characteristics were associated with endorsing a multifactorial model of cancer causation. Results Multifactorial beliefs about cancer were more common among respondents who engaged in cancer information scanning (p=.001), were motivated to process health information (p=.005), and who reported a family history of cancer (p=.0002). Respondents who reported having previous negative information seeking experiences had lower odds of endorsing multifactorial beliefs (p=.01). Multifactorial beliefs were not associated with cancer information seeking, trusting cancer information obtained from the Internet, trusting cancer information from a physician, self-efficacy for obtaining cancer information, numeracy, or being aware of direct-to-consumer genetic testing (ps>.05). Conclusion Gaining additional understanding of how people access, process, and use health information will be critical for the continued development and dissemination of effective health communication interventions and for the further translation of genomics research to public health and clinical practice. PMID:27661291

How Are Information Seeking, Scanning, and Processing Related to Beliefs About the Roles of Genetics and Behavior in Cancer Causation?

PubMed

Waters, Erika A; Wheeler, Courtney; Hamilton, Jada G

2016-01-01

Understanding that cancer is caused by both genetic and behavioral risk factors is an important component of genomic literacy. However, a considerable percentage of people in the United States do not endorse such multifactorial beliefs. Using nationally representative cross-sectional data from the U.S. Health Information National Trends Survey (N = 2,529), we examined how information seeking, information scanning, and key information-processing characteristics were associated with endorsing a multifactorial model of cancer causation. Multifactorial beliefs about cancer were more common among respondents who engaged in cancer information scanning (p = .001), were motivated to process health information (p = .005), and reported a family history of cancer (p = .0002). Respondents who reported having previous negative information-seeking experiences had lower odds of endorsing multifactorial beliefs (p = .01). Multifactorial beliefs were not associated with cancer information seeking, trusting cancer information obtained from the Internet, trusting cancer information from a physician, self-efficacy for obtaining cancer information, numeracy, or being aware of direct-to-consumer genetic testing (ps > .05). Gaining additional understanding of how people access, process, and use health information will be critical for the continued development and dissemination of effective health communication interventions and for the further translation of genomics research to public health and clinical practice.

Examining dynamic interactions among experimental factors influencing hydrologic data assimilation with the ensemble Kalman filter

NASA Astrophysics Data System (ADS)

Wang, S.; Huang, G. H.; Baetz, B. W.; Cai, X. M.; Ancell, B. C.; Fan, Y. R.

2017-11-01

The ensemble Kalman filter (EnKF) is recognized as a powerful data assimilation technique that generates an ensemble of model variables through stochastic perturbations of forcing data and observations. However, relatively little guidance exists with regard to the proper specification of the magnitude of the perturbation and the ensemble size, posing a significant challenge in optimally implementing the EnKF. This paper presents a robust data assimilation system (RDAS), in which a multi-factorial design of the EnKF experiments is first proposed for hydrologic ensemble predictions. A multi-way analysis of variance is then used to examine potential interactions among factors affecting the EnKF experiments, achieving optimality of the RDAS with maximized performance of hydrologic predictions. The RDAS is applied to the Xiangxi River watershed which is the most representative watershed in China's Three Gorges Reservoir region to demonstrate its validity and applicability. Results reveal that the pairwise interaction between perturbed precipitation and streamflow observations has the most significant impact on the performance of the EnKF system, and their interactions vary dynamically across different settings of the ensemble size and the evapotranspiration perturbation. In addition, the interactions among experimental factors vary greatly in magnitude and direction depending on different statistical metrics for model evaluation including the Nash-Sutcliffe efficiency and the Box-Cox transformed root-mean-square error. It is thus necessary to test various evaluation metrics in order to enhance the robustness of hydrologic prediction systems.

Occupational exposure and risk of breast cancer

PubMed Central

FENGA, CONCETTINA

2016-01-01

Breast cancer is a multifactorial disease and the most commonly diagnosed cancer in women. Traditional risk factors for breast cancer include reproductive status, genetic mutations, family history and lifestyle. However, increasing evidence has identified an association between breast cancer and occupational factors, including environmental stimuli. Epidemiological and experimental studies demonstrated that ionizing and non-ionizing radiation exposure, night-shift work, pesticides, polycyclic aromatic hydrocarbons and metals are defined environmental factors for breast cancer, particularly at young ages. However, the mechanisms by which occupational factors can promote breast cancer initiation and progression remains to be elucidated. Furthermore, the evaluation of occupational factors for breast cancer, particularly in the workplace, also remains to be explained. The present review summarizes the occupational risk factors and the associated mechanisms involved in breast cancer development, in order to highlight new environmental exposures that could be correlated to breast cancer and to provide new insights for breast cancer prevention in the occupational settings. Furthermore, this review suggests that there is a requirement to include, through multidisciplinary approaches, different occupational exposure risks among those associated with breast cancer development. Finally, the design of new epigenetic biomarkers may be useful to identify the workers that are more susceptible to develop breast cancer. PMID:26998264

Acute experimental hip muscle pain alters single-leg squat balance in healthy young adults.

PubMed

Hatton, Anna L; Crossley, Kay M; Hug, François; Bouma, James; Ha, Bonnie; Spaulding, Kara L; Tucker, Kylie

2015-05-01

Clinical musculoskeletal pain commonly accompanies hip pathology and can impact balance performance. Due to the cross-sectional designs of previous studies, and the multifactorial nature of musculoskeletal pain conditions, it is difficult to determine whether pain is a driver of balance impairments in this population. This study explored the effects of experimentally induced hip muscle pain on static and dynamic balance. Twelve healthy adults (4 women, mean[SD]: 27.1[3] years) performed three balance tasks on each leg, separately: single-leg standing (eyes closed), single-leg squat (eyes open), forward step (eyes open); before and after hypertonic saline injection (1ml, 5% NaCl) into the right gluteus medius. Range, standard deviation (SD), and velocity of the centre of pressure (CoP) in medio-lateral (ML) and anterior-posterior (AP) directions were considered. During the single-leg squat task, experimental hip pain was associated with significantly reduced ML range (-4[13]%, P=0.028), AP range (-14[21]%, P=0.005), APSD (-15[28]%, P=0.009), and AP velocity (-6[13]%, P=0.032), relative to the control condition, in both legs. No effect of pain was observed during single-leg standing and forward stepping. Significant between-leg differences in ML velocity were observed during the forward stepping task (P=0.034). Pain is a potentially modifiable patient-reported outcome in individuals with hip problems. This study demonstrates that acute hip muscle pain alone, without interference of musculoskeletal pathology, does not lead to the same impairments in balance as exhibited in clinical populations with hip pathologies. This is the first step in understanding how and why balance is altered in painful hip pathologies. Copyright © 2015 Elsevier B.V. All rights reserved.

Nitric oxide modulates the immunological response of bovine PBMCs in an in vitro BRDc infection model.

PubMed

Sheridan, Michael Peter; Regev-Shoshani, Gilly; Martins, James; Vimalanathan, Selvarani; Miller, Chris

2016-12-01

Bovine respiratory disease complex (BRDc) is a multi-factorial disease, involving both viral and bacterial pathogens, that negatively impacts the cattle feedlot industry. A nitric oxide releasing solution (NORS) has been developed and shown to have potential in the prevention of BRDc. This study investigated the underlying immunological mechanisms through which the nitroslyating agent NORS provides protection against the development of BRDc in susceptible cattle. An in vitro BRDc experimental model was designed using bovine peripheral blood mononuclear cells (PBMCs) which were infected with bovine herpesvirus 1 (BHV-1) and subsequently cultured with lipopolysaccharides (LPS) extracted from Mannheimia haemolytica bacteria. The cells were treated with NORS following viral infection to reflect the timing of administering the NORS treatment in feedlots during initial processing. An expression and protein analysis of key genes involved in the innate immune response was carried out. The BRDc model produced significant increases in gene expression (p<0.01) and protein release (p<0.05) of the proinflammatory cytokines IL-1β and TNF. Treatment with NORS reduced the protein levels of IL-1β (0.39-fold↓) (p<0.05) and TNF (0.48-fold↓) (p<0.01) in the BRDc experimental group when compared against the non-treatment BRDc controls. TLR4 expression, having been significantly reduced under the BRDc experimental conditions (0.33-fold↓) (p<0.05), increased significantly (0.76-fold↑) (p<0.05) following NORS treatment. This study provides evidence suggesting that NO may protect against the development of BRDc by limiting deleterious inflammation while simultaneously increasing TLR4 expression and enhancing the ability of the host to detect and respond to bacterial pathogens. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effect of coffee (caffeine) against human cataract blindness

PubMed Central

Varma, Shambhu D

2016-01-01

Previous biochemical and morphological studies with animal experiments have demonstrated that caffeine given topically or orally to certain experimental animal models has significant inhibitory effect on cataract formation. The present studies were undertaken to examine if there is a correlation between coffee drinking and incidence of cataract blindness in human beings. That has been found to be the case. Incidence of cataract blindness was found to be significantly lower in groups consuming higher amounts of coffee in comparison to the groups with lower coffee intake. Mechanistically, the caffeine effect could be multifactorial, involving its antioxidant as well as its bioenergetic effects on the lens. PMID:26869755

HoPaCI-DB: host-Pseudomonas and Coxiella interaction database

PubMed Central

Bleves, Sophie; Dunger, Irmtraud; Walter, Mathias C.; Frangoulidis, Dimitrios; Kastenmüller, Gabi; Voulhoux, Romé; Ruepp, Andreas

2014-01-01

Bacterial infectious diseases are the result of multifactorial processes affected by the interplay between virulence factors and host targets. The host-Pseudomonas and Coxiella interaction database (HoPaCI-DB) is a publicly available manually curated integrative database (http://mips.helmholtz-muenchen.de/HoPaCI/) of host–pathogen interaction data from Pseudomonas aeruginosa and Coxiella burnetii. The resource provides structured information on 3585 experimentally validated interactions between molecules, bioprocesses and cellular structures extracted from the scientific literature. Systematic annotation and interactive graphical representation of disease networks make HoPaCI-DB a versatile knowledge base for biologists and network biology approaches. PMID:24137008

Interventions for the prevention of falls in older adults: systematic review and meta-analysis of randomised clinical trials

PubMed Central

Chang, John T; Morton, Sally C; Rubenstein, Laurence Z; Mojica, Walter A; Maglione, Margaret; Suttorp, Marika J; Roth, Elizabeth A; Shekelle, Paul G

2004-01-01

Objective To assess the relative effectiveness of interventions to prevent falls in older adults to either a usual care group or control group. Design Systematic review and meta-analyses. Data sources Medline, HealthSTAR, Embase, the Cochrane Library, other health related databases, and the reference lists from review articles and systematic reviews. Data extraction Components of falls intervention: multifactorial falls risk assessment with management programme, exercise, environmental modifications, or education. Results 40 trials were identified. A random effects analysis combining trials with risk ratio data showed a reduction in the risk of falling (risk ratio 0.88, 95% confidence interval 0.82 to 0.95), whereas combining trials with incidence rate data showed a reduction in the monthly rate of falling (incidence rate ratio 0.80, 0.72 to 0.88). The effect of individual components was assessed by meta-regression. A multifactorial falls risk assessment and management programme was the most effective component on risk of falling (0.82, 0.72 to 0.94, number needed to treat 11) and monthly fall rate (0.63, 0.49 to 0.83; 11.8 fewer falls in treatment group per 100 patients per month). Exercise interventions also had a beneficial effect on the risk of falling (0.86, 0.75 to 0.99, number needed to treat 16) and monthly fall rate (0.86, 0.73 to 1.01; 2.7). Conclusions Interventions to prevent falls in older adults are effective in reducing both the risk of falling and the monthly rate of falling. The most effective intervention was a multifactorial falls risk assessment and management programme. Exercise programmes were also effective in reducing the risk of falling. PMID:15031239

A MULTI-CENTER CLUSTER-RANDOMIZED TRIAL OF A MULTI-FACTORIAL INTERVENTION TO IMPROVE ANTIHYPERTENSIVE MEDICATION ADHERENCE AND BLOOD PRESSURE CONTROL AMONG PATIENTS AT HIGH CARDIOVASCULAR RISK (The COM99 study)*

PubMed Central

Pladevall, Manel; Brotons, Carlos; Gabriel, Rafael; Arnau, Anna; Suarez, Carmen; de la Figuera, Mariano; Marquez, Emilio; Coca, Antonio; Sobrino, Javier; Divine, George; Heisler, Michele; Williams, L Keoki

2010-01-01

Background Medication non-adherence is common and results in preventable disease complications. This study assesses the effectiveness of a multifactorial intervention to improve both medication adherence and blood pressure control and to reduce cardiovascular events. Methods and Results In this multi-center, cluster-randomized trial, physicians from hospital-based hypertension clinics and primary care centers across Spain were randomized to receive and provide the intervention to their high-risk patients. Eligible patients were ≥50 years of age, had uncontrolled hypertension, and had an estimated 10-year cardiovascular risk greater than 30%. Physicians randomized to the intervention group counted patients’ pills, designated a family member to support adherence behavior, and provided educational information to patients. The primary outcome was blood pressure control at 6 months. Secondary outcomes included both medication adherence and a composite end-point of all cause mortality and cardiovascular-related hospitalizations. Seventy-nine physicians and 877 patients participated in the trial. The mean duration of follow-up was 39 months. Intervention patients were less likely to have an uncontrolled systolic blood pressure (odds ratio 0.62; 95% confidence interval [CI] 0.50–0.78) and were more likely to be adherent (OR 1.91; 95% CI 1.19–3.05) when compared with control group patients at 6 months. After five years 16% of the patients in the intervention group and 19% in the control group met the composite end-point (hazard ratio 0.97; 95% CI 0.67–1.39). Conclusions A multifactorial intervention to improve adherence to antihypertensive medication was effective in improving both adherence and blood pressure control, but it did not appear to improve long-term cardiovascular events. PMID:20823391

Memantine Attenuates Delayed Vasospasm after Experimental Subarachnoid Hemorrhage via Modulating Endothelial Nitric Oxide Synthase.

PubMed

Huang, Chih-Yuan; Wang, Liang-Chao; Shan, Yan-Shen; Pan, Chia-Hsin; Tsai, Kuen-Jer

2015-06-23

Delayed cerebral vasospasm is an important pathological feature of subarachnoid hemorrhage (SAH). The cause of vasospasm is multifactorial. Impairs nitric oxide availability and endothelial nitric oxide synthase (eNOS) dysfunction has been reported to underlie vasospasm. Memantine, a low-affinity uncompetitive N-methyl-d-aspartate (NMDA) blocker has been proven to reduce early brain injury after SAH. This study investigated the effect of memantine on attenuation of vasospasm and restoring eNOS functionality. Male Sprague-Dawley rats weighing 350-450 g were randomly divided into three weight-matched groups, sham surgery, SAH + vehicle, and SAH + memantine groups. The effects of memantine on SAH were evaluated by assessing the severity of vasospasm and the expression of eNOS. Memantine effectively ameliorated cerebral vasospasm by restoring eNOS functionality. Memantine can prevent vasospasm in experimental SAH. Treatment strategies may help combat SAH-induced vasospasm in the future.

Development and Validation of a Multifactorial Treatment Outcome Measure for Eating Disorders.

ERIC Educational Resources Information Center

Anderson, Drew A.; Williamson, Donald A.; Duchmann, Erich G.; Gleaves, David H.; Barbin, Jane M.

1999-01-01

Developed a brief self-report inventory to evaluate treatment outcome for anorexia and bulimia nervosa, the Multifactorial Assessment of Eating Disorders, and evaluated the instrument in a series of studies involving 1,054 women. Results support a stable factor structure and satisfactory reliability and validity, and establish normative data. (SLD)

Multifactorial disease risk calculator: Risk prediction for multifactorial disease pedigrees.

PubMed

Campbell, Desmond D; Li, Yiming; Sham, Pak C

2018-03-01

Construction of multifactorial disease models from epidemiological findings and their application to disease pedigrees for risk prediction is nontrivial for all but the simplest of cases. Multifactorial Disease Risk Calculator is a web tool facilitating this. It provides a user-friendly interface, extending a reported methodology based on a liability-threshold model. Multifactorial disease models incorporating all the following features in combination are handled: quantitative risk factors (including polygenic scores), categorical risk factors (including major genetic risk loci), stratified age of onset curves, and the partition of the population variance in disease liability into genetic, shared, and unique environment effects. It allows the application of such models to disease pedigrees. Pedigree-related outputs are (i) individual disease risk for pedigree members, (ii) n year risk for unaffected pedigree members, and (iii) the disease pedigree's joint liability distribution. Risk prediction for each pedigree member is based on using the constructed disease model to appropriately weigh evidence on disease risk available from personal attributes and family history. Evidence is used to construct the disease pedigree's joint liability distribution. From this, lifetime and n year risk can be predicted. Example disease models and pedigrees are provided at the website and are used in accompanying tutorials to illustrate the features available. The website is built on an R package which provides the functionality for pedigree validation, disease model construction, and risk prediction. Website: http://grass.cgs.hku.hk:3838/mdrc/current. © 2017 WILEY PERIODICALS, INC.

Abundance of the tick Dermacentor reticulatus in an ecosystem of abandoned meadows: Experimental intervention and the critical importance of mowing.

PubMed

Bajer, Anna; Rodo, Anna; Alsarraf, Mohammed; Dwużnik, Dorota; Behnke, Jerzy M; Mierzejewska, Ewa J

2017-11-15

The effect of agricultural activities on the environment has been falling in many areas of Europe in recent years and the associated abandonment of crop fields, meadows and pastures may enable an increase in tick densities. In the present study we assessed whether regular mowing would have a negative effect on Dermacentor reticulatus populations and whether the cessation of regular mowing would cause an increase in abundance of D. reticulatus ticks. Two field experiments were conducted during a five-year period (2012-2016) in the Mazowieckie (Mazovia) region of Central Poland. Experiment 1: The long-term effect of mowing on tick population was tested in the meadow ecosystem of Stoski, an old fallow land plot that was mowed three times a year. Experiment 2: Neglecting the cultivation by abandonment of arable land was evaluated in Kury village. Four areas (2 experimental 'fallow lands', 2 control meadows) were selected. The first fallow land plot was a fenced off area comprising mostly of a horse pasture and the second fallow land plot was designated in an old abandoned orchard. At each site, ticks were collected in consecutive springs and autumns by dragging at least twice during each season from experimental and control areas. Altogether 1452 D. reticulatus ticks were collected and their densities were compared by multifactorial ANOVA. In the end of the first experiment, a significant decrease (6 times) in tick abundance was observed in the mowed area in comparison to old fallow land. In the end of the second experiment, tick abundance was three times higher in the experimental fallow lands in comparison to the control meadows. In conclusion it was found that regular mowing significantly reduced the density of questing D. reticulatus ticks in open areas. Cessation of mowing may enhance the number of ticks and the associated risk of acquiring tick-borne diseases. Copyright © 2017 Elsevier B.V. All rights reserved.

A machine for the preliminary investigation of design features influencing the wear behaviour of knee prostheses.

PubMed

McGloughlin, T M; Murphy, D M; Kavanagh, A G

2004-01-01

Degradation of tibial inserts in vivo has been found to be multifactorial in nature, resulting in a complex interaction of many variables. A range of kinematic conditions occurs at the tibio-femoral interface, giving rise to various degrees of rolling and sliding at this interface. The movement of the tibio-femoral contact point may be an influential factor in the overall wear of ultra-high molecular weight polyethylene (UHMWPE) tibial components. As part of this study a three-station wear-test machine was designed and built to investigate the influence of rolling and sliding on the wear behaviour of specific design aspects of contemporary knee prostheses. Using the machine, it is possible to monitor the effect of various slide roll ratios on the performance of contemporary bearing designs from a geometrical and materials perspective.

Segregation analysis of apolipoproteins A-1 and B-100 measured before and after an exercise training program: the HERITAGE Family Study.

PubMed

An, P; Rice, T; Gagnon, J; Borecki, I B; Bergeron, J; Després, J P; Leon, A S; Skinner, J S; Wilmore, J H; Bouchard, C; Rao, D C

2000-03-01

Complex segregation analyses of apolipoproteins (apo) A-1 and B-100 were performed in a sample of 520 individuals from 99 white families who participated in the HERITAGE Family Study. In these sedentary families, plasma apo A-1 and B-100 concentrations were measured before and after a 20-week endurance exercise training program. Baseline apo A-1 and B-100 were adjusted for the effects of age (age-adjusted baseline apo A-1 and B-100) and for the effects of age and BMI (age-BMI-adjusted baseline apo A-1 and B-100). The change in response to training was computed as a simple Delta (posttraining minus baseline) and was adjusted for age and the baseline (age-baseline-adjusted apo A-1 and B-100 responses to training). In the present study, a major gene could not be inferred for baseline apo A-1. Rather, we found a major effect along with a multifactorial effect accounting for 8% to 9% and 51% to 56% of the variance, respectively. In addition, no clear evidence supported a major-gene effect for its response to training, whereas the transmission of a major effect from parents to offspring was ambiguous, ie, genetic in nature or familial environmental in origin. The major effect accounted for 15% of the variance, with an additional 21% and 58% of the variance being accounted for by a multifactorial effect in parents and offspring, respectively. It is interesting to have obtained evidence of a putative recessive major locus for baseline apo B-100, which accounted for 50% to 56% of the variance, with an additional 25% to 29% of the variance due to a multifactorial effect. In contrast, no major effect for its response to training was identified, although a multifactorial effect was found that accounted for 27% of the variance. The novel findings arising from the present study are summarized as follows. Baseline apo A-1 and its response to training were influenced by a major effect and a multifactorial effect. Baseline apo B-100 was influenced by a putative major recessive gene with a multifactorial component, but its response to training was influenced solely by a multifactorial component in these sedentary families.

Eating Patterns among Students with Intellectual Disabilities after a Multifactorial School Intervention Using the Plate Model

ERIC Educational Resources Information Center

Wallen, Eva Flygare; Mullerdorf, Maria; Christensson, Kyllike; Marcus, Claude

2013-01-01

Adolescents with intellectual disabilities (ID) have an increased prevalence of being overweight and having cardiometabolic diseases as adults, in part due to poor eating habits with an inadequate intake of vegetables. The aim of this study was to evaluate whether a multifactorial school intervention using the "Plate Model" results in…

Response surface methodology applied to the generation of casein hydrolysates with antioxidant and dipeptidyl peptidase IV inhibitory properties.

PubMed

Nongonierma, Alice B; Maux, Solène Le; Esteveny, Claire; FitzGerald, Richard J

2017-03-01

Hydrolysis parameters affecting the release of dipeptidyl peptidase IV (DPP-IV) inhibitory and antioxidant peptides from milk proteins have not been extensively studied. Therefore, a multifactorial (i.e. pH, temperature and hydrolysis time) composite design was used to optimise the release of bioactive peptides (BAPs) with DPP-IV inhibitory and antioxidant [oxygen radical absorbance capacity (ORAC)] properties from sodium caseinate. Fifteen sodium caseinate hydrolysates (H1-H15) were generated with Protamex TM , a bacillus proteinase activity. Hydrolysis time (1 to 5 h) had the highest influence on both DPP-IV inhibitory properties and ORAC activity (P < 0.05). Alteration of incubation temperature (40 to 60 °C) and pH (6.5 to 8.0) had an effect on the DPP-IV inhibitory properties but not the ORAC activity of the Protamex sodium caseinate hydrolysates. A multi-functional hydrolysate, H12, was identified having DPP-IV inhibitory (actual: 0.82 ± 0.24 vs. predicted optimum: 0.68 mg mL -1 ) and ORAC (actual: 639 ± 66 vs. predicted optimum: 639 µmol TE g -1 ) activity of the same order (P > 0.05) as the response surface methodology (RSM) predicted optimum bioactivities. Generation of milk protein hydrolysates through multifactorial design approaches may aid in the optimal enzymatic release of BAPs with serum glucose lowering and antioxidant properties. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Phytochemicals of Brassicaceae in plant protection and human health--influences of climate, environment and agronomic practice.

PubMed

Björkman, Maria; Klingen, Ingeborg; Birch, Andrew N E; Bones, Atle M; Bruce, Toby J A; Johansen, Tor J; Meadow, Richard; Mølmann, Jørgen; Seljåsen, Randi; Smart, Lesley E; Stewart, Derek

2011-05-01

In this review, we provide an overview of the role of glucosinolates and other phytochemical compounds present in the Brassicaceae in relation to plant protection and human health. Current knowledge of the factors that influence phytochemical content and profile in the Brassicaceae is also summarized and multi-factorial approaches are briefly discussed. Variation in agronomic conditions (plant species, cultivar, developmental stage, plant organ, plant competition, fertilization, pH), season, climatic factors, water availability, light (intensity, quality, duration) and CO(2) are known to significantly affect content and profile of phytochemicals. Phytochemicals such as the glucosinolates and leaf surface waxes play an important role in interactions with pests and pathogens. Factors that affect production of phytochemicals are important when designing plant protection strategies that exploit these compounds to minimize crop damage caused by plant pests and pathogens. Brassicaceous plants are consumed increasingly for possible health benefits, for example, glucosinolate-derived effects on degenerative diseases such as cancer, cardiovascular and neurodegenerative diseases. Thus, factors influencing phytochemical content and profile in the production of brassicaceous plants are worth considering both for plant and human health. Even though it is known that factors that influence phytochemical content and profile may interact, studies of plant compounds were, until recently, restricted by methods allowing only a reductionistic approach. It is now possible to design multi-factorial experiments that simulate their combined effects. This will provide important information to ecologists, plant breeders and agronomists. Copyright © 2011 Elsevier Ltd. All rights reserved.

Genetics and child psychiatry: I Advances in quantitative and molecular genetics.

PubMed

Rutter, M; Silberg, J; O'Connor, T; Simonoff, E

1999-01-01

Advances in quantitative psychiatric genetics as a whole are reviewed with respect to conceptual and methodological issues in relation to statistical model fitting, new genetic designs, twin and adoptee studies, definition of the phenotype, pervasiveness of genetic influences, pervasiveness of environmental influences, shared and nonshared environmental effects, and nature-nurture interplay. Advances in molecular genetics are discussed in relation to the shifts in research strategies to investigate multifactorial disorders (affected relative linkage designs, association strategies, and quantitative trait loci studies); new techniques and identified genetic mechanisms (expansion of trinucleotide repeats, genomic imprinting, mitochondrial DNA, fluorescent in-situ hybridisation, behavioural phenotypes, and animal models); and the successful localisation of genes.

Differential Angiogenic Regulation of Experimental Colitis

PubMed Central

Chidlow, John H.; Langston, Will; Greer, James J.M.; Ostanin, Dmitry; Abdelbaqi, Maisoun; Houghton, Jeffery; Senthilkumar, Annamalai; Shukla, Deepti; Mazar, Andrew P.; Grisham, Matthew B.; Kevil, Christopher G.

2006-01-01

Inflammatory bowel diseases (IBDs) are chronic inflammatory disorders of the intestinal tract with unknown multifactorial etiology that, among other things, result in alteration and dysfunction of the intestinal microvasculature. Clinical observations of increased colon microvascular density during IBD have been made. However, there have been no reports investigating the physiological or pathological importance of angiogenic stimulation during the development of intestinal inflammation. Here we report that the dextran sodium sulfate and CD4+CD45RBhigh T-cell transfer models of colitis stimulate angiogenesis that results in increased blood vessel density concomitant with increased histopathology, suggesting that the neovasculature contributes to tissue damage during colitis. We also show that leukocyte infiltration is an obligatory requirement for the stimulation of angiogenesis. The angiogenic response during experimental colitis was differentially regulated in that the production of various angiogenic mediators was diverse between the two models with only a small group of molecules being similarly controlled. Importantly, treatment with the anti-angiogenic agent thalidomide or ATN-161 significantly reduced angiogenic activity and associated tissue histopathology during experimental colitis. Our findings identify a direct pathological link between angiogenesis and the development of experimental colitis, representing a novel therapeutic target for IBD. PMID:17148665

The efficacy of a multifactorial memory training in older adults living in residential care settings.

PubMed

Vranić, Andrea; Španić, Ana Marija; Carretti, Barbara; Borella, Erika

2013-11-01

Several studies have shown an increase in memory performance after teaching mnemonic techniques to older participants. However, transfer effects to non-trained tasks are generally either very small, or not found. The present study investigates the efficacy of a multifactorial memory training program for older adults living in a residential care center. The program combines teaching of memory strategies with activities based on metacognitive (metamemory) and motivational aspects. Specific training-related gains in the Immediate list recall task (criterion task), as well as transfer effects on measures of short-term memory, long-term memory, working memory, motivational (need for cognition), and metacognitive aspects (subjective measure of one's memory) were examined. Maintenance of training benefits was assessed after seven months. Fifty-one older adults living in a residential care center, with no cognitive impairments, participated in the study. Participants were randomly assigned to two programs: the experimental group attended the training program, while the active control group was involved in a program in which different psychological issues were discussed. A benefit in the criterion task and substantial general transfer effects were found for the trained group, but not for the active control, and they were maintained at the seven months follow-up. Our results suggest that training procedures, which combine teaching of strategies with metacognitive-motivational aspects, can improve cognitive functioning and attitude toward cognitive activities in older adults.

Therapeutic inhibitors for the treatment of dry eye syndrome.

PubMed

Rodríguez-Pomar, Candela; Pintor, Jesus; Colligris, Basilio; Carracedo, Gonzalo

2017-12-01

Dry eye disease (DED), defined as a multifactorial disease of tears and ocular surface, results in symptoms of discomfort, ocular irritation, visual disturbance and tear film instability. This syndrome is accompanied of ocular surface inflammation and it is produced by a deficient activity of the lacrimal functional unit. In addition, it is associated with systemic autoimmune diseases such as Sjögren´s Syndrome, rheumatoid arthritis, systemic lupus erythematosus and some drug administration. The treatment of dry eye disease is based on the typical signs and symptoms of dry eye, which are associated with hyperosmolarity, ocular surface inflammation, discomfort, visual disturbance, and tear film instability. Areas covered: This review is focused on synthetic drugs currently used in clinical practice, from phase III development onwards to treat the ocular surface signs and symptoms of dry eye disease. Expert opinion: The multifactorial disease and the lack of correlation between signs and symptoms imply that not all the pharmacological approaches will be successful for dry eye. The correct design of the clinical trials, with appropriate endpoints, and the type of dry eye under study are complicated but mandatory. The anti-inflammatory and secretagogues drugs are both the main compounds to currently treat the dry eye disease.

Simultaneous in-cell derivatization pressurized liquid extraction for the determination of multiclass preservatives in leave-on cosmetics.

PubMed

Sanchez-Prado, Lucia; Lamas, J Pablo; Lores, Marta; Garcia-Jares, Carmen; Llompart, Maria

2010-11-15

An effective one-step sample preparation methodology for the determination of multiclass preservatives in cosmetics has been developed, applying, for the first time to this kind of matrix, pressurized liquid extraction (PLE) and a very simple, cheap, and fast derivatization procedure: acetylation with acetic anhydride and pyridine. A multifactorial experimental design has been used to evaluate and optimize the main experimental parameters potentially affecting the extraction process. In the final conditions the sample was mixed with Florisil as the dispersing sorbent and extracted with ethyl acetate for 15 min at 120 °C. One of the main goals of this work was to demonstrate the possibility of carrying out direct cosmetic preservative acetylation by simply adding the derivatization reagents into the PLE cell. The extract was then analyzed by GC/MS without any further cleanup or concentration step. The accuracy, precision, linearity, and detection limits (LODs) were evaluated to assess the performance of the proposed method. Quantitative recoveries were obtained, and relative standard deviation values were lower than 10% in all cases. The obtained LODs ranged from 0.000004% to 0.0001% (w/w), values far below the established restrictions in the European Cosmetics Regulation, making this multicomponent analytical method suitable for routine control. Finally, several cosmetic products such as moisturizing and antiwrinkle creams and lotions, hand creams, sunscreen and after-sun creams, baby lotions, and hair care products were analyzed. All the samples contained several of the target cosmetic ingredients, in some cases at quite high concentrations, although the actual European Cosmetics Regulation was fulfilled in all cases.

Multidimensional Single-Cell Analysis of BCR Signaling Reveals Proximal Activation Defect As a Hallmark of Chronic Lymphocytic Leukemia B Cells

PubMed Central

Palomba, M. Lia; Piersanti, Kelly; Ziegler, Carly G. K.; Decker, Hugo; Cotari, Jesse W.; Bantilan, Kurt; Rijo, Ivelise; Gardner, Jeff R.; Heaney, Mark; Bemis, Debra; Balderas, Robert; Malek, Sami N.; Seymour, Erlene; Zelenetz, Andrew D.

2014-01-01

Purpose Chronic Lymphocytic Leukemia (CLL) is defined by a perturbed B-cell receptor-mediated signaling machinery. We aimed to model differential signaling behavior between B cells from CLL and healthy individuals to pinpoint modes of dysregulation. Experimental Design We developed an experimental methodology combining immunophenotyping, multiplexed phosphospecific flow cytometry, and multifactorial statistical modeling. Utilizing patterns of signaling network covariance, we modeled BCR signaling in 67 CLL patients using Partial Least Squares Regression (PLSR). Results from multidimensional modeling were validated using an independent test cohort of 38 patients. Results We identified a dynamic and variable imbalance between proximal (pSYK, pBTK) and distal (pPLCγ2, pBLNK, ppERK) phosphoresponses. PLSR identified the relationship between upstream tyrosine kinase SYK and its target, PLCγ2, as maximally predictive and sufficient to distinguish CLL from healthy samples, pointing to this juncture in the signaling pathway as a hallmark of CLL B cells. Specific BCR pathway signaling signatures that correlate with the disease and its degree of aggressiveness were identified. Heterogeneity in the PLSR response variable within the B cell population is both a characteristic mark of healthy samples and predictive of disease aggressiveness. Conclusion Single-cell multidimensional analysis of BCR signaling permitted focused analysis of the variability and heterogeneity of signaling behavior from patient-to-patient, and from cell-to-cell. Disruption of the pSYK/pPLCγ2 relationship is uncovered as a robust hallmark of CLL B cell signaling behavior. Together, these observations implicate novel elements of the BCR signal transduction as potential therapeutic targets. PMID:24489640

Transgender populations and HIV: unique risks, challenges and opportunities.

PubMed

Wansom, Tanyaporn; Guadamuz, Thomas E; Vasan, Sandhya

2016-04-01

Due to unique social, behavioural, structural and biological issues, transgender (TG) populations, especially TG women, are at high risk for HIV acquisition. This increased risk is multifactorial, due to differing psychosocial risk factors, poorer access to TG-specific healthcare, a higher likelihood of using exogenous hormones or fillers without direct medical supervision, interactions between hormonal therapy and antiretroviral therapy, and direct effects of hormonal therapy on HIV acquisition and immune control. Further research is needed to elucidate these mechanisms of risk and to help design interventions to reduce HIV risk among transgender populations.

Susceptibility of Legionella Strains to the Chlorinated Biocide, Monochloramine

PubMed Central

Jakubek, Delphine; Guillaume, Carole; Binet, Marie; Leblon, Gérard; DuBow, Michael; Le Brun, Matthieu

2013-01-01

Members of the Legionella genus find suitable conditions for their growth and survival in nuclear power plant cooling circuits. To limit the proliferation of Legionella pathogenic bacteria in nuclear power plant cooling circuits, and ensure that levels remain below regulatory thresholds, monochloramine treatment can be used. Although the treatment is highly effective, i.e. it reduces Legionella numbers by over 99%, Legionella bacteria can still be detected at low concentrations and rapid re-colonisation of circuits can occur after the treatment has ceased. The aim of this study was to develop an in vitro methodology for determining the intrinsic susceptibility of L. pneumophila strains, collected from various nuclear power plant cooling circuits subjected to different treatment conditions. The methodology was developed by using an original approach based on response surface methodology (RSM) combined with a multifactorial experimental design. The susceptibility was evaluated by the Ct factor. The susceptibility of environmental strains varies widely and is, for some strains, greater than that of known tolerant species; however, strain susceptibility was not related to treatment conditions. Selection pressure induced by monochloramine use did not result in the selection of more tolerant Legionella strains and did not explain the detection of Legionella during treatment or the rapid re-colonisation of cooling circuits after disinfection has ceased. PMID:24005820

Bacoside A downregulates matrix metalloproteinases 2 and 9 in DEN-induced hepatocellular carcinoma.

PubMed

Janani, Panneerselvam; Sivakumari, Kanakarajan; Geetha, Arumugam; Yuvaraj, Sambandam; Parthasarathy, Chandrakesan

2010-03-01

Cancer metastasis is a complex multi-step process, responsible for a majority of cancer-related deaths by affecting the critical organs and causing complications in therapies. Hepatocellular carcinoma is a multi-factorial disease and is the third most common cause of cancer related mortality worldwide. Clinical and experimental studies have shown that MMP-2 and MMP-9 are involved in tumor invasion and metastases and their elevated expression has been associated with poor prognosis. Our recent studies showed a strong anti-oxidant and hepatoprotective effects of bacoside A (BA) against carcinogen. Nevertheless the effect of BA on the activities and expression of MMP-2 and MMP-9 during hepatocellular carcinoma is not yet recognized. Therefore, the present study was designed to assess the same. Results of gelatin zymography study showed that BA co-treatment significantly decreased the activities of MMP-2 and MMP-9, which is increased during hepatocellular carcinoma. Further immunoblot analysis showed decreased expression of MMP-2 and MMP-9 in rats co-treated with BA compared to DEN-induced hepatocellular carcinoma. Our results reveal that BA exerts its anti-metastatic effect against DEN-induced hepatocellular carcinoma by inhibiting the activities and expressions of MMP-2 and MMP-9. 2010 John Wiley & Sons, Ltd.

AACR Centennial Series: The Biology of Cancer Metastasis: Historical Perspective

PubMed Central

Talmadge, James E; Fidler, Isaiah J

2014-01-01

Metastases resistant to therapy is the major cause of death from cancer. Despite almost 200 years of study, the process of tumor metastasis remains controversial. Stephen Paget initially identified the role of host-tumor interactions on the basis of a review of autopsy records. His “seed and soil” hypothesis was substantiated a century later with experimental studies and numerous reports have confirmed these seminal observations. Inarguably, an improved understanding of the metastatic process and the attributes of the cells selected by this process are critical to the treatment of patients with systemic disease. In many patients, metastasis has occurred by the time of diagnosis, such that metastasis prevention may not be relevant, and treatment of systemic disease, as well as the identity of patients with early disease, should be our goal. During the last three decades, revitalized research has focused on new discoveries in the biology of metastasis. While our understanding of the molecular events that regulate metastasis has improved; nonetheless, the relevant contributions and timing of molecular lesion(s) potentially involved in its pathogenesis remain unclear. The history of pioneering observations and discussion of current controversies should help investigators understand the complex and multifactorial interactions between the host and selected tumor cells that contribute to fatal metastasis and allow for the design of successful therapy. PMID:20610625

Two outer membrane lipoproteins from Histophilus somni are immunogenic in rabbits and sheep and induce protection against bacterial challenge in mice.

PubMed

Guzmán-Brambila, Carolina; Rojas-Mayorquín, Argelia E; Flores-Samaniego, Beatriz; Ortuño-Sahagún, Daniel

2012-11-01

Histophilus somni is an economically important pathogen of cattle and other ruminants and is considered one of the key components of the bovine respiratory disease (BRD) complex, the leading cause of economic loss in the livestock industry. BRD is a multifactorial syndrome, in which a triad of agents, including bacteria, viruses, and predisposing factors or "stressors," combines to induce disease. Although vaccines against H. somni have been used for many decades, traditional bacterins have failed to demonstrate effective protection in vaccinated animals. Hence, the BRD complex continues to produce strong adverse effects on the health and well-being of stock and feeder cattle. The generation of recombinant proteins may facilitate the development of more effective vaccines against H. somni, which could confer better protection against BRD. In the present study, primers were designed to amplify, clone, express, and purify two recombinant lipoproteins from H. somni, p31 (Plp4) and p40 (LppB), which are structural proteins of the outer bacterial membrane. The results presented here demonstrate, to our knowledge for the first time, that when formulated, an experimental vaccine enriched with these two recombinant lipoproteins generates high antibody titers in rabbits and sheep and exerts a protective effect in mice against septicemia induced by H. somni bacterial challenge.

Application of Whole Genome Expression Analysis to Assess Bacterial Responses to Environmental Conditions

NASA Astrophysics Data System (ADS)

Vukanti, R. V.; Mintz, E. M.; Leff, L. G.

2005-05-01

Bacterial responses to environmental signals are multifactorial and are coupled to changes in gene expression. An understanding of bacterial responses to environmental conditions is possible using microarray expression analysis. In this study, the utility of microarrays for examining changes in gene expression in Escherichia coli under different environmental conditions was assessed. RNA was isolated, hybridized to Affymetrix E. coli Genome 2.0 chips and analyzed using Affymetrix GCOS and Genespring software. Major limiting factors were obtaining enough quality RNA (107-108 cells to get 10μg RNA)and accounting for differences in growth rates under different conditions. Stabilization of RNA prior to isolation and taking extreme precautions while handling RNA were crucial. In addition, use of this method in ecological studies is limited by availability and cost of commercial arrays; choice of primers for cDNA synthesis, reproducibility, complexity of results generated and need to validate findings. This method may be more widely applicable with the development of better approaches for RNA recovery from environmental samples and increased number of available strain-specific arrays. Diligent experimental design and verification of results with real-time PCR or northern blots is needed. Overall, there is a great potential for use of this technology to discover mechanisms underlying organisms' responses to environmental conditions.

Susceptibility of Legionella strains to the chlorinated biocide, monochloramine.

PubMed

Jakubek, Delphine; Guillaume, Carole; Binet, Marie; Leblon, Gérard; DuBow, Michael; Le Brun, Matthieu

2013-01-01

Members of the Legionella genus find suitable conditions for their growth and survival in nuclear power plant cooling circuits. To limit the proliferation of Legionella pathogenic bacteria in nuclear power plant cooling circuits, and ensure that levels remain below regulatory thresholds, monochloramine treatment can be used. Although the treatment is highly effective, i.e. it reduces Legionella numbers by over 99%, Legionella bacteria can still be detected at low concentrations and rapid re-colonisation of circuits can occur after the treatment has ceased. The aim of this study was to develop an in vitro methodology for determining the intrinsic susceptibility of L. pneumophila strains, collected from various nuclear power plant cooling circuits subjected to different treatment conditions. The methodology was developed by using an original approach based on response surface methodology (RSM) combined with a multifactorial experimental design. The susceptibility was evaluated by the Ct factor. The susceptibility of environmental strains varies widely and is, for some strains, greater than that of known tolerant species; however, strain susceptibility was not related to treatment conditions. Selection pressure induced by monochloramine use did not result in the selection of more tolerant Legionella strains and did not explain the detection of Legionella during treatment or the rapid re-colonisation of cooling circuits after disinfection has ceased.

Erythropoietin as a novel brain and kidney protective agent.

PubMed

Moore, E M; Bellomo, R; Nichol, A D

2011-05-01

Erythropoietin is a 30.4 kDa glycoprotein produced by the kidney, which is mostly known for its physiological function in regulating red blood cell production in the bone marrow Accumulating evidence, however suggests that erythropoietin has additional organ protective effects, which may specifically be useful in protecting the brain and kidneys from injury. Experimental evidence suggests that these protective mechanisms are multi-factorial in nature and may include inhibition of apoptotic cell death, stimulation of cellular regeneration, inhibition of deleterious pathways and promotion of recovery. In this article we review the physiology of erythropoietin, assess previous work that supports the role of erythropoietin as a general tissue protective agent and explain the mechanisms by which it may achieve this tissue protective effect. We then focus on specific laboratory and clinical data that suggest that erythropoietin has a strong brain protective and kidney protective effect. In addition, we comment on the implications of these studies for clinicians at the bedside and for researchers designing controlled trials to further elucidate the true clinical utility of erythropoietin as a neuroprotective and nephroprotective agent. Finally, we describe EPO-TBI, a double-blinded multi-centre randomised controlled trial involving the authors that is being conducted to investigate the organ protective effects of erythropoietin on the brain, and also assesses its effect on the kidneys.

Multifactorial causal model of brain (dis)organization and therapeutic intervention: Application to Alzheimer's disease.

PubMed

Iturria-Medina, Yasser; Carbonell, Félix M; Sotero, Roberto C; Chouinard-Decorte, Francois; Evans, Alan C

2017-05-15

Generative models focused on multifactorial causal mechanisms in brain disorders are scarce and generally based on limited data. Despite the biological importance of the multiple interacting processes, their effects remain poorly characterized from an integrative analytic perspective. Here, we propose a spatiotemporal multifactorial causal model (MCM) of brain (dis)organization and therapeutic intervention that accounts for local causal interactions, effects propagation via physical brain networks, cognitive alterations, and identification of optimum therapeutic interventions. In this article, we focus on describing the model and applying it at the population-based level for studying late onset Alzheimer's disease (LOAD). By interrelating six different neuroimaging modalities and cognitive measurements, this model accurately predicts spatiotemporal alterations in brain amyloid-β (Aβ) burden, glucose metabolism, vascular flow, resting state functional activity, structural properties, and cognitive integrity. The results suggest that a vascular dysregulation may be the most-likely initial pathologic event leading to LOAD. Nevertheless, they also suggest that LOAD it is not caused by a unique dominant biological factor (e.g. vascular or Aβ) but by the complex interplay among multiple relevant direct interactions. Furthermore, using theoretical control analysis of the identified population-based multifactorial causal network, we show the crucial advantage of using combinatorial over single-target treatments, explain why one-target Aβ based therapies might fail to improve clinical outcomes, and propose an efficiency ranking of possible LOAD interventions. Although still requiring further validation at the individual level, this work presents the first analytic framework for dynamic multifactorial brain (dis)organization that may explain both the pathologic evolution of progressive neurological disorders and operationalize the influence of multiple interventional strategies. Copyright © 2017 Elsevier Inc. All rights reserved.

An individually-tailored multifactorial intervention program for older fallers in a middle-income developing country: Malaysian Falls Assessment and Intervention Trial (MyFAIT)

PubMed Central

2014-01-01

Background In line with a rapidly ageing global population, the rise in the frequency of falls will lead to increased healthcare and social care costs. This study will be one of the few randomized controlled trials evaluating a multifaceted falls intervention in a low-middle income, culturally-diverse older Asian community. The primary objective of our paper is to evaluate whether individually tailored multifactorial interventions will successfully reduce the number of falls among older adults. Methods Three hundred community-dwelling older Malaysian adults with a history of (i) two or more falls, or (ii) one injurious fall in the past 12 months will be recruited. Baseline assessment will include cardiovascular, frailty, fracture risk, psychological factors, gait and balance, activities of daily living and visual assessments. Fallers will be randomized into 2 groups: to receive tailored multifactorial interventions (intervention group); or given lifestyle advice with continued conventional care (control group). Multifactorial interventions will target 6 specific risk factors. All participants will be re-assessed after 12 months. The primary outcome measure will be fall recurrence, measured with monthly falls diaries. Secondary outcomes include falls risk factors; and psychological measures including fear of falling, and quality of life. Discussion Previous studies evaluating multifactorial interventions in falls have reported variable outcomes. Given likely cultural, personal, lifestyle and health service differences in Asian countries, it is vital that individually-tailored multifaceted interventions are evaluated in an Asian population to determine applicability of these interventions in our setting. If successful, these approaches have the potential for widespread application in geriatric healthcare services, will reduce the projected escalation of falls and fall-related injuries, and improve the quality of life of our older community. Trial registration ISRCTN11674947 PMID:24951180

Metabolism-Activated Multitargeting (MAMUT): An Innovative Multitargeting Approach to Drug Design and Development.

PubMed

Mátyus, Péter; Chai, Christina L L

2016-06-20

Multitargeting is a valuable concept in drug design for the development of effective drugs for the treatment of multifactorial diseases. This concept has most frequently been realized by incorporating two or more pharmacophores into a single hybrid molecule. Many such hybrids, due to the increased molecular size, exhibit unfavorable physicochemical properties leading to adverse effects and/or an inappropriate ADME (absorption, distribution, metabolism, and excretion) profile. To avoid this limitation and achieve additional therapeutic benefits, here we describe a novel multitargeting strategy based on the synergistic effects of a parent drug and its active metabolite(s). The concept of metabolism-activated multitargeting (MAMUT) is illustrated using a number of examples. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Study protocol: a randomized controlled trial of patient navigation-activation to reduce cancer health disparities.

PubMed

Hendren, Samantha; Griggs, Jennifer J; Epstein, Ronald M; Humiston, Sharon; Rousseau, Sally; Jean-Pierre, Pascal; Carroll, Jennifer; Yosha, Amanat M; Loader, Starlene; Fiscella, Kevin

2010-10-13

Cancer health disparities affecting low-income and minority patients are well documented. Root-causes are multifactorial, including diagnostic and treatment delays, social and financial barriers, and poor communication. Patient navigation and communication coaching (activation) are potential interventions to address disparities in cancer treatment. The purpose of this clinical trial is to test the effectiveness of an intervention combining patient navigation and activation to improve cancer treatment. The Rochester Patient Navigation Research Program (PNRP) is a National Cancer Institute-sponsored, patient-level randomized trial (RCT) of patient navigation and activation, targeting newly-diagnosed breast and colorectal cancer patients in Rochester, NY. The goal of the program is to decrease cancer health disparities by addressing barriers to receipt of cancer care and promoting patient self-efficacy. The intervention uses trained, paraprofessional patient navigators recruited from the target community, and a detailed training and supervisory program. Recruited patients are randomly assigned to receive either usual care (except for baseline and follow-up questionnaires and interviews) or intervention. The intervention patients receive tailored assistance from their patient navigators, including phone calls, in-person meetings, and behind-the-scenes coordination of care. A total of 344 patients have been recruited. Outcomes measured at three month intervals include timeliness of care, patient adherence, patient satisfaction, quality of life, self-efficacy, health literacy, and cancer knowledge. This unique intervention combining patient navigation and patient activation is designed to address the multifactorial problem of cancer health disparities. If successful, this study will affect the design and implementation of patient navigation programs. clinicaltrials.gov identifier NCT00496678.

Changing paradigm from one target one ligand towards multi target directed ligand design for key drug targets of Alzheimer disease: An important role of Insilco methods in multi target directed ligands design.

PubMed

Kumar, Akhil; Tiwari, Ashish; Sharma, Ashok

2018-03-15

Alzheimer disease (AD) is now considered as a multifactorial neurodegenerative disorder and rapidly increasing to an alarming situation and causing higher death rate. One target one ligand hypothesis is not able to provide complete solution of AD due to multifactorial nature of disease and one target one drug seems to fail to provide better treatment against AD. Moreover, current available treatments are limited and most of the upcoming treatments under clinical trials are based on modulating single target. So the current AD drug discovery research shifting towards new approach for better solution that simultaneously modulate more than one targets in the neurodegenerative cascade. This can be achieved by network pharmacology, multi-modal therapies, multifaceted, and/or the more recently proposed term "multi-targeted designed drugs. Drug discovery project is tedious, costly and long term project. Moreover, multi target AD drug discovery added extra challenges such as good binding affinity of ligands for multiple targets, optimal ADME/T properties, no/less off target side effect and crossing of the blood brain barrier. These hurdles may be addressed by insilico methods for efficient solution in less time and cost as computational methods successfully applied to single target drug discovery project. Here we are summarizing some of the most prominent and computationally explored single target against AD and further we discussed successful example of dual or multiple inhibitors for same targets. Moreover we focused on ligand and structure based computational approach to design MTDL against AD. However is not an easy task to balance dual activity in a single molecule but computational approach such as virtual screening docking, QSAR, simulation and free energy are useful in future MTDLs drug discovery alone or in combination with fragment based method. However, rational and logical implementations of computational drug designing methods are capable of assisting AD drug discovery and play an important role in optimizing multi-target drug discovery. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Determination of the design space of the HPLC analysis of water-soluble vitamins.

PubMed

Wagdy, Hebatallah A; Hanafi, Rasha S; El-Nashar, Rasha M; Aboul-Enein, Hassan Y

2013-06-01

Analysis of water-soluble vitamins has been tremendously approached through the last decades. A multitude of HPLC methods have been reported with a variety of advantages/shortcomings, yet, the design space of HPLC analysis of these vitamins was not defined in any of these reports. As per the food and drug administration (FDA), implementing the quality by design approach for the analysis of commercially available mixtures is hypothesized to enhance the pharmaceutical industry via facilitating the process of analytical method development and approval. This work illustrates a multifactorial optimization of three measured plus seven calculated influential HPLC parameters on the analysis of a mixture containing seven common water-soluble vitamins (B1, B2, B6, B12, C, PABA, and PP). These three measured parameters are gradient time, temperature, and ternary eluent composition (B1/B2) and the seven calculated parameters are flow rate, column length, column internal diameter, dwell volume, extracolumn volume, %B (start), and %B (end). The design is based on 12 experiments in which, examining of the multifactorial effects of these 3 + 7 parameters on the critical resolution and selectivity, was carried out by systematical variation of all these parameters simultaneously. The 12 basic runs were based on two different gradient time each at two different temperatures, repeated at three different ternary eluent compositions (methanol or acetonitrile or a mixture of both). Multidimensional robust regions of high critical R(s) were defined and graphically verified. The optimum method was selected based on the best resolution separation in the shortest run time for a synthetic mixture, followed by application on two pharmaceutical preparations available in the market. The predicted retention times of all peaks were found to be in good match with the virtual ones. In conclusion, the presented report offers an accurate determination of the design space for critical resolution in the analysis of water-soluble vitamins by HPLC, which would help the regulatory authorities to judge the validity of presented analytical methods for approval. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

NLRP3 inflammasome is a target for development of broad-spectrum anti-infective drugs.

PubMed

Thacker, James D; Balin, Brian J; Appelt, Denah M; Sassi-Gaha, Sihem; Purohit, Mitali; Rest, Richard F; Artlett, Carol M

2012-04-01

We describe the molecular mode of action and pharmacodynamics of a new molecular entity (NME) that induces the NLRP3 inflammasome-mediated innate immune response. This innate response reduces the pathogen load in an experimentally induced methicillin-resistant Staphylococcos aureus infection, enhances survival in an experimentally induced Gram-negative bacteremia, and overrides the escape mechanism of an obligate intracellular pathogen, viz. Chlamydia pneumoniae. Furthermore, the NME is more effective than standard-of-care antibiotic therapy in a clinically established multifactorial bacterial infection. Analysis of transcriptional regulation of inflammasome signaling genes and innate/adaptive immune genes revealed consistent and significant host changes responsible for the improved outcomes in these infections. These studies pave the way for the development of first-in-class drugs that enhance inflammasome-mediated pathogen clearance and identify the NLRP3 inflammasome as a drug target to address the global problem of emerging new infectious diseases and the reemergence of old diseases in an antibiotic-resistant form.

NLRP3 Inflammasome Is a Target for Development of Broad-Spectrum Anti-Infective Drugs

PubMed Central

Balin, Brian J.; Appelt, Denah M.; Sassi-Gaha, Sihem; Purohit, Mitali; Rest, Richard F.; Artlett, Carol M.

2012-01-01

We describe the molecular mode of action and pharmacodynamics of a new molecular entity (NME) that induces the NLRP3 inflammasome-mediated innate immune response. This innate response reduces the pathogen load in an experimentally induced methicillin-resistant Staphylococcos aureus infection, enhances survival in an experimentally induced Gram-negative bacteremia, and overrides the escape mechanism of an obligate intracellular pathogen, viz. Chlamydia pneumoniae. Furthermore, the NME is more effective than standard-of-care antibiotic therapy in a clinically established multifactorial bacterial infection. Analysis of transcriptional regulation of inflammasome signaling genes and innate/adaptive immune genes revealed consistent and significant host changes responsible for the improved outcomes in these infections. These studies pave the way for the development of first-in-class drugs that enhance inflammasome-mediated pathogen clearance and identify the NLRP3 inflammasome as a drug target to address the global problem of emerging new infectious diseases and the reemergence of old diseases in an antibiotic-resistant form. PMID:22290938

Blood-brain barrier permeability during the development of experimental bacterial meningitis in the rat.

PubMed

Kim, K S; Wass, C A; Cross, A S

1997-05-01

In an attempt to examine whether routes of bacterial entry into the central nervous system have any bearing on subsequent changes in blood-brain barrier permeability, we examined cerebrospinal fluid (CSF) penetration of circulating 125I-albumin in two different models of experimental meningitis due to K1 Escherichia coli, type III group B streptococcus, or Haemophilus influenzae type b in infant rats: hematogenous meningitis subsequent to subcutaneous inoculation of bacteria vs meningitis induced by direct inoculation of bacteria into the CSF via the cisterna magna. In the model of hematogenous meningitis, the mean CSF penetration was significantly greater in animals with H. influenzae type b meningitis than in those with meningitis due to K1 E. coli or type III group B streptococcus. In contrast, the mean CSF penetration was significantly enhanced in all animals with meningitis induced by intracisternal inoculation regardless of infecting pathogens. Tumor necrosis factor activity in CSF appeared to correlate with the functional penetration of circulating albumin across the blood-brain barrier in both models of experimental meningitis. These findings suggest that the alterations of blood-brain barrier permeability during development of experimental meningitis may vary for different models of inducing meningitis and that the mechanisms responsible for these different permeability changes may be multifactorial.

Neural Tube Defects

PubMed Central

Greene, Nicholas D.E.; Copp, Andrew J.

2015-01-01

Neural tube defects (NTDs), including spina bifida and anencephaly, are severe birth defects of the central nervous system that originate during embryonic development when the neural tube fails to close completely. Human NTDs are multifactorial, with contributions from both genetic and environmental factors. The genetic basis is not yet well understood, but several nongenetic risk factors have been identified as have possibilities for prevention by maternal folic acid supplementation. Mechanisms underlying neural tube closure and NTDs may be informed by experimental models, which have revealed numerous genes whose abnormal function causes NTDs and have provided details of critical cellular and morphological events whose regulation is essential for closure. Such models also provide an opportunity to investigate potential risk factors and to develop novel preventive therapies. PMID:25032496

Applications of Two-Dimensional Electrophoresis Technology to the Study of Atherosclerosis

PubMed Central

Lepedda, Antonio J.

2008-01-01

Atherosclerosis is a multifactorial disease in which hypertension, diabetes, hyperlipidemia and other risk factors are thought to play a role. However, the molecular processes underlying plaque formation and progression are not yet completely known. In the last years some researchers applied proteomics technologies for the comprehension of biochemical pathways of atherogenesis and to search new cardiovascular biomarkers to be utilized either as early diagnostic traits or as targets for new drug therapies. Due to its intrinsic complexity, the problem has been approached by different strategies, all of which have some limitations. In this review, we summarize the most common critical experimental variables in two-dimensional electrophoresis-based techniques and recent data obtained by applying proteomic approaches in the study of atherosclerosis. PMID:27683313

Peptide assemblies: from cell scaffolds to immune adjuvants

NASA Astrophysics Data System (ADS)

Collier, Joel

2011-03-01

This talk will discuss two interrelated aspects of peptide self-assemblies in biological applications: their use as matrices for regenerative medicine, and their use as chemically defined adjuvants for directing immune responses against engineered antigens. In the first half of the presentation, the design of peptide self-assemblies as analogues for the extracellular matrix will be described, with a focus on self-assemblies displaying multiple different cell-binding peptides. We conducted multi-factorial investigations of peptide co-assemblies containing several different ligand-bearing peptides using statistical ``design of experiments'' (DoE). Using the DoE techniques of factorial experimentation and response surface modeling, we systematically explored how precise combinations of ligand-bearing peptides modulated endothelial cell growth, in the process finding interactions between ligands not previously appreciated. By investigating immune responses against the materials intended for tissue engineering applications, we discovered that the basic self-assembling peptides were minimally immunogenic or non-immunogenic, even when delivered in strong adjuvants. -But when they were appended to an appropriately restricted epitope peptide, these materials raised strong and persistent antibody responses. These responses were dependent on covalent conjugation between the epitope and self-assembling domains of the peptides, were mediated by T cells, and could be directed towards both peptide epitopes and conjugated protein antigens. In addition to their demonstrated utility as scaffolds for regenerative medicine, peptide self-assemblies may also be useful as chemically defined adjuvants for vaccines and immunotherapies. This work was funded by NIH/NIDCR (1 R21 DE017703-03), NIH/NIBIB (1 R01 EB009701-01), and NSF (CHE-0802286).

Learning from adverse incidents involving medical devices.

PubMed

Amoore, John; Ingram, Paula

While an adverse event involving a medical device is often ascribed to either user error or device failure, the causes are typically multifactorial. A number of incidents involving medical devices are explored using this approach to investigate the various causes of the incident and the protective barriers that minimised or prevented adverse consequences. User factors, including mistakes, omissions and lack of training, conspired with background factors--device controls and device design, storage conditions, hidden device damage and physical layout of equipment when in use--to cause the adverse events. Protective barriers that prevented or minimised the consequences included staff vigilance, operating procedures and alarms.

CompareSVM: supervised, Support Vector Machine (SVM) inference of gene regularity networks.

PubMed

Gillani, Zeeshan; Akash, Muhammad Sajid Hamid; Rahaman, M D Matiur; Chen, Ming

2014-11-30

Predication of gene regularity network (GRN) from expression data is a challenging task. There are many methods that have been developed to address this challenge ranging from supervised to unsupervised methods. Most promising methods are based on support vector machine (SVM). There is a need for comprehensive analysis on prediction accuracy of supervised method SVM using different kernels on different biological experimental conditions and network size. We developed a tool (CompareSVM) based on SVM to compare different kernel methods for inference of GRN. Using CompareSVM, we investigated and evaluated different SVM kernel methods on simulated datasets of microarray of different sizes in detail. The results obtained from CompareSVM showed that accuracy of inference method depends upon the nature of experimental condition and size of the network. For network with nodes (<200) and average (over all sizes of networks), SVM Gaussian kernel outperform on knockout, knockdown, and multifactorial datasets compared to all the other inference methods. For network with large number of nodes (~500), choice of inference method depend upon nature of experimental condition. CompareSVM is available at http://bis.zju.edu.cn/CompareSVM/ .

Multifactorial Likelihood Assessment of BRCA1 and BRCA2 Missense Variants Confirms That BRCA1:c.122A>G(p.His41Arg) Is a Pathogenic Mutation

PubMed Central

Whiley, Phillip J.; Parsons, Michael T.; Leary, Jennifer; Tucker, Kathy; Warwick, Linda; Dopita, Belinda; Thorne, Heather; Lakhani, Sunil R.; Goldgar, David E.; Brown, Melissa A.; Spurdle, Amanda B.

2014-01-01

Rare exonic, non-truncating variants in known cancer susceptibility genes such as BRCA1 and BRCA2 are problematic for genetic counseling and clinical management of relevant families. This study used multifactorial likelihood analysis and/or bioinformatically-directed mRNA assays to assess pathogenicity of 19 BRCA1 or BRCA2 variants identified following patient referral to clinical genetic services. Two variants were considered to be pathogenic (Class 5). BRCA1:c.4484G> C(p.Arg1495Thr) was shown to result in aberrant mRNA transcripts predicted to encode truncated proteins. The BRCA1:c.122A>G(p.His41Arg) RING-domain variant was found from multifactorial likelihood analysis to have a posterior probability of pathogenicity of 0.995, a result consistent with existing protein functional assay data indicating lost BARD1 binding and ubiquitin ligase activity. Of the remaining variants, seven were determined to be not clinically significant (Class 1), nine were likely not pathogenic (Class 2), and one was uncertain (Class 3).These results have implications for genetic counseling and medical management of families carrying these specific variants. They also provide additional multifactorial likelihood variant classifications as reference to evaluate the sensitivity and specificity of bioinformatic prediction tools and/or functional assay data in future studies. PMID:24489791

Congenital malformations according to etiology in newborns from the floricultural zone of Mexico state.

PubMed

Castillo-Cadena, Julieta; Mejia-Sanchez, Fernando; López-Arriaga, Jerónimo Amado

2017-03-01

Birth defects are the number one cause of child mortality worldwide and in 2010 it was the second cause in Mexico. Congenital malformations are a public health issue, because they cause infant mortality, chronic disease and disability. The origin can be genetic, environmental or unknown causes. Among environmental contaminants, pesticides stand out. In this study, we determine the frequency and etiology of congenital malformations in newborns (NBs) of a floricultural community and we compare it with that in the urban community. For 18 months, the NBs were monitored at the Tenancingo General Hospital and the Mother and Child Gynecology and Obstetrics Hospital (IMIEM) in Toluca. The identification of these malformations was carried out in accordance with the WHO. In Tenancingo, 1149 NBs were viewed, where 20% had some kind of congenital malformations. While in the IMIEM, 5069 were reviewed and 6% had some malformation. According to the etiology, in Tenancingo, 69% were multifactorial, 28% were monogenetic and 2% were chromosomal. In the IMIEM, 47% were multifactorial, then 18.3% were monogenetic and 2.8% were chromosomal. There was a significant difference between the global frequency of malformations and the multifactorial etiology of both institutions. Our results show that congenital malformations in the NBs occurred more frequently in the floricultural zone and that because the percentage of multifactorial etiology is higher, it is likely there is an association with exposure to pesticides.

Planning intensive care unit design using computer simulation modeling: optimizing integration of clinical, operational, and architectural requirements.

PubMed

OʼHara, Susan

2014-01-01

Nurses have increasingly been regarded as critical members of the planning team as architects recognize their knowledge and value. But the nurses' role as knowledge experts can be expanded to leading efforts to integrate the clinical, operational, and architectural expertise through simulation modeling. Simulation modeling allows for the optimal merge of multifactorial data to understand the current state of the intensive care unit and predict future states. Nurses can champion the simulation modeling process and reap the benefits of a cost-effective way to test new designs, processes, staffing models, and future programming trends prior to implementation. Simulation modeling is an evidence-based planning approach, a standard, for integrating the sciences with real client data, to offer solutions for improving patient care.

Designed multiple ligands in metabolic disease research: from concept to platform.

PubMed

Gattrell, W; Johnstone, C; Patel, S; Smith, C Sambrook; Scheel, A; Schindler, M

2013-08-01

Type 2 diabetes mellitus (T2DM) is a multifactorial disease, and drug monotherapy typically results in unsatisfactory treatment outcomes for patients. Even when used in combination, existing therapies lack efficacy in the long term. Designed multiple ligands (DMLs) are compounds developed to modulate multiple targets relevant to a disease. DMLs offer the potential to yield greater efficacy over monotherapies, either by modulating different biological pathways, or by boosting a single one. However, examples of DMLs progressing into clinical trials, or onto the market are rare; DML drug discovery is challenging, and perceived by some to be almost impossible. Nevertheless, with the judicious selection of biological targets, both from a biological and chemical perspective, it is possible to develop drug-like DMLs. Copyright © 2013 Elsevier Ltd. All rights reserved.

The therapeutics of Alzheimer's disease: where we stand and where we are heading.

PubMed

Selkoe, Dennis J

2013-09-01

Few diagnoses in modern medicine evoke more apprehension in patients and their families than Alzheimer disease (AD). Defined as a clinical and pathological entity a century ago, the disorder only came under intense molecular scrutiny in the mid-1980s. Genetic, histopathological, biochemical, and animal modeling studies have combined to provide evidence that the disease may begin with an imbalance between the production and clearance of the self-aggregating amyloid β protein (Aβ) in brain regions serving memory and cognition. This concept has been furthered by recent analyses in humans of cerebrospinal fluid and neuroimaging biomarkers that suggest an approximate sequence of AD-type brain alterations beginning >2 decades before the onset of dementia. Although the Aβ hypothesis of Alzheimer causation does not explain all features of this multifactorial syndrome, experimental agents that lower or neutralize Aβ have become the major focus of therapeutic research. Several clinical trials in mild-to-moderate AD have not met standard cognitive and functional endpoints, but there were important shortcomings in the agent and/or the trial design in each case. Based on the lessons learned, the field has moved on to test potentially disease-modifying agents in mild AD patients or via secondary prevention in presymptomatic subjects bearing amyloid plaques. Immunotherapeutic agents are receiving the most study, but other antiamyloid strategies and, importantly, nonamyloid targets such as tau and neuroinflammation are of great interest. The pace of recent developments augurs well for 1 or more experimental agents being shown to slow cognitive decline without major side effects. However, research funding from all sources will need to increase dramatically and soon to stave off the approaching tsunami of AD. Copyright © 2013 American Neurological Association.

Influence de la pression de mise en forme sur le detourage de stratifies carbone/epoxy

NASA Astrophysics Data System (ADS)

Coulon, Pierre

The need to reduce the weight of structures has led to an increasing use of composite materials in the aerospace industry. To meet the required tolerances and quality, the manufacturing processes must adapt to these new materials. The machining is one of these processes that need to be optimized to control the final part quality. This experimental study aims at understanding the relationship between manufacturing parameters of quasi-isotropic carbon fibre laminates and their machinability. After a preliminary study, it was concluded that curing pressure in autoclave was the most influential manufacturing parameter. The pressure is linked, experimentally, to the void content and then to the mechanical properties and finally to the cutting forces. The research methodology is based on a classic multifactorial design of experience in which the input factors are the curing pressure, feed rate and cutting speed. This study confirms the correlation existing between the curing pressure and void content as well as the relationship between the curing pressure and mechanical properties. The new element of this study is the correlation between the curing pressure and cutting forces during trimming. This last point is interesting because it leads to the development of a predictive model for cutting forces. Although the results of this study are hardly generalizable to other materials, the prediction of cutting forces is possible. Quality after machining is also studied through two criteria: the roughness measurement and evaluation of delamination. Roughness is measured using a roughness depth measuring equipment optimized to make best use of this technique. The study confirms the patterns already observed without being able to improve the characterization of cutting quality. Keywords: composites, trimming, curing pressure, cutting forces, void content, ILSS, delamination, roughness.

Neuroprotective and cognitive enhancing effects of a multi-targeted food intervention in an animal model of neurodegeneration and depression.

PubMed

Borre, Yuliya E; Panagaki, Theodora; Koelink, Pim J; Morgan, Mary E; Hendriksen, Hendrikus; Garssen, Johan; Kraneveld, Aletta D; Olivier, Berend; Oosting, Ronald S

2014-04-01

Rising neurodegenerative and depressive disease prevalence combined with the lack of effective pharmaceutical treatments and dangerous side effects, has created an urgent need for the development of effective therapies. Considering that these disorders are multifactorial in origin, treatments designed to interfere at different mechanistic levels may be more effective than the traditional single-targeted pharmacological concepts. To that end, an experimental diet composed of zinc, melatonin, curcumin, piperine, eicosapentaenoic acid (EPA, 20:5, n-3), docosahexaenoic acid (DHA, 22:6, n-3), uridine, and choline was formulated. This diet was tested on the olfactory bulbectomized rat (OBX), an established animal model of depression and cognitive decline. The ingredients of the diet have been individually shown to attenuate glutamate excitoxicity, exert potent anti-oxidant/anti-inflammatory properties, and improve synaptogenesis; processes that all have been implicated in neurodegenerative diseases and in the cognitive deficits following OBX in rodents. Dietary treatment started 2 weeks before OBX surgery, continuing for 6 weeks in total. The diet attenuated OBX-induced cognitive and behavioral deficits, except long-term spatial memory. Ameliorating effects of the diet extended to the control animals. Furthermore, the experimental diet reduced hippocampal atrophy and decreased the peripheral immune activation in the OBX rats. The ameliorating effects of the diet on the OBX-induced changes were comparable to those of the NMDA receptor antagonist, memantine, a drug used for the management of Alzheimer's disease. This proof-of-concept study suggests that a diet, which simultaneously targets multiple disease etiologies, can prevent/impede the development of a neurodegenerative and depressive disorders and the concomitant cognitive deficits. Copyright © 2014. Published by Elsevier Ltd.

Effect of individually tailored biopsychosocial workplace interventions on chronic musculoskeletal pain, stress and work ability among laboratory technicians: randomized controlled trial protocol.

PubMed

Jay, Kenneth; Brandt, Mikkel; Sundstrup, Emil; Schraefel, Mc; Jakobsen, Markus D; Sjøgaard, Gisela; Andersen, Lars L

2014-12-18

Among laboratory technicians, the prevalence of neck and shoulder pain is widespread possibly due to typical daily work tasks such as pipetting, preparing vial samples for analysis, and data processing on a computer including mouse work - all tasks that require precision in motor control and may result in extended periods of time spent in static positions.In populations characterized by intense chronic musculoskeletal pain and diagnosed conditions in conjunction with psycho-physiological symptoms such as stress-related pain and soreness and other disabling conditions, multifactorial approaches applying a combination of individually tailored physical and cognitive strategies targeting the areas most needed, may be an effective solution to the physical and mental health challenges.The aim of this study is therefore to investigate the effect of an individually tailored biopsychosocial intervention strategy on musculoskeletal pain, stress and work disability in lab technicians with a history of musculoskeletal pain at a single worksite in Denmark. In this single-blind two-armed parallel-group randomized controlled trial with allocation concealment, participants receive either an individualized multifactorial intervention or "usual care" for 10 weeks at the worksite. 1) female laboratory technician (18-67 years of age) and 2) Pain intensity ≥ 3 (0-10 Visual Analogue Scale) lasting ≥3 months with a frequency of ≥ 3 days per week in one or more of the following regions: i) upper back i) low back iii) neck, iv) shoulder, v) elbow and/or vi) hand. 1) life-threatening disease and 2) pregnancy. Stress, as measured by Cohen´s perceived stress questionnaire is not an inclusion criteria, thus participants can participate regardless of their stress level.We will implement an individualized intervention addressing biopsychosocial elements of musculoskeletal pain with the following components; i) increasing physical capacity through strength- and motor control training; ii) lowering or preventing development of stress through mindfulness practice and learning de-catastrophizing pain management strategies through cognitive training.The primary outcome at 10-week follow-up is the between-group difference in intensity of perceived musculoskeletal pain during the last week (average value of back, neck, shoulder, elbow and hand) assessed by questionnaire (modified visual analogue scale 0-10). This study will provide experimental evidence to guide workplace initiatives designed towards reducing chronic musculoskeletal pain and stress. ClinicalTrials.gov NCT02047669.

Falls Assessment Clinical Trial (FACT): design, interventions, recruitment strategies and participant characteristics.

PubMed

Elley, C Raina; Robertson, M Clare; Kerse, Ngaire M; Garrett, Sue; McKinlay, Eileen; Lawton, Beverley; Moriarty, Helen; Campbell, A John

2007-07-29

Guidelines recommend multifactorial intervention programmes to prevent falls in older adults but there are few randomised controlled trials in a real life health care setting. We describe the rationale, intervention, study design, recruitment strategies and baseline characteristics of participants in a randomised controlled trial of a multifactorial falls prevention programme in primary health care. Participants are patients from 19 primary care practices in Hutt Valley, New Zealand aged 75 years and over who have fallen in the past year and live independently. Two recruitment strategies were used - waiting room screening and practice mail-out. Intervention participants receive a community based nurse assessment of falls and fracture risk factors, home hazards, referral to appropriate community interventions, and strength and balance exercise programme. Control participants receive usual care and social visits. Outcome measures include number of falls and injuries over 12 months, balance, strength, falls efficacy, activities of daily living, quality of life, and physical activity levels. 312 participants were recruited (69% women). Of those who had fallen, 58% of people screened in the practice waiting rooms and 40% when screened by practice letter were willing to participate. Characteristics of participants recruited using the two methods are similar (p > 0.05). Mean age of all participants was 81 years (SD 5). On average participants have 7 medical conditions, take 5.5 medications (29% on psychotropics) with a median of 2 falls (interquartile range 1, 3) in the previous year. The two recruitment strategies and the community based intervention delivery were feasible and successful, identifying a high risk group with multiple falls. Recruitment in the waiting room gave higher response rates but was less efficient than practice mail-out. Testing the effectiveness of an evidence based intervention in a 'real life' setting is important.

Two Outer Membrane Lipoproteins from Histophilus somni Are Immunogenic in Rabbits and Sheep and Induce Protection against Bacterial Challenge in Mice

PubMed Central

Guzmán-Brambila, Carolina; Rojas-Mayorquín, Argelia E.; Flores-Samaniego, Beatriz

2012-01-01

Histophilus somni is an economically important pathogen of cattle and other ruminants and is considered one of the key components of the bovine respiratory disease (BRD) complex, the leading cause of economic loss in the livestock industry. BRD is a multifactorial syndrome, in which a triad of agents, including bacteria, viruses, and predisposing factors or “stressors,” combines to induce disease. Although vaccines against H. somni have been used for many decades, traditional bacterins have failed to demonstrate effective protection in vaccinated animals. Hence, the BRD complex continues to produce strong adverse effects on the health and well-being of stock and feeder cattle. The generation of recombinant proteins may facilitate the development of more effective vaccines against H. somni, which could confer better protection against BRD. In the present study, primers were designed to amplify, clone, express, and purify two recombinant lipoproteins from H. somni, p31 (Plp4) and p40 (LppB), which are structural proteins of the outer bacterial membrane. The results presented here demonstrate, to our knowledge for the first time, that when formulated, an experimental vaccine enriched with these two recombinant lipoproteins generates high antibody titers in rabbits and sheep and exerts a protective effect in mice against septicemia induced by H. somni bacterial challenge. PMID:22971783

Influence of environmental parameters and of their interactions on the release of metal(loid)s from a construction material in hydraulic engineering.

PubMed

Schmukat, A; Duester, L; Goryunova, E; Ecker, D; Heininger, P; Ternes, T A

2016-03-05

Besides the leaching behaviour of a construction material under standardised test-specific conditions with laboratory water, for some construction materials it is advisable to test their environmental behaviour also under close to end use conditions. The envisaged end use combined with the product characteristics (e.g. mineral phases) is decisive for the choice of environmental factors that may change the release of substance that potentially cause adverse environmental effects (e.g. fertilisation or ecotoxicity). At the moment an experimental link is missing between mono-factorial standardised test systems and non standardised complex incubation experiments such as mesocosms which are closer to environmental conditions. Multi-factorial batch experiments may have the potential to close the gap. To verify this, batch experiments with copper slag were performed which is used as armour stones in hydraulic engineering. Design of experiments (DoE) was applied to evaluate the impact of pH, ionic strength, temperature and sediment content on the release of As, Cu, Mo, Ni, Pb, Sb and Zn. The study shows that release and sediment-eluent partitioning of metal(loid)s are impacted by interactions between the studied factors. Under the prevalent test conditions sediment acts as a sink enhancing most strongly the release of elements from the material. Copyright © 2015 Elsevier B.V. All rights reserved.

Towards an Operational Definition of Clinical Competency in Pharmacy

PubMed Central

2015-01-01

Objective. To estimate the inter-rater reliability and accuracy of ratings of competence in student pharmacist/patient clinical interactions as depicted in videotaped simulations and to compare expert panelist and typical preceptor ratings of those interactions. Methods. This study used a multifactorial experimental design to estimate inter-rater reliability and accuracy of preceptors’ assessment of student performance in clinical simulations. The study protocol used nine 5-10 minute video vignettes portraying different levels of competency in student performance in simulated clinical interactions. Intra-Class Correlation (ICC) was used to calculate inter-rater reliability and Fisher exact test was used to compare differences in distribution of scores between expert and nonexpert assessments. Results. Preceptors (n=42) across 5 states assessed the simulated performances. Intra-Class Correlation estimates were higher for 3 nonrandomized video simulations compared to the 6 randomized simulations. Preceptors more readily identified high and low student performances compared to satisfactory performances. In nearly two-thirds of the rating opportunities, a higher proportion of expert panelists than preceptors rated the student performance correctly (18 of 27 scenarios). Conclusion. Valid and reliable assessments are critically important because they affect student grades and formative student feedback. Study results indicate the need for pharmacy preceptor training in performance assessment. The process demonstrated in this study can be used to establish minimum preceptor benchmarks for future national training programs. PMID:26089563

Genetics of eosinophilic esophagitis

PubMed Central

Kottyan, LC; Rothenberg, ME

2017-01-01

Eosinophilic esophagitis (EoE) is a chronic, allergic disease associated with marked mucosal eosinophil accumulation. EoE disease risk is multifactorial and includes environmental and genetic factors. This review will focus on the contribution of genetic variation to EoE risk, as well as the experimental tools and statistical methodology used to identify EoE risk loci. Specific disease-risk loci that are shared between EoE and other allergic diseases (TSLP, LRRC32) or unique to EoE (CAPN14), as well as Mendellian Disorders associated with EoE, will be reviewed in the context of the insight that they provide into the molecular pathoetiology of EoE. We will also discuss the clinical opportunities that genetic analyses provide in the form of decision support tools, molecular diagnostics, and novel therapeutic approaches. PMID:28224995

Genetics of eosinophilic esophagitis.

PubMed

Kottyan, L C; Rothenberg, M E

2017-05-01

Eosinophilic esophagitis (EoE) is a chronic, allergic disease associated with marked mucosal eosinophil accumulation. EoE disease risk is multifactorial and includes environmental and genetic factors. This review will focus on the contribution of genetic variation to EoE risk, as well as the experimental tools and statistical methodology used to identify EoE risk loci. Specific disease-risk loci that are shared between EoE and other allergic diseases (TSLP, LRRC32) or unique to EoE (CAPN14), as well as Mendellian Disorders associated with EoE, will be reviewed in the context of the insight that they provide into the molecular pathoetiology of EoE. We will also discuss the clinical opportunities that genetic analyses provide in the form of decision support tools, molecular diagnostics, and novel therapeutic approaches.

Erring and learning in clinical practice.

PubMed Central

Hurwitz, Brian

2002-01-01

This paper discusses error type their possible consequences and the doctors who make them. There is no single, all-encompassing typology of medical errors. They are frequently multifactorial in origin and use from the mental processes of individuals; from defects in perception, thinking reasoning planning and interpretation and from failures of team-working omissions and poorly executed actions. They also arise from inadequately designed and operated healthcare systems or procedures. The paper considers error-truth relatedness, the approach of UK courts to medical errors, the learning opportunities which flow from error recognition and the need for personal and professional self awareness of clinical fallibilities. PMID:12389767

A multifactorial obesity model developed from nationwide public health exposome data and modern computational analyses.

PubMed

Gittner, LisaAnn S; Kilbourne, Barbara J; Vadapalli, Ravi; Khan, Hafiz M K; Langston, Michael A

Obesity is both multifactorial and multimodal, making it difficult to identify, unravel and distinguish causative and contributing factors. The lack of a clear model of aetiology hampers the design and evaluation of interventions to prevent and reduce obesity. Using modern graph-theoretical algorithms, we are able to coalesce and analyse thousands of inter-dependent variables and interpret their putative relationships to obesity. Our modelling is different from traditional approaches; we make no a priori assumptions about the population, and model instead based on the actual characteristics of a population. Paracliques, noise-resistant collections of highly-correlated variables, are differentially distilled from data taken over counties associated with low versus high obesity rates. Factor analysis is then applied and a model is developed. Latent variables concentrated around social deprivation, community infrastructure and climate, and especially heat stress were connected to obesity. Infrastructure, environment and community organisation differed in counties with low versus high obesity rates. Clear connections of community infrastructure with obesity in our results lead us to conclude that community level interventions are critical. This effort suggests that it might be useful to study and plan interventions around community organisation and structure, rather than just the individual, to combat the nation's obesity epidemic. Copyright © 2017 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

Implementing multifactorial psychotherapy research in online virtual environments (IMPROVE-2): study protocol for a phase III trial of the MOST randomized component selection method for internet cognitive-behavioural therapy for depression.

PubMed

Watkins, Edward; Newbold, Alexandra; Tester-Jones, Michelle; Javaid, Mahmood; Cadman, Jennifer; Collins, Linda M; Graham, John; Mostazir, Mohammod

2016-10-06

Depression is a global health challenge. Although there are effective psychological and pharmaceutical interventions, our best treatments achieve remission rates less than 1/3 and limited sustained recovery. Underpinning this efficacy gap is limited understanding of how complex psychological interventions for depression work. Recent reviews have argued that the active ingredients of therapy need to be identified so that therapy can be made briefer, more potent, and to improve scalability. This in turn requires the use of rigorous study designs that test the presence or absence of individual therapeutic elements, rather than standard comparative randomised controlled trials. One such approach is the Multiphase Optimization Strategy, which uses efficient experimentation such as factorial designs to identify active factors in complex interventions. This approach has been successfully applied to behavioural health but not yet to mental health interventions. A Phase III randomised, single-blind balanced fractional factorial trial, based in England and conducted on the internet, randomized at the level of the patient, will investigate the active ingredients of internet cognitive-behavioural therapy (CBT) for depression. Adults with depression (operationalized as PHQ-9 score ≥ 10), recruited directly from the internet and from an UK National Health Service Improving Access to Psychological Therapies service, will be randomized across seven experimental factors, each reflecting the presence versus absence of specific treatment components (activity scheduling, functional analysis, thought challenging, relaxation, concreteness training, absorption, self-compassion training) using a 32-condition balanced fractional factorial design (2 IV 7-2 ). The primary outcome is symptoms of depression (PHQ-9) at 12 weeks. Secondary outcomes include symptoms of anxiety and process measures related to hypothesized mechanisms. Better understanding of the active ingredients of efficacious therapies, such as CBT, is necessary in order to improve and further disseminate these interventions. This study is the first application of a component selection experiment to psychological interventions in depression and will enable us to determine the main effect of each treatment component and its relative efficacy, and cast light on underlying mechanisms, so that we can systematically enhance internet CBT. Current Controlled Trials ISRCTN24117387 . Registered 26 August 2014.

How does obesity affect fertility in men - and what are the treatment options?

PubMed

Stokes, Victoria J; Anderson, Richard A; George, Jyothis T

2015-05-01

Adiposity is associated with reduced fertility in men. The aetiology is multifactorial, with obese men at greater risk of suffering from impaired spermatogenesis, reduced circulating testosterone levels, erectile dysfunction and poor libido. The diagnosis and treatment of reduced fertility observed in obese men therefore requires insight into the underlying pathology, which has hormonal, mechanical and psychosocial aspects. This article summarises the current epidemiological, experimental and clinical trial evidence from the perspective of a practicing clinician. The following conclusions and recommendations can be drawn: Obesity is associated with low serum testosterone concentrations, but treatment with exogenous testosterone is likely to adversely impact on fertility. It is important to discuss this with men prior to initiation of testosterone therapy. Obesity adversely affects sperm concentration and may affect sperm quality. However, whether or not weight loss will correct these factors remain to be established. Oestrogen receptor modulators (and aromatase inhibitors) are unlicensed in the treatment for male hypogonadism and/or infertility. These treatments should hence be considered experimental approach until ongoing clinical trials report their outcomes. © 2014 John Wiley & Sons Ltd.

Quest to identify geochemical risk factors associated with chronic kidney disease of unknown etiology (CKDu) in an endemic region of Sri Lanka-a multimedia laboratory analysis of biological, food, and environmental samples.

PubMed

Levine, Keith E; Redmon, Jennifer Hoponick; Elledge, Myles F; Wanigasuriya, Kamani P; Smith, Kristin; Munoz, Breda; Waduge, Vajira A; Periris-John, Roshini J; Sathiakumar, Nalini; Harrington, James M; Womack, Donna S; Wickremasinghe, Rajitha

2016-10-01

The emergence of a new form of chronic kidney disease of unknown etiology (CKDu) in Sri Lanka's North Central Province (NCP) has become a catastrophic health crisis. CKDu is characterized as slowly progressing, irreversible, and asymptomatic until late stages and, importantly, not attributed to diabetes, hypertension, or other known risk factors. It is postulated that the etiology of CKDu is multifactorial, involving genetic predisposition, nutritional and dehydration status, exposure to one or more environmental nephrotoxins, and lifestyle factors. The objective of this limited geochemical laboratory analysis was to determine the concentration of a suite of heavy metals and trace element nutrients in biological samples (human whole blood and hair) and environmental samples (drinking water, rice, soil, and freshwater fish) collected from two towns within the endemic NCP region in 2012 and 2013. This broad panel, metallomics/mineralomics approach was used to shed light on potential geochemical risk factors associated with CKDu. Based on prior literature documentation of potential nephrotoxins that may play a role in the genesis and progression of CKDu, heavy metals and fluoride were selected for analysis. The geochemical concentrations in biological and environmental media areas were quantified. Basic statistical measurements were subsequently used to compare media against applicable benchmark values, such as US soil screening levels. Cadmium, lead, and mercury were detected at concentrations exceeding US reference values in many of the biological samples, suggesting that study participants are subjected to chronic, low-level exposure to these elements. Within the limited number of environmental media samples, arsenic was determined to exceed initial risk screening and background concentration values in soil, while data collected from drinking water samples reflected the unique hydrogeochemistry of the region, including the prevalence of hard or very hard water, and fluoride, iron, manganese, sodium, and lead exceeding applicable drinking water standards in some instances. Current literature suggests that the etiology of CKDu is likely multifactorial, with no single biological or hydrogeochemical parameter directly related to disease genesis and progression. This preliminary screening identified that specific constituents may be present above levels of concern, but does not compare results against specific kidney toxicity values or cumulative risk related to a multifactorial disease process. The data collected from this limited investigation are intended to be used in the subsequent study design of a comprehensive and multifactorial etiological study of CKDu risk factors that includes sample collection, individual surveys, and laboratory analyses to more fully evaluate the potential environmental, behavioral, genetic, and lifestyle risk factors associated with CKDu.

Multifactorial Experimental Design to Optimize the Anti-Inflammatory and Proangiogenic Potential of Mesenchymal Stem Cell Spheroids.

PubMed

Murphy, Kaitlin C; Whitehead, Jacklyn; Falahee, Patrick C; Zhou, Dejie; Simon, Scott I; Leach, J Kent

2017-06-01

Mesenchymal stem cell therapies promote wound healing by manipulating the local environment to enhance the function of host cells. Aggregation of mesenchymal stem cells (MSCs) into three-dimensional spheroids increases cell survival and augments their anti-inflammatory and proangiogenic potential, yet there is no consensus on the preferred conditions for maximizing spheroid function in this application. The objective of this study was to optimize conditions for forming MSC spheroids that simultaneously enhance their anti-inflammatory and proangiogenic nature. We applied a design of experiments (DOE) approach to determine the interaction between three input variables (number of cells per spheroid, oxygen tension, and inflammatory stimulus) on MSC spheroids by quantifying secretion of prostaglandin E 2 (PGE 2 ) and vascular endothelial growth factor (VEGF), two potent molecules in the MSC secretome. DOE results revealed that MSC spheroids formed with 40,000 cells per spheroid in 1% oxygen with an inflammatory stimulus (Spheroid 1) would exhibit enhanced PGE 2 and VEGF production versus those formed with 10,000 cells per spheroid in 21% oxygen with no inflammatory stimulus (Spheroid 2). Compared to Spheroid 2, Spheroid 1 produced fivefold more PGE 2 and fourfold more VEGF, providing the opportunity to simultaneously upregulate the secretion of these factors from the same spheroid. The spheroids induced macrophage polarization, sprout formation with endothelial cells, and keratinocyte migration in a human skin equivalent model-demonstrating efficacy on three key cell types that are dysfunctional in chronic non-healing wounds. We conclude that DOE-based analysis effectively identifies optimal culture conditions to enhance the anti-inflammatory and proangiogenic potential of MSC spheroids. Stem Cells 2017;35:1493-1504. © 2017 AlphaMed Press.

A cluster randomised controlled trial of advice, exercise or multifactorial assessment to prevent falls and fractures in community-dwelling older adults: protocol for the prevention of falls injury trial (PreFIT)

PubMed Central

Lall, Ranjit; Withers, Emma J; Finnegan, Susanne; Underwood, Martin; Hulme, Claire; Sheridan, Ray; Skelton, Dawn A; Martin, Finbarr; Lamb, Sarah E

2016-01-01

Introduction Falls are the leading cause of accident-related mortality in older adults. Injurious falls are associated with functional decline, disability, healthcare utilisation and significant National Health Service (NHS)-related costs. The evidence base for multifactorial or exercise interventions reducing fractures in the general population is weak. This protocol describes a large-scale UK trial investigating the clinical and cost-effectiveness of alternative falls prevention interventions targeted at community dwelling older adults. Methods and analysis A three-arm, pragmatic, cluster randomised controlled trial, conducted within primary care in England, UK. Sixty-three general practices will be randomised to deliver one of three falls prevention interventions: (1) advice only; (2) advice with exercise; or (3) advice with multifactorial falls prevention (MFFP). We aim to recruit over 9000 community-dwelling adults aged 70 and above. Practices randomised to deliver advice will mail out advice booklets. Practices randomised to deliver ‘active’ interventions, either exercise or MFFP, send all trial participants the advice booklet and a screening survey to identify participants with a history of falling or balance problems. Onward referral to ‘active’ intervention will be based on falls risk determined from balance screen. The primary outcome is peripheral fracture; secondary outcomes include number with at least one fracture, falls, mortality, quality of life and health service resource use at 18 months, captured using self-report and routine healthcare activity data. Ethics and dissemination The study protocol has approval from the National Research Ethics Service (REC reference 10/H0401/36; Protocol V.3.1, 21/May/2013). User groups and patient representatives were consulted to inform trial design. Results will be reported at conferences and in peer-reviewed publications. A patient-friendly summary of trial findings will be published on the prevention of falls injury trial (PreFIT) website. This protocol adheres to the recommended SPIRIT Checklist. Amendments will be reported to relevant regulatory parties. Trial registration number ISRCTN 71002650; Pre-results. PMID:26781504

A cluster randomised controlled trial of advice, exercise or multifactorial assessment to prevent falls and fractures in community-dwelling older adults: protocol for the prevention of falls injury trial (PreFIT).

PubMed

Bruce, Julie; Lall, Ranjit; Withers, Emma J; Finnegan, Susanne; Underwood, Martin; Hulme, Claire; Sheridan, Ray; Skelton, Dawn A; Martin, Finbarr; Lamb, Sarah E

2016-01-18

Falls are the leading cause of accident-related mortality in older adults. Injurious falls are associated with functional decline, disability, healthcare utilisation and significant National Health Service (NHS)-related costs. The evidence base for multifactorial or exercise interventions reducing fractures in the general population is weak. This protocol describes a large-scale UK trial investigating the clinical and cost-effectiveness of alternative falls prevention interventions targeted at community dwelling older adults. A three-arm, pragmatic, cluster randomised controlled trial, conducted within primary care in England, UK. Sixty-three general practices will be randomised to deliver one of three falls prevention interventions: (1) advice only; (2) advice with exercise; or (3) advice with multifactorial falls prevention (MFFP). We aim to recruit over 9000 community-dwelling adults aged 70 and above. Practices randomised to deliver advice will mail out advice booklets. Practices randomised to deliver 'active' interventions, either exercise or MFFP, send all trial participants the advice booklet and a screening survey to identify participants with a history of falling or balance problems. Onward referral to 'active' intervention will be based on falls risk determined from balance screen. The primary outcome is peripheral fracture; secondary outcomes include number with at least one fracture, falls, mortality, quality of life and health service resource use at 18 months, captured using self-report and routine healthcare activity data. The study protocol has approval from the National Research Ethics Service (REC reference 10/H0401/36; Protocol V.3.1, 21/May/2013). User groups and patient representatives were consulted to inform trial design. Results will be reported at conferences and in peer-reviewed publications. A patient-friendly summary of trial findings will be published on the prevention of falls injury trial (PreFIT) website. This protocol adheres to the recommended SPIRIT Checklist. Amendments will be reported to relevant regulatory parties. ISRCTN 71002650; Pre-results. 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/

The Effect of Diabetes Mellitus on Apoptosis in Hippocampus: Cellular and Molecular Aspects.

PubMed

Sadeghi, Akram; Hami, Javad; Razavi, Shahnaz; Esfandiary, Ebrahim; Hejazi, Zahra

2016-01-01

Diabetes mellitus is associated with cognitive deficits in humans and animals. These deficits are paralleled by neurophysiological and structural changes in brain. In diabetic animals, impairments of spatial learning, memory, and cognition occur in association with distinct changes in hippocampus, a key brain area for many forms of learning and memory and are particularly sensitive to changes in glucose homeostasis. However, the multifactorial pathogenesis of diabetic encephalopathy is not yet completely understood. Apoptosis plays a crucial role in diabetes-induce neuronal loss in hippocampus. The effects of diabetes on hippocampus and cognitive/behavioral dysfunctions in experimental models of diabetes are reviewed, with a focus on the negative impact on increased neuronal apoptosis and related cellular and molecular mechanisms. Of all articles that were assessed, most of the experimental studies clearly showed that diabetes causes neuronal apoptosis in hippocampus through multiple mechanisms, including oxidative stress, inhibition of caspases, disturbance in expression of apoptosis regulator genes, as well as deficits in mitochondrial function. The balance between pro-apoptotic and anti-apoptotic signaling may determine the neuronal apoptotic outcome in vitro and in vivo models of experimental diabetes. Dissecting out the mechanisms responsible for diabetes-related changes in the hippocampal cell apoptosis helps improve treatment of impaired cognitive and memory functions in diabetic individuals.

[Diabetes and predictive medicine--parallax of the present time].

PubMed

Rybka, J

2010-04-01

Predictive genetics uses genetic testing to estimate the risk in asymptomatic persons. Since in the case of multifactorial diseases predictive genetic analysis deals with findings which allow wider interpretation, it has a higher predictive value in expressly qualified diseases (monogenous) with high penetration compared to multifactorial (polygenous) diseases with high participation of environmental factors. In most "civilisation" (multifactorial) diseases including diabetes, heredity and environmental factors do not play two separate, independent roles. Instead, their interactions play a principal role. The new classification of diabetes is based on the implementation of not only ethiopathogenetic, but also genetic research. Diabetes mellitus type 1 (DM1T) is a polygenous multifactorial disease with the genetic component carrying about one half of the risk, the non-genetic one the other half. The study of the autoimmune nature of DM1T in connection with genetic analysis is going to bring about new insights in DM1T prediction. The author presents new pieces of knowledge on molecular genetics concerning certain specific types of diabetes. Issues relating to heredity in diabetes mellitus type 2 (DM2T) are even more complex. The disease has a polygenous nature, and the phenotype of a patient with DM2T, in addition to environmental factors, involves at least three, perhaps even tens of different genetic variations. At present, results at the genom-wide level appear to be most promising. The current concept of prediabetes is a realistic foundation for our prediction and prevention of DM2T. A multifactorial, multimarker approach based on our understanding of new pathophysiological factors of DM2T, tries to outline a "map" of prediabetes physiology, and if these tests are combined with sophisticated methods of genetic forecasting of DM2T, this may represent a significant step in our methodology of diabetes prediction. So far however, predictive genetics is limited by the interpretation of genetic predisposition and individualisation of the level of risk. There is no doubt that interpretation calls for co-operation with clinicians, while results of genetic analyses should presently be not uncritically overestimated. Predictive medicine, however, unquestionably fulfills the preventive focus of modern medicine, and genetic analysis is a perspective diagnostic method.

Effect of a multifactorial fall-and-fracture risk assessment and management program on gait and balance performances and disability in hospitalized older adults: a controlled study.

PubMed

Trombetti, A; Hars, M; Herrmann, F; Rizzoli, R; Ferrari, S

2013-03-01

This controlled intervention study in hospitalized oldest old adults showed that a multifactorial fall-and-fracture risk assessment and management program, applied in a dedicated geriatric hospital unit, was effective in improving fall-related physical and functional performances and the level of independence in activities of daily living in high-risk patients. Hospitalization affords a major opportunity for interdisciplinary cooperation to manage fall-and-fracture risk factors in older adults. This study aimed at assessing the effects on physical performances and the level of independence in activities of daily living (ADL) of a multifactorial fall-and-fracture risk assessment and management program applied in a geriatric hospital setting. A controlled intervention study was conducted among 122 geriatric inpatients (mean ± SD age, 84 ± 7 years) admitted with a fall-related diagnosis. Among them, 92 were admitted to a dedicated unit and enrolled into a multifactorial intervention program, including intensive targeted exercise. Thirty patients who received standard usual care in a general geriatric unit formed the control group. Primary outcomes included gait and balance performances and the level of independence in ADL measured 12 ± 6 days apart. Secondary outcomes included length of stay, incidence of in-hospital falls, hospital readmission, and mortality rates. Compared to the usual care group, the intervention group had significant improvements in Timed Up and Go (adjusted mean difference [AMD] = -3.7s; 95 % CI = -6.8 to -0.7; P = 0.017), Tinetti (AMD = -1.4; 95 % CI = -2.1 to -0.8; P < 0.001), and Functional Independence Measure (AMD = 6.5; 95 %CI = 0.7-12.3; P = 0.027) test performances, as well as in several gait parameters (P < 0.05). Furthermore, this program favorably impacted adverse outcomes including hospital readmission (hazard ratio = 0.3; 95 % CI = 0.1-0.9; P = 0.02). A multifactorial fall-and-fracture risk-based intervention program, applied in a dedicated geriatric hospital unit, was effective and more beneficial than usual care in improving physical parameters related to the risk of fall and disability among high-risk oldest old patients.

Patients with recurrent falls attending Accident & Emergency benefit from multifactorial intervention--a randomised controlled trial.

PubMed

Davison, John; Bond, John; Dawson, Pamela; Steen, I Nicholas; Kenny, Rose Anne

2005-03-01

To determine the effectiveness of multifactorial intervention to prevent falls in cognitively intact older persons with recurrent falls. Randomised controlled trial of multifactorial (medical, physiotherapy and occupational therapy) post-fall assessment and intervention compared with conventional care. Accident & Emergency departments in a university teaching hospital and associated district general hospital. 313 cognitively intact men and women aged over 65 years presenting to Accident & Emergency with a fall or fall-related injury and at least one additional fall in the preceding year; 159 randomised to assessment and intervention and 154 to conventional care. primary outcome was the number of falls and fallers in 1 year after recruitment. Secondary outcomes included injury rates, fall-related hospital admissions, mortality and fear of falling. There were 36% fewer falls in the intervention group (relative risk 0.64, 95% confidence interval 0.46-0.90). The proportion of subjects continuing to fall (65% (94/144) compared with 68% (102/149) relative risk 0.95, 95% confidence interval 0.81-1.12), and the number of fall-related attendances and hospital admissions was not different between groups. Duration of hospital admission was reduced (mean difference admission duration 3.6 days, 95% confidence interval 0.1-7.6) and falls efficacy was better in the intervention group (mean difference in Activities Specific Balance Confidence Score of 7.5, 95% confidence interval 0.72-14.2). Multifactorial intervention is effective at reducing the fall burden in cognitively intact older persons with recurrent falls attending Accident & Emergency, but does not reduce the proportion of subjects still falling.

Cross-System Evaluation of Clinical Trial Search Engines

PubMed Central

Jiang, Silis Y.; Weng, Chunhua

2014-01-01

Clinical trials are fundamental to the advancement of medicine but constantly face recruitment difficulties. Various clinical trial search engines have been designed to help health consumers identify trials for which they may be eligible. Unfortunately, knowledge of the usefulness and usability of their designs remains scarce. In this study, we used mixed methods, including time-motion analysis, think-aloud protocol, and survey, to evaluate five popular clinical trial search engines with 11 users. Differences in user preferences and time spent on each system were observed and correlated with user characteristics. In general, searching for applicable trials using these systems is a cognitively demanding task. Our results show that user perceptions of these systems are multifactorial. The survey indicated eTACTS being the generally preferred system, but this finding did not persist among all mixed methods. This study confirms the value of mixed-methods for a comprehensive system evaluation. Future system designers must be aware that different users groups expect different functionalities. PMID:25954590

Cross-system evaluation of clinical trial search engines.

PubMed

Jiang, Silis Y; Weng, Chunhua

2014-01-01

Clinical trials are fundamental to the advancement of medicine but constantly face recruitment difficulties. Various clinical trial search engines have been designed to help health consumers identify trials for which they may be eligible. Unfortunately, knowledge of the usefulness and usability of their designs remains scarce. In this study, we used mixed methods, including time-motion analysis, think-aloud protocol, and survey, to evaluate five popular clinical trial search engines with 11 users. Differences in user preferences and time spent on each system were observed and correlated with user characteristics. In general, searching for applicable trials using these systems is a cognitively demanding task. Our results show that user perceptions of these systems are multifactorial. The survey indicated eTACTS being the generally preferred system, but this finding did not persist among all mixed methods. This study confirms the value of mixed-methods for a comprehensive system evaluation. Future system designers must be aware that different users groups expect different functionalities.

Loss of delta catenin function in severe autism

PubMed Central

Turner, Tychele N.; Sharma, Kamal; Oh, Edwin C.; Liu, Yangfan P.; Collins, Ryan L.; Sosa, Maria X.; Auer, Dallas R.; Brand, Harrison; Sanders, Stephan J.; Moreno-De-Luca, Daniel; Pihur, Vasyl; Plona, Teri; Pike, Kristen; Soppet, Daniel R.; Smith, Michael W.; Cheung, Sau Wai; Martin, Christa Lese; State, Matthew W.; Talkowski, Michael E.; Cook, Edwin; Huganir, Richard; Katsanis, Nicholas; Chakravarti, Aravinda

2015-01-01

SUMMARY Autism is a multifactorial neurodevelopmental disorder affecting more males than females; consequently, under a multifactorial genetic hypothesis, females are affected only when they cross a higher biological threshold. We hypothesize that deleterious variants at conserved residues are enriched in severely affected patients arising from FEMFs (female-enriched multiplex families) with severe disease, enhancing the detection of key autism genes in modest numbers of cases. We show the utility of this strategy by identifying missense and dosage sequence variants in the gene encoding the adhesive junction-associated delta catenin protein (CTNND2) in FEMFs and demonstrating their loss-of-function effect by functional analyses in zebrafish embryos and cultured hippocampal neurons from wildtype and Ctnnd2 null mouse embryos. Finally, through gene expression and network analyses, we highlight a critical role for CTNND2 in neuronal development and an intimate connection to chromatin biology. Our data contribute to the understanding of the genetic architecture of autism and suggest that genetic analyses of phenotypic extremes, such as FEMFs, are of innate value in multifactorial disorders. PMID:25807484

A framework for learning about improvement: embedded implementation and evaluation design to optimize learning

PubMed Central

Barry, Danika; Kimble, Leighann E; Nambiar, Bejoy; Parry, Gareth; Jha, Ashish; Chattu, Vijay Kumar; Massoud, M Rashad; Goldmann, Don

2018-01-01

Abstract Improving health care involves many actors, often working in complex adaptive systems. Interventions tend to be multi-factorial, implementation activities diverse, and contexts dynamic and complicated. This makes improvement initiatives challenging to describe and evaluate as matching evaluation and program designs can be difficult, requiring collaboration, trust and transparency. Collaboration is required to address important epidemiological principles of bias and confounding. If this does not take place, results may lack credibility because the association between interventions implemented and outcomes achieved is obscure and attribution uncertain. Moreover, lack of clarity about what was implemented, how it was implemented, and the context in which it was implemented often lead to disappointment or outright failure of spread and scale-up efforts. The input of skilled evaluators into the design and conduct of improvement initiatives can be helpful in mitigating these potential problems. While evaluation must be rigorous, if it is too rigid necessary adaptation and learning may be compromised. This article provides a framework and guidance on how improvers and evaluators can work together to design, implement and learn about improvement interventions more effectively. PMID:29873794

Catalyzing Transdisciplinarity: A Systems Ethnography of Cancer-Obesity Comorbidity and Risk Coincidence.

PubMed

Graham, S Scott; Harley, Amy; Kessler, Molly M; Roberts, Laura; DeVasto, Dannielle; Card, Daniel J; Neuner, Joan M; Kim, Sang-Yeon

2017-05-01

Effectively addressing wicked health problems, that is, those arising from complex multifactorial biological and socio-economic causes, requires transdisciplinary action. However, a significant body of research points toward substantial difficulties in cultivating transdisciplinary collaboration. Accordingly, this article presents the results of a study that adapts Systems Ethnography and Qualitative Modeling (SEQM) in response to wicked health problems. SEQM protocols were designed to catalyze transdisciplinary responses to national defense concerns. We adapted these protocols to address cancer-obesity comorbidity and risk coincidence. In so doing, we conducted participant-observations and interviews with a diverse range of health care providers, community health educators, and health advocacy professionals who target either cancer or obesity. We then convened a transdisciplinary conference designed to catalyze a coordinated response. The findings offer productive insights into effective ways of catalyzing transdisciplinarity in addressing wicked health problems action and demonstrate the promise of SEQM for continued use in health care contexts.

Workarounds in the Workplace: A Second Look.

PubMed

Seaman, Jennifer B; Erlen, Judith A

2015-01-01

Nursing workarounds have garnered increased attention over the past 15 years, corresponding with an increased focus on patient safety and evidence-based practice and a rise in the use of health information technologies (HITs). Workarounds have typically been viewed as deviations from best practice that put patients at risk for poor outcomes. However, this narrow view fails to take into consideration the multifactorial origins of workarounds. The authors explore the ways in which evidence-based protocols and HIT, designed to improve patient safety and quality, can have an unintended consequence of increasing the likelihood of nurses engaging in workarounds. The article also examines workarounds considering the ethical obligations of both nurses and administrative leaders to optimize patient safety and quality.

Selection of higher order regression models in the analysis of multi-factorial transcription data.

PubMed

Prazeres da Costa, Olivia; Hoffman, Arthur; Rey, Johannes W; Mansmann, Ulrich; Buch, Thorsten; Tresch, Achim

2014-01-01

Many studies examine gene expression data that has been obtained under the influence of multiple factors, such as genetic background, environmental conditions, or exposure to diseases. The interplay of multiple factors may lead to effect modification and confounding. Higher order linear regression models can account for these effects. We present a new methodology for linear model selection and apply it to microarray data of bone marrow-derived macrophages. This experiment investigates the influence of three variable factors: the genetic background of the mice from which the macrophages were obtained, Yersinia enterocolitica infection (two strains, and a mock control), and treatment/non-treatment with interferon-γ. We set up four different linear regression models in a hierarchical order. We introduce the eruption plot as a new practical tool for model selection complementary to global testing. It visually compares the size and significance of effect estimates between two nested models. Using this methodology we were able to select the most appropriate model by keeping only relevant factors showing additional explanatory power. Application to experimental data allowed us to qualify the interaction of factors as either neutral (no interaction), alleviating (co-occurring effects are weaker than expected from the single effects), or aggravating (stronger than expected). We find a biologically meaningful gene cluster of putative C2TA target genes that appear to be co-regulated with MHC class II genes. We introduced the eruption plot as a tool for visual model comparison to identify relevant higher order interactions in the analysis of expression data obtained under the influence of multiple factors. We conclude that model selection in higher order linear regression models should generally be performed for the analysis of multi-factorial microarray data.

Back posture education in elementary schoolchildren: stability of two-year intervention effects.

PubMed

Geldhof, E; Cardon, G; De Bourdeaudhuij, I; De Clercq, D

2007-09-01

The study's first objective was to evaluate class teachers' efforts to promote good body mechanics after a structured back education program was finished and to evaluate whether their support during follow-up resulted in better intervention effects at 1-year follow-up. Secondary, the stability of intervention effects on children's back posture knowledge, fear-avoidance beliefs and back pain reports following a 2-school-year multi-factorial back education program was evaluated at 1-year follow-up. An additional focus was put on what young children learned about good body mechanics in the obligatory school curriculum compared to intensive back posture promotion. The quasi-experimental study included at baseline 398 elementary schoolchildren aged 8-11 years. The back education program consisted of 13 h back education and the stimulation of postural dynamism in the class through support and environmental changes lasting 2 school-years. Controls received the obligatory curriculum, not including back education. Evaluation consisted of a questionnaire, which was filled out by 121 intervention children and 124 controls at baseline, post-test and follow-up. Teachers were interviewed at the end of the follow-up school-year. Teachers continued with initiatives to increase postural dynamism in the class when they had been instructed about that matter. However, teachers' efforts to continue the promotion of good body mechanics showed no additional effect on children's knowledge. Improved back posture knowledge demonstrated stability at 1-year follow-up. Whereas the obligatory curriculum provided children with fundamental postural knowledge, the back posture program added important aspects. Fear-avoidance beliefs and self-reported pain were not increased at 1-year follow-up. The stable intervention effects point out that intensive implementation of a structured multifactorial back education program in the elementary school curriculum is effective.

Ca2+-induced delayed afterdepolarizations are triggered by dyadic subspace Ca2+ affirming that increasing SERCA reduces aftercontractions

PubMed Central

Noble, Penelope J.; Noble, Denis

2011-01-01

Ca2+-induced delayed afterdepolarizations (DADs) are depolarizations that occur after full repolarization. They have been observed across multiple species and cell types. Experimental results have indicated that the main cause of DADs is Ca2+ overload. The main hypothesis as to their initiation has been Ca2+ overflow from the overloaded sarcoplasmic reticulum (SR). Our results using 37 previously published mathematical models provide evidence that Ca2+-induced DADs are initiated by the same mechanism as Ca2+-induced Ca2+ release, i.e., the modulation of the opening of ryanodine receptors (RyR) by Ca2+ in the dyadic subspace; an SR overflow mechanism was not necessary for the induction of DADs in any of the models. The SR Ca2+ level is better viewed as a modulator of the appearance of DADs and the magnitude of Ca2+ release. The threshold for the total Ca2+ level within the cell (not only the SR) at which Ca2+ oscillations arise in the models is close to their baseline level (∼1- to 3-fold). It is most sensitive to changes in the maximum sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) pump rate (directly proportional), the opening probability of RyRs, and the Ca2+ diffusion rate from the dyadic subspace into the cytosol (both indirectly proportional), indicating that the appearance of DADs is multifactorial. This shift in emphasis away from SR overload as the trigger for DADs toward a multifactorial analysis could explain why SERCA overexpression has been shown to suppress DADs (while increasing contractility) and why DADs appear during heart failure (at low SR Ca2+ levels). PMID:21666112

The in vitro wear behavior of experimental resin-based composites derived from a commercial formulation.

PubMed

Finlay, Nessa; Hahnel, Sebastian; Dowling, Adam H; Fleming, Garry J P

2013-04-01

To investigate the short- and long-term in vitro wear resistance of experimental resin-based composites (RBCs) derived from a commercial formulation. Six experimental RBCs were manufactured by manipulating the monomeric resin composition and the filler characteristics of Grandio (Voco GmbH, Cuxhaven, Germany). The Oregon Health Sciences University (OHSU) oral wear simulator was used in the presence of a food-like slurry to simulate three-body abrasion and attrition wear for 50,000, 150,000 and 300,000 cycles. A three-dimensional image of each wear facet was created and the total volumetric wear (mm(3)) and maximum wear depth (μm) were quantified for the RBC and antagonist. Statistical analyses of the total volumetric wear and maximum wear depth data (two- and one-way analyses of variance (ANOVA), with Tukey's post hoc tests where required) and regression analyses, were conducted at p=0.05. Two-way ANOVAs identified a significant effect of RBC material×wear cycles, RBC material and wear cycles (all p<0.0001). Regression analyses showed significant increases in the total volumetric wear (p≤0.001) and maximum wear depth data (p≤0.004) for all RBCs with increasing wear cycles. Differences between all RBC materials were evident after ≥150,000 wear cycles and antagonist wear provided valuable information to support the experimental findings. Wear simulating machines can provide an indication of the clinical performance but clinical performance is multi-factorial and wear is only a single facet. Employing experimental RBCs provided by a dental manufacturer rather than using self-manufactured RBCs or dental products provides increased experimental control by limiting the variables involved. Copyright © 2013 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

Effects of a multifactorial falls prevention program for people with stroke returning home after rehabilitation: a randomized controlled trial.

PubMed

Batchelor, Frances A; Hill, Keith D; Mackintosh, Shylie F; Said, Catherine M; Whitehead, Craig H

2012-09-01

To determine whether a multifactorial falls prevention program reduces falls in people with stroke at risk of recurrent falls and whether this program leads to improvements in gait, balance, strength, and fall-related efficacy. A single blind, multicenter, randomized controlled trial with 12-month follow-up. Participants were recruited after discharge from rehabilitation and followed up in the community. Participants (N=156) were people with stroke at risk of recurrent falls being discharged home from rehabilitation. Tailored multifactorial falls prevention program and usual care (n=71) or control (usual care, n=85). Primary outcomes were rate of falls and proportion of fallers. Secondary outcomes included injurious falls, falls risk, participation, activity, leg strength, gait speed, balance, and falls efficacy. There was no significant difference in fall rate (intervention: 1.89 falls/person-year, control: 1.76 falls/person-year, incidence rate ratio=1.10, P=.74) or the proportion of fallers between the groups (risk ratio=.83, 95% confidence interval=.60-1.14). There was no significant difference in injurious fall rate (intervention: .74 injurious falls/person-year, control: .49 injurious falls/person-year, incidence rate ratio=1.57, P=.25), and there were no significant differences between groups on any other secondary outcome. This multifactorial falls prevention program was not effective in reducing falls in people with stroke who are at risk of falls nor was it more effective than usual care in improving gait, balance, and strength in people with stroke. Further research is required to identify effective interventions for this high-risk group. Copyright © 2012 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

A Novel Approach to Proactive Primary Care-Based Case Finding and Multidisciplinary Management of Falls, Syncope, and Dizziness in a One-Stop Service: Preliminary Results.

PubMed

Parry, Steve W; Hill, Harry; Lawson, Joanna; Lawson, Nick; Green, David; Trundle, Heidi; McNaught, Judith; Strassheim, Victoria; Caldwell, Alma; Mayland, Richard; Earley, Phillip; McMeekin, Peter

2016-11-01

National and international evidence and guidelines on falls prevention and management in community-dwelling elderly adults recommend that falls services should be multifactorial and their interventions multicomponent. The way that individuals are identified as having had or being at risk of falls in order to take advantage of such services is far less clear. A novel multidisciplinary, multifactorial falls, syncope, and dizziness service model was designed with enhanced case ascertainment through proactive, primary care-based screening (of individual case notes of individuals aged ≥60) for individual fall risk factors. The service model identified 4,039 individuals, of whom 2,232 had significant gait and balance abnormalities according to senior physiotherapist assessment. Significant numbers of individuals with new diagnoses ranging from cognitive impairment to Parkinson's disease to urgent indications for a pacemaker were discovered. More than 600 individuals were found who were at high risk of osteoporosis according to World Health Association Fracture Risk Assessment Tool score, 179 with benign positional paroxysmal vertigo and 50 with atrial fibrillation. Through such screening and this approach, Comprehensive Geriatric Assessment Plus (Plus falls, syncope and dizziness expertise), unmet need was targeted on a scale far outside the numbers seen in clinical trials. Further work is needed to determine whether this approach translates into fewer falls and decreases in syncope and dizziness. © 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.

Managing Space Radiation Risks on Lunar and Mars Missions: Risk Assessment and Mitigation

NASA Technical Reports Server (NTRS)

Cucinotta, F. A.; George, K.; Hu, X.; Kim, M. H.; Nikjoo, H.

2006-01-01

Radiation-induced health risks are a primary concern for human exploration outside the Earth's magnetosphere, and require improved approaches to risk estimation and tools for mitigation including shielding and biological countermeasures. Solar proton events are the major concern for short-term lunar missions (<60 d), and for long-term missions (>60 d) such as Mars exploration, the exposures to the high energy and charge (HZE) ions that make-up the galactic cosmic rays are the major concern. Health risks from radiation exposure are chronic risks including carcinogenesis and degenerative tissue risks, central nervous system effects, and acute risk such as radiation sickness or early lethality. The current estimate is that a more than four-fold uncertainty exists in the projection of lifetime mortality risk from cosmic rays, which severely limits analysis of possible benefits of shielding or biological countermeasure designs. Uncertainties in risk projections are largely due to insufficient knowledge of HZE ion radiobiology, which has led NASA to develop a unique probabilistic approach to radiation protection. We review NASA's approach to radiation risk assessment including its impact on astronaut dose limits and application of the ALARA (As Low as Reasonably Achievable) principle. The recently opened NASA Space Radiation Laboratory (NSRL) provides the capability to simulate the cosmic rays in controlled ground-based experiments with biological and shielding models. We discuss how research at NSRL will lead to reductions in the uncertainties in risk projection models. In developing mission designs, the reduction of health risks and mission constraints including costs are competing concerns that need to be addressed through optimization procedures. Mitigating the risks from space radiation is a multi-factorial problem involving individual factors (age, gender, genetic makeup, and exposure history), operational factors (planetary destination, mission length, and period in the solar cycle), and shielding characteristics (materials, mass, and topology). We review optimization metrics for radiation protection including scenarios that integrate biophysics models of radiation risks, operational variables, and shielding design tools needed to assess exploration mission designs. We discuss the application of a crosscutting metric, based on probabilistic risk assessment, to lunar and Mars mission trade studies including the assessment of multi-factorial problems and the potential benefits of new radiation health research strategies or mitigation technologies.

Managing Space Radiation Risks On Lunar and Mars Missions: Risk Assessment and Mitigation

NASA Technical Reports Server (NTRS)

Cucinotta, F. A.; George, K.; Hu, X.; Kim, M. H.; Nikjoo, H.

2005-01-01

Radiation-induced health risks are a primary concern for human exploration outside the Earth's magnetosphere, and require improved approaches to risk estimation and tools for mitigation including shielding and biological countermeasures. Solar proton events are the major concern for short-term lunar missions (<60 d), and for long-term missions (>60 d) such as Mars exploration, the exposures to the high energy and charge (HZE) ions that make-up the galactic cosmic rays are the major concern. Health risks from radiation exposure are chronic risks including carcinogenesis and degenerative tissue risks, central nervous system effects, and acute risk such as radiation sickness or early lethality. The current estimate is that a more than four-fold uncertainty exists in the projection of lifetime mortality risk from cosmic rays, which severely limits analysis of possible benefits of shielding or biological countermeasure designs. Uncertainties in risk projections are largely due to insufficient knowledge of HZE ion radiobiology, which has led NASA to develop a unique probabilistic approach to radiation protection. We review NASA's approach to radiation risk assessment including its impact on astronaut dose limits and application of the ALARA (As Low as Reasonably Achievable) principle. The recently opened NASA Space Radiation Laboratory (NSRL) provides the capability to simulate the cosmic rays in controlled ground-based experiments with biological and shielding models. We discuss how research at NSRL will lead to reductions in the uncertainties in risk projection models. In developing mission designs, the reduction of health risks and mission constraints including costs are competing concerns that need to be addressed through optimization procedures. Mitigating the risks from space radiation is a multi-factorial problem involving individual factors (age, gender, genetic makeup, and exposure history), operational factors (planetary destination, mission length, and period in the solar cycle), and shielding characteristics (materials, mass, and topology). We review optimization metrics for radiation protection including scenarios that integrate biophysics models of radiation risks, operational variables, and shielding design tools needed to assess exploration mission designs. We discuss the application of a crosscutting metric, based on probabilistic risk assessment, to lunar and Mars mission trade studies including the assessment of multi-factorial problems and the potential benefits of new radiation health research strategies or mitigation technologies.

Managing Space Radiation Risks on Lunar and Mars Missions: Risk Assessment and Mitigation

NASA Technical Reports Server (NTRS)

Cucinotta, F. A.; George, K.; Hu, X.; Kim, M. H.; Nikjoo, H.; Ponomarev, A.; Ren, L.; Shavers, M. R.; Wu, H.

2005-01-01

Radiation-induced health risks are a primary concern for human exploration outside the Earth's magnetosphere, and require improved approaches to risk estimation and tools for mitigation including shielding and biological countermeasures. Solar proton events are the major concern for short-term lunar missions (<60 d), and for long-term missions (>60 d) such as Mars exploration, the exposures to the high energy and charge (HZE) ions that make-up the galactic cosmic rays are the major concern. Health risks from radiation exposure are chronic risks including carcinogenesis and degenerative tissue risks, central nervous system effects, and acute risk such as radiation sickness or early lethality. The current estimate is that a more than four-fold uncertainty exists in the projection of lifetime mortality risk from cosmic rays, which severely limits analysis of possible benefits of shielding or biological countermeasure designs. Uncertainties in risk projections are largely due to insufficient knowledge of HZE ion radiobiology, which has led NASA to develop a unique probabilistic approach to radiation protection. We review NASA's approach to radiation risk assessment including its impact on astronaut dose limits and application of the ALARA (As Low as Reasonably Achievable) principle. The recently opened NASA Space Radiation Laboratory (NSRL) provides the capability to simulate the cosmic rays in controlled ground-based experiments with biological and shielding models. We discuss how research at NSRL will lead to reductions in the uncertainties in risk projection models. In developing mission designs, the reduction of health risks and mission constraints including costs are competing concerns that need to be addressed through optimization procedures. Mitigating the risks from space radiation is a multi-factorial problem involving individual factors (age, gender, genetic makeup, and exposure history), operational factors (planetary destination, mission length, and period in the solar cycle), and shielding characteristics (materials, mass, and topology). We review optimization metrics for radiation protection including scenarios that integrate biophysics models of radiation risks, operational variables, and shielding design tools needed to assess exploration mission designs. We discuss the application of a crosscutting metric, based on probabilistic risk assessment, to lunar and Mars mission trade studies including the assessment of multi-factorial problems and the potential benefits of new radiation health research strategies or mitigation technologies.

Cochlear Homocysteine Metabolism at the Crossroad of Nutrition and Sensorineural Hearing Loss.

PubMed

Partearroyo, Teresa; Vallecillo, Néstor; Pajares, María A; Varela-Moreiras, Gregorio; Varela-Nieto, Isabel

2017-01-01

Hearing loss (HL) is one of the most common causes of disability, affecting 360 million people according to the World Health Organization (WHO). HL is most frequently of sensorineural origin, being caused by the irreversible loss of hair cells and/or spiral ganglion neurons. The etiology of sensorineural HL (SNHL) is multifactorial, with genetic and environmental factors such as noise, ototoxic substances and aging playing a role. The nutritional status is central in aging disability, but the interplay between nutrition and SNHL has only recently gained attention. Dietary supplementation could therefore constitute the first step for the prevention and potential repair of hearing damage before it reaches irreversibility. In this context, different epidemiological studies have shown correlations among the nutritional condition, increased total plasma homocysteine (tHcy) and SNHL. Several human genetic rare diseases are also associated with homocysteine (Hcy) metabolism and SNHL confirming this potential link. Accordingly, rodent experimental models have provided the molecular basis to understand the observed effects. Thus, increased tHcy levels and vitamin deficiencies, such as folic acid (FA), have been linked with SNHL, whereas long-term dietary supplementation with omega-3 fatty acids improved Hcy metabolism, cell survival and hearing acuity. Furthermore, pharmacological supplementations with the anti-oxidant fumaric acid that targets Hcy metabolism also improved SNHL. Overall these results strongly suggest that cochlear Hcy metabolism is a key player in the onset and progression of SNHL, opening the way for the design of prospective nutritional therapies.

Cochlear Homocysteine Metabolism at the Crossroad of Nutrition and Sensorineural Hearing Loss

PubMed Central

Partearroyo, Teresa; Vallecillo, Néstor; Pajares, María A.; Varela-Moreiras, Gregorio; Varela-Nieto, Isabel

2017-01-01

Hearing loss (HL) is one of the most common causes of disability, affecting 360 million people according to the World Health Organization (WHO). HL is most frequently of sensorineural origin, being caused by the irreversible loss of hair cells and/or spiral ganglion neurons. The etiology of sensorineural HL (SNHL) is multifactorial, with genetic and environmental factors such as noise, ototoxic substances and aging playing a role. The nutritional status is central in aging disability, but the interplay between nutrition and SNHL has only recently gained attention. Dietary supplementation could therefore constitute the first step for the prevention and potential repair of hearing damage before it reaches irreversibility. In this context, different epidemiological studies have shown correlations among the nutritional condition, increased total plasma homocysteine (tHcy) and SNHL. Several human genetic rare diseases are also associated with homocysteine (Hcy) metabolism and SNHL confirming this potential link. Accordingly, rodent experimental models have provided the molecular basis to understand the observed effects. Thus, increased tHcy levels and vitamin deficiencies, such as folic acid (FA), have been linked with SNHL, whereas long-term dietary supplementation with omega-3 fatty acids improved Hcy metabolism, cell survival and hearing acuity. Furthermore, pharmacological supplementations with the anti-oxidant fumaric acid that targets Hcy metabolism also improved SNHL. Overall these results strongly suggest that cochlear Hcy metabolism is a key player in the onset and progression of SNHL, opening the way for the design of prospective nutritional therapies. PMID:28487633

Identification of BRCA1 missense substitutions that confer partial functional activity: potential moderate risk variants?

PubMed

Lovelock, Paul K; Spurdle, Amanda B; Mok, Myth T S; Farrugia, Daniel J; Lakhani, Sunil R; Healey, Sue; Arnold, Stephen; Buchanan, Daniel; Couch, Fergus J; Henderson, Beric R; Goldgar, David E; Tavtigian, Sean V; Chenevix-Trench, Georgia; Brown, Melissa A

2007-01-01

Many of the DNA sequence variants identified in the breast cancer susceptibility gene BRCA1 remain unclassified in terms of their potential pathogenicity. Both multifactorial likelihood analysis and functional approaches have been proposed as a means to elucidate likely clinical significance of such variants, but analysis of the comparative value of these methods for classifying all sequence variants has been limited. We have compared the results from multifactorial likelihood analysis with those from several functional analyses for the four BRCA1 sequence variants A1708E, G1738R, R1699Q, and A1708V. Our results show that multifactorial likelihood analysis, which incorporates sequence conservation, co-inheritance, segregation, and tumour immunohistochemical analysis, may improve classification of variants. For A1708E, previously shown to be functionally compromised, analysis of oestrogen receptor, cytokeratin 5/6, and cytokeratin 14 tumour expression data significantly strengthened the prediction of pathogenicity, giving a posterior probability of pathogenicity of 99%. For G1738R, shown to be functionally defective in this study, immunohistochemistry analysis confirmed previous findings of inconsistent 'BRCA1-like' phenotypes for the two tumours studied, and the posterior probability for this variant was 96%. The posterior probabilities of R1699Q and A1708V were 54% and 69%, respectively, only moderately suggestive of increased risk. Interestingly, results from functional analyses suggest that both of these variants have only partial functional activity. R1699Q was defective in foci formation in response to DNA damage and displayed intermediate transcriptional transactivation activity but showed no evidence for centrosome amplification. In contrast, A1708V displayed an intermediate transcriptional transactivation activity and a normal foci formation response in response to DNA damage but induced centrosome amplification. These data highlight the need for a range of functional studies to be performed in order to identify variants with partially compromised function. The results also raise the possibility that A1708V and R1699Q may be associated with a low or moderate risk of cancer. While data pooling strategies may provide more information for multifactorial analysis to improve the interpretation of the clinical significance of these variants, it is likely that the development of current multifactorial likelihood approaches and the consideration of alternative statistical approaches will be needed to determine whether these individually rare variants do confer a low or moderate risk of breast cancer.

The design and development of a complex multifactorial falls assessment intervention for falls prevention: The Prevention of Falls Injury Trial (PreFIT).

PubMed

Bruce, Julie; Ralhan, Shvaita; Sheridan, Ray; Westacott, Katharine; Withers, Emma; Finnegan, Susanne; Davison, John; Martin, Finbarr C; Lamb, Sarah E

2017-06-01

This paper describes the design and development of a complex multifactorial falls prevention (MFFP) intervention for implementation and testing within the framework of a large UK-based falls prevention randomised controlled trial (RCT). A complex intervention was developed for inclusion within the Prevention of Falls Injury Trial (PreFIT), a multicentre pragmatic RCT. PreFIT aims to compare the clinical and cost-effectiveness of three alternative primary care falls prevention interventions (advice, exercise and MFFP), on outcomes of fractures and falls. Community-dwelling adults, aged 70 years and older, were recruited from primary care in the National Health Service (NHS), England. Development of the PreFIT MFFP intervention was informed by the existing evidence base and clinical guidelines for the assessment and management of falls in older adults. After piloting and modification, the final MFFP intervention includes seven falls risk factors: a detailed falls history interview with consideration of 'red flags'; assessment of balance and gait; vision; medication screen; cardiac screen; feet and footwear screen and home environment assessment. This complex intervention has been fully manualised with clear, documented assessment and treatment pathways for each risk factor. Each risk factor is assessed in every trial participant referred for MFFP. Referral for assessment is based upon a screening survey to identify those with a history of falling or balance problems. Intervention delivery can be adapted to the local setting. This complex falls prevention intervention is currently being tested within the framework of a large clinical trial. This paper adheres to TIDieR and CONSORT recommendations for the comprehensive and explicit reporting of trial interventions. Results from the PreFIT study will be published in due course. The effectiveness and cost-effectiveness of the PreFIT MFFP intervention, compared to advice and exercise, on the prevention of falls and fractures, will be reported at the conclusion of the trial.

Efficacy of a Student-Led, Community-Based, Multifactorial Fall Prevention Program: Stay in Balance.

PubMed

Der Ananian, Cheryl A; Mitros, Melanie; Buman, Matthew Paul

2017-01-01

Falls are a major public health concern in older adults. Recent fall prevention guidelines recommend the use of multifactorial fall prevention programs (FPPs) that include exercise for community-dwelling older adults; however, the availability of sustainable, community-based FPPs is limited. We conducted a 24-week quasi-experimental study to evaluate the efficacy of a community-based, multifactorial FPP [Stay in Balance (SIB)] on dynamic and functional balance and muscular strength. The SIB program was delivered by allied health students and included a health education program focused on fall risk factors and a progressive exercise program emphasizing lower-extremity strength and balance. All participants initially received the 12-week SIB program, and participants were non-randomly assigned at baseline to either continue the SIB exercise program at home or as a center-based program for an additional 12 weeks. Adults aged 60 and older ( n  = 69) who were at-risk of falling (fall history or 2+ fall risk factors) were recruited to participate. Mixed effects repeated measures using Statistical Application Software Proc Mixed were used to examine group, time, and group-by-time effects on dynamic balance (8-Foot Up and Go), functional balance (Berg Balance Scale), and muscular strength (30 s chair stands and 30 s arm curls). Non-normally distributed outcome variables were log-transformed. After adjusting for age, gender, and body mass index, 8-Foot Up and Go scores, improved significantly over time [ F (2,173)  = 8.92, p  = 0.0; T0 - T2 diff = 1.2 (1.0)]. Berg Balance Scores [ F (2,173)  = 29.0, p  < 0.0001; T0 - T2 diff = 4.96 (0.72)], chair stands [ F (2,171)  = 10.17, p  < 0.0001; T0 - T2 diff = 3.1 (0.7)], and arm curls [ F (2,171)  = 12.7, p  < 0.02; T0 - T2 diff = 2.7 (0.6)] also all improved significantly over time. There were no significant group-by-time effects observed for any of the outcomes. The SIB program improved dynamic and functional balance and muscular strength in older adults at-risk for falling. Our findings indicate continuing home-based strength and balance exercises at home after completion of a center-based FPP program may be an effective and feasible way to maintain improvements in balance and strength parameters.

Effectiveness of postoperative physical therapy for upper-limb impairments after breast cancer treatment: a systematic review.

PubMed

De Groef, An; Van Kampen, Marijke; Dieltjens, Evi; Christiaens, Marie-Rose; Neven, Patrick; Geraerts, Inge; Devoogdt, Nele

2015-06-01

To systematically review the effectiveness of various postoperative physical therapy modalities and timing of physical therapy after treatment of breast cancer on pain and impaired range of motion (ROM) of the upper limb. We searched the following databases: PubMed/MEDLINE, Cumulative Index to Nursing and Allied Health Literature, Embase, Physiotherapy Evidence Database, and Cochrane. Articles published until October 2012 were included. Only (pseudo) randomized controlled trials and nonrandomized experimental trials investigating the effectiveness of passive mobilization, manual stretching, myofascial therapy, and/or exercise therapy and timing of physical therapy after treatment for breast cancer are reviewed. Primary outcomes are pain of the upper limb and/or ROM of the shoulder. Secondary outcomes are decreased shoulder strength, arm lymphedema, limitations in activities of daily living, decreased quality of life, and wound drainage volume. Physical therapy modalities had to be started in the first 6 weeks after surgery. Articles were selected by 2 independent researchers in 3 phases and compared for consensus. First the titles were analyzed, and then the selected abstracts and finally the full texts were reviewed. Eighteen randomized controlled trials were included in the review. Three studies investigated the effect of multifactorial therapy: 2 studies confirmed that the combination of general exercises and stretching is effective for the treatment of impaired ROM another study showed that passive mobilization combined with massage had no beneficial effects on pain and impaired ROM. Fifteen studies investigated the effectiveness of a single physical therapy modality. One study of poor quality found evidence supporting the beneficial effects of passive mobilization. The only study investigating the effect of stretching did not find any beneficial effects. No studies were found about the effectiveness of myofascial therapy in the postoperative phase. Five studies found that active exercises were more effective than no therapy or information on the treatment of impairments of the upper limb. Three studies supported the early start of exercises for recovery of shoulder ROM, whereas 4 studies supported the delay of exercises to avoid prolonged wound healing. Multifactorial physical therapy (ie, stretching, exercises) and active exercises were effective to treat postoperative pain and impaired ROM after treatment for breast cancer. High-quality studies are necessary to determine the effectiveness of passive mobilization, stretching, and myofascial therapy as part of the multifactorial treatment. In addition, the appropriate timing and content of the exercise programs need to be further investigated. Copyright © 2015 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Complement in the Initiation and Evolution of Rheumatoid Arthritis

PubMed Central

Holers, V. Michael; Banda, Nirmal K.

2018-01-01

The complement system is a major component of the immune system and plays a central role in many protective immune processes, including circulating immune complex processing and clearance, recognition of foreign antigens, modulation of humoral and cellular immunity, removal of apoptotic and dead cells, and engagement of injury resolving and tissue regeneration processes. In stark contrast to these beneficial roles, however, inadequately controlled complement activation underlies the pathogenesis of human inflammatory and autoimmune diseases, including rheumatoid arthritis (RA) where the cartilage, bone, and synovium are targeted. Recent studies of this disease have demonstrated that the autoimmune response evolves over time in an asymptomatic preclinical phase that is associated with mucosal inflammation. Notably, experimental models of this disease have demonstrated that each of the three major complement activation pathways plays an important role in recognition of injured joint tissue, although the lectin and amplification pathways exhibit particularly impactful roles in the initiation and amplification of damage. Herein, we review the complement system and focus on its multi-factorial role in human patients with RA and experimental murine models. This understanding will be important to the successful integration of the emerging complement therapeutics pipeline into clinical care for patients with RA. PMID:29892280

Influence of moisture on the apical seal of root canal fillings with five different types of sealer.

PubMed

Roggendorf, Matthias Johannes; Ebert, Johannes; Petschelt, Anselm; Frankenberger, Roland

2007-01-01

The aim of this study was to evaluate the influence of moisture on apical leakage using five different types of sealer. There were 120 single-rooted teeth instrumented to .02/#60 and randomly assigned to 10 experimental groups, one control group (AH Plus, lateral condensation) (n = 10) or positive/negative controls (n = 5). Before obturation teeth were dried thoroughly, followed by recontamination with moisture in a wet chamber (moist groups; 37 degrees C for 7 days). The teeth of the experimental groups (a, dry; b, moist) were obturated with sealer (groups 1, AH Plus; 2, Apexit; 3, Ketac-Endo; 4, RoekoSeal; 5, Tubli-Seal) and a single gutta-percha cone .02/#55. Teeth were centrifuged (30 x g for 3 minutes) in 5% methylene blue. Linear dye penetration was measured under a stereomicroscope. Moisture led to less microleakage for Apexit, RoekoSeal, and Tubli-Seal and higher values for AH Plus and Ketac-Endo. Multifactorial ANOVA displayed a significant dependence of leakage on sealer (p < 0.001) and the combination sealer or moisture (p < 0.01). It depends on the sealer type in which way moisture affects the apical seal.

Raising of Operating a Motor Vehicle Effects on Environment in Winter

NASA Astrophysics Data System (ADS)

Ertman, S. A.; Ertman, J. A.; Zakharov, D. A.

2016-08-01

Severe low-temperature conditions, in which considerable part of Russian Motor Park is operated, affect vehicles negatively. Cold weather causes higher fuel consumption and C02 emissions always. It is because of temperature profile changing of automobile motors, other systems and materials. For enhancement of car operation efficiency in severe winter environment the dependency of engine warm-up and cooling time on ambient air temperature and wind speed described by multifactorial mathematical models is established. -On the basis of experimental research it was proved that the coolant temperature constitutes the engine representative temperature and may be used as representative temperature of engine at large. The model of generation of integrated index for vehicle adaptability to winter operating conditions by temperature profile of engines was developed. the method for evaluation of vehicle adaptability to winter operating conditions by temperature profile of engines allows to decrease higher fuel consumption in cold climate.

The effectiveness of a promotion programme on hand hygiene compliance and nosocomial infections in a neonatal intensive care unit.

PubMed

Picheansathian, Wilawan; Pearson, Alan; Suchaxaya, Prakin

2008-08-01

This quasi-experimental study aimed to identify the impact of a promotion programme on hand hygiene practices and its effect on nosocomial infection rates in a neonatal intensive care unit of a university hospital in Thailand. The study populations were 26 nursing personnel. After implementing a hand hygiene promotion programme, compliance with hand hygiene among nursing personnel improved significantly from 6.3% before the programme to 81.2% 7 months after the programme. Compliance rate did not correlate with the intensity of patient care. Nosocomial infection rate did not decrease after the intervention, probably because of the multifactorial nature of infections. All participants agreed that promotion programme implemented in this project motivated them to practise better hand hygiene. This study indicated that multiple approaches and persistent encouragement are key factors leading to a sustained high level of appropriate hand hygiene practices among nursing personnel.

Tumor morphology and phenotypic evolution driven by selective pressure from the microenvironment.

PubMed

Anderson, Alexander R A; Weaver, Alissa M; Cummings, Peter T; Quaranta, Vito

2006-12-01

Emergence of invasive behavior in cancer is life-threatening, yet ill-defined due to its multifactorial nature. We present a multiscale mathematical model of cancer invasion, which considers cellular and microenvironmental factors simultaneously and interactively. Unexpectedly, the model simulations predict that harsh tumor microenvironment conditions (e.g., hypoxia, heterogenous extracellular matrix) exert a dramatic selective force on the tumor, which grows as an invasive mass with fingering margins, dominated by a few clones with aggressive traits. In contrast, mild microenvironment conditions (e.g., normoxia, homogeneous matrix) allow clones with similar aggressive traits to coexist with less aggressive phenotypes in a heterogeneous tumor mass with smooth, noninvasive margins. Thus, the genetic make-up of a cancer cell may realize its invasive potential through a clonal evolution process driven by definable microenvironmental selective forces. Our mathematical model provides a theoretical/experimental framework to quantitatively characterize this selective pressure for invasion and test ways to eliminate it.

Honey Bee Antiviral Immune Barriers as Affected by Multiple Stress Factors: A Novel Paradigm to Interpret Colony Health Decline and Collapse.

PubMed

Nazzi, Francesco; Pennacchio, Francesco

2018-03-30

Any attempt to outline a logical framework in which to interpret the honey bee health decline and its contribution to elevated colony losses should recognize the importance of the multifactorial nature of the responsible syndrome and provide a functional model as a basis for defining and testing working hypotheses. We propose that covert infections by deformed wing virus (DWV) represent a sword of Damocles permanently threatening the survival of honey bee colonies and suggest that any factor affecting the honey bee’s antiviral defenses can turn this pathogen into a killer. Here we discuss the available experimental evidence in the framework of a model based on honey bee immune competence as affected by multiple stress factors that is proposed as a conceptual tool for analyzing bee mortality and its underlying mechanisms.

Hemostasis and malignancy.

PubMed

Francis, J L; Biggerstaff, J; Amirkhosravi, A

1998-01-01

There is considerable evidence that the hemostatic system is involved in the growth and spread of malignant disease. There is an increased incidence of thromboembolic disease in patients with cancers and hemostatic abnormalities are extremely common in such patients. Antihemostatic agents have been successfully used to treat a variety of experimental tumors, and several clinical trials in humans have been initiated. Although metastasis is undoubtedly multifactorial, intravascular coagulation activation and peritumor fibrin deposition seem to be important. The mechanisms by which hemostatic activation facilitates the malignant process remain to be completely elucidated. Of central importance may be the presence on malignant cells of tissue factor and urokinase receptor. Recent studies have suggested that these proteins, and others, may be involved at several stages of metastasis, including the key event of neovascularization. Tissue factor, the principal initiator of coagulation, may have additional roles, outside of fibrin formation, that are central to the biology of some solid tumors.

Epigenetics and obesity.

PubMed

Campión, Javier; Milagro, Fermin; Martínez, J Alfredo

2010-01-01

The etiology of obesity is multifactorial, involving complex interactions among the genetic makeup, neuroendocrine status, fetal programming, and different unhealthy environmental factors, such as sedentarism or inadequate dietary habits. Among the different mechanisms causing obesity, epigenetics, defined as the study of heritable changes in gene expression that occur without a change in the DNA sequence, has emerged as a very important determinant. Experimental evidence concerning dietary factors influencing obesity development through epigenetic mechanisms has been described. Thus, identification of those individuals who present with changes in DNA methylation profiles, certain histone modifications, or other epigenetically related processes could help to predict their susceptibility to gain or lose weight. Indeed, research concerning epigenetic mechanisms affecting weight homeostasis may play a role in the prevention of excessive fat deposition, the prediction of the most appropriate weight reduction plan, and the implementation of newer therapeutic approaches. Copyright © 2010 Elsevier Inc. All rights reserved.

The Prevention of Schizophrenia—What Can We Learn From Eco-Epidemiology?

PubMed Central

Kirkbride, James B.; Jones, Peter B.

2011-01-01

The search for the causes of schizophrenia has predominantly originated from 2 research paradigms; genetics and epidemiology. While each approach has made important contributions to etiological understanding, neither has fully resolved the exact milieu of risk factors for schizophrenia, and there is growing recognition that several pathways to the onset of such disorders may exist. Eco-epidemiology offers an integrative framework to study schizophrenia etiology, incorporating multiple, interactive levels of causation, including genetic, epigenetic, individual, familial, community, and societal domains over the life course. In this article, we review the current evidence base, through the lens of eco-epidemiology, to determine whether it warrants the design and implementation of putative prevention strategies for schizophrenia. We argue that while there are potentially large public health gains available, we do not currently have sufficient empirical data to design effective prevention strategies. It will be important for the research community to more fully elucidate the likely multifactorial, multilevel, polygenetic, and eco-epidemiological basis of schizophrenia before we can design useful prevention strategies. We conclude by speculating on the forms effective strategies might take. PMID:20974748

Fall Prediction and Prevention Systems: Recent Trends, Challenges, and Future Research Directions.

PubMed

Rajagopalan, Ramesh; Litvan, Irene; Jung, Tzyy-Ping

2017-11-01

Fall prediction is a multifaceted problem that involves complex interactions between physiological, behavioral, and environmental factors. Existing fall detection and prediction systems mainly focus on physiological factors such as gait, vision, and cognition, and do not address the multifactorial nature of falls. In addition, these systems lack efficient user interfaces and feedback for preventing future falls. Recent advances in internet of things (IoT) and mobile technologies offer ample opportunities for integrating contextual information about patient behavior and environment along with physiological health data for predicting falls. This article reviews the state-of-the-art in fall detection and prediction systems. It also describes the challenges, limitations, and future directions in the design and implementation of effective fall prediction and prevention systems.

Groin pain syndrome: an association of different pathologies and a case presentation

PubMed Central

Bisciotti, Gian Nicola; Auci, Alessio; Di Marzo, Francesco; Galli, Roberto; Pulici, Luca; Carimati, Giulia; Quaglia, Alessandro; Volpi, Piero

2015-01-01

Summary Background groin pain affects all types of athletes, especially soccer players. Many diseases with different etiologies may cause groin pain. Purpose offer a mini review of groin pain in soccer accompanied by the presentation of a case report highlighting the possible association of more clinical frameworks into the onset of groin pain syndrome, in order to recommend that clinical evaluations take into account possible associations between bone, muscle and tendon such as inguinal canal disease. Conclusion the multifactorial etiology of groin pain syndrome needs to be examined with a comprehensive approach, with standardized clinical evaluation based on an imaging protocol in order to evaluate all possible diseases. Study design Mini review- Case report (Level V). PMID:26605198

Optimizing human factors in dentistry.

PubMed

Gupta, Arpit; Ankola, Anil V; Hebbal, Mamata

2013-03-01

Occupational health hazards among dental professionals are on a continuous rise and they have a significant negative overall impact on daily life. This review is intended to provide the information regarding risk factors and to highlight the prevention strategies for optimizing human factors in dentistry. Risk factors among dentists are multifactorial, which can be categorized into biomechanical and psychosocial. To achieve a realistic target of safety and health at work, prevention is clearly the best approach; therefore, musculoskeletal disorders can be reduced through proper positioning of dental worker and patient, regular rest breaks, general good health, using ergonomic equipment, and exercises designed to counteract the particular risk factors for the dental occupation. However, substantial evidences are still required to elucidate the potential risk factors and to formulate effective prevention programs.

The ADDITION-Cambridge trial protocol: a cluster – randomised controlled trial of screening for type 2 diabetes and intensive treatment for screen-detected patients

PubMed Central

Echouffo-Tcheugui, Justin B; Simmons, Rebecca K; Williams, Kate M; Barling, Roslyn S; Prevost, A Toby; Kinmonth, Ann Louise; Wareham, Nicholas J; Griffin, Simon J

2009-01-01

Background The increasing prevalence of type 2 diabetes poses a major public health challenge. Population-based screening and early treatment for type 2 diabetes could reduce this growing burden. However, the benefits of such a strategy remain uncertain. Methods and design The ADDITION-Cambridge study aims to evaluate the effectiveness and cost-effectiveness of (i) a stepwise screening strategy for type 2 diabetes; and (ii) intensive multifactorial treatment for people with screen-detected diabetes in primary care. 63 practices in the East Anglia region participated. Three undertook the pilot study, 33 were allocated to three groups: no screening (control), screening followed by intensive treatment (IT) and screening plus routine care (RC) in an unbalanced (1:3:3) randomisation. The remaining 27 practices were randomly allocated to IT and RC. A risk score incorporating routine practice data was used to identify people aged 40–69 years at high-risk of undiagnosed diabetes. In the screening practices, high-risk individuals were invited to take part in a stepwise screening programme. In the IT group, diabetes treatment is optimised through guidelines, target-led multifactorial treatment, audit, feedback, and academic detailing for practice teams, alongside provision of educational materials for newly diagnosed participants. Primary endpoints are modelled cardiovascular risk at one year, and cardiovascular mortality and morbidity at five years after diagnosis of diabetes. Secondary endpoints include all-cause mortality, development of renal and visual impairment, peripheral neuropathy, health service costs, self-reported quality of life, functional status and health utility. Impact of the screening programme at the population level is also assessed through measures of mortality, cardiovascular morbidity, health status and health service use among high-risk individuals. Discussion ADDITION-Cambridge is conducted in a defined high-risk group accessible through primary care. It addresses the feasibility of population-based screening for diabetes, as well as the benefits and costs of screening and intensive multifactorial treatment early in the disease trajectory. The intensive treatment algorithm is based on evidence from studies including individuals with clinically diagnosed diabetes and the education materials are informed by psychological theory. ADDITION-Cambridge will provide timely evidence concerning the benefits of early intensive treatment and will inform policy decisions concerning screening for type 2 diabetes. Trial registration Current Controlled trials ISRCTN86769081 PMID:19435491

Effectiveness of a multifactorial falls prevention program in community-dwelling older people when compared to usual care: study protocol for a randomised controlled trial (Prevquedas Brazil).

PubMed

de Negreiros Cabral, Kelem; Perracini, Monica Rodrigues; Soares, Aline Thomaz; de Cristo Stein, Francine; Sera, Celisa Tiemi Nakagawa; Tiedemann, Anne; Sherrington, Cathie; Filho, Wilson Jacob; Paschoal, Sérgio Márcio Pacheco

2013-03-15

Falling in older age is a major public health concern due to its costly and disabling consequences. However very few randomised controlled trials (RCTs) have been conducted in developing countries, in which population ageing is expected to be particularly substantial in coming years. This article describes the design of an RCT to evaluate the effectiveness of a multifactorial falls prevention program in reducing the rate of falls in community-dwelling older people. Multicentre parallel-group RCT involving 612 community-dwelling men and women aged 60 years and over, who have fallen at least once in the previous year. Participants will be recruited in multiple settings in Sao Paulo, Brazil and will be randomly allocated to a control group or an intervention group. The usual care control group will undergo a fall risk factor assessment and be referred to their clinicians with the risk assessment report so that individual modifiable risk factors can be managed without any specific guidance. The intervention group will receive a 12-week Multifactorial Falls Prevention Program consisting of: an individualised medical management of modifiable risk factors, a group-based, supervised balance training exercise program plus an unsupervised home-based exercise program, an educational/behavioral intervention. Both groups will receive a leaflet containing general information about fall prevention strategies. Primary outcome measures will be the rate of falls and the proportion of fallers recorded by monthly falls diaries and telephone calls over a 12 month period. Secondary outcomes measures will include risk of falling, fall-related self-efficacy score, measures of balance, mobility and strength, fall-related health services use and independence with daily tasks. Data will be analysed using the intention-to-treat principle.The incidence of falls in the intervention and control groups will be calculated and compared using negative binomial regression analysis. This study is the first trial to be conducted in Brazil to evaluate the effectiveness of an intervention to prevent falls. If proven to reduce falls this study has the potential to benefit older adults and assist health care practitioners and policy makers to implement and promote effective falls prevention interventions. ClinicalTrials.gov (NCT01698580).

R1 autonomic nervous system in acute kidney injury.

PubMed

Hering, Dagmara; Winklewski, Pawel J

2017-02-01

Acute kidney injury (AKI) is a rapid loss of kidney function resulting in accumulation of end metabolic products and associated abnormalities in fluid, electrolyte and acid-base homeostasis. The pathophysiology of AKI is complex and multifactorial involving numerous vascular, tubular and inflammatory pathways. Neurohumoral activation with heightened activity of the sympathetic nervous system and renin-angiotensin-aldosterone system play a critical role in this scenario. Inflammation and/or local renal ischaemia are underlying mechanisms triggering renal tissue hypoxia and resultant renal microcirculation dysfunction; a common feature of AKI occurring in numerous clinical conditions leading to a high morbidity and mortality rate. The contribution of renal nerves to the pathogenesis of AKI has been extensively demonstrated in a series of experimental models over the past decades. While this has led to better knowledge of the pathogenesis of human AKI, therapeutic approaches to improve patient outcomes are scarce. Restoration of autonomic regulatory function with vagal nerve stimulation resulting in anti-inflammatory effects and modulation of centrally-mediated mechanisms could be of clinical relevance. Evidence from experimental studies suggests that a therapeutic splenic ultrasound approach may prevent AKI via activation of the cholinergic anti-inflammatory pathway. This review briefly summarizes renal nerve anatomy, basic insights into neural control of renal function in the physiological state and the involvement of the autonomic nervous system in the pathophysiology of AKI chiefly due to sepsis, cardiopulmonary bypass and ischaemia/reperfusion experimental model. Finally, potentially preventive experimental pre-clinical approaches for the treatment of AKI aimed at sympathetic inhibition and/or parasympathetic stimulation are presented. © 2016 John Wiley & Sons Australia, Ltd.

Neuroprotective Effects and Mechanisms of Action of Multifunctional Agents Targeting Free Radicals, Monoamine Oxidase B and Cholinesterase in Parkinson's Disease Model.

PubMed

Liu, Zheng; Cai, Wei; Lang, Ming; Yan, Ruizuo; Li, Zhenshen; Zhang, Gaoxiao; Yu, Pei; Wang, Yuqiang; Sun, Yewei; Zhang, Zaijun

2017-04-01

Parkinson's disease (PD) is a complex neurodegenerative disorder with multifactorial pathologies, including progressive loss of dopaminergic (DA) neurons, oxidative stress, mitochondrial dysfunction, and increased monoamine oxidase (MAO) enzyme activity. There are currently only a few agents approved to ameliorate the symptoms of PD; however, no agent is able to reverse the progression of the disease. Due to the multifactorial pathologies, it is necessary to develop multifunctional agents that can affect more than one target involved in the disease pathology. We have designed and synthesized a series of new multifunctional anti-Parkinson's compounds which can protect cerebral granular neurons from 1-methyl-4-phenylpyridinium (MPP + ) insult, scavenge free radicals, and inhibit monoamine oxidase (MAO)/cholinesterase (ChE) activities. Among them, MT-20R exhibited the most potent MAO-B inhibition both in vitro and in vivo. We further investigated the neuroprotective effects of MT-20R using a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model. In vivo, MT-20R alleviated MPTP-induced motor deficits, raised the striatal contents of dopamine and its metabolites, and restored the expression of tyrosine hydroxylase (TH) and the number of TH-positive DA neurons in the substantia nigra. Additionally, MT-20R enhanced the expression of Bcl-2, decreased the expression of Bax and Caspase 3, and activated the AKT/Nrf2/HO-1 signaling pathway. These findings suggest that MT-20R may be a novel therapeutic candidate for treatment of PD.

Effectiveness of a multifactorial intervention to reduce physical restraints in nursing home residents.

PubMed

Koczy, Petra; Becker, Clemens; Rapp, Kilian; Klie, Thomas; Beische, Denis; Büchele, Gisela; Kleiner, Andrea; Guerra, Virginia; Rissmann, Ulrich; Kurrle, Susan; Bredthauer, Doris

2011-02-01

To evaluate the effectiveness of a multifactorial intervention to reduce the use of physical restraints in residents of nursing homes. Cluster-randomized controlled trial. Forty-five nursing homes in Germany. Three hundred thirty-three residents who were being restrained at the start of the intervention. Persons responsible for the intervention in the nursing homes attended a 6-hour training course that included education about the reasons restraints are used, the adverse effects, and alternatives to their use. Technical aids, such as hip protectors and sensor mats, were provided. The training was designed to give the change agents tools for problem-solving to prevent behavioral symptoms and injuries from falls without using physical restraints. The main outcome was the complete cessation of physical restraint use on 3 consecutive days 3 months after the start of the intervention. Secondary outcomes were partial reductions in restraint use, percentage of fallers, number of psychoactive drugs, and occurrence of behavioral symptoms. The probability of being unrestrained in the intervention group (IG) was more than twice that in the control group (CG) at the end of the study (odds ratio=2.16, 95% confidence interval=1.05-4.46). A partial reduction of restraint use was also about twice as often achieved in the IG as in the CG. No negative effect was observed regarding medication or behavioral symptoms. The percentage of fallers was higher in the IG. The intervention reduced restraint use without a significant increase in falling, behavioral symptoms, or medication. © 2011, Copyright the Authors. Journal compilation © 2011, The American Geriatrics Society.

The Strategies to Reduce Injuries and Develop Confidence in Elders Intervention: Falls Risk Factor Assessment and Management, Patient Engagement, and Nurse Co-management.

PubMed

Reuben, David B; Gazarian, Priscilla; Alexander, Neil; Araujo, Katy; Baker, Dorothy; Bean, Jonathan F; Boult, Chad; Charpentier, Peter; Duncan, Pamela; Latham, Nancy; Leipzig, Rosanne M; Quintiliani, Lisa M; Storer, Thomas; McMahon, Siobhan

2017-12-01

In response to the epidemic of falls and serious falls-related injuries in older persons, in 2014, the Patient Centered Outcomes Research Institute (PCORI) and the National Institute on Aging funded a pragmatic trial, Strategies to Reduce Injuries and Develop confidence in Elders (STRIDE) to compare the effects of a multifactorial intervention with those of an enhanced usual care intervention. The STRIDE multifactorial intervention consists of five major components that registered nurses deliver in the role of falls care managers, co-managing fall risk in partnership with patients and their primary care providers (PCPs). The components include a standardized assessment of eight modifiable risk factors (medications; postural hypotension; feet and footwear; vision; vitamin D; osteoporosis; home safety; strength, gait, and balance impairment) and the use of protocols and algorithms to generate recommended management of risk factors; explanation of assessment results to the patient (and caregiver when appropriate) using basic motivational interviewing techniques to elicit patient priorities, preferences, and readiness to participate in treatments; co-creation of individualized falls care plans that patients' PCPs review, modify, and approve; implementation of the falls care plan; and ongoing monitoring of response, regularly scheduled re-assessments of fall risk, and revisions of the falls care plan. Custom-designed falls care management software facilitates risk factor assessment, the identification of recommended interventions, clinic note generation, and longitudinal care management. The trial testing the effectiveness of the STRIDE intervention is in progress, with results expected in late 2019. © 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.

TROPHI: development of a tool to measure complex, multi-factorial patient handling interventions.

PubMed

Fray, Mike; Hignett, Sue

2013-01-01

Patient handling interventions are complex and multi-factorial. It has been difficult to make comparisons across different strategies due to the lack of a comprehensive outcome measurement method. The Tool for Risk Outstanding in Patient Handling Interventions (TROPHI) was developed to address this gap by measuring outcomes and comparing performance across interventions. Focus groups were held with expert patient handling practitioners (n = 36) in four European countries (Finland, Italy, Portugal and the UK) to identify preferred outcomes to be measured for interventions. A systematic literature review identified 598 outcome measures; these were critically appraised and the most appropriate measurement tool was selected for each outcome. TROPHI was evaluated in the four EU countries (eight sites) and by an expert panel (n = 16) from the European Panel of Patient Handling Ergonomics for usability and practical application. This final stage added external validity to the research by exploring transferability potential and presenting the data and analysis to allow respondent (participant) validation. Patient handling interventions are complex and multi-factorial and it has been difficult to make comparisons due to the lack of a comprehensive outcome measurement method. The Tool for Risk Outstanding in Patient Handling Interventions (TROPHI) was developed to address this gap by measuring outcomes to compare performance across interventions.

A multifactorial intervention for the prevention of falls in psychogeriatric nursing home patients, a randomised controlled trial (RCT).

PubMed

Neyens, Jacques C L; Dijcks, Béatrice P J; Twisk, Jos; Schols, Jos M G A; van Haastregt, Jolanda C M; van den Heuvel, Wim J A; de Witte, Luc P

2009-03-01

to evaluate the effectiveness of a multifactorial intervention on incidence of falls in psychogeriatric nursing home patients. cluster-randomised controlled 12-month trial. psychogeriatric wards in 12 nursing homes in The Netherlands. psychogeriatric nursing home patients (n = 518). a general medical assessment and an additional specific fall risk evaluation tool, applied by a multidisciplinary fall prevention team, resulting in general and individual fall prevention activities. falls. there were 355 falls in 169.5 patient-years (2.09 falls per patient per year) in the intervention group and 422 falls in 166.3 patient-years (2.54 falls per patient per year) in the control group. Intention-to-treat analysis with adjustment for ward-related and patient-related parameters, and intra-cluster correlation, showed that the intervention group had a significantly lower mean fall incidence rate than the control group (rate ratio = 0.64, 95% CI = 0.43-0.96, P = 0.029). Subgroup analyses showed that fall risk declined further as patients participated longer in the intervention programme. the introduction of a structured multifactorial intervention to prevent falls in psychogeriatric nursing home patients significantly reduces the number of falls. This reduction is substantial and of high clinical relevance.

Maturity-onset diabetes of the young as a model for elucidating the multifactorial origin of type 2 diabetes mellitus.

PubMed

Horikawa, Yukio

2018-02-06

Maturity-onset diabetes of the young (MODY) is a form of diabetes classically characterized as having autosomal dominant inheritance, onset before the age of 25 years in at least one family member and partly preserved pancreatic β-cell function. The 14 responsible genes are reported to be MODY type 1~14, of which MODY 2 and 3 might be the most common forms. Although MODY is currently classified as diabetes of a single gene defect, it has become clear that mutations in rare MODYs, such as MODY 5 and MODY 6, have small mutagenic effects and low penetrance. In addition, as there are differences in the clinical phenotypes caused by the same mutation even in the same family, other phenotypic modifying factors are thought to exist; MODY could well have characteristics of type 2 diabetes mellitus, which is of multifactorial origin. Here, we outline the effects of genetic and environmental factors on the known phenotypes of MODY, focusing mainly on the examples of MODY 5 and 6, which have low penetrance, as suggestive models for elucidating the multifactorial origin of type 2 diabetes mellitus. © 2018 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

Preventing musculoskeletal disorders in clinical dentistry: strategies to address the mechanisms leading to musculoskeletal disorders.

PubMed

Valachi, Bethany; Valachi, Keith

2003-12-01

The authors reviewed studies to identify methods for dental operators to use to prevent the development of musculoskeletal disorders, or MSDs. The authors reviewed studies that related to the prevention of MSDs among dental operators. Some studies investigated the relationship between the biomechanics of seated working postures and physiological damage or pain. Other studies suggested that repeated unidirectional twisting of the trunk can lead to low back pain, while yet other studies examined the detrimental effects of working in one position for prolonged periods. Additional studies confirmed the roles that operators' flexibility and core strength can play in balanced musculoskeletal health and the need for operators to know how to properly adjust ergonomic equipment. This review indicates that strategies to prevent the multifactorial problem of dental operators' developing MSDs exist. These strategies address deficiencies in operator position, posture, flexibility, strength and ergonomics. Education and additional research are needed to promote an understanding of the complexity of the problem and to address the problem's multifactorial nature. A comprehensive approach to address the problem of MSDs in dentistry represents a paradigm shift in how operators work. New educational models that incorporate a multifactorial approach can be developed to help dental operators manage and prevent MSDs effectively.

Preventing Falls in Older Persons.

PubMed

Moncada, Lainie Van Voast; Mire, L Glen

2017-08-15

The American Geriatrics Society and British Geriatrics Society recommend that all adults older than 65 years be screened annually for a history of falls or balance impairment. The U.S. Preventive Services Task Force and American Academy of Family Physicians recommend exercise or physical therapy and vitamin D supplementation to prevent falls in community-dwelling older adults who are at increased risk of falls. Although the U.S. Preventive Services Task Force and American Academy of Family Physicians do not recommend routine multifactorial intervention to prevent falls in all community-dwelling older adults, they state that it may be appropriate in individual cases. The Centers for Disease Control and Prevention developed an algorithm to aid in the implementation of the American Geriatrics Society/British Geriatrics Society guideline. The algorithm suggests assessment and multifactorial intervention for those who have had two or more falls or one fall-related injury. Multifactorial interventions should include exercise, particularly balance, strength, and gait training; vitamin D supplementation with or without calcium; management of medications, especially psychoactive medications; home environment modification; and management of postural hypotension, vision problems, foot problems, and footwear. These interventions effectively decrease falls in the community, hospital, and nursing home settings. Fall prevention is reimbursed as part of the Medicare Annual Wellness Visit.

Prevalence of sexual desire and satisfaction among patients with screen-detected diabetes and impact of intensive multifactorial treatment: results from the ADDITION-Denmark study.

PubMed

Pedersen, Mette B; Giraldi, Annamaria; Kristensen, Ellids; Lauritzen, Torsten; Sandbæk, Annelli; Charles, Morten

2015-03-01

Sexual problems are common in people with diabetes. It is unknown whether early detection of diabetes and subsequent intensive multifactorial treatment (IT) are associated with sexual health. We report the prevalence of low sexual desire and low sexual satisfaction among people with screen-detected diabetes and compare the impact of intensive multifactorial treatment with the impact of routine care (RC) on these measures. A cross-sectional analysis of the ADDITION-Denmark trial cohort six years post-diagnosis. 190 general practices around Denmark. A total of 968 patients with screen-detected type 2 diabetes. Low sexual desire and low sexual satisfaction. Mean (standard deviation, SD) age was 64.9 (6.9) years. The prevalence of low sexual desire was 53% (RC) and 54% (IT) among women, and 24% (RC) and 25% (IT) among men. The prevalence of low sexual satisfaction was 23% (RC) and 18% (IT) among women, and 27% (RC) and 37% (IT) among men. Among men, the prevalence of low sexual satisfaction was significantly higher in the IT group than in the RC group, p = 0.01. Low sexual desire and low satisfaction are frequent among men and women with screen-detected diabetes, and IT may negatively impact men's sexual satisfaction.

A quality by design approach to optimization of emulsions for electrospinning using factorial and D-optimal designs.

PubMed

Badawi, Mariam A; El-Khordagui, Labiba K

2014-07-16

Emulsion electrospinning is a multifactorial process used to generate nanofibers loaded with hydrophilic drugs or macromolecules for diverse biomedical applications. Emulsion electrospinnability is greatly impacted by the emulsion pharmaceutical attributes. The aim of this study was to apply a quality by design (QbD) approach based on design of experiments as a risk-based proactive approach to achieve predictable critical quality attributes (CQAs) in w/o emulsions for electrospinning. Polycaprolactone (PCL)-thickened w/o emulsions containing doxycycline HCl were formulated using a Span 60/sodium lauryl sulfate (SLS) emulsifier blend. The identified emulsion CQAs (stability, viscosity and conductivity) were linked with electrospinnability using a 3(3) factorial design to optimize emulsion composition for phase stability and a D-optimal design to optimize stable emulsions for viscosity and conductivity after shifting the design space. The three independent variables, emulsifier blend composition, organic:aqueous phase ratio and polymer concentration, had a significant effect (p<0.05) on emulsion CQAs, the emulsifier blend composition exerting prominent main and interaction effects. Scanning electron microscopy (SEM) of emulsion-electrospun NFs and desirability functions allowed modeling of emulsion CQAs to predict electrospinnable formulations. A QbD approach successfully built quality in electrospinnable emulsions, allowing development of hydrophilic drug-loaded nanofibers with desired morphological characteristics. Copyright © 2014 Elsevier B.V. All rights reserved.

Economic evaluation of a multifactorial, interdisciplinary intervention versus usual care to reduce frailty in frail older people.

PubMed

Fairhall, Nicola; Sherrington, Catherine; Kurrle, Susan E; Lord, Stephen R; Lockwood, Keri; Howard, Kirsten; Hayes, Alison; Monaghan, Noeline; Langron, Colleen; Aggar, Christina; Cameron, Ian D

2015-01-01

To compare the costs and cost-effectiveness of a multifactorial interdisciplinary intervention versus usual care for older people who are frail. Cost-effectiveness study embedded within a randomized controlled trial. Community-based intervention in Sydney, Australia. A total of 241 community-dwelling people 70 years or older who met the Cardiovascular Health Study criteria for frailty. A 12-month multifactorial, interdisciplinary intervention targeting identified frailty characteristics versus usual care. Health and social service use, frailty, and health-related quality of life (EQ-5D) were measured over the 12-month intervention period. The difference between the mean cost per person for 12 months in the intervention and control groups (incremental cost) and the ratio between incremental cost and effectiveness were calculated. A total of 216 participants (90%) completed the study. The prevalence of frailty was 14.7% lower in the intervention group compared with the control group at 12 months (95% CI 2.4%-27.0%; P = .02). There was no significant between-group difference in EQ-5D utility scores. The cost for 1 extra person to transition out of frailty was $A15,955 (at 2011 prices). In the "very frail" subgroup (participants met >3 Cardiovascular Health Study frailty criteria), the intervention was both more effective and less costly than the control. A cost-effectiveness acceptability curve shows that the intervention would be cost-effective with 80% certainty if decision makers were willing to pay $A50,000 per extra person transitioning from frailty. In the very frail subpopulation, this reduced to $25,000. For frail older people residing in the community, a 12-month multifactorial intervention provided better value for money than usual care, particularly for the very frail, in whom it has a high probability of being cost saving, as well as effective. Trial registration: ACTRN12608000250336. Copyright © 2015 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

[Design of an educational tool for Primary Care patients with chronic non-specific low back pain].

PubMed

Díaz-Cerrillo, Juan Luis; Rondón-Ramos, Antonio

2015-02-01

Current scientific evidence on the management of chronic non-specific low back pain highlights the benefits of physical exercise. This goal is frequently undermined due to lack of education of the subjects on the multifactorial, benign, and non-specific nature of low back pain, which can lead to a chronic disease with genuine psychosocial risk factors. Its influence may not only interfere with individual decision to adopt more adaptive coping behaviors, but also with the endogenous mechanisms of pain neuromodulation. Thus, the educational strategies and control of these factors have become important objectives to be incorporated into the management of the disorder and research guidelines. This paper presents the theoretical models and the scientific basis on which it has based the design of an educational tool for patients with chronic non-specific low back pain treated in Primary Care physiotherapy. Structure, content and objectives are also presented. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

Identification of BRCA1 missense substitutions that confer partial functional activity: potential moderate risk variants?

PubMed Central

Lovelock, Paul K; Spurdle, Amanda B; Mok, Myth TS; Farrugia, Daniel J; Lakhani, Sunil R; Healey, Sue; Arnold, Stephen; Buchanan, Daniel; Investigators, kConFab; Couch, Fergus J; Henderson, Beric R; Goldgar, David E; Tavtigian, Sean V; Chenevix-Trench, Georgia; Brown, Melissa A

2007-01-01

Introduction Many of the DNA sequence variants identified in the breast cancer susceptibility gene BRCA1 remain unclassified in terms of their potential pathogenicity. Both multifactorial likelihood analysis and functional approaches have been proposed as a means to elucidate likely clinical significance of such variants, but analysis of the comparative value of these methods for classifying all sequence variants has been limited. Methods We have compared the results from multifactorial likelihood analysis with those from several functional analyses for the four BRCA1 sequence variants A1708E, G1738R, R1699Q, and A1708V. Results Our results show that multifactorial likelihood analysis, which incorporates sequence conservation, co-inheritance, segregation, and tumour immunohistochemical analysis, may improve classification of variants. For A1708E, previously shown to be functionally compromised, analysis of oestrogen receptor, cytokeratin 5/6, and cytokeratin 14 tumour expression data significantly strengthened the prediction of pathogenicity, giving a posterior probability of pathogenicity of 99%. For G1738R, shown to be functionally defective in this study, immunohistochemistry analysis confirmed previous findings of inconsistent 'BRCA1-like' phenotypes for the two tumours studied, and the posterior probability for this variant was 96%. The posterior probabilities of R1699Q and A1708V were 54% and 69%, respectively, only moderately suggestive of increased risk. Interestingly, results from functional analyses suggest that both of these variants have only partial functional activity. R1699Q was defective in foci formation in response to DNA damage and displayed intermediate transcriptional transactivation activity but showed no evidence for centrosome amplification. In contrast, A1708V displayed an intermediate transcriptional transactivation activity and a normal foci formation response in response to DNA damage but induced centrosome amplification. Conclusion These data highlight the need for a range of functional studies to be performed in order to identify variants with partially compromised function. The results also raise the possibility that A1708V and R1699Q may be associated with a low or moderate risk of cancer. While data pooling strategies may provide more information for multifactorial analysis to improve the interpretation of the clinical significance of these variants, it is likely that the development of current multifactorial likelihood approaches and the consideration of alternative statistical approaches will be needed to determine whether these individually rare variants do confer a low or moderate risk of breast cancer. PMID:18036263

The role of exercise in fall prevention for older adults.

PubMed

Rose, Debra J; Hernandez, Danielle

2010-11-01

This article reviews the evidence for the effectiveness of stand-alone exercise interventions and multifactorial intervention strategies that include exercise in lowering fall incidence rates and/or fall risk among older adults residing in the community, acute, subacute, and long-term care settings. Stand-alone exercise programs that emphasize multiple exercise categories are effective in reducing fall rates and fall risk in community-residing older adults, and may also be effective when conducted for a sufficient duration with older adult patients in subacute settings. In contrast, multifactorial fall risk reduction programs that include exercise as a component and are delivered by a multidisciplinary team are more effective in lowering fall rates in long-term care settings. Copyright © 2010 Elsevier Inc. All rights reserved.

Longevity and aging. Mechanisms and perspectives.

PubMed

Labat-Robert, J; Robert, L

2015-12-01

Longevity can mostly be determined with relative accuracy from birth and death registers when available. Aging is a multifactorial process, much more difficult to quantitate. Every measurable physiological function declines with specific speeds over a wide range. The mechanisms involved are also different, genetic factors are of importance for longevity determinations. The best-known genes involved are the Sirtuins, active at the genetic and epigenetic level. Aging is multifactorial, not "coded" in the genome. There are, however, a number of well-studied physical and biological parameters involved in aging, which can be determined and quantitated. We shall try to identify parameters affecting longevity as well as aging and suggest some reasonable predictions for the future. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

The removal of the trivalent chromium from the leather tannery wastewater: the optimisation of the electro-coagulation process parameters.

PubMed

GilPavas, E; Dobrosz-Gómez, I; Gómez-García, M Á

2011-01-01

The capacity of the electro-coagulation (EC) process for the treatment of the wastewater containing Cr3+, resulting from a leather tannery industry placed in Medellin (Colombia), was evaluated. In order to assess the effect of some parameters, such as: the electrode type (Al and/or Fe), the distance between electrodes, the current density, the stirring velocity, and the initial Cr3+ concentration on its efficiency of removal (%RCr+3), a multifactorial experimental design was used. The %RCr3+ was defined as the response variable for the statistical analysis. In order to optimise the operational values for the chosen parameters, the response surface method (RSM) was applied. Additionally, the Biological Oxygen Demand (BOD5), the Chemical Oxygen Demand (COD), and the Total Organic Carbon (TOC) were monitored during the EC process. The electrodes made of aluminium appeared to be the most effective in the chromium removal from the wastewater under study. At pH equal to 4.52 and at 28°C, the optimal conditions of Cr3+ removal using the EC process were found, as follows: the initial Cr3+ concentration=3,596 mg/L, the electrode gap=0.5 cm, the stirring velocity=382.3 rpm, and the current density=57.87 mA/cm2. At those conditions, it was possible to reach 99.76% of Cr3+ removal, and 64% and 61% of mineralisation (TOC) and COD removal, respectively. A kinetic analysis was performed in order to verify the response capacity of the EC process at optimised parameter values.

Factorial-design optimization of gas chromatographic analysis of tetrabrominated to decabrominated diphenyl ethers. Application to domestic dust.

PubMed

Regueiro, Jorge; Llompart, Maria; Garcia-Jares, Carmen; Cela, Rafael

2007-07-01

Gas chromatographic analysis of polybrominated diphenyl ethers (PBDEs) has been evaluated in an attempt to achieve better control of the separation process, especially for highly substituted congeners. Use of a narrow-bore capillary column enabled adequate determination of tetra, penta, hexa, hepta, octa, nona and decaBDE congeners in only one chromatographic run while maintaining resolution power similar to that of conventional columns. A micro electron-capture detector (GC-microECD) was used. Chromatographic conditions were optimized by multifactorial experimental design, with the objective of obtaining not only high sensitivity but also good precision. In this way two different approaches to maximizing response and minimizing variability were tested, and are fully discussed. These optimum chromatographic conditions were then used to determine PBDEs extracted from domestic dust samples by microwave-assisted solvent extraction (MASE). Quantitative recovery (90-108%) was achieved for all the PBDEs and method precision (RSD < 13%) was satisfactory. Accuracy was tested by use of the standard reference material SRM 2585, and sub-ng g(-1) limits of detection were obtained for all compounds except BDE-209 (1.44 ng g(-1)). Finally, several samples of house dust were analysed by use of the proposed method and all the target PBDEs were detected in all the samples. BDE-209 was the predominant congener. Amounts varied from 58 to 1615 ng g(-1) and the average contribution to the total PBDE burden of 52%. The main congeners of the octaBDE mixture (BDE-183, BDE-197, BDE-207 and BDE-196) also made an important contribution (29%) to the total. These are the first data about the presence of these compounds in European house-dust samples. Finally, the sum of the main congeners in the pentaBDE commercial mixture (BDE-47, BDE-99, and BDE-100) contributed 14% to the total. Figure Polybrominated diphenyl ethers in House Dust.

Does parenting affect children's eating and weight status?

PubMed Central

Ventura, Alison K; Birch, Leann L

2008-01-01

Background Worldwide, the prevalence of obesity among children has increased dramatically. Although the etiology of childhood obesity is multifactorial, to date, most preventive interventions have focused on school-aged children in school settings and have met with limited success. In this review, we focus on another set of influences that impact the development of children's eating and weight status: parenting and feeding styles and practices. Our review has two aims: (1) to assess the extent to which current evidence supports the hypothesis that parenting, via its effects on children's eating, is causally implicated in childhood obesity; and (2) to identify a set of promising strategies that target aspects of parenting, which can be further evaluated as possible components in childhood obesity prevention. Methods A literature review was conducted between October 2006 and January 2007. Studies published before January 2007 that assessed the association between some combination of parenting, child eating and child weight variables were included. Results A total of 66 articles met the inclusion criteria. The preponderance of these studies focused on the association between parenting and child eating. Although there was substantial experimental evidence for the influence of parenting practices, such as pressure, restriction, modeling and availability, on child eating, the majority of the evidence for the association between parenting and child weight, or the mediation of this association by child eating, was cross-sectional. Conclusion To date, there is substantial causal evidence that parenting affects child eating and there is much correlational evidence that child eating and weight influence parenting. There are few studies, however, that have used appropriate meditational designs to provide causal evidence for the indirect effect of parenting on weight status via effects on child eating. A new approach is suggested for evaluating the effectiveness of intervention components and creating optimized intervention programs using a multiphase research design. Adoption of approaches such as the Multiphase Optimization Strategy (MOST) is necessary to provide the mechanistic evidence-base needed for the design and implementation of effective childhood obesity prevention programs. PMID:18346282

Neonatal corticosterone administration in rodents as a tool to investigate the maternal programming of emotional and immune domains.

PubMed

Macrì, Simone

2017-02-01

Neonatal experiences exert persistent influences on individual development. These influences encompass numerous domains including emotion, cognition, reactivity to external stressors and immunity. The comprehensive nature of the neonatal programming of individual phenotype is reverberated in the large amount of experimental data collected by many authors in several scientific fields: biomedicine, evolutionary and molecular biology. These data support the view that variations in precocious environmental conditions may calibrate the individual phenotype at many different levels. Environmental influences have been traditionally addressed through experimental paradigms entailing the modification of the neonatal environment and the multifactorial (e.g. behaviour, endocrinology, cellular and molecular biology) analysis of the developing individual's phenotype. These protocols suggested that the role of the mother in mediating the offspring's phenotype is often associated with the short-term effects of environmental manipulations on dam's physiology. Specifically, environmental manipulations may induce fluctuations in maternal corticosteroids (corticosterone in rodents) which, in turn, are translated to the offspring through lactation. Herein, I propose that this mother-offspring transfer mechanism can be leveraged to devise experimental protocols based on the exogenous administration of corticosterone during lactation. To support this proposition, I refer to a series of studies in which these protocols have been adopted to investigate the neonatal programming of individual phenotype at the level of emotional and immune regulations. While these paradigms cannot replace traditional studies, I suggest that they can be considered a valid complement.

Protective effect of IGF-1 on experimental liver cirrhosis-induced common bile duct ligation.

PubMed

Cantürk, Nuh Zafer; Cantürk, Zeynep; Ozden, Meltem; Dalçik, Hakki; Yardimoglu, Melda; Tülübas, Feti

2003-01-01

The causes of malnutrition in liver cirrhosis are multifactorial. Levels of IGF-1 (insulin like growth factor-1) that is a crucial regulator of intermediary metabolism decreases. The aim of this study was to analyze the effect of IGF-1 supplementation during liver cirrhosis induced by common bile duct ligation. Rats were divided into five different groups: One sham and four experimental groups. Rats in three of four groups were treated with 2 micrograms/day IGF-1 with a different time of experiment in each group. Blood biochemical parameters, tissue malondialdehyde, glutathione levels and the activity of tissue antioxidant enzymes and conventional and immunohistochemical analysis of liver samples were studied for each group. Serum albumin, total protein, fibrinogen levels decreased and prothrombin time was prolonged in the bile duct ligated and transected experimental group but not in the IGF-I treated rats compared with the rats in sham group. Liver malondialdehyde levels significantly increased in control group but not in IGF-1 treated groups. The activities of antioxidant enzymes were decreased compared with the other groups. Histopathology findings of liver biopsy demonstrated intense degree fibrosis and overexpression of fibroblast growth factor and desmin in the control group but a lesser degree of those in the IGF-1 treated groups. IGF-1 treatment improves liver function and decreases oxidative liver damage and histopathological findings. Further studies are required to delineate the mechanisms of protective effects of IGF-1.

Impaired Inhibitory Force Feedback in Fixed Dystonia.

PubMed

Mugge, Winfred; Schouten, Alfred C; van Hilten, Jacobus J; van der Helm, Frans C T

2016-04-01

Complex regional pain syndrome (CRPS) is a multifactorial disorder associated with an aberrant host response to tissue injury. About 25% of CRPS patients suffer poorly understood involuntary sustained muscle contractions associated with dysfunctional reflexes that result in abnormal postures (fixed dystonia). A recent modeling study simulated fixed dystonia (FD) caused by aberrant force feedback. The current study aims to validate this hypothesis by experimentally recording the modulation of reflexive force feedback in patients with FD. CRPS patients with and without FD, patients with FD but without CRPS, as well as healthy controls participated in the experiment. Three task instructions and three perturbation characteristics were used to evoke a wide range of responses to force perturbations. During position tasks ("maintain posture"), healthy subjects as well as patients resisted the perturbations, becoming more stiff than when being relaxed (i.e., the relax task). Healthy subjects and CRPS patients without FD were both more compliant during force tasks ("maintain force") than during relax tasks, meaning they actively gave way to the imposed forces. Remarkably, the patients with FD failed to do so. A neuromuscular model was fitted to the experimental data to separate the distinct contributions of position, velocity and force feedback, as well as co-contraction to the motor behavior. The neuromuscular modeling indicated that inhibitory force feedback is deregulated in patients with FD, for both CRPS and non-CRPS patients. From previously published simulation results and the present experimental study, it is concluded that aberrant force feedback plays a role in fixed dystonia.

True and Quasi-Experimental Designs. ERIC/AE Digest.

ERIC Educational Resources Information Center

Gribbons, Barry; Herman, Joan

Among the different types of experimental design are two general categories: true experimental designs and quasi- experimental designs. True experimental designs include more than one purposively created group, common measured outcomes, and random assignment. Quasi-experimental designs are commonly used when random assignment is not practical or…

Effect of socio-cultural factors on spontaneous abortion in Burdur, Turkey: A population based case-control study.

PubMed

Catak, Binali; Oner, Can; Sutlu, Sevinc; Kilinc, Selcuk

2016-01-01

To determine the sociocultural factors that have effect on spontaneous abortion in Burdur, Turkey. Study was designed as case-control study. The case group consist of 257 women whose pregnancies ended with spontaneous abortion. The control group consisted of 514 women whose pregnancy continued since 22 weeks and more during the study. Chi-square, and backward LR logistic regression were utilized in analyses. In multifactorial-analyses it was determined that four factors (educational status of women, employment status of women, exposure to physical violence and non-receipt of ANC) created independent risk on spontaneous abortions. Pregnant women with these risk factors should be followed up more frequently and in a more qualified way in primary and secondary and tertiary health institutions.

Fall Prediction and Prevention Systems: Recent Trends, Challenges, and Future Research Directions

PubMed Central

Rajagopalan, Ramesh; Jung, Tzyy-Ping

2017-01-01

Fall prediction is a multifaceted problem that involves complex interactions between physiological, behavioral, and environmental factors. Existing fall detection and prediction systems mainly focus on physiological factors such as gait, vision, and cognition, and do not address the multifactorial nature of falls. In addition, these systems lack efficient user interfaces and feedback for preventing future falls. Recent advances in internet of things (IoT) and mobile technologies offer ample opportunities for integrating contextual information about patient behavior and environment along with physiological health data for predicting falls. This article reviews the state-of-the-art in fall detection and prediction systems. It also describes the challenges, limitations, and future directions in the design and implementation of effective fall prediction and prevention systems. PMID:29104256

Follow-up on hang gliding injuries in Colorado.

PubMed

Krissoff, W B

1976-01-01

In a period extending from July 1973 to December 1975, seven fatal hang glider accidents were recorded in Colorado, all among experienced pilots. In addition, 11 serious nonfatal injuries were reported, which may represent only a fraction of those occurring. Accidents were noted to be multifactorial, caused by (1) pilot error, (2) equipment failure, (3) terrain hazards, and (4) possible design shortcomings. Accidents can be expected to decline in frequency with improved pilot training programs, grading and regulation of sites, and standardized safety clothing. No doubt over time, the less safe standard Rogallo wing will be replaced by the more stable Superkites and controlled collapsibles, which offer a higher safety margin. In the last analysis, this sport will remain a popular yet high risk endeavor (Figs. 2 through 5).

Inflammation in irritable bowel syndrome: Myth or new treatment target?

PubMed Central

Sinagra, Emanuele; Pompei, Giancarlo; Tomasello, Giovanni; Cappello, Francesco; Morreale, Gaetano Cristian; Amvrosiadis, Georgios; Rossi, Francesca; Lo Monte, Attilio Ignazio; Rizzo, Aroldo Gabriele; Raimondo, Dario

2016-01-01

Low-grade intestinal inflammation plays a key role in the pathophysiology of irritable bowel syndrome (IBS), and this role is likely to be multifactorial. The aim of this review was to summarize the evidence on the spectrum of mucosal inflammation in IBS, highlighting the relationship of this inflammation to the pathophysiology of IBS and its connection to clinical practice. We carried out a bibliographic search in Medline and the Cochrane Library for the period of January 1966 to December 2014, focusing on publications describing an interaction between inflammation and IBS. Several evidences demonstrate microscopic and molecular abnormalities in IBS patients. Understanding the mechanisms underlying low-grade inflammation in IBS may help to design clinical trials to test the efficacy and safety of drugs that target this pathophysiologic mechanism. PMID:26900287

Observation procedure, observer gender, and behavior valence as determinants of sampling error in a behavior assessment analogue

PubMed Central

Farkas, Gary M.; Tharp, Roland G.

1980-01-01

Several factors thought to influence the representativeness of behavioral assessment data were examined in an analogue study using a multifactorial design. Systematic and unsystematic methods of observing group behavior were investigated using 18 male and 18 female observers. Additionally, valence properties of the observed behaviors were inspected. Observers' assessments of a videotape were compared to a criterion code that defined the population of behaviors. Results indicated that systematic observation procedures were more accurate than unsystematic procedures, though this factor interacted with gender of observer and valence of behavior. Additionally, males tended to sample more representatively than females. A third finding indicated that the negatively valenced behavior was overestimated, whereas the neutral and positively valenced behaviors were accurately assessed. PMID:16795631

Recent developments on dry eye disease treatment compounds.

PubMed

Colligris, Basilio; Alkozi, Hanan Awad; Pintor, Jesus

2014-01-01

Dry eye syndrome is a common tears and ocular surface multifactorial disease, described by changes in the ocular surface epithelia related to reduced tears quantity and ocular surface sensitivity, leading to inflammatory reaction. Managing the eye inflammation proved helpful to patients with dry eye disease and current treatment is based on the use of topically applied artificial tear products/lubricants, tear retention management, stimulation of tear secretion and using anti-inflammatory drugs. In this article we revise the corresponding literature and patents assembling the new treatment approaches of novel and future pharmaceutical compounds destined for the dry eye disease treatment. The most frequent categories of compounds presented are secretagogues and anti-inflammatory drugs. These compounds are the research outcome of novel therapeutic strategies designed to reduce key inflammatory pathways and restore healthy tear film.

Optimizing human factors in dentistry

PubMed Central

Gupta, Arpit; Ankola, Anil V.; Hebbal, Mamata

2013-01-01

Occupational health hazards among dental professionals are on a continuous rise and they have a significant negative overall impact on daily life. This review is intended to provide the information regarding risk factors and to highlight the prevention strategies for optimizing human factors in dentistry. Risk factors among dentists are multifactorial, which can be categorized into biomechanical and psychosocial. To achieve a realistic target of safety and health at work, prevention is clearly the best approach; therefore, musculoskeletal disorders can be reduced through proper positioning of dental worker and patient, regular rest breaks, general good health, using ergonomic equipment, and exercises designed to counteract the particular risk factors for the dental occupation. However, substantial evidences are still required to elucidate the potential risk factors and to formulate effective prevention programs. PMID:23946745

Dupuytren's: a systems biology disease

PubMed Central

2011-01-01

Dupuytren's disease (DD) is an ill-defined fibroproliferative disorder of the palm of the hands leading to digital contracture. DD commonly occurs in individuals of northern European extraction. Cellular components and processes associated with DD pathogenesis include altered gene and protein expression of cytokines, growth factors, adhesion molecules, and extracellular matrix components. Histology has shown increased but varying levels of particular types of collagen, myofibroblasts and myoglobin proteins in DD tissue. Free radicals and localised ischaemia have been suggested to trigger the proliferation of DD tissue. Although the existing available biological information on DD may contain potentially valuable (though largely uninterpreted) information, the precise aetiology of DD remains unknown. Systems biology combines mechanistic modelling with quantitative experimentation in studies of networks and better understanding of the interaction of multiple components in disease processes. Adopting systems biology may be the ideal approach for future research in order to improve understanding of complex diseases of multifactorial origin. In this review, we propose that DD is a disease of several networks rather than of a single gene, and show that this accounts for the experimental observations obtained to date from a variety of sources. We outline how DD may be investigated more effectively by employing a systems biology approach that considers the disease network as a whole rather than focusing on any specific single molecule. PMID:21943049

MASTERPLAN: study of the role of nurse practitioners in a multifactorial intervention to reduce cardiovascular risk in chronic kidney disease patients.

PubMed

Van Zuilen, Arjan D; Wetzels, Jack F M; Bots, Michiel L; Van Blankestijn, Peter J

2008-01-01

Moderate to severe chronic kidney disease (CKD) is associated with increased cardiovascular risk. Usually nephrologists are primarily responsible for the care of CKD patients. However, in many cases treatment goals, as formulated in guidelines, are not met. The addition of a nurse practitioner might improve the quality of care. The Multifactorial Approach and Superior Treatment Efficacy in Renal Patients with the Aid of Nurse Practitioners (MASTERPLAN) study is a randomized controlled multicenter trial, aimed at investigating whether a multifactorial approach in patients with moderate to severe CKD (stage 3 and 4) to achieving treatment goals using both a polydrug strategy and lifestyle treatment either with or without the addition of a nurse practitioner will reduce cardiovascular risk and slow the decline of kidney function. Patients (n=793) have been randomized to nurse care or physician care. In the nurse-care arm of the study, nurse practitioners use flowcharts to address risk factors requiring drug and/or lifestyle modification. They have been trained to coach patients by motivational interviewing with the aim of improving patient self-management. At baseline, both treatment groups show equal distributions with regard to key variables in the study. Moreover, in only 1 patient were all risk factors within the limits as defined in various guidelines, which underscores the relevance of our initiative.

Leucine Biosynthesis Is Involved in Regulating High Lipid Accumulation in Yarrowia lipolytica

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

Kerkhoven, Eduard J.; Kim, Young-Mo; Wei, Siwei

ABSTRACT The yeastYarrowia lipolyticais a potent accumulator of lipids, and lipogenesis in this organism can be influenced by a variety of factors, such as genetics and environmental conditions. Using a multifactorial study, we elucidated the effects of both genetic and environmental factors on regulation of lipogenesis inY. lipolyticaand identified how two opposite regulatory states both result in lipid accumulation. This study involved comparison of a strain overexpressing diacylglycerol acyltransferase (DGA1) with a control strain grown under either nitrogen or carbon limitation conditions. A strong correlation was observed between the responses on the transcript and protein levels. Combination ofDGA1overexpression with nitrogen limitationmore » resulted in a high level of lipid accumulation accompanied by downregulation of several amino acid biosynthetic pathways, including that of leucine in particular, and these changes were further correlated with a decrease in metabolic fluxes. This downregulation was supported by the measured decrease in the level of 2-isopropylmalate, an intermediate of leucine biosynthesis. Combining the multi-omics data with putative transcription factor binding motifs uncovered a contradictory role for TORC1 in controlling lipid accumulation, likely mediated through 2-isopropylmalate and a Leu3-like transcription factor. IMPORTANCEThe ubiquitous metabolism of lipids involves refined regulation, and an enriched understanding of this regulation would have wide implications. Various factors can influence lipid metabolism, including the environment and genetics. We demonstrated, using a multi-omics and multifactorial experimental setup, that multiple factors affect lipid accumulation in the yeastYarrowia lipolytica. Using integrative analysis, we identified novel interactions between nutrient restriction and genetic factors involving regulators that are highly conserved among eukaryotes. Given that lipid metabolism is involved in many diseases but is also vital to the development of microbial cell factories that can provide us with sustainable fuels and oleochemicals, we envision that our report introduces foundational work to further unravel the regulation of lipid accumulation in eukaryal cells.« less

Genes from a translational analysis support a multifactorial nature of white matter hyperintensities.

PubMed

Lopez, Lorna M; Hill, W David; Harris, Sarah E; Valdes Hernandez, Maria; Munoz Maniega, Susana; Bastin, Mark E; Bailey, Emma; Smith, Colin; McBride, Martin; McClure, John; Graham, Delyth; Dominiczak, Anna; Yang, Qiong; Fornage, Myriam; Ikram, M Arfan; Debette, Stephanie; Launer, Lenore; Bis, Joshua C; Schmidt, Reinhold; Seshadri, Sudha; Porteous, David J; Starr, John; Deary, Ian J; Wardlaw, Joanna M

2015-02-01

White matter hyperintensities (WMH) of presumed vascular origin increase the risk of stroke and dementia. Despite strong WMH heritability, few gene associations have been identified. Relevant experimental models may be informative. We tested the associations between genes that were differentially expressed in brains of young spontaneously hypertensive stroke-prone rats and human WMH (using volume and visual score) in 621 subjects from the Lothian Birth Cohort 1936 (LBC1936). We then attempted replication in 9361 subjects from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE). We also tested the subjects from LBC1936 for previous genome-wide WMH associations found in subjects from CHARGE. Of 126 spontaneously hypertensive stroke-prone rat genes, 10 were nominally associated with WMH volume or score in subjects from LBC1936, of which 5 (AFP, ALB, GNAI1, RBM8a, and MRPL18) were associated with both WMH volume and score (P<0.05); 2 of the 10 (XPNPEP1, P=6.7×10(-5); FARP1, P=0.024) plus another spontaneously hypertensive stroke-prone rat gene (USMG5, P=0.00014), on chromosomes 10, 13, and 10 respectively, were associated with WMH in subjects from CHARGE. Gene set enrichment showed significant associations for downregulated spontaneously hypertensive stroke-prone rat genes with WMH in humans. In subjects from LBC1936, we replicated CHARGE's genome-wide WMH associations on chromosomes 17 (TRIM65 and TRIM47) and, for the first time, 1 (PMF1). Despite not passing multiple testing thresholds individually, these genes collectively are relevant to known WMH associations, proposed WMH mechanisms, or dementia: associations with Alzheimer's disease, late-life depression, ATP production, osmotic regulation, neurodevelopmental abnormalities, and cognitive impairment. If replicated further, they suggest a multifactorial nature for WMH and argue for more consideration of vascular contributions to dementia. © 2015 The Authors.

The Epigenetic Landscape of Alcoholism

PubMed Central

Krishnan, Harish R.; Sakharkar, Amul J.; Teppen, Tara L.; Berkel, Tiffani D.M.; Pandey, Subhash C.

2015-01-01

Alcoholism is a complex psychiatric disorder that has a multifactorial etiology. Epigenetic mechanisms are uniquely capable of accounting for the multifactorial nature of the disease in that they are highly stable and are affected by environmental factors, including alcohol itself. Chromatin remodeling causes changes in gene expression in specific brain regions contributing to the endophenotypes of alcoholism such as tolerance and dependence. The epigenetic mechanisms that regulate changes in gene expression observed in addictive behaviors respond not only to alcohol exposure, but also to comorbid psychopathology such as the presence of anxiety and stress. This review summarizes recent developments in epigenetic research that may play a role in alcoholism. We propose that pharmacologically manipulating epigenetic targets, as demonstrated in various preclinical models, holds great therapeutic potential in the treatment and prevention of alcoholism. PMID:25131543

Burning Mouth Syndrome.

PubMed

Kamala, K A; Sankethguddad, S; Sujith, S G; Tantradi, Praveena

2016-01-01

Burning mouth syndrome (BMS) is multifactorial in origin which is typically characterized by burning and painful sensation in an oral cavity demonstrating clinically normal mucosa. Although the cause of BMS is not known, a complex association of biological and psychological factors has been identified, suggesting the existence of a multifactorial etiology. As the symptom of oral burning is seen in various pathological conditions, it is essential for a clinician to be aware of how to differentiate between symptom of oral burning and BMS. An interdisciplinary and systematic approach is required for better patient management. The purpose of this study was to provide the practitioner with an understanding of the local, systemic, and psychosocial factors which may be responsible for oral burning associated with BMS, and review of treatment modalities, therefore providing a foundation for diagnosis and treatment of BMS.

Theories of Memory and Aging: A Look at the Past and a Glimpse of the Future

PubMed Central

Festini, Sara B.

2017-01-01

The present article reviews theories of memory and aging over the past 50 years. Particularly notable is a progression from early single-mechanism perspectives to complex multifactorial models proposed to account for commonly observed age deficits in memory function. The seminal mechanistic theories of processing speed, limited resources, and inhibitory deficits are discussed and viewed as especially important theories for understanding age-related memory decline. Additionally, advances in multivariate techniques including structural equation modeling provided new tools that led to the development of more complex multifactorial theories than existed earlier. The important role of neuroimaging is considered, along with the current prevalence of intervention studies. We close with predictions about new directions that future research on memory and aging will take. PMID:27257229

Biological adaptive control model: a mechanical analogue of multi-factorial bone density adaptation.

PubMed

Davidson, Peter L; Milburn, Peter D; Wilson, Barry D

2004-03-21

The mechanism of how bone adapts to every day demands needs to be better understood to gain insight into situations in which the musculoskeletal system is perturbed. This paper offers a novel multi-factorial mathematical model of bone density adaptation which combines previous single-factor models in a single adaptation system as a means of gaining this insight. Unique aspects of the model include provision for interaction between factors and an estimation of the relative contribution of each factor. This interacting system is considered analogous to a Newtonian mechanical system and the governing response equation is derived as a linear version of the adaptation process. The transient solution to sudden environmental change is found to be exponential or oscillatory depending on the balance between cellular activation and deactivation frequencies.

HUGO urges genetic benefit-sharing.

PubMed

2000-01-01

In view of the fact that for-profit enterprise exceeds public expenditures on genetic research and that benefits from the Human Genome Project may accrue only to rich people in rich nations, the HUGO Ethics Committee discussed the necessity of benefit-sharing. Discussions involved case examples ranging from single-gene to multi-factorial disorders and included the difficulties of defining community, especially when multifactorial diseases are involved. The Committee discussed arguments for benefit-sharing, including common heritage, the genome as a common resource, and three types of justice: compensatory, procedural, and distributive. The Committee also discussed the importance of community participation in defining benefit, agreed that companies involved in health have special obligations beyond paying taxes, and recommended they devote 1-3% of net profits to healthcare infrastructure or humanitarian efforts.

A multifactorial analysis of obesity as CVD risk factor: use of neural network based methods in a nutrigenetics context.

PubMed

Valavanis, Ioannis K; Mougiakakou, Stavroula G; Grimaldi, Keith A; Nikita, Konstantina S

2010-09-08

Obesity is a multifactorial trait, which comprises an independent risk factor for cardiovascular disease (CVD). The aim of the current work is to study the complex etiology beneath obesity and identify genetic variations and/or factors related to nutrition that contribute to its variability. To this end, a set of more than 2300 white subjects who participated in a nutrigenetics study was used. For each subject a total of 63 factors describing genetic variants related to CVD (24 in total), gender, and nutrition (38 in total), e.g. average daily intake in calories and cholesterol, were measured. Each subject was categorized according to body mass index (BMI) as normal (BMI ≤ 25) or overweight (BMI > 25). Two artificial neural network (ANN) based methods were designed and used towards the analysis of the available data. These corresponded to i) a multi-layer feed-forward ANN combined with a parameter decreasing method (PDM-ANN), and ii) a multi-layer feed-forward ANN trained by a hybrid method (GA-ANN) which combines genetic algorithms and the popular back-propagation training algorithm. PDM-ANN and GA-ANN were comparatively assessed in terms of their ability to identify the most important factors among the initial 63 variables describing genetic variations, nutrition and gender, able to classify a subject into one of the BMI related classes: normal and overweight. The methods were designed and evaluated using appropriate training and testing sets provided by 3-fold Cross Validation (3-CV) resampling. Classification accuracy, sensitivity, specificity and area under receiver operating characteristics curve were utilized to evaluate the resulted predictive ANN models. The most parsimonious set of factors was obtained by the GA-ANN method and included gender, six genetic variations and 18 nutrition-related variables. The corresponding predictive model was characterized by a mean accuracy equal of 61.46% in the 3-CV testing sets. The ANN based methods revealed factors that interactively contribute to obesity trait and provided predictive models with a promising generalization ability. In general, results showed that ANNs and their hybrids can provide useful tools for the study of complex traits in the context of nutrigenetics.

Cost Effectiveness of Falls and Injury Prevention Strategies for Older Adults Living in Residential Aged Care Facilities.

PubMed

Church, Jody L; Haas, Marion R; Goodall, Stephen

2015-12-01

To evaluate the cost effectiveness of interventions designed to prevent falls and fall-related injuries among older people living in residential aged care facilities (RACFs) from an Australian health care perspective. A decision analytic Markov model was developed that stratified individuals according to their risk of falling and accounted for the risk of injury following a fall. The effectiveness of the interventions was derived from two Cochrane reviews of randomized controlled trials for falls/fall-related injury prevention in RACFs. Interventions were considered effective if they reduced the risk of falling or reduced the risk of injury following a fall. The interventions that were modelled included vitamin D supplementation, annual medication review, multifactorial intervention (a combination of risk assessment, medication review, vision assessment and exercise) and hip protectors. The cost effectiveness was calculated as the incremental cost relative to the incremental benefit, in which the benefit was estimated using quality-adjusted life-years (QALYs). Uncertainty was explored using univariate and probabilistic sensitivity analysis. Vitamin D supplementation and medication review both dominated 'no intervention', as these interventions were both more effective and cost saving (because of healthcare costs avoided). Hip protectors are dominated (less effective and more costly) by vitamin D and medication review. The incremental cost-effectiveness ratio (ICER) for medication review relative to vitamin D supplementation is AU$2442 per QALY gained, and the ICER for multifactorial intervention relative to medication review is AU$1,112,500 per QALY gained. The model is most sensitive to the fear of falling and the cost of the interventions. The model suggests that vitamin D supplementation and medication review are cost-effective interventions that reduce falls, provide health benefits and reduce health care costs in older adults living in RACFs.

Cytotoxicity of compounds from Xylopia aethiopica towards multi-factorial drug-resistant cancer cells.

PubMed

Kuete, Victor; Sandjo, Louis P; Mbaveng, Armelle T; Zeino, Maen; Efferth, Thomas

2015-12-15

Multidrug resistance (MDR) in cancer represent a major hurdle in chemotherapy. Previously, the methanol extract of the medicinal spice Xylopia aethiopica displayed considerable cytotoxicity against multidrug resistant (MDR) cancer cell lines. The present study was designed to assess the cytotoxicity of compounds, 16α-hydroxy-ent-kauran-19-oic acid (2), 3,4',5-trihydroxy-6″,6″-dimethylpyrano[2,3-g]flavone (3), isotetrandrine (5) and trans-tiliroside (6) derived from the methanol crude extract of Xylopia aethiopica against 9 drug-sensitive and -resistant cancer cell lines. The resazurin reduction assay was used to evaluate the cytotoxicity of these compounds, whilst caspase-Glo assay was used to detect caspase activation. Cell cycle, mitochondrial membrane potential (MMP) and levels of reactive oxygen species (ROS) were all analyzed via flow cytometry. Flavonoid 3 and alkaloid 5 also displayed IC50 values ranging from 2.61 µM (towards leukemia CCRF-CEM cells) to 18.60 µM (towards gliobastoma multiforme U87MG.ΔEGFR cells) and from 1.45 µM (towards HepG2 cells) to 7.28 µM (towards MDA-MB-231-pcDNA cells), respectively. IC50 values ranged from 0.20 µM (against CCRF-CEM cells) to 195.12 µM (against CEM/ADR5000 cells) for doxorubicin. Compound 3 induced apoptosis in leukemia CCRF-CEM cells mediated by the disruption of the MMP, whilst 5 induced apoptosis mediated by ROS production. Compounds 2 and 5 represent potential cytotoxic phytochemicals that deserve more investigations to develop novel antineoplastic drugs against multifactorial drug-resistant cancers. Copyright © 2015 Elsevier GmbH. All rights reserved.

The Multifactor Measure of Performance: Its Development, Norming, and Validation.

PubMed

Bar-On, Reuven

2018-01-01

This article describes the development as well as the initial norming and validation of the Multifactor Measure of Performance™ (MMP™), which is a psychometric instrument that is designed to study, assess and enhance key predictors of human performance to help individuals perform at a higher level. It was created by the author, for the purpose of going beyond existing conceptual and psychometric models that often focus on relatively few factors that are purported to assess performance at school, in the workplace and elsewhere. The relative sparsity of multifactorial pre-employment assessment instruments exemplifies, for the author, one of the important reasons for developing the MMP™, which attempts to comprehensively evaluate a wider array of factors that are thought to contribute to performance. In that this situation creates a need in the area of test-construction that should be addressed, the author sought to develop a multifactorial assessment and development instrument that could concomitantly evaluate a combination of physical, cognitive, intra-personal, inter-personal, and motivational factors that significantly contribute to performance. The specific aim of this article is to show why, how and if this could be done as well as to present and discuss the potential importance of the results obtained to date. The findings presented here will hopefully add to what is known about human performance and thus contribute to the professional literature, in addition to contribute to the continued development of the MMP™. The impetus for developing the MMP™ is first explained below, followed by a detailed description of the process involved and the findings obtained; and their potential application is then discussed as well as the possible limitations of the present research and the need for future studies to address them.

Physical activity prescription by primary care nurses using health assets: Study design of a randomized controlled trial in patients with cardiovascular risk factors.

PubMed

Riera-Sampol, Aina; Tauler, Pedro; Bennasar-Veny, Miquel; Leiva, Alfonso; Artigues-Vives, Guillem; De Pedro-Gómez, Joan; Pericàs, Jordi; Moreno, Carlos; Arbos, Maite; Aguilo, Antoni

2017-09-01

To analyse the efficacy of a 12-month multifactorial intervention by primary care nurses in increasing adherence to physical activity prescription (150 min/week) in patients with two or more cardiovascular risk factors and with cardiovascular risk up to 15% determined by the REGICOR equation. In Spain, cardiovascular diseases are responsible for 30.5% of deaths. Regular physical activity decreases mortality risk due to cardiovascular diseases but the effectiveness of physical activity prescription in routine in primary care settings has been shown to be low. Multicentre, single-blind, parallel randomized (in two different branches) clinical trial. At least 368 participants will be recruited (184 control and 184 intervention), to show an 8% increase in adherence to the physical activity prescription (1.2% control group and 9.2% intervention group). Participants will be patients aged 35-75 years with at least two cardiovascular risk factors and with a cardiovascular risk of up to 15% measured using the Framingham-REGICOR equation. Intervention will be performed throughout baseline and three follow-up visits. A motivational interview, the trans-theoretical stages of changes of Prochaska and DiClemente and an individualized prescription of physical exercise using physical activity assets will be used in the intervention. Data will be collected at baseline and after the 1-year intervention. The present study will allow us to find out whether this brief multifactorial intervention induces greater adherence to physical activity prescription than usual practice, improving the quality of patient care. International Standard Randomized Controlled Trial Number (ISRCTN): ISRCTN76069254. Protocol version 1.1, 6 July 2015. © 2017 John Wiley & Sons Ltd.

The role of adipose tissue in cancer-associated cachexia.

PubMed

Vaitkus, Janina A; Celi, Francesco S

2017-03-01

Adipose tissue (fat) is a heterogeneous organ, both in function and histology, distributed throughout the body. White adipose tissue, responsible for energy storage and more recently found to have endocrine and inflammation-modulatory activities, was historically thought to be the only type of fat present in adult humans. The recent demonstration of functional brown adipose tissue in adults, which is highly metabolic, shifted this paradigm. Additionally, recent studies demonstrate the ability of white adipose tissue to be induced toward the brown adipose phenotype - "beige" or "brite" adipose tissue - in a process referred to as "browning." While these adipose tissue depots are under investigation in the context of obesity, new evidence suggests a maladaptive role in other metabolic disturbances including cancer-associated cachexia, which is the topic of this review. This syndrome is multifactorial in nature and is an independent factor associated with poor prognosis. Here, we review the contributions of all three adipose depots - white, brown, and beige - to the development and progression of cancer-associated cachexia. Specifically, we focus on the local and systemic processes involving these adipose tissues that lead to increased energy expenditure and sustained negative energy balance. We highlight key findings from both animal and human studies and discuss areas within the field that need further exploration. Impact statement Cancer-associated cachexia (CAC) is a complex, multifactorial syndrome that negatively impacts patient quality of live and prognosis. This work reviews a component of CAC that lacks prior discussion: adipose tissue contributions. Uniquely, it discusses all three types of adipose tissue, white, beige, and brown, their interactions, and their contributions to the development and progression of CAC. Summarizing key bench and clinical studies, it provides information that will be useful to both basic and clinical researchers in designing experiments, studies, and clinical trials.

The Multifactor Measure of Performance: Its Development, Norming, and Validation

PubMed Central

Bar-On, Reuven

2018-01-01

This article describes the development as well as the initial norming and validation of the Multifactor Measure of Performance™ (MMP™)1, which is a psychometric instrument that is designed to study, assess and enhance key predictors of human performance to help individuals perform at a higher level. It was created by the author, for the purpose of going beyond existing conceptual and psychometric models that often focus on relatively few factors that are purported to assess performance at school, in the workplace and elsewhere. The relative sparsity of multifactorial pre-employment assessment instruments exemplifies, for the author, one of the important reasons for developing the MMP™, which attempts to comprehensively evaluate a wider array of factors that are thought to contribute to performance. In that this situation creates a need in the area of test-construction that should be addressed, the author sought to develop a multifactorial assessment and development instrument that could concomitantly evaluate a combination of physical, cognitive, intra-personal, inter-personal, and motivational factors that significantly contribute to performance. The specific aim of this article is to show why, how and if this could be done as well as to present and discuss the potential importance of the results obtained to date. The findings presented here will hopefully add to what is known about human performance and thus contribute to the professional literature, in addition to contribute to the continued development of the MMP™. The impetus for developing the MMP™ is first explained below, followed by a detailed description of the process involved and the findings obtained; and their potential application is then discussed as well as the possible limitations of the present research and the need for future studies to address them. PMID:29515479

Inverted-U shaped dopamine actions on human working memory and cognitive control

PubMed Central

Cools, R; D’Esposito, M

2011-01-01

Brain dopamine has long been implicated in cognitive control processes, including working memory. However, the precise role of dopamine in cognition is not well understood, partly because there is large variability in the response to dopaminergic drugs both across different behaviors and across different individuals. We review evidence from a series of studies with experimental animals, healthy humans and patients with Parkinson’s disease, which highlight two important factors that contribute to this large variability. First, the existence of an optimum dopamine level for cognitive function implicates the need to take into account baseline levels of dopamine when isolating dopamine’s effects. Second, cognitive control is a multi-factorial phenomenon, requiring a dynamic balance between cognitive stability and cognitive flexibility. These distinct components might implicate the prefrontal cortex and the striatum respectively. Manipulating dopamine will thus have paradoxical consequences for distinct cognitive control processes depending on distinct basal or optimal levels of dopamine in different brain regions. PMID:21531388

Toxin-Induced Models of Parkinson's Disease

PubMed Central

Bové, Jordi; Prou, Delphine; Perier, Céline; Przedborski, Serge

2005-01-01

Summary: Parkinson's disease (PD) is a common neurodegenerative disease that appears essentially as a sporadic condition. It results mainly from the death of dopaminergic neurons in the substantia nigra. PD etiology remains mysterious, whereas its pathogenesis begins to be understood as a multifactorial cascade of deleterious factors. Most insights into PD pathogenesis come from investigations performed in experimental models of PD, especially those produced by neurotoxins. Although a host of natural and synthetic molecules do exert deleterious effects on dopaminergic neurons, only a handful are used in living laboratory animals to recapitulate some of the hallmarks of PD. In this review, we discuss what we believe are the four most popular parkinsonian neurotoxins, namely 6-hydroxydopamine (6-OHDA), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), rotenone, and paraquat. The main goal is to provide an updated summary of the main characteristics of each of these four neurotoxins. However, we also try to provide the reader with an idea about the various strengths and the weaknesses of these neurotoxic models. PMID:16389312

Radiation-induced equilibrium is a balance between tumor cell proliferation and T cell-mediated killing

PubMed Central

Liang, Hua; Deng, Liufu; Chmura, Steven; Burnette, Byron; Liadis, Nicole; Darga, Thomas; Beckett, Michael A.; Lingen, Mark W.; Witt, MaryEllyn; Weichselbaum, Ralph R.; Fu, Yang-Xin

2013-01-01

Local failures following radiation therapy are multifactorial and the contributions of the tumor and the host are complex. Current models of tumor equilibrium suggest that a balance exists between cell birth and cell death due to insufficient angiogenesis, immune effects, or intrinsic cellular factors. We investigated whether host immune responses contribute to radiation induced tumor equilibrium in animal models. We report an essential role for immune cells and their cytokines in suppressing tumor cell regrowth in two experimental animal model systems. Depletion of T cells or neutralization of interferon-gamma reversed radiation-induced equilibrium leading to tumor regrowth. We also demonstrate that PD-L1 blockade augments T cell responses leading to rejection of tumors in radiation induced equilibrium. We identify an active interplay between tumor cells and immune cells that occurs in radiation-induced tumor equilibrium and suggest a potential role for disruption of the PD-L1/PD-1 axis in increasing local tumor control. PMID:23630355

Use of mathematics to guide target selection in systems pharmacology; application to receptor tyrosine kinase (RTK) pathways.

PubMed

Benson, Neil; van der Graaf, Piet H; Peletier, Lambertus A

2017-11-15

A key element of the drug discovery process is target selection. Although the topic is subject to much discussion and experimental effort, there are no defined quantitative rules around optimal selection. Often 'rules of thumb', that have not been subject to rigorous exploration, are used. In this paper we explore the 'rule of thumb' notion that the molecule that initiates a pathway signal is the optimal target. Given the multi-factorial and complex nature of this question, we have simplified an example pathway to its logical minimum of two steps and used a mathematical model of this to explore the different options in the context of typical small and large molecule drugs. In this paper, we report the conclusions of our analysis and describe the analysis tool and methods used. These provide a platform to enable a more extensive enquiry into this important topic. Copyright © 2017 Elsevier B.V. All rights reserved.

Noninflammatory Joint Contractures Arising from Immobility: Animal Models to Future Treatments

PubMed Central

Wong, Kayleigh; Trudel, Guy; Laneuville, Odette

2015-01-01

Joint contractures, defined as the limitation in the passive range of motion of a mobile joint, can be classified as noninflammatory diseases of the musculoskeletal system. The pathophysiology is not well understood; limited information is available on causal factors, progression, the pathophysiology involved, and prediction of response to treatment. The clinical heterogeneity of joint contractures combined with the heterogeneous contribution of joint connective tissues to joint mobility presents challenges to the study of joint contractures. Furthermore, contractures are often a symptom of a wide variety of heterogeneous disorders that are in many cases multifactorial. Extended immobility has been identified as a causal factor and evidence is provided from both experimental and epidemiology studies. Of interest is the involvement of the joint capsule in the pathophysiology of joint contractures and lack of response to remobilization. While molecular pathways involved in the development of joint contractures are being investigated, current treatments focus on physiotherapy, which is ineffective on irreversible contractures. Future treatments may include early diagnosis and prevention. PMID:26247029

Can We Modify the Intrauterine Environment to Halt the Intergenerational Cycle of Obesity?

PubMed Central

Adamo, Kristi B.; Ferraro, Zachary M.; Brett, Kendra E.

2012-01-01

Child obesity is a global epidemic whose development is rooted in complex and multi-factorial interactions. Once established, obesity is difficult to reverse and epidemiological, animal model, and experimental studies have provided strong evidence implicating the intrauterine environment in downstream obesity. This review focuses on the interplay between maternal obesity, gestational weight gain and lifestyle behaviours, which may act independently or in combination, to perpetuate the intergenerational cycle of obesity. The gestational period, is a crucial time of growth, development and physiological change in mother and child. This provides a window of opportunity for intervention via maternal nutrition and/or physical activity that may induce beneficial physiological alternations in the fetus that are mediated through favourable adaptations to in utero environmental stimuli. Evidence in the emerging field of epigenetics suggests that chronic, sub-clinical perturbations during pregnancy may affect fetal phenotype and long-term human data from ongoing randomized controlled trials will further aid in establishing the science behind ones predisposition to positive energy balance. PMID:22690193

Polyphenols journey through blood-brain barrier towards neuronal protection.

PubMed

Figueira, I; Garcia, G; Pimpão, R C; Terrasso, A P; Costa, I; Almeida, A F; Tavares, L; Pais, T F; Pinto, P; Ventura, M R; Filipe, A; McDougall, G J; Stewart, D; Kim, K S; Palmela, I; Brites, D; Brito, M A; Brito, C; Santos, C N

2017-09-13

Age-related complications such as neurodegenerative disorders are increasing and remain cureless. The possibility of altering the progression or the development of these multifactorial diseases through diet is an emerging and attractive approach with increasing experimental support. We examined the potential of known bioavailable phenolic sulfates, arising from colonic metabolism of berries, to influence hallmarks of neurodegenerative processes. In silico predictions and in vitro transport studies across blood-brain barrier (BBB) endothelial cells, at circulating concentrations, provided evidence for differential transport, likely related to chemical structure. Moreover, endothelial metabolism of these phenolic sulfates produced a plethora of novel chemical entities with further potential bioactivies. Pre-conditioning with phenolic sulfates improved cellular responses to oxidative, excitotoxicity and inflammatory injuries and this attenuation of neuroinflammation was achieved via modulation of NF-κB pathway. Our results support the hypothesis that these small molecules, derived from dietary (poly)phenols may cross the BBB, reach brain cells, modulate microglia-mediated inflammation and exert neuroprotective effects, with potential for alleviation of neurodegenerative diseases.

Ultrafiltration and endotoxin removal from dialysis fluids.

PubMed

Di Felice, A; Cappelli, G; Facchini, F; Tetta, C; Cornia, F; Aimo, G; Lusvarghi, E

1993-06-01

Biocompatibility in hemodialysis is now regarded as a multifactorial problem and dialysate represents a main risk. Pyrogenic fractions mostly coming from gram-negative bacteria easily pass through dialysis membrane, either by backdiffusion or by backfiltration, and induce blood cell activation. To demonstrate the long-term efficiency of a 2 m2 polyamide ultrafilter in producing a pyrogen free solution, we used an experimental circuit ultrafiltering for 240 hours (500 ml/min) a bicarbonate dialysate contaminated (5 to 48 EU/ml) by a Pseudomonas aeruginosa filtrate. The efficiency was monitored by LAL-test and IL-1 PBMC so to detect not only lipid A containing endotoxins but also other cytokines inducing bacterial fractions. At the post-ultrafilter sampling port the LAL-test was < 0.005 to 0.034 EU/ml; IL-1 PBMC was below the detection limit (20 pg/ml) being 27 to 63 pg/ml at the pre-ultrafilter level. Polyamide ultrafiltration represents an efficient system to obtain an endotoxin-free dialysate and a single filter works up to 240 hours.

Pesticides exposure as etiological factors of Parkinson's disease and other neurodegenerative diseases--a mechanistic approach.

PubMed

Baltazar, Maria Teresa; Dinis-Oliveira, Ricardo Jorge; de Lourdes Bastos, Maria; Tsatsakis, Aristidis M; Duarte, José Alberto; Carvalho, Félix

2014-10-15

The etiology of most neurodegenerative disorders is multifactorial and consists of an interaction between environmental factors and genetic predisposition. The role of pesticide exposure in neurodegenerative disease has long been suspected, but the specific causative agents and the mechanisms underlying are not fully understood. For the main neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis there are evidences linking their etiology with long-term/low-dose exposure to pesticides such as paraquat, maneb, dieldrin, pyrethroids and organophosphates. Most of these pesticides share common features, namely the ability to induce oxidative stress, mitochondrial dysfunction, α-synuclein fibrillization and neuronal cell loss. This review aims to clarify the role of pesticides as environmental risk factors in genesis of idiopathic PD and other neurological syndromes. For this purpose, the most relevant epidemiological and experimental data is highlighted in order to discuss the molecular mechanisms involved in neurodegeneration. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Cardiac Cachexia: Perspectives for Prevention and Treatment.

PubMed

Okoshi, Marina Politi; Capalbo, Rafael Verardino; Romeiro, Fernando G; Okoshi, Katashi

2017-01-01

Cachexia is a prevalent pathological condition associated with chronic heart failure. Its occurrence predicts increased morbidity and mortality independent of important clinical variables such as age, ventricular function, or heart failure functional class. The clinical consequences of cachexia are dependent on both weight loss and systemic inflammation, which accompany cachexia development. Skeletal muscle wasting is an important component of cachexia; it often precedes cachexia development and predicts poor outcome in heart failure. Cachexia clinically affects several organs and systems. It is a multifactorial condition where underlying pathophysiological mechanisms are not completely understood making it difficult to develop specific prevention and treatment therapies. Preventive strategies have largely focused on muscle mass preservation. Different treatment options have been described, mostly in small clinical studies or experimental settings. These include nutritional support, neurohormonal blockade, reducing intestinal bacterial translocation, anemia and iron deficiency treatment, appetite stimulants, immunomodulatory agents, anabolic hormones, and physical exercise regimens. Currently, nonpharmacological therapy such as nutritional support and physical exercise are considered central to cachexia prevention and treatment.

Carbon Pools in a Temperate Heathland Resist Changes in a Future Climate

NASA Astrophysics Data System (ADS)

Ambus, P.; Reinsch, S.; Nielsen, P. L.; Michelsen, A.; Schmidt, I. K.; Mikkelsen, T. N.

2014-12-01

The fate of recently plant assimilated carbon was followed into ecosystem carbon pools and fluxes in a temperate heathland after a 13CO2 pulse in the early growing season in a 6-year long multi-factorial climate change experiment. Eight days after the pulse, recently assimilated carbon was significantly higher in storage organs (rhizomes) of the grass Deschampsia flexuosa under elevated atmospheric CO2 concentration. Experimental drought induced a pronounced utilization of recently assimilated carbon belowground (roots, microbes, dissolved organic carbon) potentially counterbalancing limited nutrient availability. The fate of recently assimilated carbon was not affected by moderate warming. The full factorial combination of elevated CO2, warming and drought simulating future climatic conditions as expected for Denmark in 2075 did not change short-term carbon turnover significantly compared to ambient conditions. Overall, climate factors interacted in an unexpected way resulting in strong resilience of the heathland in terms of short-term carbon turnover in a future climate.

Honey and Diabetes: The Importance of Natural Simple Sugars in Diet for Preventing and Treating Different Type of Diabetes

PubMed Central

Dezmirean, Daniel S.

2018-01-01

Diabetes is a metabolic disorder with multifactorial and heterogeneous etiologies. Two types of diabetes are common among humans: type 1 diabetes that occurs when the immune system attacks and destroys insulin and type 2 diabetes, the most common form, that may be caused by several factors, the most important being lifestyle, but also may be determined by different genes. Honey was used in folk medicine for a long time, but the health benefits were explained in the last decades, when the scientific world was concerned in testing and thus explaining the benefits of honey. Different studies demonstrate the hypoglycemic effect of honey, but the mechanism of this effect remains unclear. This review presents the experimental studies completed in the recent years, which support honey as a novel antidiabetic agent that might be of potential significance for the management of diabetes and its complications and also highlights the potential impacts and future perspectives on the use of honey as an antidiabetic agent. PMID:29507651

Dermatoglyphics: a genetic marker of early childhood caries.

PubMed

Anitha, C; Konde, Sapna; Raj, N Sunil; Kumar, N C; Peethamber, Preetha

2014-01-01

It is an accepted fact that genetics plays an important role in determination of palmar dermatoglyphic patterns. Since caries is a multifactorial disease with the influence of genetic pattern, this study was undertaken to explore the possibility of dermatoglyphics as a noninvasive and early predictor of dental caries in children, so as to initiate preventive oral health measures at an early age. The study group comprised of 200 children aged between 4 and 5 years. The dmfs score was evaluated. The experimental group (Group 1), comprised of 100 children with early childhood caries (ECC) with dmfs >5. The control group (Group 2) comprised of 100 children with dmfs score of 0. An increased frequency of ulnar loops in caries-free children and whorls in children with ECC was observed. Low mean atd angle and low mean. Total ridge count was observed in the ECC group. There is definite variation in dermatoglyphics between the ECC and caries-free group, indicating that dermatoglyphic patterns can be used as a predictive tool for children with ECC.

On the way toward systems biology of Aspergillus fumigatus infection.

PubMed

Albrecht, Daniela; Kniemeyer, Olaf; Mech, Franziska; Gunzer, Matthias; Brakhage, Axel; Guthke, Reinhard

2011-06-01

Pathogenicity of Aspergillus fumigatus is multifactorial. Thus, global studies are essential for the understanding of the infection process. Therefore, a data warehouse was established where genome sequence, transcriptome and proteome data are stored. These data are analyzed for the elucidation of virulence determinants. The data analysis workflow starts with pre-processing including imputing of missing values and normalization. Last step is the identification of differentially expressed genes/proteins as interesting candidates for further analysis, in particular for functional categorization and correlation studies. Sequence data and other prior knowledge extracted from databases are integrated to support the inference of gene regulatory networks associated with pathogenicity. This knowledge-assisted data analysis aims at establishing mathematical models with predictive strength to assist further experimental work. Recently, first steps were done to extend the integrative data analysis and computational modeling by evaluating spatio-temporal data (movies) that monitor interactions of A. fumigatus morphotypes (e.g. conidia) with host immune cells. Copyright © 2011 Elsevier GmbH. All rights reserved.

Multifactorial skin barrier deficiency and atopic dermatitis: Essential topics to prevent the atopic march.

PubMed

Egawa, Gyohei; Kabashima, Kenji

2016-08-01

Atopic dermatitis (AD) is the most common inflammatory skin disease in the industrialized world and has multiple causes. Over the past decade, data from both experimental models and patients have highlighted the primary pathogenic role of skin barrier deficiency in patients with AD. Increased access of environmental agents into the skin results in chronic inflammation and contributes to the systemic "atopic (allergic) march." In addition, persistent skin inflammation further attenuates skin barrier function, resulting in a positive feedback loop between the skin epithelium and the immune system that drives pathology. Understanding the mechanisms of skin barrier maintenance is essential for improving management of AD and limiting downstream atopic manifestations. In this article we review the latest developments in our understanding of the pathomechanisms of skin barrier deficiency, with a particular focus on the formation of the stratum corneum, the outermost layer of the skin, which contributes significantly to skin barrier function. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Nephrotoxicity in rabbits after long-term nandrolone decanoate administration.

PubMed

Tsitsimpikou, Christina; Vasilaki, Fotini; Tsarouhas, Konstantinos; Fragkiadaki, Persefoni; Tzardi, Maria; Goutzourelas, Nikolaos; Nepka, Charitini; Kalogeraki, Alexandra; Heretis, Ioannis; Epitropaki, Zoi; Kouretas, Dimitrios; Tsatsakis, Aristidis M

2016-09-30

Among the various side effects of supra-physiological dose of anabolic androgenic steroids that are described, renal toxicity remains the least evaluated. The present study provides evidence that long-term administration of nandrolone decanoate could lead to alterations of renal function and structure in the experimental rabbit model. A pronounced increase in serum urea, creatinine, SGOT and SGPT is observed in the treated animals, with intramuscular administration being more detrimental. Histopathological evaluation of kidneys indicated hyperaemia, fibrosis and focal inflammation. Furthermore, the significantly increased telomerase activity found in the kidneys of the intramuscularly treated animals could possibly represent a counteracting survival mechanism. Oxidative stress markers that were influenced the most were TBARS, indicating lipid peroxidation, and GSH. An interesting finding in our study though, was that while intramuscular administration showed the highest biochemical derangement, oxidative stress markers provided mixed results between intramuscularly and subcutaneously treated rabbits. In conclusion, nephrotoxicity of nandrolone decanoate remains a multi-factorial, partly irreversible effect that involves augmented tissue oxidative status. Copyright © 2016. Published by Elsevier Ireland Ltd.

Retardation in Mathematics: A Consideration of Multi-Factorial Determination

ERIC Educational Resources Information Center

Lansdown, Richard

1978-01-01

Discusses mathematical retardation as a construct and examines the possible contributions of emotional factors, socioeconomic factors, poor teaching, cognitive factors, and sex difference to low achievement in mathematics. (JB)

Years of life gained by multifactorial intervention in patients with type 2 diabetes mellitus and microalbuminuria: 21 years follow-up on the Steno-2 randomised trial.

PubMed

Gæde, Peter; Oellgaard, Jens; Carstensen, Bendix; Rossing, Peter; Lund-Andersen, Henrik; Parving, Hans-Henrik; Pedersen, Oluf

2016-11-01

The aim of this work was to study the potential long-term impact of a 7.8 years intensified, multifactorial intervention in patients with type 2 diabetes mellitus and microalbuminuria in terms of gained years of life and years free from incident cardiovascular disease. The original intervention (mean treatment duration 7.8 years) involved 160 patients with type 2 diabetes and microalbuminuria who were randomly assigned (using sealed envelopes) to receive either conventional therapy or intensified, multifactorial treatment including both behavioural and pharmacological approaches. After 7.8 years the study continued as an observational follow-up with all patients receiving treatment as for the original intensive-therapy group. The primary endpoint of this follow-up 21.2 years after intervention start was difference in median survival time between the original treatment groups with and without incident cardiovascular disease. Non-fatal endpoints and causes of death were adjudicated by an external endpoint committee blinded for treatment allocation. Thirty-eight intensive-therapy patients vs 55 conventional-therapy patients died during follow-up (HR 0.55 [95% CI 0.36, 0.83], p = 0.005). The patients in the intensive-therapy group survived for a median of 7.9 years longer than the conventional-therapy group patients. Median time before first cardiovascular event after randomisation was 8.1 years longer in the intensive-therapy group (p = 0.001). The hazard for all microvascular complications was decreased in the intensive-therapy group in the range 0.52 to 0.67, except for peripheral neuropathy (HR 1.12). At 21.2 years of follow-up of 7.8 years of intensified, multifactorial, target-driven treatment of type 2 diabetes with microalbuminuria, we demonstrate a median of 7.9 years of gain of life. The increase in lifespan is matched by time free from incident cardiovascular disease. ClinicalTrials.gov registration no. NCT00320008. The study was funded by an unrestricted grant from Novo Nordisk A/S.

Effects of a multifactorial fall prevention program on fall incidence and physical function in community-dwelling older adults with risk of falls.

PubMed

Lee, Hsuei-Chen; Chang, Ku-Chou; Tsauo, Jau-Yih; Hung, Jen-Wen; Huang, Yu-Ching; Lin, Sang-I

2013-04-01

To evaluate effects of a multifactorial fall prevention program on fall incidence and physical function in community-dwelling older adults. Multicenter randomized controlled trial. Three medical centers and adjacent community health centers. Community-dwelling older adults (N=616) who have fallen in the previous year or are at risk of falling. After baseline assessment, eligible subjects were randomly allocated into the intervention group (IG) or the control group (CG), stratified by the Physiological Profile Assessment (PPA) fall risk level. The IG received a 3-month multifactorial intervention program including 8 weeks of exercise training, health education, home hazards evaluation/modification, along with medication review and ophthalmology/other specialty consults. The CG received health education brochures, referrals, and recommendations without direct exercise intervention. Primary outcome was fall incidence within 1 year. Secondary outcomes were PPA battery (overall fall risk index, vision, muscular strength, reaction time, balance, and proprioception), Timed Up & Go (TUG) test, Taiwan version of the International Physical Activity Questionnaire, EuroQol-5D, Geriatric Depression Scale (GDS), and the Falls Efficacy Scale-International at 3 months after randomization. Participants were 76±7 years old and included low risk 25.6%, moderate risk 25.6%, and marked risk 48.7%. The cumulative 1-year fall incidence was 25.2% in the IG and 27.6% in the CG (hazard ratio=.90; 95% confidence interval, .66-1.23). The IG improved more favorably than the CG on overall PPA fall risk index, reaction time, postural sway with eyes open, TUG test, and GDS, especially for those with marked fall risk. The multifactorial fall prevention program with exercise intervention improved functional performance at 3 months for community-dwelling older adults with risk of falls, but did not reduce falls at 1-year follow-up. Fall incidence might have been decreased simultaneously in both groups by heightened awareness engendered during assessments, education, referrals, and recommendations. Copyright © 2013 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Graphical Models for Quasi-Experimental Designs

ERIC Educational Resources Information Center

Kim, Yongnam; Steiner, Peter M.; Hall, Courtney E.; Su, Dan

2016-01-01

Experimental and quasi-experimental designs play a central role in estimating cause-effect relationships in education, psychology, and many other fields of the social and behavioral sciences. This paper presents and discusses the causal graphs of experimental and quasi-experimental designs. For quasi-experimental designs the authors demonstrate…

Recent developments on dry eye disease treatment compounds

PubMed Central

Colligris, Basilio; Alkozi, Hanan Awad; Pintor, Jesus

2013-01-01

Dry eye syndrome is a common tears and ocular surface multifactorial disease, described by changes in the ocular surface epithelia related to reduced tears quantity and ocular surface sensitivity, leading to inflammatory reaction. Managing the eye inflammation proved helpful to patients with dry eye disease and current treatment is based on the use of topically applied artificial tear products/lubricants, tear retention management, stimulation of tear secretion and using anti-inflammatory drugs. In this article we revise the corresponding literature and patents assembling the new treatment approaches of novel and future pharmaceutical compounds destined for the dry eye disease treatment. The most frequent categories of compounds presented are secretagogues and anti-inflammatory drugs. These compounds are the research outcome of novel therapeutic strategies designed to reduce key inflammatory pathways and restore healthy tear film. PMID:24526854

The Functional Measurement Experiment Builder suite: two Java-based programs to generate and run functional measurement experiments.

PubMed

Mairesse, Olivier; Hofmans, Joeri; Theuns, Peter

2008-05-01

We propose a free, easy-to-use computer program that does not requires prior knowledge of computer programming to generate and run experiments using textual or pictorial stimuli. Although the FM Experiment Builder suite was initially programmed for building and conducting FM experiments, it can also be applied for non-FM experiments that necessitate randomized, single, or multifactorial designs. The program is highly configurable, allowing multilingual use and a wide range of different response formats. The outputs of the experiments are Microsoft Excel compatible .xls files that allow easy copy-paste of the results into Weiss's FM CalSTAT program (2006) or any other statistical package. Its Java-based structure is compatible with both Windows and Macintosh operating systems, and its compactness (< 1 MB) makes it easily distributable over the Internet.

Clinical relevance of rare germline sequence variants in cancer genes: evolution and application of classification models.

PubMed

Spurdle, Amanda B

2010-06-01

Multifactorial models developed for BRCA1/2 variant classification have proved very useful for delineating BRCA1/2 variants associated with very high risk of cancer, or with little clinical significance. Recent linkage of this quantitative assessment of risk to clinical management guidelines has provided a basis to standardize variant reporting, variant classification and management of families with such variants, and can theoretically be applied to any disease gene. As proof of principle, the multifactorial approach already shows great promise for application to the evaluation of mismatch repair gene variants identified in families with suspected Lynch syndrome. However there is need to be cautious of the noted limitations and caveats of the current model, some of which may be exacerbated by differences in ascertainment and biological pathways to disease for different cancer syndromes.

Burning Mouth Syndrome

PubMed Central

Kamala, KA; Sankethguddad, S; Sujith, SG; Tantradi, Praveena

2016-01-01

Burning mouth syndrome (BMS) is multifactorial in origin which is typically characterized by burning and painful sensation in an oral cavity demonstrating clinically normal mucosa. Although the cause of BMS is not known, a complex association of biological and psychological factors has been identified, suggesting the existence of a multifactorial etiology. As the symptom of oral burning is seen in various pathological conditions, it is essential for a clinician to be aware of how to differentiate between symptom of oral burning and BMS. An interdisciplinary and systematic approach is required for better patient management. The purpose of this study was to provide the practitioner with an understanding of the local, systemic, and psychosocial factors which may be responsible for oral burning associated with BMS, and review of treatment modalities, therefore providing a foundation for diagnosis and treatment of BMS. PMID:26962284

Multifactorial neutropenia in a patient with acute promyelocytic leukemia and associated large granular lymphocyte expansion: A case report.

PubMed

Reda, Gianluigi; Fattizzo, Bruno; Cassin, Ramona; Flospergher, Elena; Orofino, Nicola; Gianelli, Umberto; Barcellini, Wilma; Cortelezzi, Agostino

2017-03-01

Neutropenia in the setting of acute hematological malignancies may impact disease prognosis, thus affecting therapy dose intensity. This is often due to chemotherapy-induced aplasia as well as to the disease itself. However, chronic neutropenia deserves further investigation, as the management of reversible concomitant causes may avoid treatment delay. The present study describes a case of an acute promyelocytic leukemia patient with chronic severe neutropenia of multifactorial origin, including acute leukemia itself, chemotherapy, autoimmune activation with anti-platelets and anti-neutrophil antibodies positivity, and the rare association of large granular lymphocyte (LGL) expansion. As neutropenia may challenge the diagnosis and treatment of acute malignancies, clinicians and hematopathologists must discuss the differential diagnosis in order to avoid misdiagnosing and undertreating concomitant diseases. In particular, LGL chronic expansion and autoimmunity should be considered.

The epigenetic landscape of alcoholism.

PubMed

Krishnan, Harish R; Sakharkar, Amul J; Teppen, Tara L; Berkel, Tiffani D M; Pandey, Subhash C

2014-01-01

Alcoholism is a complex psychiatric disorder that has a multifactorial etiology. Epigenetic mechanisms are uniquely capable of accounting for the multifactorial nature of the disease in that they are highly stable and are affected by environmental factors, including alcohol itself. Chromatin remodeling causes changes in gene expression in specific brain regions contributing to the endophenotypes of alcoholism such as tolerance and dependence. The epigenetic mechanisms that regulate changes in gene expression observed in addictive behaviors respond not only to alcohol exposure but also to comorbid psychopathology such as the presence of anxiety and stress. This review summarizes recent developments in epigenetic research that may play a role in alcoholism. We propose that pharmacologically manipulating epigenetic targets, as demonstrated in various preclinical models, hold great therapeutic potential in the treatment and prevention of alcoholism. © 2014 Elsevier Inc. All rights reserved.

Factors associated with fathers' caregiving activities and sensitivity with young children. NICHD Early Child Care Research Network.

PubMed

2000-06-01

A multifactorial model was used to identify child, sociodemographic, paternal, and maternal characteristics associated with 2 aspects of fathers' parenting. Fathers were interviewed about their caregiving responsibilities at 6, 15, 24, and 36 months, and a subset was videotaped during father-child play at 6 and 36 months. Caregiving activities and sensitivity during play interactions were predicted by different factors. Fathers were more involved in caregiving when fathers worked fewer hours and mothers worked more hours, when fathers and mothers were younger, when fathers had more positive personalities, when mothers reported greater marital intimacy, and when children were boys. Fathers who had less traditional child-rearing beliefs, were older, and reported more marital intimacy were more sensitive during play. These findings are consistent with a multifactorial and multidimensional view of fathering.

Multifactorial Analysis of a Biomarker Pool for Alzheimer Disease Risk in a North Indian Population.

PubMed

Talwar, Puneet; Grover, Sandeep; Sinha, Juhi; Chandna, Puneet; Agarwal, Rachna; Kushwaha, Suman; Kukreti, Ritushree

2017-01-01

Alzheimer disease (AD) is a progressive neurodegenerative disease with a complex multifactorial etiology. Here, we aim to identify a biomarker pool comprised of genetic variants and blood biomarkers as predictor of AD risk. We performed a case-control study involving 108 cases and 159 non-demented healthy controls to examine the association of multiple biomarkers with AD risk. The APOE genotyping revealed that ε4 allele frequency was significantly high (p value = 0.0001, OR = 2.66, 95% CI 1.58-4.46) in AD as compared to controls, whereas ε2 (p = 0.0430, OR = 0.29, CI 0.07-1.10) was overrepresented in controls. In biochemical assays, significant differences in levels of total copper, free copper, zinc, copper/zinc ratio, iron, epidermal growth factor receptor (EGFR), leptin, and albumin were also observed. The AD risk score (ADRS) as a linear combination of 6 candidate markers involving age, education status, APOE ε4 allele, levels of iron, Cu/Zn ratio, and EGFR was created using stepwise linear discriminant analysis. The area under the ROC curve of the ADRS panel for predicting AD risk was significantly high (AUC = 0.84, p < 0.0001, 95% CI 0.78-0.89, sensitivity = 70.0%, specificity = 83.8%) compared to individual parameters. These findings support the multifactorial etiology of AD and demonstrate the ability of a panel involving 6 biomarkers to discriminate AD cases from non-demented healthy controls. © 2017 S. Karger AG, Basel.

The spectrosome of occupational health problems

PubMed Central

de Gaudemaris, Régis; Bicout, Dominique J.

2018-01-01

Given the increased prevalence of cancer, respiratory diseases, and reproductive disorders, for which multifactorial origins are strongly suspected, the impact of the environment on the population represents a substantial public health challenge. Surveillance systems have become an essential public health decision-making tool. Networks have been constructed to facilitate the development of analyses of the multifactorial aspects of the relationships between occupational contexts and health. The aim of this study is to develop and present an approach for the optimal exploitation of observational databases to describe and improve the understanding of the (occupational) environment–health relationships, taking into account key multifactorial aspects. We have developed a spectral analysis (SA) approach that takes into account both the multi-exposure and dynamic natures of occupational health problems (OHPs) and related associations. The main results of this paper are to present the construction method of the “spectrum” and “spectrosome” of OHPs (range and structured list of occupational exposures) and describe the information contained therein with an illustrative example. The approach is illustrated using the case of non-Hodgkin lymphoma (NHL) from the French National Occupational Diseases Surveillance and Prevention Network database as a working example of an occupational disease. We found that the NHL spectrum includes 40 sets of occupational exposures characterized by important multi-exposures, especially solvent combinations or pesticide combinations, but also specific exposures such as polycyclic aromatic hydrocarbons, formaldehyde and ionizing radiation. These findings may be useful for surveillance and the assessment of occupational exposure related to health risks. PMID:29304043

Current and emerging concepts in muscle tension dysphonia: a 30-month review.

PubMed

Altman, Kenneth W; Atkinson, Cory; Lazarus, Cathy

2005-06-01

The modern theory of hoarseness is that there are multifactorial etiologies contributing to the voice problem. The hypothesis of this study is that muscle tension dysphonia is multifactorial with various contributing etiologies. This project is a retrospective chart review of all patients seen in the Voice Speech and Language Service and Swallowing Center at our institution with a diagnosis of muscle tension (functional hypertensive) dysphonia over a 30-month period. A literature search and review is also performed regarding current and emerging concepts of muscle tension dysphonia. One hundred fifty subjects were identified (60% female, 40% male, with a mean age of 42.3 years). Significant factors in patient history believed to contribute to abnormal voice production were gastroesophageal reflux in 49%, high stress levels in 18%, excessive amounts of voice use in 63%, and excessive loudness demands on voice use in 23%. Otolaryngologic evaluation was performed in 82% of patients, in whom lesions, significant vocal fold edema, or paralysis/paresis was identified in 52.3%. Speech pathology assessment revealed poor breath support, inappropriately low pitch, and visible cervical neck tension in the majority of patients. Inappropriate intensity was observed in 23.3% of patients. This set of multiple contributing factors is discussed in the context of current and emerging understanding of muscle tension dysphonia. Results confirm multifactorial etiologies contributing to hoarseness in the patients identified with muscle tension dysphonia. An interdisciplinary approach to treating all contributing factors portends the best prognosis.

A family study of dermatoglyphic traits in India: segregation analysis of accessory palmar triradii and the atd angle.

PubMed

Gilligan, S B; Borecki, I B; Mathew, S; Vijaykumar, M; Malhotra, K C; Rao, D C

1987-09-01

Accessory triradii and the atd angle were examined via complex segregation analysis in order to evaluate possible genetic effects on these dermatoglyphic traits, measured in an endogamous Brahmin caste of peninsular India. The phenotypes considered included: presence of accessory palmar triradii a' and d', associated with the interdigital areas II and IV, respectively; presence of an accessory axial triradius tt' associated with the proximal margin of the palm; and an arctanh-transformation of the atd angle measurement. For all accessory triradii considered in the present investigation familial resemblance was evident. The most parsimonious model which could account for the observed resemblance was a multifactorial model that includes polygenic effects as well as transmissible environmental effects that are inherited in the same pattern as polygenes. Evidence of familial resemblance was also found for the arctanh-transformed atd angle, which could be attributed, initially, to both a major effect and a multifactorial component. Tests of transmission of a putative major gene were performed which yielded results consistent with Mendelian transmission, although an alternative test of no transmission of the major effect also fit the data. In light of these contrasting results we are precluded from accepting with confidence the notion of a major gene influence on the atd angle. We have concluded that the accessory triradii a', d', and tt', and the atd angle are influenced by multifactorial effects, including additive polygenes and possible environmental factors, such as intrauterine effects.

The application of participatory ergonomics in a healthcare setting in Hong Kong.

PubMed

Lee, Edwin W C; Fok, Joan P C; Lam, Augustine T; Law, Rainbow K Y; Szeto, Grace P Y; Li, Philip P K

2014-01-01

Work-related musculoskeletal disorders (WRMDs) are recognized as a major source of significant pain and disability in the healthcare sector. However, they are preventable if appropriate surveillance and intervention programs are implemented. The purpose of this paper is to describe the holistic ergonomic approach that was used to address the multifactorial problems encountered by healthcare workers in their daily work. Using participatory ergonomics, healthcare workers in this study teamed up with management and staff with expertise in ergonomic analysis, design, and implementation of remedies. Selected participatory ergonomic intervention programs targeted at an organizational level are elaborated. Interventions included pre-work stretching, workplace surveillance at a psychiatric department, on-site ergonomic teaching for community nurses, and display screen equipment consultancy. Changes in workplace design, equipment re-arrangement, awareness of proper posture, and adoption of good work practices all play important roles in reducing musculoskeletal disorders among healthcare workers. Prompt occupational medicine and rehabilitation services were also provided to complement the work disability prevention process. The impact of the various intervention programs on staff health, costs and productivity of the organization are simultaneously discussed.

Decision aids to increase living donor kidney transplantation

PubMed Central

Gander, Jennifer C.; Gordon, Elisa J.; Patzer, Rachel E.

2017-01-01

Purpose of review For the more than 636,000 adults with end-stage renal disease (ESRD) in the U.S., kidney transplantation is the preferred treatment compared to dialysis. Living donor kidney transplantation (LDKT) comprised 31% of kidney transplantations in 2015, an 8% decrease since 2004. We aimed to summarize the current literature on decision aids that could be used to improve LDKT rates. Recent findings Decision aids are evidence-based tools designed to help patients and their families make difficult treatment decisions. LDKT decision aids can help ESRD patients, patients’ family and friends, and healthcare providers engage in treatment decisions and thereby overcome multifactorial LDKT barriers. Summary We identified 12 LDKT decision aids designed to provide information about LDKT, and/or to help ESRD patients identify potential living donors, and/or to help healthcare providers make decisions about treatment for ESRD or living donation. Of these, 4 were shown to be effective in increasing LDKT, donor inquiries, LDKT knowledge, and willingness to discuss LDKT. Although each LDKT decision aid has limitations, adherence to decision aid development guidelines may improve decision aid utilization and access to LDKT. PMID:29034143

Structure-Based Design and Optimization of Multitarget-Directed 2H-Chromen-2-one Derivatives as Potent Inhibitors of Monoamine Oxidase B and Cholinesterases.

PubMed

Farina, Roberta; Pisani, Leonardo; Catto, Marco; Nicolotti, Orazio; Gadaleta, Domenico; Denora, Nunzio; Soto-Otero, Ramon; Mendez-Alvarez, Estefania; Passos, Carolina S; Muncipinto, Giovanni; Altomare, Cosimo D; Nurisso, Alessandra; Carrupt, Pierre-Alain; Carotti, Angelo

2015-07-23

The multifactorial nature of Alzheimer's disease calls for the development of multitarget agents addressing key pathogenic processes. To this end, by following a docking-assisted hybridization strategy, a number of aminocoumarins were designed, prepared, and tested as monoamine oxidases (MAOs) and acetyl- and butyryl-cholinesterase (AChE and BChE) inhibitors. Highly flexible N-benzyl-N-alkyloxy coumarins 2-12 showed good inhibitory activities at MAO-B, AChE, and BChE but low selectivity. More rigid inhibitors, bearing meta- and para-xylyl linkers, displayed good inhibitory activities and high MAO-B selectivity. Compounds 21, 24, 37, and 39, the last two featuring an improved hydrophilic/lipophilic balance, exhibited excellent activity profiles with nanomolar inhibitory potency toward hMAO-B, high hMAO-B over hMAO-A selectivity and submicromolar potency at hAChE. Cell-based assays of BBB permeation, neurotoxicity, and neuroprotection supported the potential of compound 37 as a BBB-permeant neuroprotective agent against H2O2-induced oxidative stress with poor interaction as P-gp substrate and very low cytotoxicity.

Pathogenesis, Experimental Models and Contemporary Pharmacotherapy of Irritable Bowel Syndrome: Story About the Brain-Gut Axis

PubMed Central

Tsang, S.W.; Auyeung, K.K.W.; Bian, Z.X.; Ko, J.K.S.

2016-01-01

Background Although the precise pathophysiology of irritable bowel syndrome (IBS) remains unknown, it is generally considered to be a disorder of the brain-gut axis, representing the disruption of communication between the brain and the digestive system. The present review describes advances in understanding the pathophysiology and experimental approaches in studying IBS, as well as providing an update of the therapies targeting brain-gut axis in the treatment of the disease. Methods Causal factors of IBS are reviewed. Following this, the preclinical experimental models of IBS will be introduced. Besides, both current and future therapeutic approaches of IBS will be discussed. Results When signal of the brain-gut axis becomes misinterpreted, it may lead to dysregulation of both central and enteric nervous systems, altered intestinal motility, increased visceral sensitivity and consequently contributing to the development of IBS. Interference of the brain-gut axis can be modulated by various psychological and environmental factors. Although there is no existing animal experiment that can represent this complex multifactorial disease, these in vivo models are clinically relevant readouts of gastrointestinal functions being essential to the identification of effective treatments of IBS symptoms as well as their molecular targets. Understanding the brain-gut axis is essential in developing the effective therapy for IBS. Therapies include improvement of GI motor functions, relief of visceral hypersensitivity and pain, attenuation of autonomic dysfunctions and suppression of mucosal immune activation. Conclusion Target-oriented therapies that provide symptomatic, psychological and physiological benefits could surely help to improve the quality of life of IBS patients. PMID:27009115

Intrapopulation variability shaping isotope discrimination and turnover: experimental evidence in arctic foxes.

PubMed

Lecomte, Nicolas; Ahlstrøm, Oystein; Ehrich, Dorothée; Fuglei, Eva; Ims, Rolf A; Yoccoz, Nigel G

2011-01-01

Tissue-specific stable isotope signatures can provide insights into the trophic ecology of consumers and their roles in food webs. Two parameters are central for making valid inferences based on stable isotopes, isotopic discrimination (difference in isotopic ratio between consumer and its diet) and turnover time (renewal process of molecules in a given tissue usually measured when half of the tissue composition has changed). We investigated simultaneously the effects of age, sex, and diet types on the variation of discrimination and half-life in nitrogen and carbon stable isotopes (δ¹⁵N and δ¹³C, respectively) in five tissues (blood cells, plasma, muscle, liver, nail, and hair) of a top predator, the arctic fox Vulpes lagopus. We fed 40 farmed foxes (equal numbers of adults and yearlings of both sexes) with diet capturing the range of resources used by their wild counterparts. We found that, for a single species, six tissues, and three diet types, the range of discrimination values can be almost as large as what is known at the scale of the whole mammalian or avian class. Discrimination varied depending on sex, age, tissue, and diet types, ranging from 0.3‰ to 5.3‰ (mean  = 2.6‰) for δ¹⁵N and from 0.2‰ to 2.9‰ (mean  = 0.9‰) for δ¹³C. We also found an impact of population structure on δ¹⁵N half-life in blood cells. Varying across individuals, δ¹⁵N half-life in plasma (6 to 10 days) was also shorter than for δ¹³C (14 to 22 days), though δ¹⁵N and δ¹³C half-lives are usually considered as equal. Overall, our multi-factorial experiment revealed that at least six levels of isotopic variations could co-occur in the same population. Our experimental analysis provides a framework for quantifying multiple sources of variation in isotopic discrimination and half-life that needs to be taken into account when designing and analysing ecological field studies.

The Influence of Organic Material and Temperature on the Burial Tolerance of the Blue Mussel, Mytilus edulis: Considerations for the Management of Marine Aggregate Dredging

PubMed Central

Cottrell, Richard S.; Black, Kenny D.; Hutchison, Zoë L.; Last, Kim S.

2016-01-01

Rationale and Experimental Approach Aggregate dredging is a growing source of anthropogenic disturbance in coastal UK waters and has the potential to impact marine systems through the smothering of benthic fauna with organically loaded screening discards. This study investigates the tolerance of the blue mussel, Mytilus edulis to such episodic smothering events using a multi-factorial design, including organic matter concentration, temperature, sediment fraction size and duration of burial as important predictor variables. Results and Discussion Mussel mortality was significantly higher in organically loaded burials when compared to control sediments after just 2 days. Particularly, M. edulis specimens under burial in fine sediment with high (1%) concentrations of organic matter experienced a significantly higher mortality rate (p<0.01) than those under coarse control aggregates. Additionally, mussels exposed to the summer maximum temperature treatment (20°C) exhibited significantly increased mortality (p<0.01) compared to those in the ambient treatment group (15°C). Total Oxygen Uptake rates of experimental aggregates were greatest (112.7 mmol m-2 day-1) with 1% organic loadings in coarse sediment at 20°C. Elevated oxygen flux rates in porous coarse sediments are likely to be a function of increased vertical migration of anaerobically liberated sulphides to the sediment-water interface. However, survival of M. edulis under bacterial mats of Beggiatoa spp. indicates the species’ resilience to sulphides and so we propose that the presence of reactive organic matter within the burial medium may facilitate bacterial growth and increase mortality through pathogenic infection. This may be exacerbated under the stable interstitial conditions in fine sediment and increased bacterial metabolism under high temperatures. Furthermore, increased temperature may impose metabolic demands upon the mussel that cannot be met during burial-induced anaerobiosis. Summary Lack of consideration for the role of organic matter and temperature during sedimentation events may lead to an overestimation of the tolerance of benthic species to smothering from dredged material. PMID:26809153

Knowledge discovery and system biology in molecular medicine: an application on neurodegenerative diseases.

PubMed

Fattore, Matteo; Arrigo, Patrizio

2005-01-01

The possibility to study an organism in terms of system theory has been proposed in the past, but only the advancement of molecular biology techniques allow us to investigate the dynamical properties of a biological system in a more quantitative and rational way than before . These new techniques can gave only the basic level view of an organisms functionality. The comprehension of its dynamical behaviour depends on the possibility to perform a multiple level analysis. Functional genomics has stimulated the interest in the investigation the dynamical behaviour of an organism as a whole. These activities are commonly known as System Biology, and its interests ranges from molecules to organs. One of the more promising applications is the 'disease modeling'. The use of experimental models is a common procedure in pharmacological and clinical researches; today this approach is supported by 'in silico' predictive methods. This investigation can be improved by a combination of experimental and computational tools. The Machine Learning (ML) tools are able to process different heterogeneous data sources, taking into account this peculiarity, they could be fruitfully applied to support a multilevel data processing (molecular, cellular and morphological) that is the prerequisite for the formal model design; these techniques can allow us to extract the knowledge for mathematical model development. The aim of our work is the development and implementation of a system that combines ML and dynamical models simulations. The program is addressed to the virtual analysis of the pathways involved in neurodegenerative diseases. These pathologies are multifactorial diseases and the relevance of the different factors has not yet been well elucidated. This is a very complex task; in order to test the integrative approach our program has been limited to the analysis of the effects of a specific protein, the Cyclin dependent kinase 5 (CDK5) which relies on the induction of neuronal apoptosis. The system has a modular structure centred on a textual knowledge discovery approach. The text mining is the only way to enhance the capability to extract ,from multiple data sources, the information required for the dynamical simulator. The user may access the publically available modules through the following site: http://biocomp.ge.ismac.cnr.it.

Experimental studies on the nature of sensitive skin.

PubMed

Kligman, A M; Sadiq, Iqbal; Zhen, Yaxian; Crosby, Marilyn

2006-11-01

In the USA, Europe and Japan 40 to 50% of women report that they have sensitive skin, defined as abnormal sub-clinical sensory responses to drugs, cosmetics and toiletries in the absence of visible signs of irritation. Itching, burning, stinging and tightness are the commonest complaints, which mainly afflict women. Manufacturers of skin care products have made available a large variety of products which are designed for persons with sensitive skin. Such products are not required by regulatory agencies to submit evidence of safety and efficacy, allowing marketers to make claims that are often exaggerated, irrational and even preposterous. The consumer with self-assessed sensitive skin has no way of judging which products are likely to be most beneficial and least harmful. The marketplace is awash with products for which there is no evidence that the rosy claims have been substantiated by appropriate testing procedures. There is no internationally accepted consensus regarding the criteria which define sensitive skin. Many papers have been published in the last 15 years, mainly originating from industry, which express widely differing views regarding what constitutes sensitive skin. For some, any adverse reaction to a product topically applied to sensitive skin, including breakouts, redness, scaling etc., a panoply of adverse reactions which is virtually meaningless. Others include environmental factors as causative, including cold, dry wind, heat and high humidity, solar radiation, etc., which add to the manifest complexities of the subject. This is the first paper in a series which provides a comprehensive review of the subject, emphasizing the all too many controversies and confusions arising from the lack of a consensus regarding the identification, classification, epidemiology, prevalence and pathogenesis of sensitive skin. Sensitive skin is a biologic reality and not a psychological, fashionable fantasy on the part of impressionable women. There is an urgent necessity to establish rigorous methodologies for estimating the quality and severity of sensitive skin, a heterogeneous condition involving multi-factorial factors. Subsequent papers in this series will describe in detail the experimental approach our group has used to bring some clarity and credibility to this querulous, but important subject.

Phenotypic plasticity in a complex world: interactive effects of food and temperature on fitness components of a seed beetle.

PubMed

Stillwell, R Craig; Wallin, William G; Hitchcock, Lisa J; Fox, Charles W

2007-08-01

Most studies of phenotypic plasticity investigate the effects of an individual environmental factor on organism phenotypes. However, organisms exist in an ecologically complex world where multiple environmental factors can interact to affect growth, development and life histories. Here, using a multifactorial experimental design, we examine the separate and interactive effects of two environmental factors, rearing host species (Vigna radiata, Vigna angularis and Vigna unguiculata) and temperature (20, 25, 30 and 35 degrees C), on growth and life history traits in two populations [Burkina Faso (BF) and South India (SI)] of the seed beetle, Callosobruchus maculatus. The two study populations of beetles responded differently to both rearing host and temperature. We also found a significant interaction between rearing host and temperature for body size, growth rate and female lifetime fecundity but not larval development time or larval survivorship. The interaction was most apparent for growth rate; the variance in growth rate among hosts increased with increasing temperature. However, the details of host differences differed between our two study populations; the degree to which V. unguiculata was a better host than V. angularis or V. radiata increased at higher temperatures for BF beetles, whereas the degree to which V. unguiculata was the worst host increased at higher temperatures for SI beetles. We also found that the heritabilities of body mass, growth rate and fecundity were similar among rearing hosts and temperatures, and that the cross-temperature genetic correlation was not affected by rearing host, suggesting that genetic architecture is generally stable across rearing conditions. The most important finding of our study is that multiple environmental factors can interact to affect organism growth, but the degree of interaction, and thus the degree of complexity of phenotypic plasticity, varies among traits and between populations.

BEEHAVE: a systems model of honeybee colony dynamics and foraging to explore multifactorial causes of colony failure

PubMed Central

Becher, Matthias A; Grimm, Volker; Thorbek, Pernille; Horn, Juliane; Kennedy, Peter J; Osborne, Juliet L

2014-01-01

A notable increase in failure of managed European honeybee Apis mellifera L. colonies has been reported in various regions in recent years. Although the underlying causes remain unclear, it is likely that a combination of stressors act together, particularly varroa mites and other pathogens, forage availability and potentially pesticides. It is experimentally challenging to address causality at the colony scale when multiple factors interact. In silico experiments offer a fast and cost-effective way to begin to address these challenges and inform experiments. However, none of the published bee models combine colony dynamics with foraging patterns and varroa dynamics. We have developed a honeybee model, BEEHAVE, which integrates colony dynamics, population dynamics of the varroa mite, epidemiology of varroa-transmitted viruses and allows foragers in an agent-based foraging model to collect food from a representation of a spatially explicit landscape. We describe the model, which is freely available online (www.beehave-model.net). Extensive sensitivity analyses and tests illustrate the model's robustness and realism. Simulation experiments with various combinations of stressors demonstrate, in simplified landscape settings, the model's potential: predicting colony dynamics and potential losses with and without varroa mites under different foraging conditions and under pesticide application. We also show how mitigation measures can be tested. Synthesis and applications. BEEHAVE offers a valuable tool for researchers to design and focus field experiments, for regulators to explore the relative importance of stressors to devise management and policy advice and for beekeepers to understand and predict varroa dynamics and effects of management interventions. We expect that scientists and stakeholders will find a variety of applications for BEEHAVE, stimulating further model development and the possible inclusion of other stressors of potential importance to honeybee colony dynamics. PMID:25598549

BEEHAVE: a systems model of honeybee colony dynamics and foraging to explore multifactorial causes of colony failure.

PubMed

Becher, Matthias A; Grimm, Volker; Thorbek, Pernille; Horn, Juliane; Kennedy, Peter J; Osborne, Juliet L

2014-04-01

A notable increase in failure of managed European honeybee Apis mellifera L. colonies has been reported in various regions in recent years. Although the underlying causes remain unclear, it is likely that a combination of stressors act together, particularly varroa mites and other pathogens, forage availability and potentially pesticides. It is experimentally challenging to address causality at the colony scale when multiple factors interact. In silico experiments offer a fast and cost-effective way to begin to address these challenges and inform experiments. However, none of the published bee models combine colony dynamics with foraging patterns and varroa dynamics.We have developed a honeybee model, BEEHAVE, which integrates colony dynamics, population dynamics of the varroa mite, epidemiology of varroa-transmitted viruses and allows foragers in an agent-based foraging model to collect food from a representation of a spatially explicit landscape.We describe the model, which is freely available online (www.beehave-model.net). Extensive sensitivity analyses and tests illustrate the model's robustness and realism. Simulation experiments with various combinations of stressors demonstrate, in simplified landscape settings, the model's potential: predicting colony dynamics and potential losses with and without varroa mites under different foraging conditions and under pesticide application. We also show how mitigation measures can be tested. Synthesis and applications . BEEHAVE offers a valuable tool for researchers to design and focus field experiments, for regulators to explore the relative importance of stressors to devise management and policy advice and for beekeepers to understand and predict varroa dynamics and effects of management interventions. We expect that scientists and stakeholders will find a variety of applications for BEEHAVE, stimulating further model development and the possible inclusion of other stressors of potential importance to honeybee colony dynamics.

R516Q mutation in Melanoma differentiation-associated protein 5 (MDA5) and its pathogenic role towards rare Singleton-Merten syndrome; a signature associated molecular dynamics study.

PubMed

Raghuraman, P; Sudandiradoss, C

2018-02-20

Singleton-Merten syndrome, a critical and rare multifactorial disorder that is closely linked to R516Q mutation in MDA5 protein associated with an enhanced interferon response in the affected individual. In the present study, we provide conclusive key evidence on R516Q mutation and their connectivity towards sequence-structural basis dysfunction of MDA5 protein. Among the various mutations, we found R516Q is the most pathogenic mutation based on mutational signature Q-A-[RE]-G-R-[GA]-R-A-[ED]-[DE]-S-[ST]-Y-[TSAV]-L-V designed from our work. Further, we derived a distant ortholog for this mutational signature from which we identified 343 intra-residue interactions that fall communally in the position required to maintain the structural and functional integration of protein architecture. This identification served us to understand the critical role of hot spots in residual aggregation that holds a native form of folding conformation in the functional region. In addition, the long-range molecular dynamics simulation demarcated the residual dependencies of conformational transition in distinct regions ( L29 360-370 α18 , α19 380-410 L31 , α21 430-480 L33-α22-L35 and α24 510-520 L38 ) occurring upon R516Q mutation. Together, our results emphasise that the dislocation of functional hot spots Pro229, Arg414, Val498, Met510, Ala513, Gly515 and Arg516 in MDA5 protein which is important for interior structural packing and fold arrangements. In a nutshell, our findings are perfectly conceded with other experimental reports and will have potential implications in immune therapeutical advancement for rare singleton-merten syndrome.

Brief ethanol exposure and stress-related factors disorganize neonatal breathing plasticity during the brain growth spurt period in the rat.

PubMed

Macchione, A F; Anunziata, F; Haymal, B O; Abate, P; Molina, J C

2018-04-01

The effects of early ethanol exposure upon neonatal respiratory plasticity have received progressive attention given a multifactorial perspective related with sudden infant death syndrome or hypoxia-associated syndromes. The present preclinical study was performed in 3-9-day-old pups, a stage in development characterized by a brain growth spurt that partially overlaps with the 3rd human gestational trimester. Breathing frequencies and apneas were examined in pups receiving vehicle or a relatively moderate ethanol dose (2.0 g/kg) utilizing a whole body plethysmograph. The experimental design also considered possible associations between drug administration stress and exteroceptive cues (plethysmographic context or an artificial odor). Ethanol exposure progressively exerted a detrimental effect upon breathing frequencies. A test conducted at PD9 when pups were under the state of sobriety confirmed ethanol's detrimental effects upon respiratory plasticity (breathing depression). Pre-exposure to the drug also resulted in a highly disorganized respiratory response following a hypoxic event, i.e., heightened apneic episodes. Associative processes involving drug administration procedures and placement in the plethysmographic context also affected respiratory plasticity. Pups that experienced intragastric administrations in close temporal contiguity with such a context showed diminished hyperventilation during hypoxia. In a 2nd test conducted at PD9 while pups were intoxicated and undergoing hypoxia, an attenuated hyperventilatory response was observed. In this test, there were also indications that prior ethanol exposure depressed breathing frequencies during hypoxia and a recovery normoxia phase. As a whole, the results demonstrated that brief ethanol experience and stress-related factors significantly disorganize respiratory patterns as well as arousal responses linked to hypoxia in neonatal rats.

Neuropharmacological Properties of Withania somnifera - Indian Ginseng: An Overview on Experimental Evidence with Emphasis on Clinical Trials and Patents.

PubMed

Yenisetti, Sarat C; Manjunath, M J; Muralidhara, C

2016-01-01

Owing to the increasing aged population globally, disorders and diseases of the CNS are anticipated to increase and profoundly impact the health care. As these neurodegenerative diseases (NDD) are complex, multifactorial and do not have identified etiological factors, unfortunately, drugs developed for the purpose have not met with the expected success. Hence, there has been a constant demand for the development of natural therapeutic adjuvants which are safe and possess the potential to attenuate multiple pathways. Numerous herbal/natural products have been used as therapeutics in Ayurvedic system of medicine to treat NDD and other memory-related disorders. Withania somnifera (Ashwagandha, WS), popularly called as "Indian Ginseng" is one such plant which possesses a variety of beneficial neuropharmacological properties. In this review, we have attempted to review critically the existing literature and patents related to the neuroprotective efficacy of WS roots and the underlying mechanism/s. Standardized extracts of Withania somnifera (WS) have been demonstrated to possess multidimensional neuromodulatory effects both in vitro and animal models. The spectrum of effects evidenced comprises of attenuation of oxidative damage by enhancing the antioxidant defense system with concomitant enhancement of the expression of marker proteins responsible for growth, differentiation and communication of neural cells. Specific effects of WS are attributable to its potential to modulate neurotrophic factors, cytoskeletal elements, cell adhesion molecules and synaptic proteins. Generation of new data by employing systematic contemporary approaches such as bioinformatics, molecular docking studies, identification of specific gene targets and epigenetic regulation would provide the necessary impetus to validate fully the neurotherapeutic potential of the phytochemicals derived from WS. More importantly, well-designed clinical trials are required to exploit the neuromodulatory propensity of WS extract/bioactives in specific neurodegenerative diseases such as AD and PD.

Development of a Model for Measuring Scientific Processing Skills Based on Brain-Imaging Technology: Focused on the Experimental Design Process

ERIC Educational Resources Information Center

Lee, Il-Sun; Byeon, Jung-Ho; Kim, Young-shin; Kwon, Yong-Ju

2014-01-01

The purpose of this study was to develop a model for measuring experimental design ability based on functional magnetic resonance imaging (fMRI) during biological inquiry. More specifically, the researchers developed an experimental design task that measures experimental design ability. Using the developed experimental design task, they measured…

Genetics Home Reference: esophageal atresia/tracheoesophageal fistula

MedlinePlus

... are some genetic conditions more common in particular ethnic groups? Genetic Changes Isolated EA/TEF is considered to be a multifactorial condition, which means that multiple gene variations and environmental factors likely contribute to its occurrence. ...

Neurovascular unit dysfunction with blood-brain barrier hyperpermeability contributes to major depressive disorder: a review of clinical and experimental evidence

PubMed Central

2013-01-01

About one-third of people with major depressive disorder (MDD) fail at least two antidepressant drug trials at 1 year. Together with clinical and experimental evidence indicating that the pathophysiology of MDD is multifactorial, this observation underscores the importance of elucidating mechanisms beyond monoaminergic dysregulation that can contribute to the genesis and persistence of MDD. Oxidative stress and neuroinflammation are mechanistically linked to the presence of neurovascular dysfunction with blood-brain barrier (BBB) hyperpermeability in selected neurological disorders, such as stroke, epilepsy, multiple sclerosis, traumatic brain injury, and Alzheimer’s disease. In contrast to other major psychiatric disorders, MDD is frequently comorbid with such neurological disorders and constitutes an independent risk factor for morbidity and mortality in disorders characterized by vascular endothelial dysfunction (cardiovascular disease and diabetes mellitus). Oxidative stress and neuroinflammation are implicated in the neurobiology of MDD. More recent evidence links neurovascular dysfunction with BBB hyperpermeability to MDD without neurological comorbidity. We review this emerging literature and present a theoretical integration between these abnormalities to those involving oxidative stress and neuroinflammation in MDD. We discuss our hypothesis that alterations in endothelial nitric oxide levels and endothelial nitric oxide synthase uncoupling are central mechanistic links in this regard. Understanding the contribution of neurovascular dysfunction with BBB hyperpermeability to the pathophysiology of MDD may help to identify novel therapeutic and preventative approaches. PMID:24289502

Antioxidants in experimental ischemia-reperfusion injury of the testis: Where are we heading towards?

PubMed Central

Vaos, George; Zavras, Nick

2017-01-01

Testicular torsion (TT) is a medical emergency that primary affects newborns and young adolescents. It causes testicular injury due to the torsion of the spermatic cord and its components, initially in the venous blood flow and finally in the arterial blood flow. Prompt diagnosis and early surgical management are necessary in managing this urgent situation. The process of the pathophysiological events in ischemia-reperfusion is multifactorial and deals with the perception of the oxidative stress responsible for the consequences of ischemia/reperfusion (I/R) stress following TT. Duration and severity of torsion also play a significant role in the oxidative stress. A detrimental result of the defense system of the testes takes place resulting finally in testicular atrophy and impaired function. Antioxidant factors have been experimentally studied in an effort to front this state. They have been classified as endogenous or exogenous antioxidants. Endogenous antioxidants comprise a structure of enzymic enzymatic and non-enzymic enzymatic particles presented within cytoplasm and numerous other subunits in the cells. Exogenous antioxidants include a variety of natural and pharmaceutical agents that may prevent or ameliorate the harmful effects of I/R injury. In this study we review those factors and their ability to enhance the oxidative status of the testis. A feature insight into where we are heading is attempted. PMID:28706858

Metabolomics and In-Silico Analysis Reveal Critical Energy Deregulations in Animal Models of Parkinson’s Disease

PubMed Central

Poliquin, Pierre O.; Chen, Jingkui; Cloutier, Mathieu; Trudeau, Louis-Éric; Jolicoeur, Mario

2013-01-01

Parkinson’s disease (PD) is a multifactorial disease known to result from a variety of factors. Although age is the principal risk factor, other etiological mechanisms have been identified, including gene mutations and exposure to toxins. Deregulation of energy metabolism, mostly through the loss of complex I efficiency, is involved in disease progression in both the genetic and sporadic forms of the disease. In this study, we investigated energy deregulation in the cerebral tissue of animal models (genetic and toxin induced) of PD using an approach that combines metabolomics and mathematical modelling. In a first step, quantitative measurements of energy-related metabolites in mouse brain slices revealed most affected pathways. A genetic model of PD, the Park2 knockout, was compared to the effect of CCCP, a complex I blocker. Model simulated and experimental results revealed a significant and sustained decrease in ATP after CCCP exposure, but not in the genetic mice model. In support to data analysis, a mathematical model of the relevant metabolic pathways was developed and calibrated onto experimental data. In this work, we show that a short-term stress response in nucleotide scavenging is most probably induced by the toxin exposure. In turn, the robustness of energy-related pathways in the model explains how genetic perturbations, at least in young animals, are not sufficient to induce significant changes at the metabolite level. PMID:23935941

In Silico Identification and Experimental Validation of Novel Anti-Alzheimer's Multitargeted Ligands from a Marine Source Featuring a "2-Aminoimidazole plus Aromatic Group" Scaffold.

PubMed

Vitale, Rosa Maria; Rispoli, Vincenzo; Desiderio, Doriana; Sgammato, Roberta; Thellung, Stefano; Canale, Claudio; Vassalli, Massimo; Carbone, Marianna; Ciavatta, Maria Letizia; Mollo, Ernesto; Felicità, Vera; Arcone, Rosaria; Gavagnin Capoggiani, Margherita; Masullo, Mariorosario; Florio, Tullio; Amodeo, Pietro

2018-03-07

Multitargeting or polypharmacological approaches, looking for single chemical entities retaining the ability to bind two or more molecular targets, are a potentially powerful strategy to fight complex, multifactorial pathologies. Unfortunately, the search for multiligand agents is challenging because only a small subset of molecules contained in molecular databases are bioactive and even fewer are active on a preselected set of multiple targets. However, collections of natural compounds feature a significantly higher fraction of bioactive molecules than synthetic ones. In this view, we searched our library of 1175 natural compounds from marine sources for molecules including a 2-aminoimidazole+aromatic group motif, found in known compounds active on single relevant targets for Alzheimer's disease (AD). This identified two molecules, a pseudozoanthoxanthin (1) and a bromo-pyrrole alkaloid (2), which were predicted by a computational approach to possess interesting multitarget profiles on AD target proteins. Biochemical assays experimentally confirmed their biological activities. The two compounds inhibit acetylcholinesterase, butyrylcholinesterase, and β-secretase enzymes in high- to sub-micromolar range. They are also able to prevent and revert β-amyloid (Aβ) aggregation of both Aβ 1-40 and Aβ 1-42 peptides, with 1 being more active than 2. Preliminary in vivo studies suggest that compound 1 is able to restore cholinergic cortico-hippocampal functional connectivity.

Gene therapy in liver diseases: state-of-the-art and future perspectives.

PubMed

Domvri, Kalliopi; Zarogoulidis, Paul; Porpodis, Konstantinos; Koffa, Maria; Lambropoulou, Maria; Kakolyris, Stylianos; Kolios, George; Zarogoulidis, Konstantinos; Chatzaki, Ekaterini

2012-12-01

Gene therapy is a fundamentally novel therapeutic approach that involves introducing genetic material into target cells in order to fight or prevent disease. A number of different strategies of gene therapy are tested at experimental and clinical levels, including: a) replacing a mutated gene that causes disease with a healthy copy of the gene, b) inactivating a mutated gene that its improper function causes pathogenesis, c) introducing a new gene coding a therapeutic compound to fight a disease, d) introducing to the target organ an enzyme converting an inactive pro-drug to its cytotoxic metabolite. In gene therapy, the transcriptional machinery of the patient is used to produce the active factor that exerts the intended therapeutic effect, ideally in a permanent, tissue-specific and manageable way. The liver is a major target for gene therapy, presenting inherited metabolic defects of single-gene etiology, but also severe multifactorial pathologies with limited therapeutic options such as hepatocellular carcinoma. The initial promising results from gene therapy strategies in liver diseases were followed by skepticism on the actual clinical value due to specificity, efficacy, toxicity and immune limitations, but are recently re-evaluated due to progress in vector technology and monitoring techniques. The significant amount of experimental data along with the available information from clinical trials are systematically reviewed here and presented per pathological entity. Finally, future perspectives of gene therapy protocols in hepatology are summarized.

Quasi-Experimental Designs for Causal Inference

ERIC Educational Resources Information Center

Kim, Yongnam; Steiner, Peter

2016-01-01

When randomized experiments are infeasible, quasi-experimental designs can be exploited to evaluate causal treatment effects. The strongest quasi-experimental designs for causal inference are regression discontinuity designs, instrumental variable designs, matching and propensity score designs, and comparative interrupted time series designs. This…

Design and Implementation of the International Genetics and Translational Research in Transplantation Network.

PubMed

2015-11-01

Genetic association studies of transplantation outcomes have been hampered by small samples and highly complex multifactorial phenotypes, hindering investigations of the genetic architecture of a range of comorbidities which significantly impact graft and recipient life expectancy. We describe here the rationale and design of the International Genetics & Translational Research in Transplantation Network. The network comprises 22 studies to date, including 16494 transplant recipients and 11669 donors, of whom more than 5000 are of non-European ancestry, all of whom have existing genomewide genotype data sets. We describe the rich genetic and phenotypic information available in this consortium comprising heart, kidney, liver, and lung transplant cohorts. We demonstrate significant power in International Genetics & Translational Research in Transplantation Network to detect main effect association signals across regions such as the MHC region as well as genomewide for transplant outcomes that span all solid organs, such as graft survival, acute rejection, new onset of diabetes after transplantation, and for delayed graft function in kidney only. This consortium is designed and statistically powered to deliver pioneering insights into the genetic architecture of transplant-related outcomes across a range of different solid-organ transplant studies. The study design allows a spectrum of analyses to be performed including recipient-only analyses, donor-recipient HLA mismatches with focus on loss-of-function variants and nonsynonymous single nucleotide polymorphisms.

Epigenetics and cardiovascular disease

USDA-ARS?s Scientific Manuscript database

Despite advances in the prevention and management of cardiovascular disease (CVD), this group of multifactorial disorders remains a leading cause of mortality worldwide. CVD is associated with multiple genetic and modifiable risk factors; however, known environmental and genetic influences can only...

Factorials of real negative and imaginary numbers - A new perspective.

PubMed

Thukral, Ashwani K

2014-01-01

Presently, factorials of real negative numbers and imaginary numbers, except for zero and negative integers are interpolated using the Euler's gamma function. In the present paper, the concept of factorials has been generalised as applicable to real and imaginary numbers, and multifactorials. New functions based on Euler's factorial function have been proposed for the factorials of real negative and imaginary numbers. As per the present concept, the factorials of real negative numbers, are complex numbers. The factorials of real negative integers have their imaginary part equal to zero, thus are real numbers. Similarly, the factorials of imaginary numbers are complex numbers. The moduli of the complex factorials of real negative numbers, and imaginary numbers are equal to their respective real positive number factorials. Fractional factorials and multifactorials have been defined in a new perspective. The proposed concept has also been extended to Euler's gamma function for real negative numbers and imaginary numbers, and beta function.

[Acute inpatient conservative multimodal treatment of complex and multifactorial orthopedic diseases in the ANOA concept].

PubMed

Psczolla, M

2013-10-01

In Germany there is a clear deficit in the non-operative treatment of chronic and complex diseases and pain disorders in acute care hospitals. Only about 20 % of the treatments are carried out in orthopedic hospitals. Hospitals specialized in manual medicine have therefore formed a working group on non-operative orthopedic manual medicine acute care clinics (ANOA). The ANOA has developed a multimodal assessment procedure called the OPS 8-977 which describes the structure and process quality of multimodal and interdisciplinary diagnosis and treatment of the musculoskeletal system. Patients are treated according to clinical pathways oriented on the clinical findings. The increased duration of treatment in the German diagnosis-related groups (DRG) system is compensated for with a supplemental remuneration. Thus, complex and multifactorial orthopedic diseases and pain disorders are conservatively and appropriately treated as inpatient departments of acute care hospitals.

A More Rigorous Quasi-Experimental Alternative to the One-Group Pretest-Posttest Design.

ERIC Educational Resources Information Center

Johnson, Craig W.

1986-01-01

A simple quasi-experimental design is described which may have utility in a variety of applied and laboratory research settings where ordinarily the one-group pretest-posttest pre-experimental design might otherwise be the procedure of choice. The design approaches the internal validity of true experimental designs while optimizing external…

Preparation and evaluation of novel metronidazole sustained release and floating matrix tablets.

PubMed

Asnaashari, Solmaz; Khoei, Nazaninossadat Seyed; Zarrintan, Mohammad Hosein; Adibkia, Khosro; Javadzadeh, Yousef

2011-08-01

In the present study, metronidazole was used for preparing floating dosage forms that are designed to retain in the stomach for a long time and have developed as a drug delivery system for better eradication of Helicobacter Pylori in peptic ulcer diseases. For this means, various formulations were designed using multi-factorial design. HPMC, psyllium and carbopol in different concentrations were used as floating agents, and sodium bicarbonate was added as a gas-forming agent. Hardness, friability, drug loading, floating ability and release profiles as well as kinetics of release were assessed. Formulations containing HPMC as filler showed prolonged lag times for buoyancy. Adding psyllium to these formulations had reduced relative lag times. Overall, selected formulations were able to float immediately and showed buoyancy for at least 8?h. Meanwhile, sustained profiles of drug release were also obtained. Kinetically, among the 10 assessed models, the release pattern of metronidazole from the tablets fitted best to Power law, Weibull and Higuchi models in respect overall to mean percentage error values of 3.8, 4.73 and 5.77, respectively, for calcium carbonate-based tablets and, 2.95, 6.39 and 3.9, respectively, for calcium silicate-based tablets. In general, these systems can float in the gastric condition and control the drug release from the tablets.

Review: Factors affecting fouling in conventional pens for slaughter pigs.

PubMed

Larsen, M L V; Bertelsen, M; Pedersen, L J

2018-02-01

This review assesses factors affecting fouling in conventional pens for slaughter pigs. Fouling of the pen happens when pigs change their excretory behaviour from occurring in the designated dunging area to the lying area. This can result in a lower hygiene, bad air quality, extra work for the farmer, disturbance of the pigs' resting behaviour and an increase in agonistic interactions. A systematic search was conducted and results narrowed down to 21 articles. Four factors were found to affect fouling directly: insufficient space allowance, the flooring design of the pen, the thermal climate and pigs' earlier experience. Further, these primary factors are affected by secondary factors such as the shape of the pen, the weight of the pigs and especially the heat balance of the pigs, which is affected by several tertiary factors including, for example, temperature, humidity and draught. Results indicate that the most important factor to control when trying to prevent fouling of a pen is the pen climate. An appropriate climate may be accomplished through floor cooling in the designated lying area, sprinklers above the designated dunging area and by ensuring a more optimal ambient temperature curve that also fits the weight of the pigs in different stages of the production. All in all, fouling of the pen in conventional slaughter pigs is a multifactorial problem, but it is important to focus on increasing the comfortability, and especially the climate, of the designated lying area.

Elements that contribute to healthy building design.

PubMed

Loftness, Vivian; Hakkinen, Bert; Adan, Olaf; Nevalainen, Aino

2007-06-01

The elements that contribute to a healthy building are multifactorial and can be discussed from different perspectives. WE PRESENT THREE VIEWPOINTS OF DESIGNING A HEALTHY BUILDING: the importance of sustainable development, the role of occupants for ensuring indoor air quality, and ongoing developments related to indoor finishes with low chemical emissions and good fungal resistance. Sustainable design rediscovers the social, environmental, and technical values of pedestrian and mixed-use communities, using existing infrastructures including "main streets" and small-town planning principles and recapturing indoor-outdoor relationships. This type of design introduces nonpolluting materials and assemblies with lower energy requirements and higher durability and recyclability. Building occupants play a major role in maintaining healthy indoor environments, especially in residences. Contributors to indoor air quality include cleaning habits and other behaviors; consumer products, furnishings, and appliances purchases, as well as where and how the occupants use them. Certification of consumer products and building materials as low-emitting products is a primary control measure for achieving good indoor air quality. Key products in this respect are office furniture, flooring, paints and coatings, adhesives and sealants, wall coverings, wood products, textiles, insulation, and cleaning products. Finishing materials play a major role in the quality of indoor air as related to moisture retention and mold growth. Sustainable design emphasizes the needs of infrastructure, lower energy consumption, durability, and recyclability. To ensure good indoor air quality, the product development for household use should aim to reduce material susceptibility to contaminants such as mold and should adopt consumer-oriented product labeling.

Approaches and advances in the genetic causes of autoimmune disease and their implications.

PubMed

Inshaw, Jamie R J; Cutler, Antony J; Burren, Oliver S; Stefana, M Irina; Todd, John A

2018-06-20

Genome-wide association studies are transformative in revealing the polygenetic basis of common diseases, with autoimmune diseases leading the charge. Although the field is just over 10 years old, advances in understanding the underlying mechanistic pathways of these conditions, which result from a dense multifactorial blend of genetic, developmental and environmental factors, have already been informative, including insights into therapeutic possibilities. Nevertheless, the challenge of identifying the actual causal genes and pathways and their biological effects on altering disease risk remains for many identified susceptibility regions. It is this fundamental knowledge that will underpin the revolution in patient stratification, the discovery of therapeutic targets and clinical trial design in the next 20 years. Here we outline recent advances in analytical and phenotyping approaches and the emergence of large cohorts with standardized gene-expression data and other phenotypic data that are fueling a bounty of discovery and improved understanding of human physiology.

The Influence of Nurse Manager Leadership Style on Staff Nurse Work Engagement.

PubMed

Manning, Jennifer

2016-09-01

Nursing literature supports the importance of an engaged nursing workforce as a means to positively influence performance. Nurse manager leadership style plays a critical role in engaging staff nurses. These relationships have been minimally studied in nurse managers and staff nurses. The aim of this study is to evaluate the influence of nurse manager leadership style factors on staff nurse work engagement. Using a descriptive correlational research design, 441 staff nurses working in 3 acute care hospitals were surveyed. Survey instruments included the Utrecht Work Engagement Scale and the Multifactorial Leadership Questionnaire 5X short form. Transactional and transformational leadership styles in nurse managers positively influenced staff nurse work engagement. Passive-avoidant leadership style in nurse managers negatively influenced staff nurse work engagement. Nurse managers who provide support and communication through transformational and transactional leadership styles can have a positive impact on staff nurse work engagement and ultimately improve organizational outcomes.

(-)-Meptazinol-melatonin hybrids as novel dual inhibitors of cholinesterases and amyloid-β aggregation with high antioxidant potency for Alzheimer's therapy.

PubMed

Cheng, Shaobing; Zheng, Wei; Gong, Ping; Zhou, Qiang; Xie, Qiong; Yu, Lining; Zhang, Peiyi; Chen, Liangkang; Li, Juan; Chen, Jianxing; Chen, Hailin; Chen, Hongzhuan

2015-07-01

The multifactorial pathogenesis of Alzheimer's disease (AD) implicates that multi-target-directed ligands (MTDLs) intervention may represent a promising therapy for AD. Amyloid-β (Aβ) aggregation and oxidative stress, two prominent neuropathological hallmarks in patients, play crucial roles in the neurotoxic cascade of this disease. In the present study, a series of novel (-)-meptazinol-melatonin hybrids were designed, synthesized and biologically characterized as potential MTDLs against AD. Among them, hybrids 7-7c displayed higher dual inhibitory potency toward cholinesterases (ChEs) and better oxygen radical absorbance capacity (ORAC) than the parental drugs. Furthermore, compound 7c could effectively inhibit Aβ self-aggregation, showed favorable safety and the blood-brain barrier (BBB) permeability. Therefore, 7c may serve as a valuable candidate that is worthy of further investigations in the treatment of AD. Copyright © 2015 Elsevier Ltd. All rights reserved.

We Have Enough Information to Act.

PubMed

Shapiro, Jo

2018-06-01

Evidence clearly indicates that physicians are suffering. This is harming our profession, our colleagues, other health care team members, and sometimes our patients. There are efforts nationally and internationally to explore ways of promoting wellness and decreasing the high levels of burnout among physicians. While promoting wellness is a complex challenge, and the solutions will need to be multifactorial, the literature suggests that the most effective interventions are organizational. Instead of putting the burden solely on us as individuals to be able to cope with challenging environments, we should be working toward improving the culture and processes in the workplace. Some technical solutions will be needed, but the challenges will also require adaptive solutions that address issues of trust and support. Our Center for Professionalism and Peer Support offers organizational initiatives designed to foster a culture of trust and respect through professionalism, conflict management, peer support, and disclosure coaching programs.

Promoting healthful diet and physical activity in the Mexican school system for the prevention of obesity in children.

PubMed

Safdie, Margarita; Lévesque, Lucie; González-Casanova, Inés; Salvo, Deborah; Islas, Ana; Hernández-Cordero, Sonia; Bonvecchio, Anabelle; Rivera, Juan A

2013-01-01

This paper describes the rationale, design, and methods of a two-year randomized controlled trial conducted to evaluate the effectiveness of an environmental intervention in 27 elementary schools in Mexico City. There were two units of analysis, school level addressing changes in elementary public part-time schools, and individual-level addressing behavioral changes in students 9 to 11 years of age. Two intensities of an intervention program were implemented (basic and plus), each containing two intervention components: physical activity and nutrition, supported by a communication/education component. Evaluation of the intervention was carried out during the school cycles 2006-2007 and 2007-2008. Primary outcomes were overweight and obesity prevalence and fitness; environmental and behavioural measures were also examined. This is the first institutional multilevel, multifactorial project, consistent with the best practices available in current literature, carried out in Mexico to prevent childhood obesity in schools.

Genetic variants influencing effectiveness of weight loss strategies.

PubMed

Deram, Sophie; Villares, Sandra M F

2009-03-01

Body weight excess has an increasingly high prevalence in the world. Obesity is a complex disease of multifactorial origin with a polygenic condition affected by environmental factors. Weight loss is a primary strategy to treat obesity and its morbidities. Weight changes through life depend on the interaction of environmental, behavioral and genetic factors. Interindividual variation of weight loss in response to different types of interventions (behavioral, caloric restriction, exercise, drug or surgery) has been observed. In this article, currently available data on the role of candidate gene polymorphisms in weight loss are reviewed. Even though control of weight loss by genotype was described in twin and family studies, it is premature to recommend use of genotyping in the design of therapeutic diets or drug treatment. Future studies will have to be large in order to assess the effects of multiple polymorphisms, and will have to control factors other than diet.

Amplifying Health Through Community Gardens: A Framework for Advancing Multicomponent, Behaviorally Based Neighborhood Interventions.

PubMed

Alaimo, Katherine; Beavers, Alyssa W; Crawford, Caroline; Snyder, Elizabeth Hodges; Litt, Jill S

2016-09-01

The article presents a framework for understanding the relationship between community garden participation, and the myriad ways gardens and participation lead to emotional, social, and health impacts. Existing empirical research relating community gardens to health behaviors, such as physical activity and diet, and longer-term chronic disease-related outcomes is summarized. The research areas discussed include the effects of community garden participation on individual, social, emotional, and environmental processes; health behaviors including diet and physical activity; and health outcomes such as self-rated health, obesity, and mental health. Other mechanisms through which community gardens may affect population health are described. Applying a multitheoretical lens to explore associations between community garden participation and health enables us to delineate key aspects of gardening that elicit positive health behaviors and multifactorial health assets that could be applied to designing other types of health interventions.

Factors related to drug approvals: predictors of outcome?

PubMed

Liberti, Lawrence; Breckenridge, Alasdair; Hoekman, Jarno; McAuslane, Neil; Stolk, Pieter; Leufkens, Hubert

2017-06-01

There is growing interest in characterising factors associated with positive regulatory outcomes for drug marketing authorisations. We assessed empirical studies published over the past 15 years seeking to identify predictive factors. Factors were classified to one of four 'factor clusters': evidentiary support; product or indication characteristics; company experience or strategy; social and regulatory factors. We observed a heterogeneous mix of technical factors (e.g., study designs, clinical evidence of efficacy) and less studied social factors (e.g., company-regulator interactions). We confirmed factors known to be of relevance to drug approval decisions (imperative) and a cohort of less understood (compensatory) social factors. Having robust supportive clinical evidence, addressing rare or serious illness, following scientific advice and prior company experience were associated with positive outcomes, which illustrated the multifactorial nature of regulatory decision making and factors need to be considered holistically while having varying, context-dependent importance. Copyright © 2017 Elsevier Ltd. All rights reserved.

Full-mouth composite rehabilitation of a mixed erosion and attrition patient: a case report with v-shaped veneers and ultra-thin CAD/CAM composite overlays.

PubMed

Bahillo, Jose; Jané, Luis; Bortolotto, Tissiana; Krejci, Ivo; Roig, Miguel

2014-10-01

Loss of tooth substance has become a common pathology in modern society. It is of multifactorial origin, may be induced by a chemical process or by excessive attrition, and frequently has a combined etiology. Particular care should be taken when diagnosing the cause of dental tissue loss, in order to minimize its impact. Several publications have proposed the use of minimally invasive procedures to treat such patients in preference to traditional full-crown rehabilitation. The use of composite resins, in combination with improvements in dental adhesion, allows a more conservative approach. In this paper, we describe the step-by-step procedure of full-mouth composite rehabilitation with v-shaped veneers and ultra-thin computer-aided design/computer-assisted manufacture (CAD/CAM)- generated composite overlays in a young patient with a combination of erosion and attrition disorder.

Cost-effectiveness analysis of a multifactorial fall prevention intervention in older home care clients at risk for falling.

PubMed

Isaranuwatchai, Wanrudee; Perdrizet, Johnna; Markle-Reid, Maureen; Hoch, Jeffrey S

2017-09-01

Falls among older adults can cause serious morbidity and pose economic burdens on society. Older age is a known risk factor for falls and age has been shown to influence the effectiveness of fall prevention programs. To our knowledge, no studies have explicitly investigated whether cost-effectiveness of a multifactorial fall prevention intervention (the intervention) is influenced by age. This economic evaluation explores: 1) the cost-effectiveness of a multifactorial fall prevention intervention compared to usual care for community-dwelling adults ≥ 75 years at risk of falling in Canada; and 2) the influence of age on the cost-effectiveness of the intervention. Net benefit regression was used to examine the cost-effectiveness of the intervention with willingness-to-pay values ranging from $0-$50,000. Effects were measured as change in the number of falls, from baseline to 6-month follow-up. Costs were measured using a societal perspective. The cost-effectiveness analysis was conducted for both the total sample and by age subgroups (75-84 and 85+ years). For the total sample, the intervention was not economically attractive. However, the intervention was cost-effective at higher willingness-to-pay (WTP) (≥ $25,000) for adults 75-84 years and at lower WTP (< $5,000) for adults 85+ years. The cost-effectiveness of the intervention depends on age and decision makers' WTP to prevent falls. Understanding the influence of age on the cost-effectiveness of an intervention may help to target resources to those who benefit most. Retrospectively registered. Clinicaltrials.gov identifier: NCT00463658 (18 April 2007).

Issues in Personality Conceptualizations of Addictive Behaviors.

ERIC Educational Resources Information Center

Sutker, Patricia B.; Allain, Albert N., Jr.

1988-01-01

Describes issues and implications associated with personality conceptualizations of addictive behaviors. Directs attention toward characterizing the sociopolitical climate's effect on identification, evaluation, and management of substance abuse disorders. Explores alcohol and drug use in conceptual schemata encompassing multifactorial,…

Epigenetics lights up the obesity field

USDA-ARS?s Scientific Manuscript database

Despite advances in the prevention and management of cardiovascular disease (CVD), this group of multifactorial disorders remains a leading cause of mortality worldwide. CVD is associated with multiple genetic and modifiable risk factors; however, known environmental and genetic influences can only ...

Interventions to Prevent Falls in Community-Dwelling Older Adults: US Preventive Services Task Force Recommendation Statement.

PubMed

Grossman, David C; Curry, Susan J; Owens, Douglas K; Barry, Michael J; Caughey, Aaron B; Davidson, Karina W; Doubeni, Chyke A; Epling, John W; Kemper, Alex R; Krist, Alex H; Kubik, Martha; Landefeld, Seth; Mangione, Carol M; Pignone, Michael; Silverstein, Michael; Simon, Melissa A; Tseng, Chien-Wen

2018-04-24

Falls are the leading cause of injury-related morbidity and mortality among older adults in the United States. In 2014, 28.7% of community-dwelling adults 65 years or older reported falling, resulting in 29 million falls (37.5% of which needed medical treatment or restricted activity for a day or longer) and an estimated 33 000 deaths in 2015. To update the 2012 US Preventive Services Task Force (USPSTF) recommendation on the prevention of falls in community-dwelling older adults. The USPSTF reviewed the evidence on the effectiveness and harms of primary care-relevant interventions to prevent falls and fall-related morbidity and mortality in community-dwelling older adults 65 years or older who are not known to have osteoporosis or vitamin D deficiency. The USPSTF found adequate evidence that exercise interventions have a moderate benefit in preventing falls in older adults at increased risk for falls and that multifactorial interventions have a small benefit. The USPSTF found adequate evidence that vitamin D supplementation has no benefit in preventing falls in older adults. The USPSTF found adequate evidence to bound the harms of exercise and multifactorial interventions as no greater than small. The USPSTF found adequate evidence that the overall harms of vitamin D supplementation are small to moderate. The USPSTF recommends exercise interventions to prevent falls in community-dwelling adults 65 years or older who are at increased risk for falls. (B recommendation) The USPSTF recommends that clinicians selectively offer multifactorial interventions to prevent falls in community-dwelling adults 65 years or older who are at increased risk for falls. Existing evidence indicates that the overall net benefit of routinely offering multifactorial interventions to prevent falls is small. When determining whether this service is appropriate for an individual, patients and clinicians should consider the balance of benefits and harms based on the circumstances of prior falls, presence of comorbid medical conditions, and the patient's values and preferences. (C recommendation) The USPSTF recommends against vitamin D supplementation to prevent falls in community-dwelling adults 65 years or older. (D recommendation) These recommendations apply to community-dwelling adults who are not known to have osteoporosis or vitamin D deficiency.

Experimental design methods for bioengineering applications.

PubMed

Keskin Gündoğdu, Tuğba; Deniz, İrem; Çalışkan, Gülizar; Şahin, Erdem Sefa; Azbar, Nuri

2016-01-01

Experimental design is a form of process analysis in which certain factors are selected to obtain the desired responses of interest. It may also be used for the determination of the effects of various independent factors on a dependent factor. The bioengineering discipline includes many different areas of scientific interest, and each study area is affected and governed by many different factors. Briefly analyzing the important factors and selecting an experimental design for optimization are very effective tools for the design of any bioprocess under question. This review summarizes experimental design methods that can be used to investigate various factors relating to bioengineering processes. The experimental methods generally used in bioengineering are as follows: full factorial design, fractional factorial design, Plackett-Burman design, Taguchi design, Box-Behnken design and central composite design. These design methods are briefly introduced, and then the application of these design methods to study different bioengineering processes is analyzed.

75 FR 48672 - Pesticides; Revised Fee Schedule for Registration Applications

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-11

... follows B772 118 Amend or extend Experimental 3 11,577 Use Permit; minor changes to experimental design...,942 Experimental Use Permit; minor changes to experimental design; extend established temporary... revision of experimental design B780 121 New active ingredient; non- 12 144,704 food/feed; no SAP review...

[Hyperosmolarity: Intracellular effects and implication in dry eye disease].

PubMed

Warcoin, E; Clouzeau, C; Brignole-Baudouin, F; Baudouin, C

2016-09-01

Dry eye disease is a multifactorial disease affecting the lacrimal functional unit and which has a significant impact on the quality of life of patients. This pathology works as a vicious circle at the ocular surface in which hyperosmolarity of the tear film plays a key role. This review intends to describe the different reported intracellular effects induced by hyperosmolarity in cells: alteration of cytoskeleton, cell cycle slowdown, adaptation mechanisms triggered as restoration of cell volume and accumulation of compatible osmolytes, the crucial role of the osmoprotectant factor Nuclear Factor of the Activated T cells-5 (NFAT5), apoptosis, as well as oxidative stress and inflammatory responses caused by this particular condition. Reported effects of hyperosmolarity in the experimental studies specific of dry eye disease concerning ocular surface cells will be described in parallel. Indeed, these data allow to understand a part of the pathophysiology of the disease, and specially the links between tear hyperosmolarity and inflammation of the ocular surface, the second key of the pathology phenomenon. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Efficacy of quercetin against chemically induced murine oral squamous cell carcinoma

PubMed Central

DROGUETT, DANIEL; CASTILLO, CHRISTIAN; LEIVA, ELBA; THEODULOZ, CRISTINA; SCHMEDA-HIRSCHMANN, GUILLERMO; KEMMERLING, ULRIKE

2015-01-01

Oral squamous cell carcinoma (OSCC) is the most common form of head and neck cancer, and oxidative damage is associated with the development of OSCCs. Antioxidants have therefore been proposed for use as chemoprotective agents against different types of cancer. In the present study, the effect of the antioxidant quercetin, administered at doses of 10 and 100 mg/kg/day, was investigated in an experimental murine model of 4-nitroquinoline 1-oxide (4-NQO)-induced carcinogenesis. The survival of the treated animals, the plasmatic levels of reduced glutathione and the type and severity of lesions (according the International Histological Classification of Tumors and Bryne's Multifactorial Grading System for the Invasive Tumor Front) were assessed. Additionally, the organization of the extracellular matrix was analyzed by carbohydrate and collagen histochemistry, and immunohistochemistry was used to assess the expression of the tumor markers proliferating cell nuclear antigen and mutated p53. The results indicate that, despite the promising effect of quercetin in other studies, this drug is ineffective as a chemoprotective agent against 4-NQO-induced OSCC in mice at the assayed doses. PMID:26622865

Recent advances on the neuroprotective potential of antioxidants in experimental models of Parkinson's disease.

PubMed

Koppula, Sushruta; Kumar, Hemant; More, Sandeep Vasant; Kim, Byung Wook; Kim, In Su; Choi, Dong Kug

2012-01-01

Parkinson's disease (PD), a neurodegenerative movement disorder of the central nervous system (CNS) is characterized by a progressive loss of dopaminergic neurons in the substantia nigra pars compacta region of the midbrain. Although the etiology of PD is not completely understood and is believed to be multifactorial, oxidative stress and mitochondrial dysfunction are widely considered major consequences, which provide important clues to the disease mechanisms. Studies have explored the role of free radicals and oxidative stress that contributes to the cascade of events leading to dopamine cell degeneration in PD. In general, in-built protective mechanisms consisting of enzymatic and non-enzymatic antioxidants in the CNS play decisive roles in preventing neuronal cell loss due to free radicals. But the ability to produce these antioxidants decreases with aging. Therefore, antioxidant therapy alone or in combination with current treatment methods may represent an attractive strategy for treating or preventing the neurodegeneration seen in PD. Here we summarize the recent discoveries of potential antioxidant compounds for modulating free radical mediated oxidative stress leading to neurotoxicity in PD.

Recent Advances on the Neuroprotective Potential of Antioxidants in Experimental Models of Parkinson’s Disease

PubMed Central

Koppula, Sushruta; Kumar, Hemant; More, Sandeep Vasant; Kim, Byung Wook; Kim, In Su; Choi, Dong Kug

2012-01-01

Parkinson’s disease (PD), a neurodegenerative movement disorder of the central nervous system (CNS) is characterized by a progressive loss of dopaminergic neurons in the substantia nigra pars compacta region of the midbrain. Although the etiology of PD is not completely understood and is believed to be multifactorial, oxidative stress and mitochondrial dysfunction are widely considered major consequences, which provide important clues to the disease mechanisms. Studies have explored the role of free radicals and oxidative stress that contributes to the cascade of events leading to dopamine cell degeneration in PD. In general, in-built protective mechanisms consisting of enzymatic and non-enzymatic antioxidants in the CNS play decisive roles in preventing neuronal cell loss due to free radicals. But the ability to produce these antioxidants decreases with aging. Therefore, antioxidant therapy alone or in combination with current treatment methods may represent an attractive strategy for treating or preventing the neurodegeneration seen in PD. Here we summarize the recent discoveries of potential antioxidant compounds for modulating free radical mediated oxidative stress leading to neurotoxicity in PD. PMID:22949883

Agrochemicals, α-synuclein, and Parkinson's disease.

PubMed

Silva, Blanca A; Breydo, Leonid; Fink, Anthony L; Uversky, Vladimir N

2013-04-01

Epidemiological, population-based case-control, and experimental studies at the molecular, cellular, and organism levels revealed that exposure to various environmental agents, including a number of structurally different agrochemicals, may contribute to the pathogenesis of Parkinson's disease (PD) and several other neurodegenerative disorders. The role of genetic predisposition in PD has also been increasingly acknowledged, driven by the identification of a number of disease-related genes [e.g., α-synuclein, parkin, DJ-1, ubiquitin C-terminal hydrolase isozyme L1 (UCH-L1), and nuclear receptor-related factor 1]. Therefore, the etiology of this multifactorial disease is likely to involve both genetic and environmental factors. Various neurotoxicants, including agrochemicals, have been shown to elevate the levels of α-synuclein expression in neurons and to promote aggregation of this protein in vivo. Many agrochemicals physically interact with α-synuclein and accelerate the fibrillation and aggregation rates of this protein in vitro. This review analyzes some of the aspects linking α-synuclein to PD, provides brief structural and functional descriptions of this important protein, and represents some data connecting exposure to agrochemicals with α-synuclein aggregation and PD pathogenesis.

Immunotherapy for recurrent malignant glioma: an interim report on survival.

PubMed

Ingram, M; Buckwalter, J G; Jacques, D B; Freshwater, D B; Abts, R M; Techy, G B; Miyagi, K; Shelden, C H; Rand, R W; English, L W

1990-12-01

We present interim survival data for a group of 83 adult patients with recurrent malignant glioma treated by implanting stimulated autologous lymphocytes into the tumour bed following surgical debulking. The patients were treated 6 months or more prior to data analysis. Fifty-nine patients were male and 24 female. The mean age for the entire group was 48.4 years and the mean Karnofsky rating (KR) was 67.2. Eight of the patients had grade II tumours, 33 had grade III tumours and 42 had grade IV tumours. Statistical analysis focuses on tumour grade, KR and patient age, factors that have been shown to affect survival in previous studies. Multifactorial analyses are employed to identify interrelationships among factors related to survival. Seven patients (8%) did not respond to immunotherapy, 76 (92%) had a good initial response. Twenty-five patients (30.1%) are living and 18 (22%) have shown no evidence of recurrence. Results are evaluated in the light of those obtained in trials of other experimental therapies for recurrent malignant gliomas. It is concluded that the present protocol offers a safe and comparatively effective treatment option.

Tea and cinnamon polyphenols improve the metabolic syndrome

USDA-ARS?s Scientific Manuscript database

The metabolic syndrome is often a precursor of chronic diseases including type 2 diabetes, cardiovascular diseases, and neurodegenerative diseases including Alzheimer’s disease. Since the metabolic syndrome is multi-factorial, strategies for reducing its incidence and consequences must also be mult...

Integrating gene expression data with demographic, clinical, and environmental exposure information to reveal endotypes of childhood asthma

EPA Science Inventory

RATIONALE. Childhood asthma is a multifactorial disease whose pathogenesis involves complex interplay between genetic susceptibility and modulating external factors. Therefore, effectively characterizing these multiple etiological pathways, or “endotypes”, requires an integrative...

The Contribution of Developmental Behavioural Genetics towards a Multifactorial Understanding of Reading Disabilities.

ERIC Educational Resources Information Center

Crawford, Shawn; And Others

1990-01-01

The utility of developmental behavioral genetics in the study of reading disability is considered. Research which has found reading disability to be partly genetically determined is cited, and future research applications are discussed. (Author/JDD)

Development and Validation of a Rubric for Diagnosing Students’ Experimental Design Knowledge and Difficulties

PubMed Central

Dasgupta, Annwesa P.; Anderson, Trevor R.

2014-01-01

It is essential to teach students about experimental design, as this facilitates their deeper understanding of how most biological knowledge was generated and gives them tools to perform their own investigations. Despite the importance of this area, surprisingly little is known about what students actually learn from designing biological experiments. In this paper, we describe a rubric for experimental design (RED) that can be used to measure knowledge of and diagnose difficulties with experimental design. The development and validation of the RED was informed by a literature review and empirical analysis of undergraduate biology students’ responses to three published assessments. Five areas of difficulty with experimental design were identified: the variable properties of an experimental subject; the manipulated variables; measurement of outcomes; accounting for variability; and the scope of inference appropriate for experimental findings. Our findings revealed that some difficulties, documented some 50 yr ago, still exist among our undergraduate students, while others remain poorly investigated. The RED shows great promise for diagnosing students’ experimental design knowledge in lecture settings, laboratory courses, research internships, and course-based undergraduate research experiences. It also shows potential for guiding the development and selection of assessment and instructional activities that foster experimental design. PMID:26086658

A global sensitivity analysis approach for morphogenesis models.

PubMed

Boas, Sonja E M; Navarro Jimenez, Maria I; Merks, Roeland M H; Blom, Joke G

2015-11-21

Morphogenesis is a developmental process in which cells organize into shapes and patterns. Complex, non-linear and multi-factorial models with images as output are commonly used to study morphogenesis. It is difficult to understand the relation between the uncertainty in the input and the output of such 'black-box' models, giving rise to the need for sensitivity analysis tools. In this paper, we introduce a workflow for a global sensitivity analysis approach to study the impact of single parameters and the interactions between them on the output of morphogenesis models. To demonstrate the workflow, we used a published, well-studied model of vascular morphogenesis. The parameters of this cellular Potts model (CPM) represent cell properties and behaviors that drive the mechanisms of angiogenic sprouting. The global sensitivity analysis correctly identified the dominant parameters in the model, consistent with previous studies. Additionally, the analysis provided information on the relative impact of single parameters and of interactions between them. This is very relevant because interactions of parameters impede the experimental verification of the predicted effect of single parameters. The parameter interactions, although of low impact, provided also new insights in the mechanisms of in silico sprouting. Finally, the analysis indicated that the model could be reduced by one parameter. We propose global sensitivity analysis as an alternative approach to study the mechanisms of morphogenesis. Comparison of the ranking of the impact of the model parameters to knowledge derived from experimental data and from manipulation experiments can help to falsify models and to find the operand mechanisms in morphogenesis. The workflow is applicable to all 'black-box' models, including high-throughput in vitro models in which output measures are affected by a set of experimental perturbations.

Tiny giants of gene regulation: experimental strategies for microRNA functional studies

PubMed Central

Steinkraus, Bruno R.; Toegel, Markus

2016-01-01

The discovery over two decades ago of short regulatory microRNAs (miRNAs) has led to the inception of a vast biomedical research field dedicated to understanding these powerful orchestrators of gene expression. Here we aim to provide a comprehensive overview of the methods and techniques underpinning the experimental pipeline employed for exploratory miRNA studies in animals. Some of the greatest challenges in this field have been uncovering the identity of miRNA–target interactions and deciphering their significance with regard to particular physiological or pathological processes. These endeavors relied almost exclusively on the development of powerful research tools encompassing novel bioinformatics pipelines, high‐throughput target identification platforms, and functional target validation methodologies. Thus, in an unparalleled manner, the biomedical technology revolution unceasingly enhanced and refined our ability to dissect miRNA regulatory networks and understand their roles in vivo in the context of cells and organisms. Recurring motifs of target recognition have led to the creation of a large number of multifactorial bioinformatics analysis platforms, which have proved instrumental in guiding experimental miRNA studies. Subsequently, the need for discovery of miRNA–target binding events in vivo drove the emergence of a slew of high‐throughput multiplex strategies, which now provide a viable prospect for elucidating genome‐wide miRNA–target binding maps in a variety of cell types and tissues. Finally, deciphering the functional relevance of miRNA post‐transcriptional gene silencing under physiological conditions, prompted the evolution of a host of technologies enabling systemic manipulation of miRNA homeostasis as well as high‐precision interference with their direct, endogenous targets. WIREs Dev Biol 2016, 5:311–362. doi: 10.1002/wdev.223 For further resources related to this article, please visit the WIREs website. PMID:26950183

Nutrition and physical activity programs for obesity treatment (PRONAF study): methodological approach of the project

PubMed Central

2012-01-01

Background At present, scientific consensus exists on the multifactorial etiopatogenia of obesity. Both professionals and researchers agree that treatment must also have a multifactorial approach, including diet, physical activity, pharmacology and/or surgical treatment. These two last ones should be reserved for those cases of morbid obesities or in case of failure of the previous ones. The aim of the PRONAF study is to determine what type of exercise combined with caloric restriction is the most appropriate to be included in overweigth and obesity intervention programs, and the aim of this paper is to describe the design and the evaluation methods used to carry out the PRONAF study. Methods/design One-hundred nineteen overweight (46 males) and 120 obese (61 males) subjects aged 18–50 years were randomly assigned to a strength training group, an endurance training group, a combined strength + endurance training group or a diet and physical activity recommendations group. The intervention period was 22 weeks (in all cases 3 times/wk of training for 22 weeks and 2 weeks for pre and post evaluation). All subjects followed a hypocaloric diet (25-30% less energy intake than the daily energy expenditure estimated by accelerometry). 29–34% of the total energy intake came from fat, 14–20% from protein, and 50–55% from carbohydrates. The mayor outcome variables assesed were, biochemical and inflamatory markers, body composition, energy balance, physical fitness, nutritional habits, genetic profile and quality of life. 180 (75.3%) subjects finished the study, with a dropout rate of 24.7%. Dropout reasons included: personal reasons 17 (28.8%), low adherence to exercise 3 (5.1%), low adherence to diet 6 (10.2%), job change 6 (10.2%), and lost interest 27 (45.8%). Discussion Feasibility of the study has been proven, with a low dropout rate which corresponds to the estimated sample size. Transfer of knowledge is foreseen as a spin-off, in order that overweight and obese subjects can benefit from the results. The aim is to transfer it to sports centres. Effectiveness on individual health-related parameter in order to determine the most effective training programme will be analysed in forthcoming publications. Trial registration ClinicalTrials.gov NCT01116856 PMID:23259716

A multifactorial analysis of obesity as CVD risk factor: Use of neural network based methods in a nutrigenetics context

PubMed Central

2010-01-01

Background Obesity is a multifactorial trait, which comprises an independent risk factor for cardiovascular disease (CVD). The aim of the current work is to study the complex etiology beneath obesity and identify genetic variations and/or factors related to nutrition that contribute to its variability. To this end, a set of more than 2300 white subjects who participated in a nutrigenetics study was used. For each subject a total of 63 factors describing genetic variants related to CVD (24 in total), gender, and nutrition (38 in total), e.g. average daily intake in calories and cholesterol, were measured. Each subject was categorized according to body mass index (BMI) as normal (BMI ≤ 25) or overweight (BMI > 25). Two artificial neural network (ANN) based methods were designed and used towards the analysis of the available data. These corresponded to i) a multi-layer feed-forward ANN combined with a parameter decreasing method (PDM-ANN), and ii) a multi-layer feed-forward ANN trained by a hybrid method (GA-ANN) which combines genetic algorithms and the popular back-propagation training algorithm. Results PDM-ANN and GA-ANN were comparatively assessed in terms of their ability to identify the most important factors among the initial 63 variables describing genetic variations, nutrition and gender, able to classify a subject into one of the BMI related classes: normal and overweight. The methods were designed and evaluated using appropriate training and testing sets provided by 3-fold Cross Validation (3-CV) resampling. Classification accuracy, sensitivity, specificity and area under receiver operating characteristics curve were utilized to evaluate the resulted predictive ANN models. The most parsimonious set of factors was obtained by the GA-ANN method and included gender, six genetic variations and 18 nutrition-related variables. The corresponding predictive model was characterized by a mean accuracy equal of 61.46% in the 3-CV testing sets. Conclusions The ANN based methods revealed factors that interactively contribute to obesity trait and provided predictive models with a promising generalization ability. In general, results showed that ANNs and their hybrids can provide useful tools for the study of complex traits in the context of nutrigenetics. PMID:20825661

Adaptive design of visual perception experiments

NASA Astrophysics Data System (ADS)

O'Connor, John D.; Hixson, Jonathan; Thomas, James M., Jr.; Peterson, Matthew S.; Parasuraman, Raja

2010-04-01

Meticulous experimental design may not always prevent confounds from affecting experimental data acquired during visual perception experiments. Although experimental controls reduce the potential effects of foreseen sources of interference, interaction, or noise, they are not always adequate for preventing the confounding effects of unforeseen forces. Visual perception experimentation is vulnerable to unforeseen confounds because of the nature of the associated cognitive processes involved in the decision task. Some confounds are beyond the control of experimentation, such as what a participant does immediately prior to experimental participation, or the participant's attitude or emotional state. Other confounds may occur through ignorance of practical control methods on the part of the experiment's designer. The authors conducted experiments related to experimental fatigue and initially achieved significant results that were, upon re-examination, attributable to a lack of adequate controls. Re-examination of the original results and the processes and events that led to them yielded a second experimental design with more experimental controls and significantly different results. The authors propose that designers of visual perception experiments can benefit from planning to use a test-fix-test or adaptive experimental design cycle, so that unforeseen confounds in the initial design can be remedied.

Quasi experimental designs in pharmacist intervention research.

PubMed

Krass, Ines

2016-06-01

Background In the field of pharmacist intervention research it is often difficult to conform to the rigorous requirements of the "true experimental" models, especially the requirement of randomization. When randomization is not feasible, a practice based researcher can choose from a range of "quasi-experimental designs" i.e., non-randomised and at time non controlled. Objective The aim of this article was to provide an overview of quasi-experimental designs, discuss their strengths and weaknesses and to investigate their application in pharmacist intervention research over the previous decade. Results In the literature quasi experimental studies may be classified into five broad categories: quasi-experimental design without control groups; quasi-experimental design that use control groups with no pre-test; quasi-experimental design that use control groups and pre-tests; interrupted time series and stepped wedge designs. Quasi-experimental study design has consistently featured in the evolution of pharmacist intervention research. The most commonly applied of all quasi experimental designs in the practice based research literature are the one group pre-post-test design and the non-equivalent control group design i.e., (untreated control group with dependent pre-tests and post-tests) and have been used to test the impact of pharmacist interventions in general medications management as well as in specific disease states. Conclusion Quasi experimental studies have a role to play as proof of concept, in the pilot phases of interventions when testing different intervention components, especially in complex interventions. They serve to develop an understanding of possible intervention effects: while in isolation they yield weak evidence of clinical efficacy, taken collectively, they help build a body of evidence in support of the value of pharmacist interventions across different practice settings and countries. However, when a traditional RCT is not feasible for logistical and/or ethical reasons researchers should endeavour to use the more robust of the quasi experimental designs.

Relation between experimental and non-experimental study designs. HB vaccines: a case study

PubMed Central

Jefferson, T.; Demicheli, V.

1999-01-01

STUDY OBJECTIVE: To examine the relation between experimental and non- experimental study design in vaccinology. DESIGN: Assessment of each study design's capability of testing four aspects of vaccine performance, namely immunogenicity (the capacity to stimulate the immune system), duration of immunity conferred, incidence and seriousness of side effects, and number of infections prevented by vaccination. SETTING: Experimental and non-experimental studies on hepatitis B (HB) vaccines in the Cochrane Vaccines Field Database. RESULTS: Experimental and non-experimental vaccine study designs are frequently complementary but some aspects of vaccine quality can only be assessed by one of the types of study. More work needs to be done on the relation between study quality and its significance in terms of effect size.   PMID:10326054

Estimating Intervention Effects across Different Types of Single-Subject Experimental Designs: Empirical Illustration

ERIC Educational Resources Information Center

Moeyaert, Mariola; Ugille, Maaike; Ferron, John M.; Onghena, Patrick; Heyvaert, Mieke; Beretvas, S. Natasha; Van den Noortgate, Wim

2015-01-01

The purpose of this study is to illustrate the multilevel meta-analysis of results from single-subject experimental designs of different types, including AB phase designs, multiple-baseline designs, ABAB reversal designs, and alternating treatment designs. Current methodological work on the meta-analysis of single-subject experimental designs…

Experimental Test Rig for Optimal Control of Flexible Space Robotic Arms

DTIC Science & Technology

2016-12-01

was used to refine the test bed design and the experimental workflow. Three concepts incorporated various strategies to design a robust flexible link...used to refine the test bed design and the experimental workflow. Three concepts incorporated various strategies to design a robust flexible link... designed to perform the experimentation . The first and second concepts use traditional elastic springs in varying configurations while a third uses a

Research Methods in Healthcare Epidemiology and Antimicrobial Stewardship-Quasi-Experimental Designs.

PubMed

Schweizer, Marin L; Braun, Barbara I; Milstone, Aaron M

2016-10-01

Quasi-experimental studies evaluate the association between an intervention and an outcome using experiments in which the intervention is not randomly assigned. Quasi-experimental studies are often used to evaluate rapid responses to outbreaks or other patient safety problems requiring prompt, nonrandomized interventions. Quasi-experimental studies can be categorized into 3 major types: interrupted time-series designs, designs with control groups, and designs without control groups. This methods paper highlights key considerations for quasi-experimental studies in healthcare epidemiology and antimicrobial stewardship, including study design and analytic approaches to avoid selection bias and other common pitfalls of quasi-experimental studies. Infect Control Hosp Epidemiol 2016;1-6.

Research Methods in Healthcare Epidemiology and Antimicrobial Stewardship – Quasi-Experimental Designs

PubMed Central

Schweizer, Marin L.; Braun, Barbara I.; Milstone, Aaron M.

2016-01-01

Quasi-experimental studies evaluate the association between an intervention and an outcome using experiments in which the intervention is not randomly assigned. Quasi-experimental studies are often used to evaluate rapid responses to outbreaks or other patient safety problems requiring prompt non-randomized interventions. Quasi-experimental studies can be categorized into three major types: interrupted time series designs, designs with control groups, and designs without control groups. This methods paper highlights key considerations for quasi-experimental studies in healthcare epidemiology and antimicrobial stewardship including study design and analytic approaches to avoid selection bias and other common pitfalls of quasi-experimental studies. PMID:27267457

An experimental infection model to induce digital dermatitis infection in cattle.

PubMed

Gomez, A; Cook, N B; Bernardoni, N D; Rieman, J; Dusick, A F; Hartshorn, R; Socha, M T; Read, D H; Döpfer, D

2012-04-01

Bovine digital dermatitis (DD), also known as papillomatous digital dermatitis (foot warts), has been recognized as a major cause of lameness in cattle, with important economic and welfare consequences. The evaluation of therapeutic and preventive interventions aiming to control DD infections in dairy cattle is often challenged by the complex multifactorial etiology of the disease. An experimental infection model to induce acute DD lesions in a controlled environment is proposed. The goal was to provide a standard way of reproducing DD infections independent of external factors that could confound the natural course of the disease, such as management practices or infection pressure, resulting in transmission of DD between animals. A group of 4 yearling Holstein heifers free of any clinical evidence of hoof disease was recruited from a commercial dairy farm and housed in an experimental facility in 1 pen with slatted flooring. The hind feet were wrapped to mimic conditions of prolonged moisture (maceration) and reduced access to air (closure) and inoculated at the heel and dewclaw areas with a homogenate of a naturally occurring DD lesion skin biopsy or a culture broth of Treponema spp. After a period of 12 to 25 d, 4 of 6 and 1 of 4 dewclaw areas inoculated with biopsied DD lesion or a Treponema spp. culture, respectively, had gross lesions compatible with DD. Histopathology confirmed the gross diagnosis in the sites inoculated with tissue homogenate. In the site inoculated with Treponema spp. culture broth, histopathology revealed an incipient DD lesion. Treponema spp. were detected by PCR in both naturally occurring DD homogenate and Treponema spp. culture broth inoculation sites. An experimental infection model to induce acute DD in cattle was developed, which may be used to evaluate interventions to control DD and study the pathogenesis of this infectious hoof disease in a controlled manner. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Finite Element Model of the Knee for Investigation of Injury Mechanisms: Development and Validation

PubMed Central

Kiapour, Ali; Kiapour, Ata M.; Kaul, Vikas; Quatman, Carmen E.; Wordeman, Samuel C.; Hewett, Timothy E.; Demetropoulos, Constantine K.; Goel, Vijay K.

2014-01-01

Multiple computational models have been developed to study knee biomechanics. However, the majority of these models are mainly validated against a limited range of loading conditions and/or do not include sufficient details of the critical anatomical structures within the joint. Due to the multifactorial dynamic nature of knee injuries, anatomic finite element (FE) models validated against multiple factors under a broad range of loading conditions are necessary. This study presents a validated FE model of the lower extremity with an anatomically accurate representation of the knee joint. The model was validated against tibiofemoral kinematics, ligaments strain/force, and articular cartilage pressure data measured directly from static, quasi-static, and dynamic cadaveric experiments. Strong correlations were observed between model predictions and experimental data (r > 0.8 and p < 0.0005 for all comparisons). FE predictions showed low deviations (root-mean-square (RMS) error) from average experimental data under all modes of static and quasi-static loading, falling within 2.5 deg of tibiofemoral rotation, 1% of anterior cruciate ligament (ACL) and medial collateral ligament (MCL) strains, 17 N of ACL load, and 1 mm of tibiofemoral center of pressure. Similarly, the FE model was able to accurately predict tibiofemoral kinematics and ACL and MCL strains during simulated bipedal landings (dynamic loading). In addition to minimal deviation from direct cadaveric measurements, all model predictions fell within 95% confidence intervals of the average experimental data. Agreement between model predictions and experimental data demonstrates the ability of the developed model to predict the kinematics of the human knee joint as well as the complex, nonuniform stress and strain fields that occur in biological soft tissue. Such a model will facilitate the in-depth understanding of a multitude of potential knee injury mechanisms with special emphasis on ACL injury. PMID:24763546

SICK BUILDING SYNDROME: POSSIBLE ASSOCIATIONS WITH EXPOSURE TO MYCOTOXINS FROM INDOOR AIR FUNGI.

EPA Science Inventory

Introduction. Chronic human illness associated with residential or occupational buildings, commonly referred to as sick building syndrome (SBS), may be a multifactorial condition, involving in some cases volatile organic compounds, CO or CO2, pesticides, biologic agents, temperat...

Suicidal Tendencies in the Elderly.

ERIC Educational Resources Information Center

Achte, Kalle

1988-01-01

Claims elderly suicides are more frequent, and more likely to be multifactorial, including loneliness, isolation, depression, somatic illnesses, having suffered numerous losses, and injuries to the self-esteem (concerns regarding emptiness, uselessness, and body image). Aggressive impulses previously neutralized by work and social life now break…

A case of coffee-ground emesis in an elderly patient

PubMed Central

De Palma, Giovanni D; Persico, Marcello; Forestieri, Pietro

2014-01-01

Key Clinical Message Black esophagus is an exceeding rare disorder with a multifactorial etiology. Clinical presentation is generally related to upper gastrointestinal bleeding. Diagnosis is based on endoscopic images. Overall mortality is largely related to the underlying medical condition. PMID:25356232

Optimizing Experimental Designs: Finding Hidden Treasure.

USDA-ARS?s Scientific Manuscript database

Classical experimental design theory, the predominant treatment in most textbooks, promotes the use of blocking designs for control of spatial variability in field studies and other situations in which there is significant variation among heterogeneity among experimental units. Many blocking design...

How scientific experiments are designed: Problem solving in a knowledge-rich, error-rich environment

NASA Astrophysics Data System (ADS)

Baker, Lisa M.

While theory formation and the relation between theory and data has been investigated in many studies of scientific reasoning, researchers have focused less attention on reasoning about experimental design, even though the experimental design process makes up a large part of real-world scientists' reasoning. The goal of this thesis was to provide a cognitive account of the scientific experimental design process by analyzing experimental design as problem-solving behavior (Newell & Simon, 1972). Three specific issues were addressed: the effect of potential error on experimental design strategies, the role of prior knowledge in experimental design, and the effect of characteristics of the space of alternate hypotheses on alternate hypothesis testing. A two-pronged in vivo/in vitro research methodology was employed, in which transcripts of real-world scientific laboratory meetings were analyzed as well as undergraduate science and non-science majors' design of biology experiments in the psychology laboratory. It was found that scientists use a specific strategy to deal with the possibility of error in experimental findings: they include "known" control conditions in their experimental designs both to determine whether error is occurring and to identify sources of error. The known controls strategy had not been reported in earlier studies with science-like tasks, in which participants' responses to error had consisted of replicating experiments and discounting results. With respect to prior knowledge: scientists and undergraduate students drew on several types of knowledge when designing experiments, including theoretical knowledge, domain-specific knowledge of experimental techniques, and domain-general knowledge of experimental design strategies. Finally, undergraduate science students generated and tested alternates to their favored hypotheses when the space of alternate hypotheses was constrained and searchable. This result may help explain findings of confirmation bias in earlier studies using science-like tasks, in which characteristics of the alternate hypothesis space may have made it unfeasible for participants to generate and test alternate hypotheses. In general, scientists and science undergraduates were found to engage in a systematic experimental design process that responded to salient features of the problem environment, including the constant potential for experimental error, availability of alternate hypotheses, and access to both theoretical knowledge and knowledge of experimental techniques.

The current crisis in emergency care and the impact on disaster preparedness.

PubMed

Cherry, Robert A; Trainer, Marcia

2008-05-01

The Homeland Security Act (HSA) of 2002 provided for the designation of a critical infrastructure protection program. This ultimately led to the designation of emergency services as a targeted critical infrastructure. In the context of an evolving crisis in hospital-based emergency care, the extent to which federal funding has addressed disaster preparedness will be examined. After 9/11, federal plans, procedures and benchmarks were mandated to assure a unified, comprehensive disaster response, ranging from local to federal activation of resources. Nevertheless, insufficient federal funding has contributed to a long-standing counter-trend which has eroded emergency medical care. The causes are complex and multifactorial, but they have converged to present a severely overburdened system that regularly exceeds emergency capacity and capabilities. This constant acute overcrowding, felt in communities all across the country, indicates a nation at risk. Federal funding has not sufficiently prioritized the improvements necessary for an emergency care infrastructure that is critical for an all hazards response to disaster and terrorist emergencies. Currently, the nation is unable to meet presidential preparedness mandates for emergency and disaster care. Federal funding strategies must therefore be re-prioritized and targeted in a way that reasonably and consistently follows need.

Multiobjective Multifactorial Optimization in Evolutionary Multitasking.

PubMed

Gupta, Abhishek; Ong, Yew-Soon; Feng, Liang; Tan, Kay Chen

2016-05-03

In recent decades, the field of multiobjective optimization has attracted considerable interest among evolutionary computation researchers. One of the main features that makes evolutionary methods particularly appealing for multiobjective problems is the implicit parallelism offered by a population, which enables simultaneous convergence toward the entire Pareto front. While a plethora of related algorithms have been proposed till date, a common attribute among them is that they focus on efficiently solving only a single optimization problem at a time. Despite the known power of implicit parallelism, seldom has an attempt been made to multitask, i.e., to solve multiple optimization problems simultaneously. It is contended that the notion of evolutionary multitasking leads to the possibility of automated transfer of information across different optimization exercises that may share underlying similarities, thereby facilitating improved convergence characteristics. In particular, the potential for automated transfer is deemed invaluable from the standpoint of engineering design exercises where manual knowledge adaptation and reuse are routine. Accordingly, in this paper, we present a realization of the evolutionary multitasking paradigm within the domain of multiobjective optimization. The efficacy of the associated evolutionary algorithm is demonstrated on some benchmark test functions as well as on a real-world manufacturing process design problem from the composites industry.

Timed up and go test combined with self-rated multifactorial questionnaire on falls risk and sociodemographic factors predicts falls among community-dwelling older adults better than the timed up and go test on its own

PubMed Central

Ibrahim, Azianah; Singh, Devinder Kaur Ajit; Shahar, Suzana; Omar, Mohd Azahadi

2017-01-01

Background Early detection of falls risk among older adults using simple tools may assist in fall prevention strategies. The aim of this study was to identify the best parameters associated with previous falls, either the timed up and go (TUG) test combined with sociodemographic factors and a self-rated multifactorial questionnaire (SRMQ) on falls risk or the TUG on its own. Falls risk was determined based on parameters associated with previous falls. Design This was a retrospective cohort study. Setting The study was conducted in a community setting. Participants The participants were 1,086 community-dwelling older adults, with mean age of 69.6±5.6 years. Participants were categorized into fallers and nonfallers based on their history of falls in the past 12 months. Method Participants’ sociodemographic data was taken, and SRMQ consisting of five falls-related questions was administered. Participants performed the TUG test twice, and the mean was taken as the result. Results A total of 161 participants were categorized as fallers (14.8%). Multivariate logistic regression analysis showed that the model (χ2(6)=61.0, p<0.001, Nagelkerke R2=0.10) consisting of the TUG test, sociodemographic factors (gender, cataract/glaucoma and joint pain), as well as the SRMQ items “previous falls history” (Q1) and “worried of falls” (Q5), was more robust in terms of falls risk association compared to that with TUG on its own (χ2(1)=10.3, p<0.001, Nagelkerke R2=0.02). Conclusion Combination of sociodemographic factors and SRMQ with TUG is more favorable as an initial falls risk screening tool among community-dwelling older adults. Subsequently, further comprehensive falls risk assessment may be performed in clinical settings to identify the specific impairments for effective management. PMID:29138571

Technologies for participatory medicine and health promotion in the elderly population

PubMed Central

Nieto-Riveiro, Laura; Groba, Betania; Miranda, M. Carmen; Concheiro, Patricia; Pazos, Alejandro; Pousada, Thais; Pereira, Javier

2018-01-01

Abstract Introduction: The progressive aging of the population is a socio-demographic phenomenon experienced by most countries in the world in recent decades, especially in Japan and in many European Union countries. During this process, so-called “geriatric syndromes” frequently occur. The focus of this study is the quality of life of the elderly in relation to these 3 factors: risk of falls, urinary incontinence, and insomnia. Objective: The main purpose is to determine the impact of a multifactorial intervention program implemented with institutionalized elderly people. The program is focused on the treatment of the aforementioned factors. Methods and Analysis: The study will be carried out with elderly people living in three residences for the elderly in A Coruña Province (Galicia, Spain).It is a prospective and longitudinal study, with a temporary series design of a “quasi-experimental” type that evaluates the effect of an intervention in 1 given population by doing assessments pre- and post-intervention, but there is no comparison with a control group. The intervention will be based on a multifactorial program, including the following phases: the use of wearable devices (wearable fitness trackers to register physical activity and sleep), the use of an App on a Tablet to record the participants’ occupations and activities, counseling about performance in activities of daily living, the implementation of a physical activity program, and the treatment of the pelvic floor (according to each research line). The Quality of Life (QoL) will be assessed before and after the intervention, with the use of the questionnaire EuroQol-5D-5L. Data analysis will be applied with all registered variables through a quantitative perspective. Ethics and Dissemination: The protocol has been approved by the host institution's ethics committee (Research Ethics Committee of Galicia) under the number 2017/106. Results will be disseminated via peer-reviewed journal articles and conferences. This clinical trial is registered at ClinicalTrials.gov identifier: NCT03504813. PMID:29768372

Increased alcohol consumption as a cause of alcoholism, without similar evidence for depression: a Mendelian randomization study.

PubMed

Wium-Andersen, Marie Kim; Ørsted, David Dynnes; Tolstrup, Janne Schurmann; Nordestgaard, Børge Grønne

2015-04-01

Increased alcohol consumption has been associated with depression and alcoholism, but whether these associations are causal remains unclear. We tested whether alcohol consumption is causally associated with depression and alcoholism. We included 78,154 men and women aged 20-100 years randomly selected in 1991-2010 from the general population of Copenhagen, Denmark, and genotyped 68,486 participants for two genetic variants in two alcohol dehydrogenase (ADH) genes, ADH-1B (rs1229984) and ADH-1C (rs698). We performed observational and causal analyses using a Mendelian randomization design with antidepressant medication use and hospitalization/death, with depression and alcoholism as outcomes. In prospective analyses, the multifactorially adjusted hazard ratio for participants reporting >6 drinks/day vs participants reporting 0.1-1 drinks/day was 1.28 (95% confidence interval, 1.00-1.65) for prescription antidepressant use, with a corresponding hazard ratio of 0.80 (0.45-1.45) for hospitalization/death with depression and of 11.7 (8.77-15.6) for hospitalization/death with alcoholism. For hospitalization/death with alcoholism, instrumental variable analysis yielded a causal odds ratio of 28.6 (95 % confidence interval 6.47-126) for an increase of 1 drink/day estimated from the combined genotype combination, whereas the corresponding multifactorially adjusted observational odds ratio was 1.28 (1.25-1.31). Corresponding odds ratios were 1.11 (0.67-1.83) causal and 1.04 (1.03-1.06) observational for prescription antidepressant use, and 4.52 (0.99-20.5) causal and 0.98 (0.94-1.03) observational for hospitalization/death with depression. These data indicate that the association between increased alcohol consumption and alcoholism is causal, without similar strong evidence for depression. © The Author 2014; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.

A Multifactorial, Criteria-based Progressive Algorithm for Hamstring Injury Treatment.

PubMed

Mendiguchia, Jurdan; Martinez-Ruiz, Enrique; Edouard, Pascal; Morin, Jean-Benoît; Martinez-Martinez, Francisco; Idoate, Fernando; Mendez-Villanueva, Alberto

2017-07-01

Given the prevalence of hamstring injuries in football, a rehabilitation program that effectively promotes muscle tissue repair and functional recovery is paramount to minimize reinjury risk and optimize player performance and availability. This study aimed to assess the concurrent effectiveness of administering an individualized and multifactorial criteria-based algorithm (rehabilitation algorithm [RA]) on hamstring injury rehabilitation in comparison with using a general rehabilitation protocol (RP). Implementing a double-blind randomized controlled trial approach, two equal groups of 24 football players (48 total) completed either an RA group or a validated RP group 5 d after an acute hamstring injury. Within 6 months after return to sport, six hamstring reinjuries occurred in RP versus one injury in RA (relative risk = 6, 90% confidence interval = 1-35; clinical inference: very likely beneficial effect). The average duration of return to sport was possibly quicker (effect size = 0.34 ± 0.42) in RP (23.2 ± 11.7 d) compared with RA (25.5 ± 7.8 d) (-13.8%, 90% confidence interval = -34.0% to 3.4%; clinical inference: possibly small effect). At the time to return to sport, RA players showed substantially better 10-m time, maximal sprinting speed, and greater mechanical variables related to speed (i.e., maximum theoretical speed and maximal horizontal power) than the RP. Although return to sport was slower, male football players who underwent an individualized, multifactorial, criteria-based algorithm with a performance- and primary risk factor-oriented training program from the early stages of the process markedly decreased the risk of reinjury compared with a general protocol where long-length strength training exercises were prioritized.

Effectiveness of a multifactorial intervention based on an application for smartphones, heart-healthy walks and a nutritional workshop in patients with type 2 diabetes mellitus in primary care (EMID): study protocol for a randomised controlled trial

PubMed Central

Alonso-Domínguez, Rosario; Gómez-Marcos, Manuel A; Patino-Alonso, Maria C; Sánchez-Aguadero, Natalia; Agudo-Conde, Cristina; Castaño-Sánchez, Carmen; García-Ortiz, Luis; Recio-Rodríguez, José I

2017-01-01

Introduction New information and communication technologies (ICTs) may promote lifestyle changes, but no adequate evidence is available on their combined effect of ICTs with multifactorial interventions aimed at improving diet and increasing physical activity in patients with type 2 diabetes mellitus (DM2). The primary objective of this study is to assess the effect of a multifactorial intervention to increase physical activity and adherence to Mediterranean diet in DM2. Methods and analysis Study scope and population: The study will be conducted at ‘La Alamedilla’ primary care research unit in Salamanca (Spain). 200 patients with DM2 of both sexes, aged 25–70 years and who meet the inclusion criteria and sign the informed consent will be recruited. Each participant will attend the clinic at baseline and 3 and 12 months after intervention. Intervention Both groups will be given short advice on diet and physical activity. The intervention group will also take five heart-healthy walks and attend a group session on diet education and will be trained on use of an application for smartphone (EVIDENT II) for 3 months. Variables and measurement instruments The main study endpoints will be changes in physical activity, as assessed by a pedometer and the International Physical Activity Questionnaire, and adherence to the Mediterranean diet, as evaluated by an adherence questionnaire and the Diet Quality Index. Anthropometric parameters and laboratory values, lifestyles and quality of life will also be assessed. Ethics and dissemination It was approved by the Clinical Research Ethics Committee of Salamanca on 28/11/2016. Trial registration NCT02991079; Pre-results. PMID:28912193

Multifactorial assessment and targeted intervention to reduce falls among the oldest-old: a randomized controlled trial

PubMed Central

Ferrer, Assumpta; Formiga, Francesc; Sanz, Héctor; de Vries, Oscar J; Badia, Teresa; Pujol, Ramón

2014-01-01

Background The purpose of this study was to assess the effectiveness of a multifactorial intervention to reduce falls among the oldest-old people, including individuals with cognitive impairment or comorbidities. Methods A randomized, single-blind, parallel-group clinical trial was conducted from January 2009 to December 2010 in seven primary health care centers in Baix Llobregat (Barcelona). Of 696 referred people who were born in 1924, 328 were randomized to an intervention group or a control group. The intervention model used an algorithm and was multifaceted for both patients and their primary care providers. Primary outcomes were risk of falling and time until falls. Data analyses were by intention-to-treat. Results Sixty-five (39.6%) subjects in the intervention group and 48 (29.3%) in the control group fell during follow-up. The difference in the risk of falls was not significant (relative risk 1.28, 95% confidence interval [CI] 0.94–1.75). Cox regression models with time from randomization to the first fall were not significant. Cox models for recurrent falls showed that intervention had a negative effect (hazard ratio [HR] 1.46, 95% CI 1.03–2.09) and that functional impairment (HR 1.42, 95% CI 0.97–2.12), previous falls (HR 1.09, 95% CI 0.74–1.60), and cognitive impairment (HR 1.08, 95% CI 0.72–1.60) had no effect on the assessment. Conclusion This multifactorial intervention among octogenarians, including individuals with cognitive impairment or comorbidities, did not result in a reduction in falls. A history of previous falls, disability, and cognitive impairment had no effect on the program among the community-dwelling subjects in this study. PMID:24596458

Combined diabetes-renal multifactorial intervention in patients with advanced diabetic nephropathy: Proof-of-concept.

PubMed

Fogelfeld, Leon; Hart, Peter; Miernik, Jadwiga; Ko, Jocelyn; Calvin, Donna; Tahsin, Bettina; Adhami, Anwar; Mehrotra, Rajeev; Fogg, Louis

2017-03-01

To evaluate efficacy of a multifactorial-multidisciplinary approach in delaying CKD 3-4 progression to ESRD. Two-year proof-of-concept stratified randomized control trial conducted in an outpatient clinic of a large public hospital system. This intervention, led by a team of endocrinologists, nephrologists, nurse practitioners, and registered dietitians, integrated intensive diabetes-renal care with behavioral/dietary and pharmacological interventions. 120 low-income adults with T2DM and CKD 3-4 enrolled; 58% male, 55% African American, 23% Hispanic. Primary outcome was progression rate from CKD 3-4 to ESRD. Fewer intervention (13%) than control (28%) developed ESRD, p<0.05. Intervention had greater albumin/creatinine ratio (ACR) decrease (62% vs. 42%, p<0.05) and A1C<7% attainment (50% vs. 30%, p<0.05) and trended toward better lipid/blood pressure control (p=NS). Significant differences between 25 ESRD and 95 ESRD-free patients were baseline eGFR (28 vs. 40ml/min/1.73m 2 ), annual eGFR decline (15 vs. 3ml/min/year), baseline ACR (2362 vs. 1139mg/g), final ACR (2896 vs. 1201mg/g), and final A1C (6.9 vs. 7.8%). In multivariate Cox analysis, receiving the intervention reduced hazard ratio to develop ESRD (0.125, CI 0.029-0.54) as did higher baseline eGFR (0.69, CI 0.59-0.80). Greater annual eGFR decline increased hazard ratio (1.59, CI 1.34-1.87). The intervention delayed ESRD. Improved A1C and ACR plus not-yet-identified variables may have influenced better outcomes. Multifactorial-multidisciplinary care may serve as a CKD 3-4 treatment paradigm. Copyright © 2017 Elsevier Inc. All rights reserved.

Multifactorial etiology of Torus mandibularis: study of twins.

PubMed

Auškalnis, Adomas; Rutkūnas, Vygandas; Bernhardt, Olaf; Šidlauskas, Mantas; Šalomskienė, Loreta; Basevičienė, Nomeda

2015-01-01

The aim of this study is to investigate the multifactorial etiology of mandibular tori analyzing the influence of genetics, occlusal overload, various clinical variables and their interactions. Overall, plaster casts of 162 twins (81 twin pairs) were analyzed for the presence or absence of mandibular tori. Atypical wear facets on canine tips or incisors were recorded to diagnose bruxism. Angle Class, any kind of anterior open bite and positive, negative or flat curve of Wilson were recorded. Zygosity determination was carried out using a DNA test. Mandibular tori were found in 56.8% of the cases. In 93.6% of all monozygotic twin pairs both individuals had or did not have mandibular tori (κ=0.96±0.04; p<0.001), compared to 79.4% concordance of mandibular tori in dizygotic co-twins (κ=0.7±0.12; p<0.001). Prevalence of mandibular tori was significantly higher in the group of bruxers (67.5%) compared to non-bruxers (31.3%) (p<0.001). Significant association between mandibular tori and negative or flat curve of Wilson in the maxillary second premolars and first molars was found (OR=2.55, 95% CI (1.19-5.46), p=0.016). In all monozygotic bruxers, 97.1% showed concordance of mandibular tori presence in both co-twins compared to 78.9% dizygotic bruxers, and this difference is statistically significant (p=0.007). Our results suggest that the mandibular tori are of a multifactorial origin. Mandibular tori seem to have genetic predisposition, and may be associated with teeth grinding as well as with negative or flat CW in region of maxillary second premolar and first molar.

Using Multiple Dialog Modes in a User-System Interface to Accomodate Different Levels of User Experience: An Experimental Study.

DTIC Science & Technology

1986-01-01

Chapter it Research Methodology This chapter describes the methodology and the experimental design used for this research. Prior to discussing the...50 Experimental Design ............................... 50 Task/Treatm ent ................................... 55 Task Design ...Figure 3.3 Interface Experiment Elements ............... 54 Figure 3.4 Experimental Design ....................... 55 Figure 3.5 Subject Assignment

Quality by design: a systematic and rapid liquid chromatography and mass spectrometry method for eprosartan mesylate and its related impurities using a superficially porous particle column.

PubMed

Kalariya, Pradipbhai D; Kumar Talluri, Murali V N; Gaitonde, Vinay D; Devrukhakar, Prashant S; Srinivas, Ragampeta

2014-08-01

The present work describes the systematic development of a robust, precise, and rapid reversed-phase liquid chromatography method for the simultaneous determination of eprosartan mesylate and its six impurities using quality-by-design principles. The method was developed in two phases, screening and optimization. During the screening phase, the most suitable stationary phase, organic modifier, and pH were identified. The optimization was performed for secondary influential parameters--column temperature, gradient time, and flow rate using eight experiments--to examine multifactorial effects of parameters on the critical resolution and generated design space representing the robust region. A verification experiment was performed within the working design space and the model was found to be accurate. This study also describes other operating features of the column packed with superficially porous particles that allow very fast separations at pressures available in most liquid chromatography instruments. Successful chromatographic separation was achieved in less than 7 min using a fused-core C18 (100 mm × 2.1 mm, 2.6 μm) column with linear gradient elution of 10 mM ammonium formate (pH 3.0) and acetonitrile as the mobile phase. The method was validated for specificity, linearity, accuracy, precision, and robustness in compliance with the International Conference on Harmonization Q2 (R1) guidelines. The impurities were identified by liquid chromatography with mass spectrometry. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Experimental Validation of an Integrated Controls-Structures Design Methodology

NASA Technical Reports Server (NTRS)

Maghami, Peiman G.; Gupta, Sandeep; Elliot, Kenny B.; Walz, Joseph E.

1996-01-01

The first experimental validation of an integrated controls-structures design methodology for a class of large order, flexible space structures is described. Integrated redesign of the controls-structures-interaction evolutionary model, a laboratory testbed at NASA Langley, was described earlier. The redesigned structure was fabricated, assembled in the laboratory, and experimentally tested against the original structure. Experimental results indicate that the structure redesigned using the integrated design methodology requires significantly less average control power than the nominal structure with control-optimized designs, while maintaining the required line-of-sight pointing performance. Thus, the superiority of the integrated design methodology over the conventional design approach is experimentally demonstrated. Furthermore, amenability of the integrated design structure to other control strategies is evaluated, both analytically and experimentally. Using Linear-Quadratic-Guassian optimal dissipative controllers, it is observed that the redesigned structure leads to significantly improved performance with alternate controllers as well.

Mining Internet search and social media for epidemiology

EPA Science Inventory

Many pervasive and multifactorial disorders of modern non-communicable and non-infectious diseases (i.e. obesity, asthma, migraine, autism) need to be better understood and explored. The cost of these disorders to the healthcare system and the general public’s quality of life are...

The etiology of digital dermatitis in ruminants: recent perspectives

USDA-ARS?s Scientific Manuscript database

Digital dermatitis is a multifactorial polymicrobial infectious disease originally described in dairy cattle but is increasingly recognized in beef cattle, sheep and more recently, elk. Clinical bovine lesions typically appear on the plantar surface of the hind foot from the interdigital space and h...

Marginal socio-economic effects of an employer's efforts to improve the work environment.

PubMed

Rezagholi, Mahmoud

2018-01-01

Workplace health promotion (WHP) strongly requires the employer's efforts to improve the psychosocial, ergonomic, and physical environments of the workplace. There are many studies discussing the socio-economic advantage of WHP intervention programmes and thus the internal and external factors motivating employers to implement and integrate such programmes. However, the socio-economic impacts of the employer's multifactorial efforts to improve the work environment need to be adequately assessed. Data were collected from Swedish company Sandvik Materials Technology (SMT) through a work environment survey in April 2014. Different regression equations were analysed to assess marginal effects of the employer's efforts on overall labour effectiveness (OLE), informal work impairments (IWI), lost working hours (LWH), and labour productivity loss (LPL) in terms of money. The employer's multifactorial efforts resulted in increasing OLE, decreasing IWI and illness-related LWH, and cost savings in terms of decreasing LPL. Environmental factors at the workplace are the important determinant factor for OLE, and the latter is where socio-economic impacts of the employer's efforts primarily manifest.

Prolotherapy for Osteoarthritis and Tendinopathy: a Descriptive Review.

PubMed

Rabago, David; Nourani, Bobby

2017-06-01

Osteoarthritis and overuse tendinopathy are common chronic conditions of high societal and patient burden. The precise etiology of pain and disability in both conditions is multifactorial and not well understood. Patients are often refractory to conservative therapy. The development of new therapeutic options in both conditions is a public health priority. Prolotherapy is an injection-based outpatient regenerative therapy for chronic musculoskeletal conditions, including osteoarthritis and tendinopathy. The authors reviewed the basic science and clinical literature associated with prolotherapy for these conditions. Systematic review, including meta-analysis, and randomized controlled trials suggest that prolotherapy may be associated with symptom improvement in mild to moderate symptomatic knee osteoarthritis and overuse tendinopathy. Although the mechanism of action is not well understood and is likely multifactorial, a growing body of literature suggests that prolotherapy for knee osteoarthritis may be appropriate for the treatment of symptoms associated with knee osteoarthritis in carefully selected patients who are refractory to conservative therapy and deserves further basic and clinical science investigation for the treatment of osteoarthritis and tendinopathy.

Segregation analysis reveals evidence of a major gene for Alzheimer disease.

PubMed Central

Farrer, L A; Myers, R H; Connor, L; Cupples, L A; Growdon, J H

1991-01-01

In an attempt to resolve the relative influences of major genes, multifactorial heritability, and cohort effects on the susceptibility to Alzheimer disease (AD), complex segregation analysis was performed on 232 nuclear families. All families were consecutively ascertained through a single proband who was referred for diagnostic evaluation of a memory disorder. The results suggest that susceptibility to AD is determined, in part, by a major autosomal dominant allele with an additional multifactorial component. Single-locus, polygenic, sporadic, and no-transmission models, as well as recessive inheritance of the major effect, were significantly rejected. Excess transmission from the heterozygote was marginally significant and probably reflects the presence of phenocopies or perhaps the existence of two or more major loci for AD. The frequency of the AD susceptibility allele was estimated to be .038, but the major locus accounts for only 24% of the transmission variance, indicating a substantial role for other genetic and nongenetic mechanisms in the causation of AD. PMID:2035523

Enhanced efficacy and reduced toxicity of multifactorial adjuvants compared with unitary adjuvants as cancer vaccines.

PubMed

Ahonen, Cory L; Wasiuk, Anna; Fuse, Shinichiro; Turk, Mary Jo; Ernstoff, Marc S; Suriawinata, Arief A; Gorham, James D; Kedl, Ross M; Usherwood, Edward J; Noelle, Randolph J

2008-03-15

Identification of Toll-like receptors (TLRs) and their ligands, and tumor necrosis factor-tumor necrosis factor receptor (TNF-TNFR) pairs have provided the first logical, hypothesis-based strategies to molecularly concoct adjuvants to elicit potent cell-mediated immunity via activation of innate and adaptive immunity. However, isolated activation of one immune pathway in the absence of others can be toxic, ineffective, and detrimental to long-term, protective immunity. Effective engineered vaccines must include agents that trigger multiple immunologic pathways. Here, we report that combinatorial use of CD40 and TLR agonists as a cancer vaccine, compared with monotherapy, elicits high frequencies of self-reactive CD8(+) T cells, potent tumor-specific CD8(+) memory, CD8(+) T cells that efficiently infiltrate the tumor-burdened target organ; therapeutic efficacy; heightened ratios of CD8(+) T cells to FoxP3(+) cells at the tumor site; and reduced hepatotoxicity. These findings provide intelligent strategies for the formulation of multifactorial vaccines to achieve maximal efficacy in cancer vaccine trials in humans.

Theory of signs and statistical approach to big data in assessing the relevance of clinical biomarkers of inflammation and oxidative stress.

PubMed

Ghezzi, Pietro; Davies, Kevin; Delaney, Aidan; Floridi, Luciano

2018-03-06

Biomarkers are widely used not only as prognostic or diagnostic indicators, or as surrogate markers of disease in clinical trials, but also to formulate theories of pathogenesis. We identify two problems in the use of biomarkers in mechanistic studies. The first problem arises in the case of multifactorial diseases, where different combinations of multiple causes result in patient heterogeneity. The second problem arises when a pathogenic mediator is difficult to measure. This is the case of the oxidative stress (OS) theory of disease, where the causal components are reactive oxygen species (ROS) that have very short half-lives. In this case, it is usual to measure the traces left by the reaction of ROS with biological molecules, rather than the ROS themselves. Borrowing from the philosophical theories of signs, we look at the different facets of biomarkers and discuss their different value and meaning in multifactorial diseases and system medicine to inform their use in patient stratification in personalized medicine.

Mental Models of Cause and Inheritance for Type 2 Diabetes Among Unaffected Individuals Who Have a Positive Family History.

PubMed

Daack-Hirsch, Sandra; Shah, Lisa L; Cady, Alyssa D

2018-03-01

Using the familial risk perception (FRP) model as a framework, we elicited causal and inheritance explanations for type 2 diabetes (T2D) from people who do not have T2D but have a family history for it. We identified four composite mental models for cause of T2D: (a) purely genetic; (b) purely behavioral/environmental; (c) direct multifactorial, in which risk factors interact and over time directly lead to T2D; and (d) indirect multifactorial, in which risk factors interact and over time cause a precursor health condition (such as obesity or metabolic syndrome) that leads to T2D. Interestingly, participants described specific risk factors such as genetics, food habits, lifestyle, weight, and culture as "running in the family." Our findings provide insight into lay beliefs about T2D that can be used by clinicians to anticipate or make sense of responses to questions they pose to patients about mental models for T2D.

Falls prevention in the elderly: translating evidence into practice.

PubMed

Luk, James K H; Chan, T Y; Chan, Daniel K Y

2015-04-01

Falls are a common problem in the elderly. A common error in their management is that injury from the fall is treated, without finding its cause. Thus a proactive approach is important to screen for the likelihood of fall in the elderly. Fall assessment usually includes a focused history and a targeted examination. Timed up-and-go test can be performed quickly and is able to predict the likelihood of fall. Evidence-based fall prevention interventions include multi-component group or home-based exercises, participation in Tai Chi, environmental modifications, medication review, management of foot and footwear problems, vitamin D supplementation, and management of cardiovascular problems. If possible, these are best implemented in the form of multifactorial intervention. Bone health enhancement for residential care home residents and appropriate community patients, and prescription of hip protectors for residential care home residents are also recommended. Multifactorial intervention may also be useful in a hospital and residential care home setting. Use of physical restraints is not recommended for fall prevention.

Relation between experimental and non-experimental study designs. HB vaccines: a case study.

PubMed

Jefferson, T; Demicheli, V

1999-01-01

To examine the relation between experimental and non-experimental study design in vaccinology. Assessment of each study design's capability of testing four aspects of vaccine performance, namely immunogenicity (the capacity to stimulate the immune system), duration of immunity conferred, incidence and seriousness of side effects, and number of infections prevented by vaccination. Experimental and non-experimental studies on hepatitis B (HB) vaccines in the Cochrane Vaccines Field Database. Experimental and non-experimental vaccine study designs are frequently complementary but some aspects of vaccine quality can only be assessed by one of the types of study. More work needs to be done on the relation between study quality and its significance in terms of effect size.

Elements That Contribute to Healthy Building Design

PubMed Central

Loftness, Vivian; Hakkinen, Bert; Adan, Olaf; Nevalainen, Aino

2007-01-01

Background The elements that contribute to a healthy building are multifactorial and can be discussed from different perspectives. Objectives We present three viewpoints of designing a healthy building: the importance of sustainable development, the role of occupants for ensuring indoor air quality, and ongoing developments related to indoor finishes with low chemical emissions and good fungal resistance. Discussion Sustainable design rediscovers the social, environmental, and technical values of pedestrian and mixed-use communities, using existing infrastructures including “main streets” and small-town planning principles and recapturing indoor–outdoor relationships. This type of design introduces nonpolluting materials and assemblies with lower energy requirements and higher durability and recyclability. Building occupants play a major role in maintaining healthy indoor environments, especially in residences. Contributors to indoor air quality include cleaning habits and other behaviors; consumer products, furnishings, and appliances purchases, as well as where and how the occupants use them. Certification of consumer products and building materials as low-emitting products is a primary control measure for achieving good indoor air quality. Key products in this respect are office furniture, flooring, paints and coatings, adhesives and sealants, wall coverings, wood products, textiles, insulation, and cleaning products. Finishing materials play a major role in the quality of indoor air as related to moisture retention and mold growth. Conclusions Sustainable design emphasizes the needs of infrastructure, lower energy consumption, durability, and recyclability. To ensure good indoor air quality, the product development for household use should aim to reduce material susceptibility to contaminants such as mold and should adopt consumer-oriented product labeling. PMID:17589608

Stent Design Affects Femoropopliteal Artery Deformation.

PubMed

MacTaggart, Jason; Poulson, William; Seas, Andreas; Deegan, Paul; Lomneth, Carol; Desyatova, Anastasia; Maleckis, Kaspars; Kamenskiy, Alexey

2018-03-23

Poor durability of femoropopliteal artery (FPA) stenting is multifactorial, and severe FPA deformations occurring with limb flexion are likely involved. Different stent designs result in dissimilar stent-artery interactions, but the degree of these effects in the FPA is insufficiently understood. To determine how different stent designs affect limb flexion-induced FPA deformations. Retrievable markers were deployed into n = 28 FPAs of lightly embalmed human cadavers. Bodies were perfused and CT images were acquired with limbs in the standing, walking, sitting, and gardening postures. Image analysis allowed measurement of baseline FPA foreshortening, bending, and twisting associated with each posture. Markers were retrieved and 7 different stents were deployed across the adductor hiatus in the same limbs. Markers were then redeployed in the stented FPAs, and limbs were reimaged. Baseline and stented FPA deformations were compared to determine the influence of each stent design. Proximal to the stent, Innova, Supera, and SmartFlex exacerbated foreshortening, SmartFlex exacerbated twisting, and SmartControl restricted bending of the FPA. Within the stent, all devices except Viabahn restricted foreshortening; Supera, SmartControl, and AbsolutePro restricted twisting; SmartFlex and Innova exacerbated twisting; and Supera and Viabahn restricted bending. Distal to the stents, all devices except AbsolutePro and Innova exacerbated foreshortening, and Viabahn, Supera, Zilver, and SmartControl exacerbated twisting. All stents except Supera were pinched in flexed limb postures. Peripheral self-expanding stents significantly affect limb flexion-induced FPA deformations, but in different ways. Although certain designs seem to accommodate some deformation modes, no device was able to match all FPA deformations.

The Experimental Design Ability Test (EDAT)

ERIC Educational Resources Information Center

Sirum, Karen; Humburg, Jennifer

2011-01-01

Higher education goals include helping students develop evidence based reasoning skills; therefore, scientific thinking skills such as those required to understand the design of a basic experiment are important. The Experimental Design Ability Test (EDAT) measures students' understanding of the criteria for good experimental design through their…

14 CFR 437.85 - Allowable design changes; modification of an experimental permit.

Code of Federal Regulations, 2014 CFR

2014-01-01

... Conditions of an Experimental Permit § 437.85 Allowable design changes; modification of an experimental... 14 Aeronautics and Space 4 2014-01-01 2014-01-01 false Allowable design changes; modification of an experimental permit. 437.85 Section 437.85 Aeronautics and Space COMMERCIAL SPACE TRANSPORTATION...

14 CFR 437.85 - Allowable design changes; modification of an experimental permit.

Code of Federal Regulations, 2012 CFR

2012-01-01

... Conditions of an Experimental Permit § 437.85 Allowable design changes; modification of an experimental... 14 Aeronautics and Space 4 2012-01-01 2012-01-01 false Allowable design changes; modification of an experimental permit. 437.85 Section 437.85 Aeronautics and Space COMMERCIAL SPACE TRANSPORTATION...

14 CFR 437.85 - Allowable design changes; modification of an experimental permit.

Code of Federal Regulations, 2011 CFR

2011-01-01

... Conditions of an Experimental Permit § 437.85 Allowable design changes; modification of an experimental... 14 Aeronautics and Space 4 2011-01-01 2011-01-01 false Allowable design changes; modification of an experimental permit. 437.85 Section 437.85 Aeronautics and Space COMMERCIAL SPACE TRANSPORTATION...

14 CFR 437.85 - Allowable design changes; modification of an experimental permit.

Code of Federal Regulations, 2013 CFR

2013-01-01

... Conditions of an Experimental Permit § 437.85 Allowable design changes; modification of an experimental... 14 Aeronautics and Space 4 2013-01-01 2013-01-01 false Allowable design changes; modification of an experimental permit. 437.85 Section 437.85 Aeronautics and Space COMMERCIAL SPACE TRANSPORTATION...

14 CFR 437.85 - Allowable design changes; modification of an experimental permit.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Conditions of an Experimental Permit § 437.85 Allowable design changes; modification of an experimental... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Allowable design changes; modification of an experimental permit. 437.85 Section 437.85 Aeronautics and Space COMMERCIAL SPACE TRANSPORTATION...

Quiet Clean Short-Haul Experimental Engine (QSCEE). Preliminary analyses and design report, volume 1

NASA Technical Reports Server (NTRS)

1974-01-01

The experimental propulsion systems to be built and tested in the 'quiet, clean, short-haul experimental engine' program are presented. The flight propulsion systems are also presented. The following areas are discussed: acoustic design; emissions control; engine cycle and performance; fan aerodynamic design; variable-pitch actuation systems; fan rotor mechanical design; fan frame mechanical design; and reduction gear design.

Effect of experimental design on the prediction performance of calibration models based on near-infrared spectroscopy for pharmaceutical applications.

PubMed

Bondi, Robert W; Igne, Benoît; Drennen, James K; Anderson, Carl A

2012-12-01

Near-infrared spectroscopy (NIRS) is a valuable tool in the pharmaceutical industry, presenting opportunities for online analyses to achieve real-time assessment of intermediates and finished dosage forms. The purpose of this work was to investigate the effect of experimental designs on prediction performance of quantitative models based on NIRS using a five-component formulation as a model system. The following experimental designs were evaluated: five-level, full factorial (5-L FF); three-level, full factorial (3-L FF); central composite; I-optimal; and D-optimal. The factors for all designs were acetaminophen content and the ratio of microcrystalline cellulose to lactose monohydrate. Other constituents included croscarmellose sodium and magnesium stearate (content remained constant). Partial least squares-based models were generated using data from individual experimental designs that related acetaminophen content to spectral data. The effect of each experimental design was evaluated by determining the statistical significance of the difference in bias and standard error of the prediction for that model's prediction performance. The calibration model derived from the I-optimal design had similar prediction performance as did the model derived from the 5-L FF design, despite containing 16 fewer design points. It also outperformed all other models estimated from designs with similar or fewer numbers of samples. This suggested that experimental-design selection for calibration-model development is critical, and optimum performance can be achieved with efficient experimental designs (i.e., optimal designs).

Integrating Demographic, Clinical,and Environmental Exposure Information to Identify Genomic Biomarkers Associated With Subtypes of Childhood Asthma

EPA Science Inventory

Childhood asthma is a multifactorial disease with a disturbingly high incidence in urbanized areas. The pathogenesis of asthma is poorly understood due to the complex relationship between genetic susceptibility and modulating environmental factors. The Mechanistic Indicators of C...

Autism Spectrum Disorders and Epigenetics

ERIC Educational Resources Information Center

Grafodatskaya, Daria; Chung, Brian; Szatmari, Peter; Weksberg, Rosanna

2010-01-01

Objective: Current research suggests that the causes of autism spectrum disorders (ASD) are multifactorial and include both genetic and environmental factors. Several lines of evidence suggest that epigenetics also plays an important role in ASD etiology and that it might, in fact, integrate genetic and environmental influences to dysregulate…

The Intergenerational Transmission of Parenting Styles of Irish Immigrant Mothers

ERIC Educational Resources Information Center

O'Brien, Helen G.

2010-01-01

The research on child developmental outcomes underscores the importance of exploring parenting styles and identifying their multifactorial and intergenerational influences. This descriptive study examined the individual parenting styles of a sample of 82 Irish immigrant mothers and investigated the factors that influenced their individual…

Autism Spectrum Disorders Associated with Chromosomal Abnormalities

ERIC Educational Resources Information Center

Lo-Castro, Adriana; Benvenuto, Arianna; Galasso, Cinzia; Porfirio, Cristina; Curatolo, Paolo

2010-01-01

Autism spectrum disorders (ASDs) constitute a class of severe neurodevelopmental conditions with complex multifactorial and heterogeneous etiology. Despite high estimates of heritability, genetic causes of ASDs remain elusive, due to a high degree of genetic and phenotypic heterogeneity. So far, several "monogenic" forms of autism have been…

ANTHROPOGENIC NUTRIENT INPUT AND ITS INFLUENCE ON PLANT COMPETITIVE OUTCOMES: IMPLICATIONS FOR HABITAT DEGRADATION AND COMMUNITY SHIFTS

EPA Science Inventory

By taking a multifactorial approach, the study will document complex aquatic plant responses to NPS nutrient contamination, providing fundamental insight into the broader impacts of environmental degradation, its impacts on plant function, and implications for ecosystem ser...

A Developmental-Genetic Model of Alcoholism: Implications for Genetic Research.

ERIC Educational Resources Information Center

Devor, Eric J.

1994-01-01

Research for biological-genetic markers of alcoholism is discussed in context of a multifactorial, heterogeneous, developmental model. Suggested that strategies used in linkage and association studies will require modification. Also suggested several extant associations of genetic markers represent true secondary interactive phenomena that alter…

Co-existent Presence of Alopecia Areata in Siblings: A Rare Presentation.

PubMed

Mohanty, Sandip; Rohatgi, Pallavi C; Manchanda, Kajal

2014-04-01

Alopecia areata (AA) is a T cell mediated autoimmune disease with multifactorial etiology resulting in partial and total nonscarring alopecia. We hereby report a case of two brothers (aged 7 and 5 years) presenting with coincidental AA over scalp which is a rare presentation.

Parotid sialolithiasis.

PubMed

Moghe, Swapnil; Pillai, Ajay; Thomas, Shaji; Nair, Preeti P

2012-12-14

Salivary dysfunction may be due to systemic diseases and medications. The development of sialoliths is a multifactorial event in which disturbance in secretion, microliths and bacteria may play a major role. A case of sialolith in the parotid gland of a 25-year-old man, with no relevant medical history is reported here.

75 FR 7573 - Office of Safe and Drug-Free Schools; Overview Information; Models of Exemplary, Effective, and...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-22

... to the research, then a quasi- experimental evaluation of the program's implementation on the... experimental or quasi- experimental research design, with the evaluation results suggesting effectiveness in... this grant competition, a research design of the highest quality means an experimental design in which...

Web Based Learning Support for Experimental Design in Molecular Biology.

ERIC Educational Resources Information Center

Wilmsen, Tinri; Bisseling, Ton; Hartog, Rob

An important learning goal of a molecular biology curriculum is a certain proficiency level in experimental design. Currently students are confronted with experimental approaches in textbooks, in lectures and in the laboratory. However, most students do not reach a satisfactory level of competence in the design of experimental approaches. This…

75 FR 43172 - Maternal, Infant, and Early Childhood Home Visiting Program

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-23

... the evaluation results have been published in a peer-reviewed journal; or (bb) quasi-experimental... design (i.e. randomized controlled trial [RCT] or quasi-experimental design [QED]), level of attrition... a quasi-experimental design as a study design in which sample members are selected for the program...

75 FR 23775 - Agency Information Collection Activities; Proposed Collection; Comment Request; Experimental...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-04

... for research entitled ``Experimental Study of Patient Information Prototypes.'' This study is designed..., the working group refined several prototypes and designed a study to investigate the usefulness of... Design and Protocol The study is experimental and will have two independent variables in a 3 x 2 design...

Risk Assessment and Communication Tools for Genotype Associations with Multifactorial Phenotypes: The Concept of “Edge Effect” and Cultivating an Ethical Bridge between Omics Innovations and Society

PubMed Central

Suarez-Kurtz, Guilherme; Stenne, Raphaëlle; Somogyi, Andrew A.; Someya, Toshiyuki; Kayaalp, S. Oğuz; Kolker, Eugene

2009-01-01

Abstract Applications of omics technologies in the postgenomics era swiftly expanded from rare monogenic disorders to multifactorial common complex diseases, pharmacogenomics, and personalized medicine. Already, there are signposts indicative of further omics technology investment in nutritional sciences (nutrigenomics), environmental health/ecology (ecogenomics), and agriculture (agrigenomics). Genotype–phenotype association studies are a centerpiece of translational research in omics science. Yet scientific and ethical standards and ways to assess and communicate risk information obtained from association studies have been neglected to date. This is a significant gap because association studies decisively influence which genetic loci become genetic tests in the clinic or products in the genetic test marketplace. A growing challenge concerns the interpretation of large overlap typically observed in distribution of quantitative traits in a genetic association study with a polygenic/multifactorial phenotype. To remedy the shortage of risk assessment and communication tools for association studies, this paper presents the concept of edge effect. That is, the shift in population edges of a multifactorial quantitative phenotype is a more sensitive measure (than population averages) to gauge the population level impact and by extension, policy significance of an omics marker. Empirical application of the edge effect concept is illustrated using an original analysis of warfarin pharmacogenomics and the VKORC1 genetic variation in a Brazilian population sample. These edge effect analyses are examined in relation to regulatory guidance development for association studies. We explain that omics science transcends the conventional laboratory bench space and includes a highly heterogeneous cast of stakeholders in society who have a plurality of interests that are often in conflict. Hence, communication of risk information in diagnostic medicine also demands attention to processes involved in production of knowledge and human values embedded in scientific practice, for example, why, how, by whom, and to what ends association studies are conducted, and standards are developed (or not). To ensure sustainability of omics innovations and forecast their trajectory, we need interventions to bridge the gap between omics laboratory and society. Appreciation of scholarship in history of omics science is one remedy to responsibly learn from the past to ensure a sustainable future in omics fields, both emerging (nutrigenomics, ecogenomics), and those that are more established (pharmacogenomics). Another measure to build public trust and sustainability of omics fields could be legislative initiatives to create a multidisciplinary oversight body, at arm's length from conflict of interests, to carry out independent, impartial, and transparent innovation analyses and prospective technology assessment. PMID:19290811

Risk assessment and communication tools for genotype associations with multifactorial phenotypes: the concept of "edge effect" and cultivating an ethical bridge between omics innovations and society.

PubMed

Ozdemir, Vural; Suarez-Kurtz, Guilherme; Stenne, Raphaëlle; Somogyi, Andrew A; Someya, Toshiyuki; Kayaalp, S Oğuz; Kolker, Eugene

2009-02-01

Applications of omics technologies in the postgenomics era swiftly expanded from rare monogenic disorders to multifactorial common complex diseases, pharmacogenomics, and personalized medicine. Already, there are signposts indicative of further omics technology investment in nutritional sciences (nutrigenomics), environmental health/ecology (ecogenomics), and agriculture (agrigenomics). Genotype-phenotype association studies are a centerpiece of translational research in omics science. Yet scientific and ethical standards and ways to assess and communicate risk information obtained from association studies have been neglected to date. This is a significant gap because association studies decisively influence which genetic loci become genetic tests in the clinic or products in the genetic test marketplace. A growing challenge concerns the interpretation of large overlap typically observed in distribution of quantitative traits in a genetic association study with a polygenic/multifactorial phenotype. To remedy the shortage of risk assessment and communication tools for association studies, this paper presents the concept of edge effect. That is, the shift in population edges of a multifactorial quantitative phenotype is a more sensitive measure (than population averages) to gauge the population level impact and by extension, policy significance of an omics marker. Empirical application of the edge effect concept is illustrated using an original analysis of warfarin pharmacogenomics and the VKORC1 genetic variation in a Brazilian population sample. These edge effect analyses are examined in relation to regulatory guidance development for association studies. We explain that omics science transcends the conventional laboratory bench space and includes a highly heterogeneous cast of stakeholders in society who have a plurality of interests that are often in conflict. Hence, communication of risk information in diagnostic medicine also demands attention to processes involved in production of knowledge and human values embedded in scientific practice, for example, why, how, by whom, and to what ends association studies are conducted, and standards are developed (or not). To ensure sustainability of omics innovations and forecast their trajectory, we need interventions to bridge the gap between omics laboratory and society. Appreciation of scholarship in history of omics science is one remedy to responsibly learn from the past to ensure a sustainable future in omics fields, both emerging (nutrigenomics, ecogenomics), and those that are more established (pharmacogenomics). Another measure to build public trust and sustainability of omics fields could be legislative initiatives to create a multidisciplinary oversight body, at arm's length from conflict of interests, to carry out independent, impartial, and transparent innovation analyses and prospective technology assessment.

Experimental validation of an integrated controls-structures design methodology for a class of flexible space structures

NASA Technical Reports Server (NTRS)

Maghami, Peiman G.; Gupta, Sandeep; Elliott, Kenny B.; Joshi, Suresh M.; Walz, Joseph E.

1994-01-01

This paper describes the first experimental validation of an optimization-based integrated controls-structures design methodology for a class of flexible space structures. The Controls-Structures-Interaction (CSI) Evolutionary Model, a laboratory test bed at Langley, is redesigned based on the integrated design methodology with two different dissipative control strategies. The redesigned structure is fabricated, assembled in the laboratory, and experimentally compared with the original test structure. Design guides are proposed and used in the integrated design process to ensure that the resulting structure can be fabricated. Experimental results indicate that the integrated design requires greater than 60 percent less average control power (by thruster actuators) than the conventional control-optimized design while maintaining the required line-of-sight performance, thereby confirming the analytical findings about the superiority of the integrated design methodology. Amenability of the integrated design structure to other control strategies is considered and evaluated analytically and experimentally. This work also demonstrates the capabilities of the Langley-developed design tool CSI DESIGN which provides a unified environment for structural and control design.

City Connects: Building an Argument for Effects on Student Achievement with a Quasi-Experimental Design

ERIC Educational Resources Information Center

Walsh, Mary; Raczek, Anastasia; Sibley, Erin; Lee-St. John, Terrence; An, Chen; Akbayin, Bercem; Dearing, Eric; Foley, Claire

2015-01-01

While randomized experimental designs are the gold standard in education research concerned with causal inference, non-experimental designs are ubiquitous. For researchers who work with non-experimental data and are no less concerned for causal inference, the major problem is potential omitted variable bias. In this presentation, the authors…

Experimental Design and Some Threats to Experimental Validity: A Primer

ERIC Educational Resources Information Center

Skidmore, Susan

2008-01-01

Experimental designs are distinguished as the best method to respond to questions involving causality. The purpose of the present paper is to explicate the logic of experimental design and why it is so vital to questions that demand causal conclusions. In addition, types of internal and external validity threats are discussed. To emphasize the…

Analyzing Data from a Pretest-Posttest Control Group Design: The Importance of Statistical Assumptions

ERIC Educational Resources Information Center

Zientek, Linda; Nimon, Kim; Hammack-Brown, Bryn

2016-01-01

Purpose: Among the gold standards in human resource development (HRD) research are studies that test theoretically developed hypotheses and use experimental designs. A somewhat typical experimental design would involve collecting pretest and posttest data on individuals assigned to a control or experimental group. Data from such a design that…

Multifactorial antimicrobial wood protectants

Treesearch

Robert D. Coleman; Carol A. Clausen

2008-01-01

It is unlikely that a single antimicrobial compound, whether synthetic or natural, will provide the ‘magic bullet’ for eliminating multiple biological agents affecting wood products. Development of synergistic combinations of selected compounds, especially those derived from natural sources, is recognized as a promising approach to improved wood protection. Recent...

Increased Serum Levels of Epidermal Growth Factor in Children with Autism

ERIC Educational Resources Information Center

Iseri, Elvan; Guney, Esra; Ceylan, Mehmet F.; Yucel, Aysegul; Aral, Arzu; Bodur, Sahin; Sener, Sahnur

2011-01-01

The etiology of autism is unclear, however autism is considered as a multifactorial disorder that is influenced by neurological, environmental, immunological and genetic factors. Growth factors, including epidermal growth factor (EGF), play an important role in the celluler proliferation and the differentiation of the central and peripheral…

Variables Affecting Emerging Adults' Self-Reported Risk and Reckless Behaviors

ERIC Educational Resources Information Center

Duangpatra, Krisna N. K.; Bradley, Graham L.; Glendon, A. Ian

2009-01-01

Young adults' behaviors are frequently characterized by risk-taking and recklessness. Few studies have examined the correlates of risk and reckless behaviors in emerging adults. Drawing on theories emphasising multifactorial effects of personality, social, and cognitive variables, this study explores psychosocial factors contributing to risk and…

Aetiology of Autism: Findings and Questions

ERIC Educational Resources Information Center

Rutter, M.

2005-01-01

Background Although there is good evidence that autism is a multifactorial disorder, an adequate understanding of the genetic and non-genetic causes has yet to be achieved. Methods Empirical research findings and conceptual reviews are reviewed with respect to evidence on possible causal influences. Results Much the strongest evidence concerns the…

Acute and chronic effects of transportation stress in the honey bee, Apis mellifera

USDA-ARS?s Scientific Manuscript database

Owing to the continued impact of colony collapse disorder (CCD) on the beekeeping industry, numerous stressors including nutrition, pests and pathogens and biocides are being investigated as potential contributors to what appears to be a multi-factorial disorder. Because honey bee hives are transpo...

Association of Autism Spectrum Disorders and Inflammatory Bowel Disease

ERIC Educational Resources Information Center

Lee, Maunoo; Krishnamurthy, Jayasree; Susi, Apryl; Sullivan, Carolyn; Gorman, Gregory H.; Hisle-Gorman, Elizabeth; Erdie-Lalena, Christine R.; Nylund, Cade M.

2018-01-01

Autism spectrum disorders (ASD) and inflammatory bowel disease (IBD) both have multifactorial pathogenesis with an increasing number of studies demonstrating gut-brain associations. We aim to examine the association between ASD and IBD using strict classification criteria for IBD. We conducted a retrospective case-cohort study using records from…

Bovine coronavirus antibody titers at weaning negatively correlate with incidence of bovine respiratory disease in the feed yard

USDA-ARS?s Scientific Manuscript database

Bovine respiratory disease complex (BRDC) is a multifactorial disease caused by complex interactions among viral and bacterial pathogens, stressful management practices and host genetic variability. Although vaccines and antibiotic treatments are readily available to prevent and treat infection caus...

Parents Psychopathology of Children with Attention Deficit Hyperactivity Disorder

ERIC Educational Resources Information Center

Margari, Francesco; Craig, Francesco; Petruzzelli, Maria Giuseppina; Lamanna, Annalinda; Matera, Emilia; Margari, Lucia

2013-01-01

Attention Deficit Hyperactivity Disorder (ADHD) is a disorder with extremely complex etiology, not yet well defined but certainly multi-factorial. This study investigated the possible etiopathogenetic role of ADHD symptoms and psychopathology disorders in parents of children with ADHD. We present a case-control study of parents of 50 children…

The volatilization of SPLAT® for use in pheromone mating disruption of cranberry pests

USDA-ARS?s Scientific Manuscript database

The paraffin-based pheromone carrier, SPLAT, was tested for its volatilization rate. A multi-factorial study was initiated to examine the interactive effects of point-source size, shape, and duration. The study showed that tremendous amounts of the pheromone were released early, followed by a gradua...

Foreign-Accented Speech Perception Ratings: A Multifactorial Case Study

ERIC Educational Resources Information Center

Kraut, Rachel; Wulff, Stefanie

2013-01-01

Seventy-eight native English speakers rated the foreign-accented speech (FAS) of 24 international students enrolled in an Intensive English programme at a public university in Texas on degree of accent, comprehensibility and communicative ability. Variables considered to potentially impact listeners' ratings were the sex of the speaker, the first…

Parotid sialolithiasis

PubMed Central

Moghe, Swapnil; Pillai, Ajay; Thomas, Shaji; Nair, Preeti P

2012-01-01

Salivary dysfunction may be due to systemic diseases and medications. The development of sialoliths is a multifactorial event in which disturbance in secretion, microliths and bacteria may play a major role. A case of sialolith in the parotid gland of a 25-year-old man, with no relevant medical history is reported here. PMID:23242089

Engaging Community-Based Organizations in Fall Prevention Education

ERIC Educational Resources Information Center

Kramer, B. Josea; Vivrette, Rebecca L.; Rubenstein, Laurence Z.

2011-01-01

Falls are a major public health problem for older adults, and community-based organizations play a key role in educating seniors about falls prevention (FP). We conducted a qualitative process evaluation at six sites to report community-based centers' perspectives on adoption, adaptation, and sustainability of an evidence-based multifactorial FP…

Effect of 2-hydroxy-4-(methylthio)butanoate (HMTBa) on risk of biohydrogenation-induced milk fat depression

USDA-ARS?s Scientific Manuscript database

Diet-induced milk fat depression (MFD) is a multifactorial condition resulting from the interaction of numerous risk factors including diet fermentability and unsaturated fatty acids (FA) concentration, feed additives, and individual cow effects. 2-hydroxy-4-(methylthio)butanoate (HMTBa) is a methio...

Mild Thyroid Hormone Insufficiency During Development Compromises Activity-Dependent Neuroplasticity in the Hippocampus of Adult Make Rats

EPA Science Inventory

Severe thyroid hormone (TH) deficiency during critical phases of brain development results in irreversible neurological and cognitive impairments. The mechanisms accounting for this are likely multifactorial, and are not fully understood. Here we pursue the possibility that one i...

The Multifactorial Nature of Extraversion-Introversion in the Myers-Briggs Type Indicator and Eysenck Personality Inventory.

ERIC Educational Resources Information Center

Sipps, Gary J.; Alexander, Ralph A.

1987-01-01

The construct validity of extraversion-introversion was explored, as measured by the Myers Briggs Type Indicator (MBTI) and the Eysenck Personality Inventory. Findings supported the complexity of extraversion-introversion. Two MBTI scales, Extraversion Introversion and Judging Perceiving, were factorially valid measures of impulsivity…

Military Personnel Attrition and Retention: Research in Progress

DTIC Science & Technology

1981-10-01

designed to assess the relative risks of attrition among non -h.gh. school graduate Army enlistees. As a group, these individuals historically...this methodology see the Majcýhrzak paper in this volume) Research in the PlanningStaaqe Stage ’TV: Administrative Experimentation In order to derive...different research designs : 1. True experimental designs ; 2. Correlational research designs ; 3. Quasi- experimental research designs . We rejected the idea

A Robust Adaptive Autonomous Approach to Optimal Experimental Design

NASA Astrophysics Data System (ADS)

Gu, Hairong

Experimentation is the fundamental tool of scientific inquiries to understand the laws governing the nature and human behaviors. Many complex real-world experimental scenarios, particularly in quest of prediction accuracy, often encounter difficulties to conduct experiments using an existing experimental procedure for the following two reasons. First, the existing experimental procedures require a parametric model to serve as the proxy of the latent data structure or data-generating mechanism at the beginning of an experiment. However, for those experimental scenarios of concern, a sound model is often unavailable before an experiment. Second, those experimental scenarios usually contain a large number of design variables, which potentially leads to a lengthy and costly data collection cycle. Incompetently, the existing experimental procedures are unable to optimize large-scale experiments so as to minimize the experimental length and cost. Facing the two challenges in those experimental scenarios, the aim of the present study is to develop a new experimental procedure that allows an experiment to be conducted without the assumption of a parametric model while still achieving satisfactory prediction, and performs optimization of experimental designs to improve the efficiency of an experiment. The new experimental procedure developed in the present study is named robust adaptive autonomous system (RAAS). RAAS is a procedure for sequential experiments composed of multiple experimental trials, which performs function estimation, variable selection, reverse prediction and design optimization on each trial. Directly addressing the challenges in those experimental scenarios of concern, function estimation and variable selection are performed by data-driven modeling methods to generate a predictive model from data collected during the course of an experiment, thus exempting the requirement of a parametric model at the beginning of an experiment; design optimization is performed to select experimental designs on the fly of an experiment based on their usefulness so that fewest designs are needed to reach useful inferential conclusions. Technically, function estimation is realized by Bayesian P-splines, variable selection is realized by Bayesian spike-and-slab prior, reverse prediction is realized by grid-search and design optimization is realized by the concepts of active learning. The present study demonstrated that RAAS achieves statistical robustness by making accurate predictions without the assumption of a parametric model serving as the proxy of latent data structure while the existing procedures can draw poor statistical inferences if a misspecified model is assumed; RAAS also achieves inferential efficiency by taking fewer designs to acquire useful statistical inferences than non-optimal procedures. Thus, RAAS is expected to be a principled solution to real-world experimental scenarios pursuing robust prediction and efficient experimentation.

Age 60 Study. Part 1. Bibliographic Database

DTIC Science & Technology

1994-10-01

seven of these aircraft types participated in a spectacle design study. Experimental spectacles were designed for each pilot and evaluated for...observation flight administered by observers who were uninformed of the details of the experimental design . Students and instructors also completed a critique...intraindividual lability in field-dependence-field independence, and (4) various measurement, sampling, and experimental design concerns associated

Mixed reality virtual pets to reduce childhood obesity.

PubMed

Johnsen, Kyle; Ahn, Sun Joo; Moore, James; Brown, Scott; Robertson, Thomas P; Marable, Amanda; Basu, Aryabrata

2014-04-01

Novel approaches are needed to reduce the high rates of childhood obesity in the developed world. While multifactorial in cause, a major factor is an increasingly sedentary lifestyle of children. Our research shows that a mixed reality system that is of interest to children can be a powerful motivator of healthy activity. We designed and constructed a mixed reality system that allowed children to exercise, play with, and train a virtual pet using their own physical activity as input. The health, happiness, and intelligence of each virtual pet grew as its associated child owner exercised more, reached goals, and interacted with their pet. We report results of a research study involving 61 children from a local summer camp that shows a large increase in recorded and observed activity, alongside observational evidence that the virtual pet was responsible for that change. These results, and the ease at which the system integrated into the camp environment, demonstrate the practical potential to impact the exercise behaviors of children with mixed reality.

Oxidative damage to macromolecules in human Parkinson’s disease and the rotenone model

PubMed Central

Sanders, Laurie H.; Greenamyre, J. Timothy

2013-01-01

Parkinson’s disease (PD), the most common neurodegenerative movement disorder, is associated with selective degeneration of nigrostriatal dopamine neurons. While the underlying mechanisms contributing to neurodegeneration in PD appear to be multifactorial, mitochondrial impairment and oxidative stress are widely considered to be central to many forms of the disease. Whether oxidative stress is a cause or consequence of dopaminergic death, there is substantial evidence for oxidative stress in both human PD patients and in animal models of PD, especially using rotenone, a complex I inhibitor. There are many indices of oxidative stress, but this review covers the recent evidence for oxidative damage to nucleic acids, lipids and proteins in both the brain and peripheral tissues in human PD and in the rotenone model. Limitations of the existing literature and future perspectives are discussed. Understanding how each particular macromolecule is damaged by oxidative stress and the interplay of secondary damage to other biomolecules may help design better targets for treatment of PD. PMID:23328732

Factors influencing adherence among Irish haemodialysis patients.

PubMed

Mellon, Lisa; Regan, Daniel; Curtis, Ruth

2013-07-01

Adherence to dietary and fluid restrictions among haemodialysis patients with end stage renal failure (ESRD) is a multi-factorial concept. This study seeks to assess the predictive value of demographic and psychological variables in non-adherence. A multi-centre cross sectional design assessed 50 haemodialysis patients on self reported adherence, attitudes towards dietary restrictions, quality of life, depression and anxiety. Adherence to fluid and dietary restrictions was measured objectively using potassium (K), phosphorus (PO4) and inter-dialytic weight gain (IDWG) parameters. 62% of patients were non-adherent with at least one aspect of the treatment regime. Regression analysis revealed age as significantly associated with adherence, in particular IDWG, with younger patients displaying poorer adherence. Younger patients may experience greater difficulty integrating complex treatment demands into their lifestyles, and non-adherence may be a consequence of the severe lifestyle limitations imposed by the haemodialysis treatment regime. Individualised interventions may be more effective than traditional methods of adherence monitoring in reducing the non-adherent behaviour. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

VerSeDa: vertebrate secretome database

PubMed Central

Cortazar, Ana R.; Oguiza, José A.

2017-01-01

Based on the current tools, de novo secretome (full set of proteins secreted by an organism) prediction is a time consuming bioinformatic task that requires a multifactorial analysis in order to obtain reliable in silico predictions. Hence, to accelerate this process and offer researchers a reliable repository where secretome information can be obtained for vertebrates and model organisms, we have developed VerSeDa (Vertebrate Secretome Database). This freely available database stores information about proteins that are predicted to be secreted through the classical and non-classical mechanisms, for the wide range of vertebrate species deposited at the NCBI, UCSC and ENSEMBL sites. To our knowledge, VerSeDa is the only state-of-the-art database designed to store secretome data from multiple vertebrate genomes, thus, saving an important amount of time spent in the prediction of protein features that can be retrieved from this repository directly. Database URL: VerSeDa is freely available at http://genomics.cicbiogune.es/VerSeDa/index.php PMID:28365718

TOWARD GREATER IMPLEMENTATION OF THE EXPOSOME RESEARCH PARADIGM WITHIN ENVIRONMENTAL EPIDEMIOLOGY

PubMed Central

Stingone, Jeanette A.; Buck Louis, Germaine M.; Nakayama, Shoji F.; Vermeulen, Roel C. H.; Kwok, Richard K.; Cui, Yuxia; Balshaw, David M.; Teitelbaum, Susan L.

2017-01-01

Investigating a single environmental exposure in isolation does not reflect the actual human exposure circumstance nor does it capture the multifactorial etiology of health and disease. The exposome, defined as the totality of environmental exposures from conception onward, may advance our understanding of environmental contributors to disease by more fully assessing the multitude of human exposures across the life course. Implementation into studies of human health has been limited, in part owing to theoretical and practical challenges including a lack of infrastructure to support comprehensive exposure assessment, difficulty in differentiating physiologic variation from environmentally induced changes, and the need for study designs and analytic methods that accommodate specific aspects of the exposome, such as high-dimensional exposure data and multiple windows of susceptibility. Recommendations for greater data sharing and coordination, methods development, and acknowledgment and minimization of multiple types of measurement error are offered to encourage researchers to embark on exposome research to promote the environmental health and well-being of all populations. PMID:28125387

From helical supramolecular arrays to gel-forming networks: lattice restructuring and aggregation control in peptide-based sulfamides to integrate new functional attributes.

PubMed

Raghava, Saripalli V; Srivastava, Bhartendu K; Ramshad, Kalluruttimmal; Antharjanam, Sudhadevi; Varghese, Babu; Muraleedharan, Kannoth M

2018-03-28

While supramolecular organisation is central to both crystallization and gelation, the latter is more complex considering its dynamic nature and multifactorial dependence. This makes the rational design of gelators an extremely difficult task. In this report, the assembly preference of a group of peptide-based sulfamides was modulated by making them part of an acid-amine two-component system to drive the tendency from crystallization to gelation. Here, the peptide core directed the assembly while the long-chain amines, introduced through salt-bridges, promoted layering and anisotropic development of primary aggregates. This proved to be very successful, leading to gelation of a number of solvents. Apart from this, it was possible to fine-tune their aggregation using an amphiphilic polymer like F-127 as an additive to get honey-comb-like 3D molecular architectures. These gels also proved to be excellent matrices for entrapping silver nanoparticles with superior emissive properties.

Interaction between Calpain 5, Peroxisome proliferator-activated receptor-gamma and Peroxisome proliferator-activated receptor-delta genes: a polygenic approach to obesity

PubMed Central

Sáez, María E; Grilo, Antonio; Morón, Francisco J; Manzano, Luis; Martínez-Larrad, María T; González-Pérez, Antonio; Serrano-Hernando, Javier; Ruiz, Agustín; Ramírez-Lorca, Reposo; Serrano-Ríos, Manuel

2008-01-01

Context Obesity is a multifactorial disorder, that is, a disease determined by the combined effect of genes and environment. In this context, polygenic approaches are needed. Objective To investigate the possibility of the existence of a crosstalk between the CALPAIN 10 homologue CALPAIN 5 and nuclear receptors of the peroxisome proliferator-activated receptors family. Design Cross-sectional, genetic association study and gene-gene interaction analysis. Subjects The study sample comprise 1953 individuals, 725 obese (defined as body mass index ≥ 30) and 1228 non obese subjects. Results In the monogenic analysis, only the peroxisome proliferator-activated receptor delta (PPARD) gene was associated with obesity (OR = 1.43 [1.04–1.97], p = 0.027). In addition, we have found a significant interaction between CAPN5 and PPARD genes (p = 0.038) that reduces the risk for obesity in a 55%. Conclusion Our results suggest that CAPN5 and PPARD gene products may also interact in vivo. PMID:18657264

Falls and Fall Prevention in Older Adults With Early-Stage Dementia: An Integrative Review.

PubMed

Lach, Helen W; Harrison, Barbara E; Phongphanngam, Sutthida

2017-05-01

Older adults with mild cognitive impairment (MCI) and early-stage dementia have an increased risk of falling, with risks to their health and quality of life. The purpose of the current integrative review was to evaluate evidence on fall risk and fall prevention in this population. Studies were included if they examined falls or fall risk factors in older adults with MCI or early-stage dementia, or reported interventions in this population; 40 studies met criteria. Evidence supports the increased risk of falls in individuals even in the early stages of dementia or MCI, and changes in gait, balance, and fear of falling that may be related to this increased fall risk. Interventions included exercise and multifactorial interventions that demonstrated some potential to reduce falls in this population. Few studies had strong designs to provide evidence for recommendations. Further study in this area is warranted. [Res Gerontol Nurs. 2017; 10(03):139-148.]. Copyright 2016, SLACK Incorporated.

Barriers to Liposomal Gene Delivery: from Application Site to the Target.

PubMed

Saffari, Mostafa; Moghimi, Hamid Reza; Dass, Crispin R

2016-01-01

Gene therapy is a therapeutic approach to deliver genetic material into cells to alter their function in entire organism. One promising form of gene delivery system (DDS) is liposomes. The success of liposome-mediated gene delivery is a multifactorial issue and well-designed liposomal systems might lead to optimized gene transfection particularly in vivo. Liposomal gene delivery systems face different barriers from their site of application to their target, which is inside the cells. These barriers include presystemic obstacles (epithelial barriers), systemic barriers in blood circulation and cellular barriers. Epithelial barriers differ depending on the route of administration. Systemic barriers include enzymatic degradation, binding and opsonisation. Both of these barriers can act as limiting hurdles that genetic material and their vector should overcome before reaching the cells. Finally liposomes should overcome cellular barriers that include cell entrance, endosomal escape and nuclear uptake. These barriers and their impact on liposomal gene delivery will be discussed in this review.

Advanced biological and chemical discovery (ABCD): centralizing discovery knowledge in an inherently decentralized world.

PubMed

Agrafiotis, Dimitris K; Alex, Simson; Dai, Heng; Derkinderen, An; Farnum, Michael; Gates, Peter; Izrailev, Sergei; Jaeger, Edward P; Konstant, Paul; Leung, Albert; Lobanov, Victor S; Marichal, Patrick; Martin, Douglas; Rassokhin, Dmitrii N; Shemanarev, Maxim; Skalkin, Andrew; Stong, John; Tabruyn, Tom; Vermeiren, Marleen; Wan, Jackson; Xu, Xiang Yang; Yao, Xiang

2007-01-01

We present ABCD, an integrated drug discovery informatics platform developed at Johnson & Johnson Pharmaceutical Research & Development, L.L.C. ABCD is an attempt to bridge multiple continents, data systems, and cultures using modern information technology and to provide scientists with tools that allow them to analyze multifactorial SAR and make informed, data-driven decisions. The system consists of three major components: (1) a data warehouse, which combines data from multiple chemical and pharmacological transactional databases, designed for supreme query performance; (2) a state-of-the-art application suite, which facilitates data upload, retrieval, mining, and reporting, and (3) a workspace, which facilitates collaboration and data sharing by allowing users to share queries, templates, results, and reports across project teams, campuses, and other organizational units. Chemical intelligence, performance, and analytical sophistication lie at the heart of the new system, which was developed entirely in-house. ABCD is used routinely by more than 1000 scientists around the world and is rapidly expanding into other functional areas within the J&J organization.

Flavonoids and Reduction of Cardiovascular Disease (CVD) in Chronic Obstructive Pulmonary Disease (COPD).

PubMed

Russo, Patrizia; Prinzi, Giulia; Lamonaca, Palma; Cardaci, Vittorio; Fini, Massimo

2018-05-13

Chronic obstructive pulmonary disease (COPD) and cardiovascular diseases (CV) often coexist. COPD and CVD are complex diseases characterized by a strict interaction between environment and genetic. The mechanisms linking these two diseases are complex, multifactorial and not entirely understood, influencing the therapeutic approach. COPD is characterized by several comorbidities, it is hypothesizable that treatment of cardiovascular co-morbidities may reduce morbidity and mortality. Flavonoids are an important class of plant low molecular weight secondary metabolites (SMs). Convincing data from laboratory, epidemiological, and human clinical studies point to an important effects on CVD risk prevention. This review aims to provide up-to-date information on the ability of Flavonoids to reduce the CVD risk. Current studies support the potential of Flavonoids to prevent the risk of CVD. Well-designed clinical studies are suggested to evaluate advantages and limits of Flavonoids for managing CVD comorbidity in COPD. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Targeting monoamine oxidases with multipotent ligands: an emerging strategy in the search of new drugs against neurodegenerative diseases.

PubMed

Pisani, L; Catto, M; Leonetti, F; Nicolotti, O; Stefanachi, A; Campagna, F; Carotti, A

2011-01-01

The socioeconomic burden of multi-factorial pathologies, such as neurodegenerative diseases (NDs), is enormous worldwide. Unfortunately, no proven disease-modifying therapy is available yet and in most cases (e.g., Alzheimer's and Parkinson's disease) the approved drugs exert only palliative and symptomatic effects. Nowadays, an emerging strategy for the discovery of disease-modifying drugs is based on the multi-target directed ligand (MTDL) design, an innovative shift from the traditional approach one-drug-one-target to the more ambitious one-drug-more-targets goal. Herein, we review the discovery strategy, the mechanism of action and the biopharmacological evaluation of multipotent ligands exhibiting monoamine oxidase (MAO) inhibition as the core activity with a potential for the treatment of NDs. In particular, MAO inhibitors exhibiting additional acetylcholinesterase (AChE) or nitric oxide synthase (NOS) inhibition, or ion chelation/antioxidant-radical scavenging/anti-inflammatory/A2A receptor antagonist/APP processing modulating activities have been thoroughly examined.

VerSeDa: vertebrate secretome database.

PubMed

Cortazar, Ana R; Oguiza, José A; Aransay, Ana M; Lavín, José L

2017-01-01

Based on the current tools, de novo secretome (full set of proteins secreted by an organism) prediction is a time consuming bioinformatic task that requires a multifactorial analysis in order to obtain reliable in silico predictions. Hence, to accelerate this process and offer researchers a reliable repository where secretome information can be obtained for vertebrates and model organisms, we have developed VerSeDa (Vertebrate Secretome Database). This freely available database stores information about proteins that are predicted to be secreted through the classical and non-classical mechanisms, for the wide range of vertebrate species deposited at the NCBI, UCSC and ENSEMBL sites. To our knowledge, VerSeDa is the only state-of-the-art database designed to store secretome data from multiple vertebrate genomes, thus, saving an important amount of time spent in the prediction of protein features that can be retrieved from this repository directly. VerSeDa is freely available at http://genomics.cicbiogune.es/VerSeDa/index.php. © The Author(s) 2017. Published by Oxford University Press.

Quiet Clean Short-Haul Experimental Engine (QCSEE). Preliminary analyses and design report, volume 2

NASA Technical Reports Server (NTRS)

1974-01-01

The experimental and flight propulsion systems are presented. The following areas are discussed: engine core and low pressure turbine design; bearings and seals design; controls and accessories design; nacelle aerodynamic design; nacelle mechanical design; weight; and aircraft systems design.

Proceedings of the Symposium on Psychology in the Department of Defense (8th) Held in Colorado Springs, Colorado on 21-23 April 1982

DTIC Science & Technology

1982-12-01

readily visible but still represent low level flight. 33 Experimental Design and Pc,cedures. The experimental design used in this study was a 3 X 2...October 1979. Winer, B.J. Statistical principles in experimental design . New York: McGraw-Hill, 1971. 47 NONTRADITIONAL ADMISSIONS FACTORS: THE SPECIAL...Quasi- Experimental Designs for Research. Chicago: Rand McNally, 1963. R.C. Carter and H. Sbisa. Human Performance tests for repeated measurements

78 FR 79622 - Endangered and Threatened Species: Designation of a Nonessential Experimental Population of...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-31

... Experimental Population of Central Valley Spring-Run Chinook Salmon Below Friant Dam in the San Joaquin River..., the National Marine Fisheries Service (NMFS), designate a nonessential experimental population of... experimental population for particular activities inside the experimental population's geographic range and...

Methodological convergence of program evaluation designs.

PubMed

Chacón-Moscoso, Salvador; Anguera, M Teresa; Sanduvete-Chaves, Susana; Sánchez-Martín, Milagrosa

2014-01-01

Nowadays, the confronting dichotomous view between experimental/quasi-experimental and non-experimental/ethnographic studies still exists but, despite the extensive use of non-experimental/ethnographic studies, the most systematic work on methodological quality has been developed based on experimental and quasi-experimental studies. This hinders evaluators and planners' practice of empirical program evaluation, a sphere in which the distinction between types of study is changing continually and is less clear. Based on the classical validity framework of experimental/quasi-experimental studies, we carry out a review of the literature in order to analyze the convergence of design elements in methodological quality in primary studies in systematic reviews and ethnographic research. We specify the relevant design elements that should be taken into account in order to improve validity and generalization in program evaluation practice in different methodologies from a practical methodological and complementary view. We recommend ways to improve design elements so as to enhance validity and generalization in program evaluation practice.

The influence of the design matrix on treatment effect estimates in the quantitative analyses of single-subject experimental design research.

PubMed

Moeyaert, Mariola; Ugille, Maaike; Ferron, John M; Beretvas, S Natasha; Van den Noortgate, Wim

2014-09-01

The quantitative methods for analyzing single-subject experimental data have expanded during the last decade, including the use of regression models to statistically analyze the data, but still a lot of questions remain. One question is how to specify predictors in a regression model to account for the specifics of the design and estimate the effect size of interest. These quantitative effect sizes are used in retrospective analyses and allow synthesis of single-subject experimental study results which is informative for evidence-based decision making, research and theory building, and policy discussions. We discuss different design matrices that can be used for the most common single-subject experimental designs (SSEDs), namely, the multiple-baseline designs, reversal designs, and alternating treatment designs, and provide empirical illustrations. The purpose of this article is to guide single-subject experimental data analysts interested in analyzing and meta-analyzing SSED data. © The Author(s) 2014.

Development and Validation of a Rubric for Diagnosing Students' Experimental Design Knowledge and Difficulties.

PubMed

Dasgupta, Annwesa P; Anderson, Trevor R; Pelaez, Nancy

2014-01-01

It is essential to teach students about experimental design, as this facilitates their deeper understanding of how most biological knowledge was generated and gives them tools to perform their own investigations. Despite the importance of this area, surprisingly little is known about what students actually learn from designing biological experiments. In this paper, we describe a rubric for experimental design (RED) that can be used to measure knowledge of and diagnose difficulties with experimental design. The development and validation of the RED was informed by a literature review and empirical analysis of undergraduate biology students' responses to three published assessments. Five areas of difficulty with experimental design were identified: the variable properties of an experimental subject; the manipulated variables; measurement of outcomes; accounting for variability; and the scope of inference appropriate for experimental findings. Our findings revealed that some difficulties, documented some 50 yr ago, still exist among our undergraduate students, while others remain poorly investigated. The RED shows great promise for diagnosing students' experimental design knowledge in lecture settings, laboratory courses, research internships, and course-based undergraduate research experiences. It also shows potential for guiding the development and selection of assessment and instructional activities that foster experimental design. © 2014 A. P. Dasgupta et al. CBE—Life Sciences Education © 2014 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

78 FR 3381 - Endangered and Threatened Species: Designation of a Nonessential Experimental Population of...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-16

... Experimental Population of Central Valley Spring-Run Chinook Salmon Below Friant Dam in the San Joaquin River... Fisheries Service (NMFS), propose a rule to designate a nonessential experimental population of Central... nonessential experimental population for particular activities inside the experimental population's geographic...

Quasi-experimental study designs series-paper 9: collecting data from quasi-experimental studies.

PubMed

Aloe, Ariel M; Becker, Betsy Jane; Duvendack, Maren; Valentine, Jeffrey C; Shemilt, Ian; Waddington, Hugh

2017-09-01

To identify variables that must be coded when synthesizing primary studies that use quasi-experimental designs. All quasi-experimental (QE) designs. When designing a systematic review of QE studies, potential sources of heterogeneity-both theory-based and methodological-must be identified. We outline key components of inclusion criteria for syntheses of quasi-experimental studies. We provide recommendations for coding content-relevant and methodological variables and outlined the distinction between bivariate effect sizes and partial (i.e., adjusted) effect sizes. Designs used and controls used are viewed as of greatest importance. Potential sources of bias and confounding are also addressed. Careful consideration must be given to inclusion criteria and the coding of theoretical and methodological variables during the design phase of a synthesis of quasi-experimental studies. The success of the meta-regression analysis relies on the data available to the meta-analyst. Omission of critical moderator variables (i.e., effect modifiers) will undermine the conclusions of a meta-analysis. Copyright © 2017 Elsevier Inc. All rights reserved.

Engineering Design Handbook. Army Weapon Systems Analysis. Part 2

DTIC Science & Technology

1979-10-01

EXPERIMENTAL DESIGN ............................... ............ 41-3 41-5 RESULTS OF THE ASARS lIX SIMULATIONS ........................... 41-4 41-6 LATIN...sciences and human factors engineering fields utilizing experimental methodology and multi-variable statistical techniques drawn from experimental ...randomly to grenades for the test design . The nine experimental types of hand grenades (first’ nine in Table 33-2) had a "pip" on their spherical

Optimal Experimental Design for Model Discrimination

PubMed Central

Myung, Jay I.; Pitt, Mark A.

2009-01-01

Models of a psychological process can be difficult to discriminate experimentally because it is not easy to determine the values of the critical design variables (e.g., presentation schedule, stimulus structure) that will be most informative in differentiating them. Recent developments in sampling-based search methods in statistics make it possible to determine these values, and thereby identify an optimal experimental design. After describing the method, it is demonstrated in two content areas in cognitive psychology in which models are highly competitive: retention (i.e., forgetting) and categorization. The optimal design is compared with the quality of designs used in the literature. The findings demonstrate that design optimization has the potential to increase the informativeness of the experimental method. PMID:19618983

Quasi-experimental Studies in the Fields of Infection Control and Antibiotic Resistance, Ten Years Later: A Systematic Review.

PubMed

Alsaggaf, Rotana; O'Hara, Lyndsay M; Stafford, Kristen A; Leekha, Surbhi; Harris, Anthony D

2018-02-01

OBJECTIVE A systematic review of quasi-experimental studies in the field of infectious diseases was published in 2005. The aim of this study was to assess improvements in the design and reporting of quasi-experiments 10 years after the initial review. We also aimed to report the statistical methods used to analyze quasi-experimental data. DESIGN Systematic review of articles published from January 1, 2013, to December 31, 2014, in 4 major infectious disease journals. METHODS Quasi-experimental studies focused on infection control and antibiotic resistance were identified and classified based on 4 criteria: (1) type of quasi-experimental design used, (2) justification of the use of the design, (3) use of correct nomenclature to describe the design, and (4) statistical methods used. RESULTS Of 2,600 articles, 173 (7%) featured a quasi-experimental design, compared to 73 of 2,320 articles (3%) in the previous review (P<.01). Moreover, 21 articles (12%) utilized a study design with a control group; 6 (3.5%) justified the use of a quasi-experimental design; and 68 (39%) identified their design using the correct nomenclature. In addition, 2-group statistical tests were used in 75 studies (43%); 58 studies (34%) used standard regression analysis; 18 (10%) used segmented regression analysis; 7 (4%) used standard time-series analysis; 5 (3%) used segmented time-series analysis; and 10 (6%) did not utilize statistical methods for comparisons. CONCLUSIONS While some progress occurred over the decade, it is crucial to continue improving the design and reporting of quasi-experimental studies in the fields of infection control and antibiotic resistance to better evaluate the effectiveness of important interventions. Infect Control Hosp Epidemiol 2018;39:170-176.

Mitochondrial alterations in Parkinson's disease: new clues.

PubMed

Vila, Miquel; Ramonet, David; Perier, Celine

2008-10-01

Mitochondrial dysfunction has long been associated with Parkinson's disease (PD). In particular, complex I impairment and subsequent oxidative stress have been widely demonstrated in experimental models of PD and in post-mortem PD samples. A recent wave of new studies is providing novel clues to the potential involvement of mitochondria in PD. In particular, (i) mitochondria-dependent programmed cell death pathways have been shown to be critical to PD-related dopaminergic neurodegeneration, (ii) many disease-causing proteins associated with familial forms of PD have been demonstrated to interact either directly or indirectly with mitochondria, (iii) aging-related mitochondrial changes, such as alterations in mitochondrial DNA, are increasingly being associated with PD, and (iv) anomalies in mitochondrial dynamics and intra-neuronal distribution are emerging as critical participants in the pathogenesis of PD. These new findings are revitalizing the field and reinforcing the potential role of mitochondria in the pathogenesis of PD. Whether a primary or secondary event, or part of a multi-factorial pathogenic process, mitochondrial dysfunction remains at the forefront of PD research and holds the promise as a potential molecular target for the development of new therapeutic strategies for this devastating, currently incurable, disease.

Silica-gelatin hybrid sol-gel coatings: a proteomic study with biocompatibility implications.

PubMed

Araújo-Gomes, N; Romero-Gavilán, F; Lara-Sáez, I; Elortza, F; Azkargorta, M; Iloro, I; Martínez-Ibañez, M; Martín de Llano, J J; Gurruchaga, M; Goñi, I; Suay, J; Sánchez-Pérez, A M

2018-05-21

Osseointegration, including the foreign body reaction to biomaterials, is an immune-modulated, multifactorial, and complex healing process in which various cells and mediators are involved. The buildup of the osseointegration process is immunological and inflammation-driven, often triggered by the adsorption of proteins on the surfaces of the biomaterials and complement activation. New strategies for improving osseointegration use coatings as vehicles for osteogenic biomolecules delivery from implants. Natural polymers, such as gelatin, can mimic collagen I and enhance the biocompatibility of a material. In this experimental study, two different base sol-gel formulations and their combination with gelatin, were applied as coatings on sandblasted, acid-etched titanium (SAE-Ti) substrates and their biological potential as osteogenic biomaterials was tested. We examined the proteins adsorbed onto each surface and their in vitro and in vivo effects. In vitro results showed an improvement in cell proliferation and mineralization in gelatin-containing samples. In vivo testing showed the presence of a looser connective tissue layer in those coatings with substantially more complement activation proteins adsorbed, especially those containing gelatin. Vitronectin and FETUA, proteins associated with mineralization process, were significantly more adsorbed in gelatin coatings. This article is protected by copyright. All rights reserved.

[Physiopathology of overactive bladder syndrome].

PubMed

Sacco, Emilio

2012-01-01

The pathophysiology of OAB is complex, multifactorial and still largely unknown. Several pathophysiological mechanisms have been highlighted that may play a different role in different patient groups. There are now experimental evidences that support both the myogenic and neurogenic hypothesis, but in recent years the "integrative" hypothesis has been gaining more and more acceptance, where a disruption in the multiple interactions between different cell types (neurons, urothelium, interstitial cells, myocytes) and network functions represent a central element of lower urinary tract dysfunctions. Of utmost importance, a disorder in the urothelial sensory function and in the urothelial/suburothelial non-neural cholinergic system, favored by age and comorbidities, appears to be crucial for the development of the OAB. Neuroplastic and detrusor changes in OAB are broadly similar to those observed in bladders exposed to outlet obstruction, neuropathies, inflammation or aging, and may be driven by a common urothelial dysfunction. Several signaling substances and their receptors were found to be involved in central pathways of bidirectional communication between the different cell types in the bladder, and were shown to be modified in several animal models of OAB as well as in human models, indicating new potential therapeutic targets.

Prostaglandins in the gut and their relationship to non-steroidal anti-inflammatory drugs.

PubMed

Semble, E L; Wu, W C

1989-08-01

Prostaglandins are long-chain, saturated, oxygenated fatty acids. Relatively large quantities of prostaglandins have been found in gut mucosa, suggesting that these substances play an important role in gastrointestinal physiology. Non-steroidal anti-inflammatory drugs (NSAIDs) cause damage to the gastric, intestinal, and colonic mucosa in experimental animals and in humans. Prostaglandins protect the gastric mucosa against injury induced by NSAIDs, and this property has been labelled cytoprotection. The mechanisms of cytoprotection have been extensively evaluated and are probably multifactorial, including effects on the gastric mucosal barrier, gastric blood flow, mucus, bicarbonate, and fluid section, ionic transport, cyclic AMP, and surface-active phospholipids. Prostaglandins may also prevent NSAID-induced injury in the small intestine and colon. The mechanisms responsible for prostaglandin protection in the lower gut against injurious agents are unknown. Further studies of the role of prostaglandins in the gut and their relationship to the effects of NSAIDs are needed. The results of these investigations may lead to a better understanding of the importance of prostaglandins in the physiology of the gastrointestinal tract, and may provide information regarding actions of NSAIDs on the functional integrity of the gastric, intestinal, and colonic mucosa.

Effect of docosahexaenoic acid on hippocampal neurons in high-glucose condition: involvement of PI3K/AKT/nuclear factor-κB-mediated inflammatory pathways.

PubMed

Yang, R-H; Lin, J; Hou, X-H; Cao, R; Yu, F; Liu, H-Q; Ji, A-L; Xu, X-N; Zhang, L; Wang, F

2014-08-22

Accumulating evidence suggested that hyperglycemia played a critical role in hippocampus dysfunction in patients with diabetes mellitus. However, the multifactorial pathogenesis of hyperglycemia-induced impairments of hippocampal neurons has not been fully elucidated. Docosahexaenoic acid (DHA) has been shown to enhance learning and memory and affect neural function in various experimental conditions. The present study investigated the effects of DHA on the lipid peroxidation, the level of inflammatory cytokines and neuron apoptosis in the hippocampal neurons in high-glucose condition. High-glucose administration increased the level of tumor necrosis factor α (TNF-α) and IL-6, induced oxidative stress and apoptosis of hippocampal neurons in vitro. DHA treatment reduced oxidative stress and TNF-α expression, protected the hippocampal neurons by increasing AKT phosphorylation and decreasing caspase-3 and caspase-9 expression. These results suggested that high-glucose exposure induced injury of hippocampal neurons in vitro, and the principle mechanisms involved in the neuroprotective effect of DHA were its antioxidant and anti-apoptotic potential. DHA may thus be of use in preventing or treating neuron-degeneration resulting from hyperglycemia. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

On the parallels between cosmology and astrobiology: a transdisciplinary approach to the search for extraterrestrial life

NASA Astrophysics Data System (ADS)

Santos, Charles Morphy D.; Alabi, Leticia P.; Friaça, Amâncio C. S.; Galante, Douglas

2016-10-01

The establishment of cosmology as a science provides a parallel to the building-up of the scientific status of astrobiology. The rise of astrobiological studies is explicitly based on a transdisciplinary approach that reminds of the Copernican Revolution, which eroded the basis of a closed Aristotelian worldview and reinforced the notion that the frontiers between disciplines are artificial. Given the intrinsic complexity of the astrobiological studies, with its multifactorial evidences and theoretical/experimental approaches, multi- and interdisciplinary perspectives are mandatory. Insulated expertise cannot grasp the vastness of the astrobiological issues. This need for integration among disciplines and research areas is antagonistic to excessive specialization and compartmentalization, allowing astrobiology to be qualified as a truly transdisciplinary enterprise. The present paper discusses the scientific status of astrobiological studies, based on the view that every kind of life, Earth-based or not, should be considered in a cosmic context. A confluence between 'astro' and 'bio' seeks the understanding of life as an emerging phenomenon in the universe. Thus, a new epistemological niche is opened, pointing to the development of a pluralistic vision for the philosophy of astrobiology.

Ion Channels in Obesity: Pathophysiology and Potential Therapeutic Targets

PubMed Central

Vasconcelos, Luiz H. C.; Souza, Iara L. L.; Pinheiro, Lílian S.; Silva, Bagnólia A.

2016-01-01

Obesity is a multifactorial disease related to metabolic disorders and associated with genetic determinants. Currently, ion channels activity has been linked to many of these disorders, in addition to the central regulation of food intake, energetic balance, hormone release and response, as well as the adipocyte cell proliferation. Therefore, the objective of this work is to review the current knowledge about the influence of ion channels in obesity development. This review used different sources of literature (Google Scholar, PubMed, Scopus, and Web of Science) to assess the role of ion channels in the pathophysiology of obesity. Ion channels present diverse key functions, such as the maintenance of physiological homeostasis and cell proliferation. Cell biology and pharmacological experimental evidences demonstrate that proliferating cells exhibit ion channel expression, conductance, and electrical properties different from the resting cells. Thereby, a large variety of ion channels has been identified in the pathogenesis of obesity such as potassium, sodium, calcium and chloride channels, nicotinic acetylcholine receptor and transient receptor potential channels. The fundamental involvement of these channels on the generation of obesity leads to the progress in the knowledge about the mechanisms responsible for the obesity pathophysiology, consequently emerging as new targets for pharmacological modulation. PMID:27065858

Platelet Lysate-Modified Porous Silicon Microparticles for Enhanced Cell Proliferation in Wound Healing Applications.

PubMed

Fontana, Flavia; Mori, Michela; Riva, Federica; Mäkilä, Ermei; Liu, Dongfei; Salonen, Jarno; Nicoletti, Giovanni; Hirvonen, Jouni; Caramella, Carla; Santos, Hélder A

2016-01-13

The new frontier in the treatment of chronic nonhealing wounds is the use of micro- and nanoparticles to deliver drugs or growth factors into the wound. Here, we used platelet lysate (PL), a hemoderivative of platelets, consisting of a multifactorial cocktail of growth factors, to modify porous silicon (PSi) microparticles and assessed both in vitro and ex vivo the properties of the developed microsystem. PL-modified PSi was assessed for its potential to induce proliferation of fibroblasts. The wound closure-promoting properties of the microsystem were then assessed in an in vitro wound healing assay. Finally, the PL-modified PSi microparticles were evaluated in an ex vivo experiment over human skin. It was shown that PL-modified PSi microparticles were cytocompatible and enhanced the cell proliferation in different experimental settings. In addition, this microsystem promoted the closure of the gap between the fibroblast cells in the wound healing assay, in periods of time comparable with the positive control, and induced a proliferation and regeneration process onto the human skin in an ex vivo experiment. Overall, our results show that PL-modified PSi microparticles are suitable microsystems for further development toward applications in the treatment of chronic nonhealing wounds.

Chronic inflammation and impaired development of the preterm brain.

PubMed

Bennet, Laura; Dhillon, Simerdeep; Lear, Chris A; van den Heuij, Lotte; King, Victoria; Dean, Justin M; Wassink, Guido; Davidson, Joanne O; Gunn, Alistair Jan

2018-02-01

The preterm newborn is at significant risk of neural injury and impaired neurodevelopment. Infants with mild or no evidence of injury may also be at risk of altered brain development, with evidence impaired cell maturation. The underlying causes are multifactorial and include exposure of both the fetus and newborn to hypoxia-ischemia, inflammation (chorioamnionitis) and infection, adverse maternal lifestyle choices (smoking, drug and alcohol use, diet) and obesity, as well as the significant demand that adaptation to post-natal life places on immature organs. Further, many fetuses and infants may have combinations of these events, and repeated (multi-hit) events that may induce tolerance to injury or sensitize to greater injury. Currently there are no treatments to prevent preterm injury or impaired neurodevelopment. However, inflammation is a common pathway for many of these insults, and clinical and experimental evidence demonstrates that acute and chronic inflammation is associated with impaired brain development. This review examines our current knowledge about the relationship between inflammation and preterm brain development, and the potential for stem cell therapy to provide neuroprotection and neurorepair through reducing inflammation and release of trophic factors, which promote cell maturation and repair. Copyright © 2017 Elsevier B.V. All rights reserved.

[The role of stress-induced chronic subclinical inflammation in the pathogenesis of the chronic pelvic pain syndrome IIIB in men].

PubMed

Shormanov, I S; Mozhaev, I I; Sokolova, Kh A; Solovev, A S

2017-12-01

This literature review of recent clinical and experimental studies describes the role of oxidative stress in the multifactorial and interdisciplinary pathogenesis of non-inflammatory chronic pelvic pain syndrome IIIB (CPPS-IIIB) in men. The authors outline general biological nature of oxidative stress and its mechanisms. More detailed information is presented on cytokine-mediated chronic subclinical inflammation, one of the key mechanisms of oxidative stress, which is currently being actively studied. It is shown that the imbalance between pro- and anti-inflammatory cytokines observed in patients with CPPS-IIIB can explain some features of the clinical course (in particular, the characteristics of the pain syndrome) and the progression of this disease. In this regard, cytokine profiling of prostatic secretion can provide valuable diagnostic, prognostic and monitoring information in the management of this category of patients. Recently published evidence has demonstrated the essential role of the cytokine-mediated chronic inflammatory response as a mechanism of oxidative stress in the pathogenesis of CPPS-IIIB. Further studies in this area are warranted and in the long term may become a basis for the development of new effective pathogenetic pharmacotherapy of CPPS-IIIB.

Mapping Heart Development in Flies: Src42A Acts Non-Autonomously to Promote Heart Tube Formation in Drosophila

PubMed Central

Vanderploeg, Jessica; Jacobs, J. Roger

2017-01-01

Congenital heart defects, clinically identified in both small and large animals, are multifactorial and complex. Although heritable factors are known to have a role in cardiovascular disease, the full genetic aetiology remains unclear. Model organism research has proven valuable in providing a deeper understanding of the essential factors in heart development. For example, mouse knock-out studies reveal a role for the Integrin adhesion receptor in cardiac tissue. Recent research in Drosophila melanogaster (the fruit fly), a powerful experimental model, has demonstrated that the link between the extracellular matrix and the cell, mediated by Integrins, is required for multiple aspects of cardiogenesis. Here we test the hypothesis that Integrins signal to the heart cells through Src42A kinase. Using the powerful genetics and cell biology analysis possible in Drosophila, we demonstrate that Src42A acts in early events of heart tube development. Careful examination of mutant heart tissue and genetic interaction data suggests that Src42A’s role is independent of Integrin and the Integrin-related Focal Adhesion Kinase. Rather, Src42A acts non-autonomously by promoting programmed cell death of the amnioserosa, a transient tissue that neighbors the developing heart. PMID:29056682

Impact factors on development of cirrhosis and subsequent hepatocellular carcinoma.

PubMed

Holmes-McNary, M

2001-07-01

Hepatocellular carcinoma (HCC), on the rise in many countries, is of multifactorial etiology. Its etiological associations differ between populations at high and low risk. Africans and Chinese have the highest incidence of HCC, but other affected groups include African Americans, Japanese, and Native Americans. Chronic infections by hepatitis B and hepatitis C viruses are major risk factors worldwide, although mechanisms through which the infections cause liver cancer are yet to be explained. Other documented risk factors have been postulated and include dietary exposure, cigarette smoking, alcohol consumption, diabetes, oral infection, and oral contraceptive use. In addition, many naturally occurring and synthetic chemicals to which humans are exposed via accidental contamination of food or water are shown to induce liver cancer in experimental animals. Consequently, assessment of possible human liver cancer risk associated with such exposures is complex. Early diagnosis and transplantation are the best treatments presently, although transplantation is not widely available due to donor shortage. Every effort should be directed toward the prevention of HCC, through the treatment and prevention of hepatitis and oral infections, prevention of chronic hepatitis progressing to cirrhosis, and prevention of the cirrhotic liver from developing HCC through chemopreventive modalities. However, at present, very few such studies exist.

Botulinum toxin as a therapeutic agent to prevent relapse in deep bite patients.

PubMed

Mücke, Thomas; Löffel, Anja; Kanatas, Anastasios; Karnezi, Sandy; Rana, Majeed; Fichter, Andreas; Haarmann, Stephan; Wolff, Klaus-Dietrich; Loeffelbein, Denys John

2016-05-01

The etiology of deep bite is multifactorial. One of the causes is increased muscular activity. This makes the treatment of deep bite malocclusions difficult and often results in relapse in many cases. In this work we compared patients with surgical orthognathic treatment only and surgical orthognathic treatment with additional injections of botulinum toxin after mandibular advancement for class II division 2 malocclusion. This is a prospective study. Adult patients were assessed pretreatment (T1), posttreatment (T2), and long-term after 1 year (T3). In total, 32 patients (mean age, 30.7 years; 23 women and 9 men) reached the study end point (T3); 24 patients were treated without botulinum toxin and 8 patients received preoperative injections of botulinum toxin. Significant differences between both groups were observed, with a more stable result for the experimental group treated with botulinum toxin. In a selective group of adult patients with a class II division II incisor relationship and with a class II skeletal base, botulinum toxin injections can effectively prevent relapse. This may present an alternative to a conventional myotomy. Copyright © 2016 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Antiluteolytic strategies to improve fertility in cattle.

PubMed

Binelli, M; Thatcher, W W; Mattos, R; Baruselli, P S

2001-12-01

During early pregnancy, a "critical period" may be defined between Days 15 and 17. Embryonic mortality associated with this period causes significant economic losses to the cattle industry. During this period, the endometrium will follow a default program to release luteolytic pulses of PGF2alpha, unless the conceptus sends appropriate antiluteolytic signals to block PGF2alpha, production. Maintenance of pregnancy is dependent on a successful blockage of endometrial PGF2alpha production. Biology of the critical period is complex and multifactorial. Endocrine, cellular and molecular factors, both from maternal and conceptus origins act in concert to determine whether luteolysis or maintenance of pregnancy will prevail. Understanding the influences of such factors in the biology of the critical period allowed researchers to produce a series of strategies aiming to favor maintenance of pregnancy in lieu of luteolysis. Strategies include hormonal and nutritional manipulations to decrease plasma concentrations of estradiol 17beta (E2) while increasing those of progesterone (P4), and inhibiting the PGF2alpha-synthesizing enzymatic machinery in the endometrium during the critical period. Experimental results indicate that use of such strategies has improved pregnancy rates following artificial insemination and embryo transfer programs.

Contribution of Beta-HPV Infection and UV-Damage to Rapid-onset Cutaneous Squamous Cell Carcinoma during BRAF-inhibition Therapy

PubMed Central

Cohen, Daniel N.; Lawson, Steven K.; Shaver, Aaron C.; Du, Liping; Nguyen, Harrison P.; He, Qin; Johnson, Douglas B.; Lumbang, Wilfred A.; Moody, Brent R.; Prescott, James L.; Chandra, Pranil K.; Boyd, Alan S.; Zwerner, Jeffrey P.; Robbins, Jason B.; Tyring, Stephen K.; Rady, Peter L.; Chappell, James D.; Shyr, Yu; Infante, Jeffrey R.; Sosman, Jeffrey A.

2015-01-01

Purpose BRAF-inhibition (BRAFi) therapy for advanced melanoma carries a high rate of secondary cutaneous squamous cell carcinoma (cSCC) and risk of other cancers. Ultraviolet (UV) radiation and α-genus human papillomavirus (HPV) are highly associated with SCC, but a novel role for β-genus HPV is suspected in BRAFi-cSCC. Cutaneous β-HPV may act in concert with host and environmental factors in BRAFi-cSCC. Experimental Design Primary BRAFi-cSCC tissue DNA isolated from patients receiving vemurafenib (Vem) or dabrafenib from two cancer centers was analyzed for the presence of cutaneous oncogenic viruses and host genetic mutations. Diagnostic specimens underwent consensus dermatopathology review. Clinical parameters for UV exposure and disease course were statistically analyzed in conjunction with histopathology. Results Twenty-nine patients contributed 69 BRAFi-cSCC lesions. BRAFi-cSCC had wart-like features (BRAFi-cSCC-WF) in 22% of specimens. During Vem therapy, BRAFi-cSCC-WF arose 11.6 weeks more rapidly than conventional-cSCC when controlled for gender and UV-exposure (p-value=0.03). Among all BRAFi-cSCC, β-genus HPV-17, HPV-38, HPV-111 were most frequently isolated and novel β-HPV genotypes were discovered (CTR, CRT-11, CRT-22). Sequencing revealed 63% of evaluated BRAFi-cSCCs harbored RAS mutations with PIK3CA, CKIT, ALK and EGFR mutations also detected. Conclusions We examined clinical, histopathologic, viral and genetic parameters in BRAFi-cSCC demonstrating rapid onset; wart-like histomorphology; β-HPV-17, HPV-38, and HPV-111 infection; UV damage; and novel ALK and CKIT mutations. Discovered β-HPV genotypes expand the spectrum of tumor-associated viruses. These findings enhance our understanding of factors cooperating with BRAF inhibition that accelerate keratinocyte oncogenesis as well as broaden the knowledge base of multifactorial mediators of cancer in general. PMID:25724524

Animal Models for the Study of Female Sexual Dysfunction

PubMed Central

Marson, Lesley; Giamberardino, Maria Adele; Costantini, Raffaele; Czakanski, Peter; Wesselmann, Ursula

2017-01-01

Introduction Significant progress has been made in elucidating the physiological and pharmacological mechanisms of female sexual function through preclinical animal research. The continued development of animal models is vital for the understanding and treatment of the many diverse disorders that occur in women. Aim To provide an updated review of the experimental models evaluating female sexual function that may be useful for clinical translation. Methods Review of English written, peer-reviewed literature, primarily from 2000 to 2012, that described studies on female sexual behavior related to motivation, arousal, physiological monitoring of genital function and urogenital pain. Main Outcomes Measures Analysis of supporting evidence for the suitability of the animal model to provide measurable indices related to desire, arousal, reward, orgasm, and pelvic pain. Results The development of female animal models has provided important insights in the peripheral and central processes regulating sexual function. Behavioral models of sexual desire, motivation, and reward are well developed. Central arousal and orgasmic responses are less well understood, compared with the physiological changes associated with genital arousal. Models of nociception are useful for replicating symptoms and identifying the neurobiological pathways involved. While in some cases translation to women correlates with the findings in animals, the requirement of circulating hormones for sexual receptivity in rodents and the multifactorial nature of women’s sexual function requires better designed studies and careful analysis. The current models have studied sexual dysfunction or pelvic pain in isolation; combining these aspects would help to elucidate interactions of the pathophysiology of pain and sexual dysfunction. Conclusions Basic research in animals has been vital for understanding the anatomy, neurobiology, and physiological mechanisms underlying sexual function and urogenital pain. These models are important for understanding the etiology of female sexual function and for future development of pharmacological treatments for sexual dysfunctions with or without pain. PMID:27784584

75 FR 81979 - Proposed Notice of Funding Opportunity (NOFO) for Social Innovation Fund 2011 Awards; Request for...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-29

... well-implemented experimental or quasi-experimental studies that demonstrate the program has a sizeable... study or well- designed and well-implemented quasi-experimental study that supports the effectiveness of... moderate evidence: (1) At least one well-designed and well-implemented experimental or quasi-experimental...

GENOMIC IDENTIFICATION OF POTENTIAL RISK FACTORS DURING ACETAMINOPHEN-INDUCED LIVER DISEASE IN SUSCEPTIBLE AND RESISTANT STRAINS OF MICE

EPA Science Inventory

Drug-induced liver disease (DILD) continues to cause significant morbidity and mortality and impair new drug development. Mounting evidence suggests that DILD is a complex, multifactorial disease in which no one factor is likely to be an absolute indicator of susceptibility. As a...

Role of imaging in female infertility [Dr. K.M. Rai Memorial Oration Award

PubMed Central

Rastogi, Rajul

2010-01-01

Infertility in females is multifactorial in origin. Though hysterolaparoscopy is the gold-standard investigation, USG is usually the first-line investigation. MRI has expanded the usefulness of imaging in female infertility. This pictorial essay reviews the role of imaging in the evaluation of female infertility. PMID:21042438

Cognitive Predictors of Language Development in Children with Specific Language Impairment (SLI)

ERIC Educational Resources Information Center

van Daal, John; Verhoeven, Ludo; van Balkom, Hans

2009-01-01

Background: Language development is generally viewed as a multifactorial process. There are increasing indications that this similarly holds for the problematic language development process. Aims: A population of 97 young Dutch children with specific language impairment (SLI) was followed over a 2-year period to provide additional evidence for the…

Variation in pestivirus growth in testicle primary cell culture is more dependent on the individual cell donor than cattle breed

USDA-ARS?s Scientific Manuscript database

Bovine respiratory disease complex (BRDC) affects cattle from all breeds living in all regions. However, different breeds of cattle appear to have different susceptibilities to developing BRDC. The causes of BRDC are multifactorial and include infection with both viral and bacterial pathogens. Infec...

Decision tree-based method for integrating gene expression, demographic, and clinical data to determine disease endotypes

EPA Science Inventory

Complex diseases are often difficult to diagnose, treat, and study due to the multi-factorial nature of the etiology. Significant challenges exist with regard to how to segregate indivdiuals into suitable subtypes of the disease. Here, we examine a range of methods for evaluati...

HOW EXPOSURE TO ENVIRONMENTAL TOBACCO SMOKE, OUTDOOR AIR POLLUTANTS,AND INCREASED POLLEN BURDENS INFLUENCES THE INCIDENCE OF ASTHMA

EPA Science Inventory

Asthma is a multifactorial airway disease that arises from a relatively common genetic background interphased with exposures to allergens and airborne irritants. The rapid rise in asthma over the past three decades in Western societies has been attributed to numerous diverse fact...

MicroRNA regulation of bovine monocyte inflammatory and metabolic networks in an in vivo infection model

USDA-ARS?s Scientific Manuscript database

Bovine mastitis is an inflammation-driven disease of the bovine mammary gland that costs the global dairy industry several billion dollars per annum. Because disease susceptibility is a multi-factorial complex phenotype, a multi-omic integrative biology approach is required to dissect the multilayer...

Fatigue and gynecologic cancer.

PubMed

Olt, George J

2003-02-01

Fatigue is common in women with gynecologic cancers and is thought to be multifactorial. Anemia, cachexia, pain, and depression are frequently associated with cancer and treatment-related fatigue and should be evaluated and treated. The National Comprehensive Cancer Network Fatigue Practice Guidelines are helpful in the assessment and treatment of women with gynecologic cancer-related fatigue.

QUANTITATIVE IMAGING AND STATISTICAL ANALYSIS OF FLUORESCENCE IN SITU HYBRIDIZATION (FISH) OF AUREOBASIDIUM PULLULANS. (R823845)

EPA Science Inventory

Abstract

Image and multifactorial statistical analyses were used to evaluate the intensity of fluorescence signal from cells of three strains of A. pullulans and one strain of Rhodosporidium toruloides, as an outgroup, hybridized with either a universal o...

Emerging pharmacological therapy for functional dyspepsia.

PubMed

Hojo, Mariko; Nagahara, Akihito; Asaoka, Daisuke; Watanabe, Sumio

2013-10-01

Functional dyspepsia (FD) is a multifactorial disease with complex underlying pathophysiology. To date, there is no established treatment for FD. This review summarizes recent progress in pharmacological therapy for the disease. A newly developed drug, acotiamide, is expected to improve symptoms of postprandial distress syndrome. Herbal medicines are also expected to become options for FD treatment.

Viewing a Phonological Deficit within a Multifactorial Model of Dyslexia

ERIC Educational Resources Information Center

Catts, Hugh W.; McIlraith, Autumn; Bridges, Mindy Sittner; Nielsen, Diane Corcoran

2017-01-01

Participants were administered multiple measures of phonological awareness, oral language, and rapid automatized naming at the beginning of kindergarten and multiple measures of word reading at the end of second grade. A structural equation model was fit to the data and latent scores were used to identify children with a deficit in phonological…

Community Ecology and Capacity: Keys to Progressing the Environmental Communication of Wicked Problems

ERIC Educational Resources Information Center

Caron, Rosemary M.; Serrell, Nancy

2009-01-01

Wicked problems are multifactorial in nature and possess no clear resolution due to numerous community stakeholder involvement. We demonstrate childhood lead poisoning as a wicked problem and illustrate how understanding a community's ecology can build community capacity to affect local environmental management by (1) forming an academic-community…

Interfering with Inner Speech Selectively Disrupts Problem Solving and Is Linked with Real-World Executive Functioning

ERIC Educational Resources Information Center

Wallace, Gregory L.; Peng, Cynthia S.; Williams, David

2017-01-01

Purpose: According to Vygotskian theory, verbal thinking serves to guide our behavior and underpins critical self-regulatory functions. Indeed, numerous studies now link inner speech usage with performance on tests of executive function (EF). However, the selectivity of inner speech contributions to multifactorial executive planning performance…

Insights into jumonji c-domain containing protein 6 (JMJD6): a multifactorial role in FMDV replication in cells

USDA-ARS?s Scientific Manuscript database

The Jumonji C-domain containing protein 6 (JMJD6) has had a convoluted history. It was first identified as the phosphatidylserine receptor (PSR) on the cell surface responsible for recognizing phosphatidylserine on the surface of apoptotic cells resulting in their engulfment by phagocytic cells. Sub...

Dietary compound score and risk of age-related macular degeneration in the Age-Related Eye Disease Study

USDA-ARS?s Scientific Manuscript database

Purpose: Because foods provide many nutrients, which may interact with each other to modify risk for multifactorial diseases such as age-related macular degeneration (AMD), we sought to develop a composite scoring system to summarize the combined effect of multiple dietary nutrients on AMD risk. Th...

A Cross-Sectional Analysis of Publication Types in Quality Improvement Journals.

PubMed

Wong, Christopher J; White, Andrew A; Merel, Susan E; Brock, Douglas M; Staiger, Thomas O

2016-07-01

Despite widespread engagement in quality improvement activities, little is known about the designs of studies currently published in quality improvement journals. This study's goal is to establish the prevalence of the types of research conducted in articles published in journals dedicated to quality improvement. A cross-sectional analysis was performed of 145 research articles published in 11 quality improvement journals in 2011. The majority of study designs were considered pre-experimental (95%), with a small percentage of quasi-experimental and experimental designs. Of the studies that reported the results of an intervention (n = 60), the most common research designs were pre-post studies (33%) and case studies (25%). There were few randomized controlled trials or quasi-experimental study designs (12% of intervention studies). These results suggest that there are opportunities for increased use of quasi-experimental study designs. © The Author(s) 2015.

Diverticular Disease: An Update on Pathogenesis and Management

PubMed Central

Rezapour, Mona; Ali, Saima

2018-01-01

Diverticular disease is one of the most common conditions in the Western world and one of the most common findings identified at colonoscopy. Recently, there has been a significant paradigm shift in our understanding of diverticular disease and its management. The pathogenesis of diverticular disease is thought to be multifactorial and include both environmental and genetic factors in addition to the historically accepted etiology of dietary fiber deficiency. Symptomatic uncomplicated diverticular disease (SUDD) is currently considered a type of chronic diverticulosis that is perhaps akin to irritable bowel syndrome. Mesalamine, rifaximin and probiotics may achieve symptomatic relief in some patients with SUDD, although their role(s) in preventing complications remain unclear. Antibiotic use for acute diverticulitis and elective prophylactic resection surgery are considered more individualized treatment modalities that take into account the clinical status, comorbidities and lifestyle of the patient. Our understanding of the pathogenesis of diverticular disease continues to evolve and is likely to be diverse and multifactorial. Paradigm shifts in several areas of the pathogenesis and management of diverticular disease are explored in this review. PMID:28494576

A Multi-factorial Model for Examining Racial and Ethnic Disparities in Acute Asthma Visits by Children

PubMed Central

Feldman, Jonathan M.; Serebrisky, Denise; Spray, Amanda

2012-01-01

Background Causes of children’s asthma health disparities are complex. Parents’ asthma illness representations may play a role. Purpose The study aims to test a theoretically based, multi-factorial model for ethnic disparities in children’s acute asthma visits through parental illness representations. Methods Structural equation modeling investigated the association of parental asthma illness representations, sociodemographic characteristics, health care provider factors, and social–environmental context with children’s acute asthma visits among 309 White, Puerto Rican, and African American families was conducted. Results Forty-five percent of the variance in illness representations and 30% of the variance in acute visits were accounted for. Statistically significant differences in illness representations were observed by ethnic group. Approximately 30% of the variance in illness representations was explained for whites, 23% for African Americans, and 26% for Puerto Ricans. The model accounted for >30% of the variance in acute visits for African Americans and Puerto Ricans but only 19% for the whites. Conclusion The model provides preliminary support that ethnic heterogeneity in asthma illness representations affects children’s health outcomes. PMID:22160799

Examination of a multi-factorial model of body-related experiences during pregnancy: the relationships among physical symptoms, sleep quality, depression, self-esteem, and negative body attitudes.

PubMed

Kamysheva, Ekaterina; Skouteris, Helen; Wertheim, Eleanor H; Paxton, Susan J; Milgrom, Jeannette

2008-06-01

The aim of this cross-sectional study was to investigate relationships among women's body attitudes, physical symptoms, self-esteem, depression, and sleep quality during pregnancy. Pregnant women (N=215) at 15-25 weeks gestation completed a questionnaire including four body image subscales assessing self-reported feeling fat, attractiveness, strength/fitness, and salience of weight and shape. Women reported on 29 pregnancy-related physical complaints, and completed the Beck Depression Inventory, Rosenberg Self-esteem Scale, and Pittsburgh Sleep Quality Index. In regressions, controlling for retrospective reports of body image, more frequent and intense physical symptoms were related to viewing the self as less strong/fit, and to poorer sleep quality and more depressive symptoms. In a multi-factorial model extending previous research, paths were found from sleep quality to depressive symptoms to self-esteem; self-esteem was found to be a mediator associated with lower scores on feeling fat and salience of weight and shape, and on higher perceived attractiveness.

78 FR 25990 - Applications for New Awards; Investing in Innovation Fund, Validation Grants

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-03

...-- (1) Correlational study with statistical controls for selection bias; (2) Quasi-experimental study... Higher Education Act of 1965, as amended. Quasi-experimental design study means a study using a design that attempts to approximate an experimental design by identifying a comparison group that is similar...

34 CFR 77.1 - Definitions that apply to all Department programs.

Code of Federal Regulations, 2014 CFR

2014-07-01

... statistical controls for selection bias; (B) Quasi-experimental study that meets the What Works Clearinghouse... administrative supervision or control of a government other than the Federal Government. Quasi-experimental design study means a study using a design that attempts to approximate an experimental design by...

The Implications of "Contamination" for Experimental Design in Education

ERIC Educational Resources Information Center

Rhoads, Christopher H.

2011-01-01

Experimental designs that randomly assign entire clusters of individuals (e.g., schools and classrooms) to treatments are frequently advocated as a way of guarding against contamination of the estimated average causal effect of treatment. However, in the absence of contamination, experimental designs that randomly assign intact clusters to…

77 FR 18251 - Development of Animal Models of Pregnancy To Address Medical Countermeasures for Influenza in the...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-27

... during pregnancy. Specifically, this workshop will address experimental design issues in selecting the... countermeasures, including influenza therapies, that may be used during pregnancy; and (3) experimental design... pharmacokinetic studies, and (3) additional issues in experimental design. Background information on the public...

Revealing Student Thinking about Experimental Design and the Roles of Control Experiments

ERIC Educational Resources Information Center

Shi, Jia; Power, Joy M.; Klymkowsky, Michael W.

2011-01-01

Well-designed "controls" distinguish experimental from non-experimental studies. Surprisingly, we found that a high percentage of students had difficulty identifying control experiments even after completing three university-level laboratory courses. To address this issue, we designed and ran a revised cell biology lab course in which…

Segmented Polynomial Models in Quasi-Experimental Research.

ERIC Educational Resources Information Center

Wasik, John L.

1981-01-01

The use of segmented polynomial models is explained. Examples of design matrices of dummy variables are given for the least squares analyses of time series and discontinuity quasi-experimental research designs. Linear combinations of dummy variable vectors appear to provide tests of effects in the two quasi-experimental designs. (Author/BW)

Teaching Experimental Design to Elementary School Pupils in Greece

ERIC Educational Resources Information Center

Karampelas, Konstantinos

2016-01-01

This research is a study about the possibility to promote experimental design skills to elementary school pupils. Experimental design and the experiment process are foundational elements in current approaches to Science Teaching, as they provide learners with profound understanding about knowledge construction and science inquiry. The research was…

76 FR 39343 - Reducing Regulatory Burden; Retrospective Review Under E.O. 13563

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-06

... on ED regulations. c. How, if at all, will the agency incorporate experimental designs into retrospective analyses? Although ED will not be incorporating experimental designs into its analyses, its... evaluations, including those that use experimental designs, reveal about the efficacy of the regulations and...

Measuring and Advancing Experimental Design Ability in an Introductory Course without Altering Existing Lab Curriculum.

PubMed

Shanks, Ryan A; Robertson, Chuck L; Haygood, Christian S; Herdliksa, Anna M; Herdliska, Heather R; Lloyd, Steven A

2017-01-01

Introductory biology courses provide an important opportunity to prepare students for future courses, yet existing cookbook labs, although important in their own way, fail to provide many of the advantages of semester-long research experiences. Engaging, authentic research experiences aid biology students in meeting many learning goals. Therefore, overlaying a research experience onto the existing lab structure allows faculty to overcome barriers involving curricular change. Here we propose a working model for this overlay design in an introductory biology course and detail a means to conduct this lab with minimal increases in student and faculty workloads. Furthermore, we conducted exploratory factor analysis of the Experimental Design Ability Test (EDAT) and uncovered two latent factors which provide valid means to assess this overlay model's ability to increase advanced experimental design abilities. In a pre-test/post-test design, we demonstrate significant increases in both basic and advanced experimental design abilities in an experimental and comparison group. We measured significantly higher gains in advanced experimental design understanding in students in the experimental group. We believe this overlay model and EDAT factor analysis contribute a novel means to conduct and assess the effectiveness of authentic research experiences in an introductory course without major changes to the course curriculum and with minimal increases in faculty and student workloads.

Preoperative Plasma Aldosterone Levels and Postoperative Atrial Fibrillation Occurrence Following Cardiac Surgery: A Review of Literature and Design of the ALDO-POAF Study (ALDOsterone for Prediction of Post-Operative Atrial Fibrillation).

PubMed

Chequel, Mathieu; Ollitrault, Pierre; Saloux, Eric; Parienti, Jean-Jacques; Fischer, Marc-Olivier; Desgué, Julien; Allouche, Stéphane; Milliez, Paul; Alexandre, Joachim

2016-01-01

Post-operative atrial fibrillation (POAF) is a major and frequent complication occurring after cardiac surgery, contributing to prolonged intensive care and hospital stays and is associated with several cardiovascular complications. The exact mechanisms and signaling pathways involved in the development of POAF seem to be multifactorial and remain to date incompletely understood. β-blockers and amiodarone are the first line preventive drugs but are partially effective and near 30% of POAF resist to these strategies. In this work, we review the current knowledge about pathophysiological POAF mechanisms and preventive pharmacological strategies. We also discuss the rational for the use of pre-operative plasma aldosterone and galectin-3 (Gal-3) levels as predictive biomarkers of POAF and the potential role of aldosterone antagonists in the POAF preventive strategy. POAF is a major complication occurring after cardiac surgery. In this context, there is some evidence indicating that renin-angiotensin-aldosterone system and Gal-3 could be very useful predictive biomarkers of POAF and potentially interesting therapeutic target to prevent POAF occurrence. We present the rationale and the design of the ALDO-POAF trial (ALDOsterone for prediction of Post- Operative Atrial Fibrillation, NCT 02814903).

Patellofemoral Arthroplasty: Current Concepts and Review of the Literature

PubMed Central

Pisanu, Gabriele; Rosso, Federica; Bertolo, Corrado; Dettoni, Federico; Blonna, Davide; Bonasia, Davide Edoardo; Rossi, Roberto

2017-01-01

Patellofemoral osteoarthritis (PFOA) can be associated with anterior knee pain, stiffness, and functional impairment. Some authors report that PFOA affects approximately 9% of patients older than 40 years with a greater prevalence in females. Etiology of PFOA is multifactorial and is related to the presence of abnormal stresses at the PF joint due to knee- and patient-related factors. The need for a joint preserving treatment by isolated replacement of the injured compartment of the knee led to the development of PF arthroplasty (PFA). When a correct PF replacement is performed, PFA preserves physiologic tibiofemoral joint, thus allowing patients for a rapid recovery with a high satisfaction. The outcomes for PFA are quite variable with a trend toward good to excellent results, mainly owing to the improvement in surgical techniques, patient selection, and implant design. The development of the second generation of PFA improved the outcomes, which is attributed to the different trochlear designs. Recently, encouraging results have been provided by the association of PFA and unicompartmental knee arthroplasty (UKA). In many studies, the main cause of PFA failure is progression of tibiofemoral OA. The aim of this brief review of literature is to summarize the clinical features, indications and contraindications, surgical techniques, complications, and outcomes of PFA. PMID:29270562

Addressing weight stigma in physiotherapy: Development of a theory-driven approach to (re)thinking weight-related interactions.

PubMed

Setchell, J; Gard, M; Jones, L; Watson, B M

2017-08-01

In this article, we propose a theory-driven approach to developing interventions for reducing weight stigma in physiotherapy and discuss the design and exploratory trial of such an intervention. Weight stigma has been identified in physiotherapists in empirical investigations. However, there has been little consideration of how this stigma might be addressed. We highlight Goffman's work on stigma that provides social and embodied understandings of stigma. Goffman's approach, however, is notably apolitical, ahistorical and lacks mechanisms for understanding power. We suggest that post-structuralist perspectives can provide insight into these areas. Drawing on these theories, we critically examine the literature on weight stigma reduction, finding that trials have largely been unsuccessful. We argue that this may be due to overly passive and simplistic intervention designs. As context-specific understandings are desirable, we examine the nature of physiotherapy to determine what might be relevant to (re)thinking weight in this profession. We then discuss the development of a multifactorial, active weight stigma intervention we trialed with eight physiotherapists. Supported by theory, the outcomes of the exploratory study suggest that physiotherapy-specific factors such as fostering professional reflexivity and improving understandings of stigma need to be incorporated into an active intervention that considers the complex determinants of weight stigma.

The Current Crisis in Emergency Care and the Impact on Disaster Preparedness

PubMed Central

Cherry, Robert A; Trainer, Marcia

2008-01-01

Background The Homeland Security Act (HSA) of 2002 provided for the designation of a critical infrastructure protection program. This ultimately led to the designation of emergency services as a targeted critical infrastructure. In the context of an evolving crisis in hospital-based emergency care, the extent to which federal funding has addressed disaster preparedness will be examined. Discussion After 9/11, federal plans, procedures and benchmarks were mandated to assure a unified, comprehensive disaster response, ranging from local to federal activation of resources. Nevertheless, insufficient federal funding has contributed to a long-standing counter-trend which has eroded emergency medical care. The causes are complex and multifactorial, but they have converged to present a severely overburdened system that regularly exceeds emergency capacity and capabilities. This constant acute overcrowding, felt in communities all across the country, indicates a nation at risk. Federal funding has not sufficiently prioritized the improvements necessary for an emergency care infrastructure that is critical for an all hazards response to disaster and terrorist emergencies. Summary Currently, the nation is unable to meet presidential preparedness mandates for emergency and disaster care. Federal funding strategies must therefore be re-prioritized and targeted in a way that reasonably and consistently follows need. PMID:18452615

Graphical Models for Quasi-Experimental Designs

ERIC Educational Resources Information Center

Steiner, Peter M.; Kim, Yongnam; Hall, Courtney E.; Su, Dan

2017-01-01

Randomized controlled trials (RCTs) and quasi-experimental designs like regression discontinuity (RD) designs, instrumental variable (IV) designs, and matching and propensity score (PS) designs are frequently used for inferring causal effects. It is well known that the features of these designs facilitate the identification of a causal estimand…

Factors in Human-Computer Interface Design (A Pilot Study).

DTIC Science & Technology

1994-12-01

This study used a pretest - posttest control group experimental design to test the effect of consistency on speed, retention, and user satisfaction. Four...analysis. The overall methodology was a pretest - posttest control group experimental design using different prototypes to test the effects of...methodology used for this study was a pretest - posttest control group experimental design using different prototypes to test for features of the human

Combining two potential causes of metalloproteinase secretion causes abdominal aortic aneurysms in rats: a new experimental model

PubMed Central

Mata, Karina M; Prudente, Paula S; Rocha, Fabio S; Prado, Cibele M; Floriano, Elaine M; Elias, Jorge; Rizzi, Elen; Gerlach, Raquel F; Rossi, Marcos A; Ramos, Simone G

2011-01-01

Progress in understanding the pathophysiology of abdominal aortic aneurysms (AAA) is dependent in part on the development and application of effective animal models that recapitulate key aspects of the disease. The objective was to produce an experimental model of AAA in rats by combining two potential causes of metalloproteinase (MMP) secretion: inflammation and turbulent blood flow. Male Wistar rats were randomly divided in four groups: Injury, Stenosis, Aneurysm and Control (40/group). The Injury group received a traumatic injury to the external aortic wall. The Stenosis group received an extrinsic stenosis at a corresponding location. The Aneurysm group received both the injury and stenosis simultaneously, and the Control group received a sham operation. Animals were euthanized at days 1, 3, 7 and 15. Aorta and/or aneurysms were collected and the fragments were fixed for morphologic, immunohistochemistry and morphometric analyses or frozen for MMP assays. AAAs had developed by day 3 in 60–70% of the animals, reaching an aortic dilatation ratio of more than 300%, exhibiting intense wall remodelling initiated at the adventitia and characterized by an obvious inflammatory infiltrate, mesenchymal proliferation, neoangiogenesis, elastin degradation and collagen deposition. Immunohistochemistry and zymography studies displayed significantly increased expressions of MMP-2 and MMP-9 in aneurysm walls compared to other groups. The haemo-dynamic alterations caused by the stenosis may have provided additional contribution to the MMPs liberation. This new model illustrated that AAA can be multifactorial and confirmed the key roles of MMP-2 and MMP-9 in this dynamic remodelling process. PMID:21039990

Animal models of tic disorders: A translational perspective

PubMed Central

Godar, Sean C.; Mosher, Laura J.; Di Giovanni, Giuseppe; Bortolato, Marco

2014-01-01

Tics are repetitive, sudden movements and/or vocalizations, typically enacted as maladaptive responses to intrusive premonitory urges. The most severe tic disorder, Tourette syndrome (TS), is a childhood-onset condition featuring multiple motor and at least one phonic tic for a duration longer than 1 year. The pharmacological treatment of TS is mainly based on antipsychotic agents; while these drugs are often effective in reducing tic severity and frequency, their therapeutic compliance is limited by serious motor and cognitive side effects. The identification of novel therapeutic targets and development of better treatments for tic disorders is conditional on the development of animal models with high translational validity. In addition, these experimental tools can prove extremely useful to test hypotheses on the etiology and neurobiological bases of TS and related conditions. In recent years, the translational value of these animal models has been enhanced, thanks to a significant re-organization of our conceptual framework of neuropsychiatric disorders, with a greater focus on endophenotypes and quantitative indices, rather than qualitative descriptors. Given the complex and multifactorial nature of TS and other tic disorders, the selection of animal models that can appropriately capture specific symptomatic aspects of these conditions can pose significant theoretical and methodological challenges. In this article, we will review the state of the art on the available animal models of tic disorders, based on genetic mutations, environmental interventions as well as pharmacological manipulations. Furthermore, we will outline emerging lines of translational research showing how some of these experimental preparations have led to significant progress in the identification of novel therapeutic targets for tic disorders. PMID:25244952

Strategies to Prevent, Treat, and Provoke Corynebacterium-Associated Hyperkeratosis in Athymic Nude Mice

PubMed Central

Burr, Holly N; Lipman, Neil S; White, Julie R; Zheng, Junting; Wolf, Felix R

2011-01-01

Athymic nude mice infected with Corynebacterium bovis typically exhibit transient hyperkeratotic dermatitis. Our vivarium experienced an increased incidence of disease characterized by persistent skin lesions and increased mortality, leading to this study. For detection of infection, skin and buccal swab methods showed comparable sensitivities in nude mice. Various prevention, treatment, and eradication strategies were evaluated through clinical assessment, microbiology, and histopathology. In experimentally naïve athymic nude mice, a 2-wk course of prophylactic amoxicillin-containing diet (1200 ppm amoxicillin; effective dose, 200 mg/kg) was ineffective at preventing infection or disease. There was also no significant difference in disease duration or severity in athymic nude mice that received amoxicillin diet or penicillin–streptomycin topical spray (penicillin, 2500 U/mL; streptomycin, 2500 µg/mL). Prolonged treatment with 4 or 8 wk of amoxicillin diet cleared only a small number of athymic nude mice that had subclinical C. bovis infections. Antibiotic sensitivity of C. bovis isolates demonstrated a small colony isolate with less susceptibility to all antibiotics compared with a large colony isolate. Resistance did not appear to develop after prolonged treatment with amoxicillin. Provocation testing by administration of cyclophosphamide (50 mg/kg IP every 48 to 72 h for 90 d) to subclinically infected athymic nude mice resulted in prolonged clinical disease that waxed and waned without progression to severe disease. Our findings suggest that antibiotic prophylaxis and treatment of clinical disease in experimentally naïve mice is unrewarding, eradication of bacterial infection is difficult, and severe disease associated with C. bovis is likely multifactorial. PMID:21640035

Industrial Noise and Tooth Wear - Experimental Study

PubMed Central

Cavacas, Maria Alzira; Tavares, Vitor; Borrecho, Gonçalo; Oliveira, Maria João; Oliveira, Pedro; Brito, José; Águas, Artur; dos Santos, José Martins

2015-01-01

Tooth wear is a complex multifactorial process that involves the loss of hard dental tissue. Parafunctional habits have been mentioned as a self-destructive process caused by stress, which results in hyperactivity of masticatory muscles. Stress manifests itself through teeth grinding, leading to progressive teeth wear. The effects of continuous exposure to industrial noise, a “stressor” agent, cannot be ignored and its effects on the teeth must be evaluated. Aims: The aim of this study was to ascertain the effects of industrial noise on dental wear over time, by identifying and quantifying crown area loss. Material and Methods: 39 Wistar rats were used. Thirty rats were divided in 3 experimental groups of 10 animals each. Animals were exposed to industrial noise, rich in LFN components, for 1, 4 and 7 months, with an average weekly exposure of 40 hours (8h/day, 5 days/week with the weekends in silence). The remaining 9 animals were kept in silence. The areas of the three main cusps of the molars were measured under light microscopy. Statistical analysis used: A two-way ANOVA model was applied at significance level of 5%. Results: The average area of the molar cusps was significantly different between exposed and non-exposed animals. The most remarkable differences occurred between month 1 and 4. The total crown loss from month 1 to month 7 was 17.3% in the control group, and 46.5% in the exposed group, and the differences between these variations were significant (p<0.001). Conclusions: Our data suggest that industrial noise is an important factor in the pathogenesis of tooth wear. PMID:25798052

Design of a factorial experiment with randomization restrictions to assess medical device performance on vascular tissue.

PubMed

Diestelkamp, Wiebke S; Krane, Carissa M; Pinnell, Margaret F

2011-05-20

Energy-based surgical scalpels are designed to efficiently transect and seal blood vessels using thermal energy to promote protein denaturation and coagulation. Assessment and design improvement of ultrasonic scalpel performance relies on both in vivo and ex vivo testing. The objective of this work was to design and implement a robust, experimental test matrix with randomization restrictions and predictive statistical power, which allowed for identification of those experimental variables that may affect the quality of the seal obtained ex vivo. The design of the experiment included three factors: temperature (two levels); the type of solution used to perfuse the artery during transection (three types); and artery type (two types) resulting in a total of twelve possible treatment combinations. Burst pressures of porcine carotid and renal arteries sealed ex vivo were assigned as the response variable. The experimental test matrix was designed and carried out as a split-plot experiment in order to assess the contributions of several variables and their interactions while accounting for randomization restrictions present in the experimental setup. The statistical software package SAS was utilized and PROC MIXED was used to account for the randomization restrictions in the split-plot design. The combination of temperature, solution, and vessel type had a statistically significant impact on seal quality. The design and implementation of a split-plot experimental test-matrix provided a mechanism for addressing the existing technical randomization restrictions of ex vivo ultrasonic scalpel performance testing, while preserving the ability to examine the potential effects of independent factors or variables. This method for generating the experimental design and the statistical analyses of the resulting data are adaptable to a wide variety of experimental problems involving large-scale tissue-based studies of medical or experimental device efficacy and performance.

Experimental and Quasi-Experimental Design.

ERIC Educational Resources Information Center

Cottrell, Edward B.

With an emphasis on the problems of control of extraneous variables and threats to internal and external validity, the arrangement or design of experiments is discussed. The purpose of experimentation in an educational institution, and the principles governing true experimentation (randomization, replication, and control) are presented, as are…

Effectiveness of a multifactorial intervention based on an application for smartphones, heart-healthy walks and a nutritional workshop in patients with type 2 diabetes mellitus in primary care (EMID): study protocol for a randomised controlled trial.

PubMed

Alonso-Domínguez, Rosario; Gómez-Marcos, Manuel A; Patino-Alonso, Maria C; Sánchez-Aguadero, Natalia; Agudo-Conde, Cristina; Castaño-Sánchez, Carmen; García-Ortiz, Luis; Recio-Rodríguez, José I

2017-09-14

New information and communication technologies (ICTs) may promote lifestyle changes, but no adequate evidence is available on their combined effect of ICTs with multifactorial interventions aimed at improving diet and increasing physical activity in patients with type 2 diabetes mellitus (DM2). The primary objective of this study is to assess the effect of a multifactorial intervention to increase physical activity and adherence to Mediterranean diet in DM2. METHODS AND ANALYSIS: Study scope and population: The study will be conducted at 'La Alamedilla' primary care research unit in Salamanca (Spain). 200 patients with DM2 of both sexes, aged 25-70 years and who meet the inclusion criteria and sign the informed consent will be recruited. Each participant will attend the clinic at baseline and 3 and 12 months after intervention. Both groups will be given short advice on diet and physical activity. The intervention group will also take five heart-healthy walks and attend a group session on diet education and will be trained on use of an application for smartphone (EVIDENT II) for 3 months. The main study endpoints will be changes in physical activity, as assessed by a pedometer and the International Physical Activity Questionnaire, and adherence to the Mediterranean diet, as evaluated by an adherence questionnaire and the Diet Quality Index. Anthropometric parameters and laboratory values, lifestyles and quality of life will also be assessed. It was approved by the Clinical Research Ethics Committee of Salamanca on 28/11/2016. NCT02991079; Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Falls in elderly people: a multifactorial analysis of risk markers using data from the Swedish general population study 'Good ageing in Skåne'.

PubMed

Stenhagen, Magnus; Nordell, Eva; Elmståhl, Sölve

2013-04-01

The aim of this study was to describe the prevalence of falls in a general older population, especially among the most elderly, and the risk markers associated with falls. This is a cross-sectional study in which 38 fall risk markers were analysed in non-, occasional- and frequent-fallers. The population was 2,865 individuals (aged 60-93), randomly selected from the general population register. The risk of falling was calculated as age-adjusted odds ratios. The relation between the number of risk markers for an individual and falls was also analysed. About one in ten reported falling during the past 6 months, 35% of which were over 90 years old. Twenty-one risk markers were significantly related to falls confirming falling as a multifactorial problem. These included a variety of diseases, symptoms, medical and physical functions, life-style factors and the taking of certain drugs. The five risk markers with the highest odds ratio in frequent fallers were 'tendency to fall' (37.9), 'low walking speed' (12.8), consumption of 'neuroleptics' (10.9), 'impaired mobility' (10.0) and 'dementia' (5.4). Subjects with more than four and seven risk markers showed a 9- respectively 28-fold increase in the risk of falling, especially among frequent fallers and those aged over 90 years. Falls are common in the elderly population and the risk is multifactorial. The results imply that there is an overrepresentation of fallers in a distinct subgroup of the very elderly and those with multiple risk markers. The self-perceived clinical sign 'tendency to fall' seems highly sensitive as indicator of individuals at risk. Several risk markers may be treatable. Fall risk seems to increase in a non-linear, almost exponential way with increasing number of risk markers.

Adoption of Evidence-Based Fall Prevention Practices in Primary Care for Older Adults with a History of Falls.

PubMed

Phelan, Elizabeth A; Aerts, Sally; Dowler, David; Eckstrom, Elizabeth; Casey, Colleen M

2016-01-01

A multifactorial approach to assess and manage modifiable risk factors is recommended for older adults with a history of falls. Limited research suggests that this approach does not routinely occur in clinical practice, but most related studies are based on provider self-report, with the last chart audit of United States practice published over a decade ago. We conducted a retrospective chart review to assess the extent to which patients aged 65+ years with a history of repeated falls or fall-related health-care use received multifactorial risk assessment and interventions. The setting was an academic primary care clinic in the Pacific Northwest. Among the 116 patients meeting our inclusion criteria, 48% had some type of documented assessment. Their mean age was 79 ± 8 years; 68% were female, and 10% were non-white. They averaged six primary care visits over a 12-month period subsequent to their index fall. Frequency of assessment of fall-risk factors varied from 24% (for home safety) to 78% (for vitamin D). An evidence-based intervention was recommended for identified risk factors 73% of the time, on average. Two risk factors were addressed infrequently: medications (21%) and home safety (24%). Use of a structured visit note template independently predicted assessment of fall-risk factors (p = 0.003). Geriatrics specialists were more likely to use a structured note template (p = 0.04) and perform more fall-risk factor assessments (4.6 vs. 3.6, p = 0.007) than general internists. These results suggest opportunities for improving multifactorial fall-risk assessment and management of older adults at high fall risk in primary care. A structured visit note template facilitates assessment. Given that high-risk medications have been found to be independent risk factors for falls, increasing attention to medications should become a key focus of both public health educational efforts and fall prevention in primary care practice.

Adoption of Evidence-Based Fall Prevention Practices in Primary Care for Older Adults with a History of Falls

PubMed Central

Phelan, Elizabeth A.; Aerts, Sally; Dowler, David; Eckstrom, Elizabeth; Casey, Colleen M.

2016-01-01

A multifactorial approach to assess and manage modifiable risk factors is recommended for older adults with a history of falls. Limited research suggests that this approach does not routinely occur in clinical practice, but most related studies are based on provider self-report, with the last chart audit of United States practice published over a decade ago. We conducted a retrospective chart review to assess the extent to which patients aged 65+ years with a history of repeated falls or fall-related health-care use received multifactorial risk assessment and interventions. The setting was an academic primary care clinic in the Pacific Northwest. Among the 116 patients meeting our inclusion criteria, 48% had some type of documented assessment. Their mean age was 79 ± 8 years; 68% were female, and 10% were non-white. They averaged six primary care visits over a 12-month period subsequent to their index fall. Frequency of assessment of fall-risk factors varied from 24% (for home safety) to 78% (for vitamin D). An evidence-based intervention was recommended for identified risk factors 73% of the time, on average. Two risk factors were addressed infrequently: medications (21%) and home safety (24%). Use of a structured visit note template independently predicted assessment of fall-risk factors (p = 0.003). Geriatrics specialists were more likely to use a structured note template (p = 0.04) and perform more fall-risk factor assessments (4.6 vs. 3.6, p = 0.007) than general internists. These results suggest opportunities for improving multifactorial fall-risk assessment and management of older adults at high fall risk in primary care. A structured visit note template facilitates assessment. Given that high-risk medications have been found to be independent risk factors for falls, increasing attention to medications should become a key focus of both public health educational efforts and fall prevention in primary care practice. PMID:27660753

Multifactorial Understanding of Ion Abundance in Tandem Mass Spectrometry Experiments.

PubMed

Fazal, Zeeshan; Southey, Bruce R; Sweedler, Jonathan V; Rodriguez-Zas, Sandra L

2013-01-29

In a bottom-up shotgun approach, the proteins of a mixture are enzymatically digested, separated, and analyzed via tandem mass spectrometry. The mass spectra relating fragment ion intensities (abundance) to the mass-to-charge are used to deduce the amino acid sequence and identify the peptides and proteins. The variables that influence intensity were characterized using a multi-factorial mixed-effects model, a ten-fold cross-validation, and stepwise feature selection on 6,352,528 fragment ions from 61,543 peptide ions. Intensity was higher in fragment ions that did not have neutral mass loss relative to any mass loss or that had a +1 charge state. Peptide ions classified for proton mobility as non-mobile had lowest intensity of all mobility levels. Higher basic residue (arginine, lysine or histidine) counts in the peptide ion and low counts in the fragment ion were associated with lower fragment ion intensities. Higher counts of proline in peptide and fragment ions were associated with lower intensities. These results are consistent with the mobile proton theory. Opposite trends between peptide and fragment ion counts and intensity may be due to the different impact of factor under consideration at different stages of the MS/MS experiment or to the different distribution of observations across peptide and fragment ion levels. Presence of basic residues at all three positions next to the fragmentation site was associated with lower fragment ion intensity. The presence of proline proximal to the fragmentation site enhanced fragmentation and had the opposite trend when located distant from the site. A positive association between fragment ion intensity and presence of sulfur residues (cysteine and methionine) on the vicinity of the fragmentation site was identified. These results highlight the multi-factorial nature of fragment ion intensity and could improve the algorithms for peptide identification and the simulation in tandem mass spectrometry experiments.

Multifactorial Understanding of Ion Abundance in Tandem Mass Spectrometry Experiments

PubMed Central

Fazal, Zeeshan; Southey, Bruce R; Sweedler, Jonathan V.; Rodriguez-Zas, Sandra L.

2013-01-01

In a bottom-up shotgun approach, the proteins of a mixture are enzymatically digested, separated, and analyzed via tandem mass spectrometry. The mass spectra relating fragment ion intensities (abundance) to the mass-to-charge are used to deduce the amino acid sequence and identify the peptides and proteins. The variables that influence intensity were characterized using a multi-factorial mixed-effects model, a ten-fold cross-validation, and stepwise feature selection on 6,352,528 fragment ions from 61,543 peptide ions. Intensity was higher in fragment ions that did not have neutral mass loss relative to any mass loss or that had a +1 charge state. Peptide ions classified for proton mobility as non-mobile had lowest intensity of all mobility levels. Higher basic residue (arginine, lysine or histidine) counts in the peptide ion and low counts in the fragment ion were associated with lower fragment ion intensities. Higher counts of proline in peptide and fragment ions were associated with lower intensities. These results are consistent with the mobile proton theory. Opposite trends between peptide and fragment ion counts and intensity may be due to the different impact of factor under consideration at different stages of the MS/MS experiment or to the different distribution of observations across peptide and fragment ion levels. Presence of basic residues at all three positions next to the fragmentation site was associated with lower fragment ion intensity. The presence of proline proximal to the fragmentation site enhanced fragmentation and had the opposite trend when located distant from the site. A positive association between fragment ion intensity and presence of sulfur residues (cysteine and methionine) on the vicinity of the fragmentation site was identified. These results highlight the multi-factorial nature of fragment ion intensity and could improve the algorithms for peptide identification and the simulation in tandem mass spectrometry experiments. PMID:24031159

The Experimental Design Assistant.

PubMed

Percie du Sert, Nathalie; Bamsey, Ian; Bate, Simon T; Berdoy, Manuel; Clark, Robin A; Cuthill, Innes; Fry, Derek; Karp, Natasha A; Macleod, Malcolm; Moon, Lawrence; Stanford, S Clare; Lings, Brian

2017-09-01

Addressing the common problems that researchers encounter when designing and analysing animal experiments will improve the reliability of in vivo research. In this article, the Experimental Design Assistant (EDA) is introduced. The EDA is a web-based tool that guides the in vivo researcher through the experimental design and analysis process, providing automated feedback on the proposed design and generating a graphical summary that aids communication with colleagues, funders, regulatory authorities, and the wider scientific community. It will have an important role in addressing causes of irreproducibility.

The Experimental Design Assistant

PubMed Central

Bamsey, Ian; Bate, Simon T.; Berdoy, Manuel; Clark, Robin A.; Cuthill, Innes; Fry, Derek; Karp, Natasha A.; Macleod, Malcolm; Moon, Lawrence; Stanford, S. Clare; Lings, Brian

2017-01-01

Addressing the common problems that researchers encounter when designing and analysing animal experiments will improve the reliability of in vivo research. In this article, the Experimental Design Assistant (EDA) is introduced. The EDA is a web-based tool that guides the in vivo researcher through the experimental design and analysis process, providing automated feedback on the proposed design and generating a graphical summary that aids communication with colleagues, funders, regulatory authorities, and the wider scientific community. It will have an important role in addressing causes of irreproducibility. PMID:28957312

Development of the Biological Experimental Design Concept Inventory (BEDCI)

ERIC Educational Resources Information Center

Deane, Thomas; Nomme, Kathy; Jeffery, Erica; Pollock, Carol; Birol, Gulnur

2014-01-01

Interest in student conception of experimentation inspired the development of a fully validated 14-question inventory on experimental design in biology (BEDCI) by following established best practices in concept inventory (CI) design. This CI can be used to diagnose specific examples of non-expert-like thinking in students and to evaluate the…

76 FR 17107 - Fisheries of the Exclusive Economic Zone Off Alaska; Application for an Exempted Fishing Permit

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-28

... experimental design requires this quantity of salmon to ensure statistically valid results. The applicant also... encounters sufficient concentrations of salmon and pollock for meeting the experimental design. Groundfish... of the groundfish harvested is expected to be pollock. The experimental design requires this quantity...

77 FR 69796 - Fisheries of the Exclusive Economic Zone Off Alaska; Application for an Exempted Fishing Permit

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-21

...-year EFP. The experimental design requires this quantity of salmon to ensure statistically valid... of the groundfish harvested each year from the EFP is expected to be pollock. The experimental design... concentrations of salmon and pollock for addressing experimental design criteria. The activities under the EFP...

Web-Based Learning Support for Experimental Design in Molecular Biology: A Top-Down Approach

ERIC Educational Resources Information Center

Aegerter-Wilmsen, Tinri; Hartog, Rob; Bisseling, Ton

2003-01-01

An important learning goal of a molecular biology curriculum is the attainment of a certain competence level in experimental design. Currently, undergraduate students are confronted with experimental approaches in textbooks, lectures and laboratory courses. However, most students do not reach a satisfactory level of competence in the designing of…

"Using Power Tables to Compute Statistical Power in Multilevel Experimental Designs"

ERIC Educational Resources Information Center

Konstantopoulos, Spyros

2009-01-01

Power computations for one-level experimental designs that assume simple random samples are greatly facilitated by power tables such as those presented in Cohen's book about statistical power analysis. However, in education and the social sciences experimental designs have naturally nested structures and multilevel models are needed to compute the…

Considering RNAi experimental design in parasitic helminths.

PubMed

Dalzell, Johnathan J; Warnock, Neil D; McVeigh, Paul; Marks, Nikki J; Mousley, Angela; Atkinson, Louise; Maule, Aaron G

2012-04-01

Almost a decade has passed since the first report of RNA interference (RNAi) in a parasitic helminth. Whilst much progress has been made with RNAi informing gene function studies in disparate nematode and flatworm parasites, substantial and seemingly prohibitive difficulties have been encountered in some species, hindering progress. An appraisal of current practices, trends and ideals of RNAi experimental design in parasitic helminths is both timely and necessary for a number of reasons: firstly, the increasing availability of parasitic helminth genome/transcriptome resources means there is a growing need for gene function tools such as RNAi; secondly, fundamental differences and unique challenges exist for parasite species which do not apply to model organisms; thirdly, the inherent variation in experimental design, and reported difficulties with reproducibility undermine confidence. Ideally, RNAi studies of gene function should adopt standardised experimental design to aid reproducibility, interpretation and comparative analyses. Although the huge variations in parasite biology and experimental endpoints make RNAi experimental design standardization difficult or impractical, we must strive to validate RNAi experimentation in helminth parasites. To aid this process we identify multiple approaches to RNAi experimental validation and highlight those which we deem to be critical for gene function studies in helminth parasites.

Aviation Human-in-the-Loop Simulation Studies: Experimental Planning, Design, and Data Management

DTIC Science & Technology

2014-01-01

Aviation Human-in-the-Loop Simulation Studies: Experimental Planning, Design , and Data Management Kevin W. Williams1 Bonny Christopher2 Gena...Simulation Studies: Experimental Planning, Design , and Data Management January 2014 6. Performing Organization Code 7. Author(s) 8. Performing...describe the process by which we designed our human-in-the-loop (HITL) simulation study and the methodology used to collect and analyze the results

Research designs for studies evaluating the effectiveness of change and improvement strategies.

PubMed

Eccles, M; Grimshaw, J; Campbell, M; Ramsay, C

2003-02-01

The methods of evaluating change and improvement strategies are not well described. The design and conduct of a range of experimental and non-experimental quantitative designs are considered. Such study designs should usually be used in a context where they build on appropriate theoretical, qualitative and modelling work, particularly in the development of appropriate interventions. A range of experimental designs are discussed including single and multiple arm randomised controlled trials and the use of more complex factorial and block designs. The impact of randomisation at both group and individual levels and three non-experimental designs (uncontrolled before and after, controlled before and after, and time series analysis) are also considered. The design chosen will reflect both the needs (and resources) in any particular circumstances and also the purpose of the evaluation. The general principle underlying the choice of evaluative design is, however, simple-those conducting such evaluations should use the most robust design possible to minimise bias and maximise generalisability.

Abfraction, abrasion, biocorrosion, and the enigma of noncarious cervical lesions: a 20-year perspective.

PubMed

Grippo, John O; Simring, Marvin; Coleman, Thomas A

2012-02-01

Hitherto, noncarious cervical lesions (NCCLs) of teeth have been generally ascribed to either toothbrush-dentifrice abrasion or acid "erosion." The last two decades have provided a plethora of new studies concerning such lesions. The most significant studies are reviewed and integrated into a practical approach to the understanding and designation of these lesions. A paradigm shift is suggested regarding use of the term "biocorrosion" to supplant "erosion" as it continues to be misused in the United States and many other countries of the world. Biocorrosion embraces the chemical, biochemical, and electrochemical degradation of tooth substance caused by endogenous and exogenous acids, proteolytic agents, as well as the piezoelectric effects only on dentin. Abfraction, representing the microstructural loss of tooth substance in areas of stress concentration, should not be used to designate all NCCLs because these lesions are commonly multifactorial in origin. Appropriate designation of a particular NCCL depends upon the interplay of the specific combination of three major mechanisms: stress, friction, and biocorrosion, unique to that individual case. Modifying factors, such as saliva, tongue action, and tooth form, composition, microstructure, mobility, and positional prominence are elucidated. By performing a comprehensive medical and dental history, using precise terms and concepts, and utilizing the Revised Schema of Pathodynamic Mechanisms, the dentist may successfully identify and treat the etiology of root surface lesions. Preventive measures may be instituted if the causative factors are detected and their modifying factors are considered. © 2011 Wiley Periodicals, Inc.

[The design of a nationwide cohort study in Germany : the pretest studies of the German National Cohort (GNC)].

PubMed

Ahrens, W; Greiser, H; Linseisen, J; Kluttig, A; Schipf, S; Schmidt, B; Günther, K

2014-11-01

The German National Cohort (GNC) is the largest population-based cohort study in Germany. Beginning in 2014, a total of 200,000 women and men aged 20-69 years will be examined in 18 study centers. The aim of the study is to investigate the etiology of chronic diseases in relation to lifestyle, genetic, socioeconomic, and environmental factors and to develop appropriate methods for early diagnosis and prevention of diseases such as cardiovascular and respiratory diseases, cancer, diabetes, neurodegenerative/psychiatric diseases, as well as musculoskeletal and infectious diseases. Pretest studies (phase 1 and 2) were conducted to select methods, instruments, and procedures for the main study, to develop standard operating procedures, and to design and test the examination program according to acceptance, expected duration, and feasibility. The pretest studies included testing of interviews, questionnaires, anthropometric measurements, several medical examinations, and the collection of biosamples. In addition, the logistic, technical, and personnel infrastructure for the main study could be established including the study centers, the central infrastructure for data management, processes to coordinate the study, and data protection and quality management concepts. The examination program for the main phase of the GNC was designed and optimized based on the results of the pretest studies. The GNC is a population-based, highly standardized and excellently phenotyped cohort that will be the basis for new strategies for risk assessment and identification, early diagnosis, and prevention of multifactorial diseases.

Unique considerations in the design and experimental evaluation of tailored wings with elastically produced chordwise camber

NASA Technical Reports Server (NTRS)

Rehfield, Lawrence W.; Zischka, Peter J.; Fentress, Michael L.; Chang, Stephen

1992-01-01

Some of the unique considerations that are associated with the design and experimental evaluation of chordwise deformable wing structures are addressed. Since chordwise elastic camber deformations are desired and must be free to develop, traditional rib concepts and experimental methodology cannot be used. New rib design concepts are presented and discussed. An experimental methodology based upon the use of a flexible sling support and load application system has been created and utilized to evaluate a model box beam experimentally. Experimental data correlate extremely well with design analysis predictions based upon a beam model for the global properties of camber compliance and spanwise bending compliance. Local strain measurements exhibit trends in agreement with intuition and theory but depart slightly from theoretical perfection based upon beam-like behavior alone. It is conjectured that some additional refinement of experimental technique is needed to explain or eliminate these (minor) departures from asymmetric behavior of upper and lower box cover strains. Overall, a solid basis for the design of box structures based upon the bending method of elastic camber production has been confirmed by the experiments.

Lipid Screening in Childhood and Adolescence for Detection of Multifactorial Dyslipidemia: Evidence Report and Systematic Review for the US Preventive Services Task Force.

PubMed

Lozano, Paula; Henrikson, Nora B; Morrison, Caitlin C; Dunn, John; Nguyen, Matt; Blasi, Paula R; Whitlock, Evelyn P

2016-08-09

Multifactorial dyslipidemia, characterized by elevated total cholesterol (TC) or low-density lipoprotein cholesterol (LDL-C), is associated with dyslipidemia and markers of atherosclerosis in young adulthood. Screening for dyslipidemia in childhood could delay or reduce cardiovascular events in adulthood. To systematically review the evidence on benefits and harms of screening adolescents and children for multifactorial dyslipidemia for the US Preventive Services Task Force (USPSTF). MEDLINE, Cochrane Central Register of Controlled Trials, and PubMed were searched for studies published between January 1, 2005, and June 2, 2015; studies included in a previous USPSTF evidence report and reference lists of relevant studies and ongoing trials were also searched. Surveillance was conducted through April 9, 2016. Fair- and good-quality studies in English with participants 0 to 20 years of age. Two investigators independently reviewed abstracts and full-text articles and extracted data into evidence tables. Results were qualitatively summarized. Outcomes included dyslipidemia (TC≥200 mg/dL or LDL-C≥130 mg/dL) and atherosclerosis in childhood; myocardial infarction and ischemic stroke in adulthood; diagnostic yield (number of confirmed cases per children screened); and harms of screening or treatment. Simulated diagnostic yield was calculated as initial screening yield × positive predictive value from a study with confirmatory testing. Screening of children for multifactorial dyslipidemia has not been evaluated in randomized clinical trials. Based on 1 observational study (n = 6500) and nationally representative prevalence estimates, the simulated diagnostic yield of screening for elevated TC varies between 4.8% and 12.3% (higher in obese children [12.3%] and at the ages when TC naturally peaks-7.2% at age 9-11 years and 7.2% at age 16-19 years). One good-quality randomized clinical trial (n = 663) found a modest effect of intensive dietary counseling for a low-fat, low-cholesterol diet on lipid levels at 1 year in children aged 8 to 10 years with mild to moderate dyslipidemia; mean between-group difference in TC change from baseline was -6.1 mg/dL (95% CI, -9.1 to -3.2 mg/dL; P < .001). Between-group differences dissipated by year 5. The intervention did not adversely affect nutritional status, growth, or development over the 18-year study period. One observational study (n = 9245) found that TC concentration at age 12 to 39 years was not associated with death before age 55 years. The diagnostic yield of lipid screening varies by age and body mass index. No direct evidence was identified for benefits or harms of childhood screening or treatment on outcomes in adulthood. Intensive dietary interventions may be safe, with modest short-term benefit of uncertain clinical significance.