Comparison of humanized IgG and FvFc anti-CD3 monoclonal antibodies expressed in CHO cells.

PubMed

Serpieri, Flavia; Inocencio, Andre; de Oliveira, Jose Marcelino; Pimenta, Alécio A; Garbuio, Angélica; Kalil, Jorge; Brigido, Marcelo M; Moro, Ana Maria

2010-07-01

Two humanized monoclonal antibody constructs bearing the same variable regions of an anti-CD3 monoclonal antibody, whole IgG and FvFc, were expressed in CHO cells. Random and site-specific integration were used resulting in similar expression levels. The transfectants were selected with appropriate selection agent, and the surviving cells were plated in semi-solid medium for capture with FITC-conjugated anti-human IG antibody and picked with the robotic ClonePix FL. Conditioned media from selected clones were purified by affinity chromatography and characterized by SDS-PAGE, Western-blot, SEC-HPLC, and isoelectric focusing. Binding to the target present in healthy human mononuclear cells was assessed by flow cytometry, as well as by competition between the two constructs and the original murine monoclonal antibody. The humanized constructs were not able to dislodge the murine antibody while the murine anti-CD3 antibody could dislodge around 20% of the FvFc or IgG humanized versions. Further in vitro and in vivo pre-clinical analyses will be carried out to verify the ability of the humanized versions to demonstrate the immunoregulatory profile required for a humanized anti-CD3 monoclonal antibody.

Human cooperation by lethal group competition.

PubMed

Egas, Martijn; Kats, Ralph; van der Sar, Xander; Reuben, Ernesto; Sabelis, Maurice W

2013-01-01

Why humans are prone to cooperate puzzles biologists, psychologists and economists alike. Between-group conflict has been hypothesized to drive within-group cooperation. However, such conflicts did not have lasting effects in laboratory experiments, because they were about luxury goods, not needed for survival ("looting"). Here, we find within-group cooperation to last when between-group conflict is implemented as "all-out war" (eliminating the weakest groups). Human subjects invested in helping group members to avoid having the lowest collective pay-off, whereas they failed to cooperate in control treatments with random group elimination or with no subdivision in groups. When the game was repeated, experience was found to promote helping. Thus, not within-group interactions alone, not random group elimination, but pay-off-dependent group elimination was found to drive within-group cooperation in our experiment. We suggest that some forms of human cooperation are maintained by multi-level selection: reciprocity within groups and lethal competition among groups acting together.

Affinity selection of Nipah and Hendra virus-related vaccine candidates from a complex random peptide library displayed on bacteriophage virus-like particles

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

Peabody, David S.; Chackerian, Bryce; Ashley, Carlee

The invention relates to virus-like particles of bacteriophage MS2 (MS2 VLPs) displaying peptide epitopes or peptide mimics of epitopes of Nipah Virus envelope glycoprotein that elicit an immune response against Nipah Virus upon vaccination of humans or animals. Affinity selection on Nipah Virus-neutralizing monoclonal antibodies using random sequence peptide libraries on MS2 VLPs selected peptides with sequence similarity to peptide sequences found within the envelope glycoprotein of Nipah itself, thus identifying the epitopes the antibodies recognize. The selected peptide sequences themselves are not necessarily identical in all respects to a sequence within Nipah Virus glycoprotein, and therefore may be referredmore » to as epitope mimics VLPs displaying these epitope mimics can serve as vaccine. On the other hand, display of the corresponding wild-type sequence derived from Nipah Virus and corresponding to the epitope mapped by affinity selection, may also be used as a vaccine.« less

Differential privacy-based evaporative cooling feature selection and classification with relief-F and random forests.

PubMed

Le, Trang T; Simmons, W Kyle; Misaki, Masaya; Bodurka, Jerzy; White, Bill C; Savitz, Jonathan; McKinney, Brett A

2017-09-15

Classification of individuals into disease or clinical categories from high-dimensional biological data with low prediction error is an important challenge of statistical learning in bioinformatics. Feature selection can improve classification accuracy but must be incorporated carefully into cross-validation to avoid overfitting. Recently, feature selection methods based on differential privacy, such as differentially private random forests and reusable holdout sets, have been proposed. However, for domains such as bioinformatics, where the number of features is much larger than the number of observations p≫n , these differential privacy methods are susceptible to overfitting. We introduce private Evaporative Cooling, a stochastic privacy-preserving machine learning algorithm that uses Relief-F for feature selection and random forest for privacy preserving classification that also prevents overfitting. We relate the privacy-preserving threshold mechanism to a thermodynamic Maxwell-Boltzmann distribution, where the temperature represents the privacy threshold. We use the thermal statistical physics concept of Evaporative Cooling of atomic gases to perform backward stepwise privacy-preserving feature selection. On simulated data with main effects and statistical interactions, we compare accuracies on holdout and validation sets for three privacy-preserving methods: the reusable holdout, reusable holdout with random forest, and private Evaporative Cooling, which uses Relief-F feature selection and random forest classification. In simulations where interactions exist between attributes, private Evaporative Cooling provides higher classification accuracy without overfitting based on an independent validation set. In simulations without interactions, thresholdout with random forest and private Evaporative Cooling give comparable accuracies. We also apply these privacy methods to human brain resting-state fMRI data from a study of major depressive disorder. Code available at http://insilico.utulsa.edu/software/privateEC . brett-mckinney@utulsa.edu. Supplementary data are available at Bioinformatics online. © The Author (2017). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Prioritizing Conservation of Ungulate Calving Resources in Multiple-Use Landscapes

PubMed Central

Dzialak, Matthew R.; Harju, Seth M.; Osborn, Robert G.; Wondzell, John J.; Hayden-Wing, Larry D.; Winstead, Jeffrey B.; Webb, Stephen L.

2011-01-01

Background Conserving animal populations in places where human activity is increasing is an ongoing challenge in many parts of the world. We investigated how human activity interacted with maternal status and individual variation in behavior to affect reliability of spatially-explicit models intended to guide conservation of critical ungulate calving resources. We studied Rocky Mountain elk (Cervus elaphus) that occupy a region where 2900 natural gas wells have been drilled. Methodology/Principal Findings We present novel applications of generalized additive modeling to predict maternal status based on movement, and of random-effects resource selection models to provide population and individual-based inference on the effects of maternal status and human activity. We used a 2×2 factorial design (treatment vs. control) that included elk that were either parturient or non-parturient and in areas either with or without industrial development. Generalized additive models predicted maternal status (parturiency) correctly 93% of the time based on movement. Human activity played a larger role than maternal status in shaping resource use; elk showed strong spatiotemporal patterns of selection or avoidance and marked individual variation in developed areas, but no such pattern in undeveloped areas. This difference had direct consequences for landscape-level conservation planning. When relative probability of use was calculated across the study area, there was disparity throughout 72–88% of the landscape in terms of where conservation intervention should be prioritized depending on whether models were based on behavior in developed areas or undeveloped areas. Model validation showed that models based on behavior in developed areas had poor predictive accuracy, whereas the model based on behavior in undeveloped areas had high predictive accuracy. Conclusions/Significance By directly testing for differences between developed and undeveloped areas, and by modeling resource selection in a random-effects framework that provided individual-based inference, we conclude that: 1) amplified selection or avoidance behavior and individual variation, as responses to increasing human activity, complicate conservation planning in multiple-use landscapes, and 2) resource selection behavior in places where human activity is predictable or less dynamic may provide a more reliable basis from which to prioritize conservation action. PMID:21297866

A seamless phase IIB/III adaptive outcome trial: design rationale and implementation challenges.

PubMed

Chen, Y H Joshua; Gesser, Richard; Luxembourg, Alain

2015-02-01

The licensed four-valent prophylactic human papillomavirus vaccine is highly efficacious in preventing cervical, vulvar, vaginal, and anal cancers and related precancers caused by human papillomavirus types 6, 11, 16, and 18. These four types account for approximately 70% of cervical cancers. A nine-valent human papillomavirus vaccine, including the four original types (6, 11, 16, and 18) plus the next five most prevalent types in cervical cancer (31, 33, 45, 52, and 58) could provide approximately 90% overall cervical cancer coverage. To expedite the nine-valent human papillomavirus vaccine clinical development, an adaptive, seamless Phase IIB/III outcome trial with ∼ 15,000 subjects was conducted to facilitate dose formulation selection and provide pivotal evidence of safety and efficacy for regulatory registrations. We discuss the design rationale and implementation challenges of the outcome trial, focusing on the adaptive feature of the seamless Phase IIB/III design. Subjects were enrolled in two parts (Part A and Part B). Approximately 1240 women, 16-26 years of age, were enrolled in Part A for Phase IIB evaluation and equally randomized to one of three dose formulations of the nine-valent human papillomavirus vaccine or the four-valent human papillomavirus vaccine (active control). Based on an interim analysis of immunogenicity and safety, one dose formulation of the nine-valent human papillomavirus vaccine was selected for evaluation in the Phase III part of the study. Subjects enrolled in Part A who received the selected dose formulation of the nine-valent human papillomavirus vaccine or four-valent human papillomavirus vaccine continued to be followed up and contributed to the final efficacy and safety analyses. In addition, ∼ 13,400 women 16-26 years of age were enrolled in Part B, randomized to nine-valent human papillomavirus vaccine at the selected dose formulation or four-valent human papillomavirus vaccine, and followed for immunogenicity, efficacy, and safety. A seamless Phase IIB/III design was justified by the extensive pre-existing knowledge of the licensed four-valent human papillomavirus vaccine and the development objectives for the nine-valent human papillomavirus vaccine. Subjects enrolled in Part A who received either the selected nine-valent human papillomavirus formulation or four-valent human papillomavirus vaccine contributed ∼ 10% of person-years of follow-up due to its earlier start-thereby maximizing the overall efficiency of the trial. Some of the challenges encountered in the implementation of the adaptive design included practical considerations during Phase IIB formulation selection by internal and external committees, End-of-Phase II discussion with health authorities and managing changes in the assay for immunological endpoints. Application of the experience and lesson learned from this seamless adaptive design to other clinical programs may depend on case-by-case consideration. A seamless Phase IIB/III adaptive design was successfully implemented in this large outcome study. The development time of the second-generation nine-valent human papillomavirus vaccine was shortened due to improved statistical efficiency. © The Author(s) 2014.

Meta-Analysis of DNA Tumor-Viral Integration Site Selection Indicates a Role for Repeats, Gene Expression and Epigenetics

PubMed Central

Doolittle-Hall, Janet M.; Cunningham Glasspoole, Danielle L.; Seaman, William T.; Webster-Cyriaque, Jennifer

2015-01-01

Oncoviruses cause tremendous global cancer burden. For several DNA tumor viruses, human genome integration is consistently associated with cancer development. However, genomic features associated with tumor viral integration are poorly understood. We sought to define genomic determinants for 1897 loci prone to hosting human papillomavirus (HPV), hepatitis B virus (HBV) or Merkel cell polyomavirus (MCPyV). These were compared to HIV, whose enzyme-mediated integration is well understood. A comprehensive catalog of integration sites was constructed from the literature and experimentally-determined HPV integration sites. Features were scored in eight categories (genes, expression, open chromatin, histone modifications, methylation, protein binding, chromatin segmentation and repeats) and compared to random loci. Random forest models determined loci classification and feature selection. HPV and HBV integrants were not fragile site associated. MCPyV preferred integration near sensory perception genes. Unique signatures of integration-associated predictive genomic features were detected. Importantly, repeats, actively-transcribed regions and histone modifications were common tumor viral integration signatures. PMID:26569308

Changing climates of conflict: A social network experiment in 56 schools

PubMed Central

Paluck, Elizabeth Levy; Shepherd, Hana; Aronow, Peter M.

2016-01-01

Theories of human behavior suggest that individuals attend to the behavior of certain people in their community to understand what is socially normative and adjust their own behavior in response. An experiment tested these theories by randomizing an anticonflict intervention across 56 schools with 24,191 students. After comprehensively measuring every school’s social network, randomly selected seed groups of 20–32 students from randomly selected schools were assigned to an intervention that encouraged their public stance against conflict at school. Compared with control schools, disciplinary reports of student conflict at treatment schools were reduced by 30% over 1 year. The effect was stronger when the seed group contained more “social referent” students who, as network measures reveal, attract more student attention. Network analyses of peer-to-peer influence show that social referents spread perceptions of conflict as less socially normative. PMID:26729884

The variability of software scoring of the CDMAM phantom associated with a limited number of images

NASA Astrophysics Data System (ADS)

Yang, Chang-Ying J.; Van Metter, Richard

2007-03-01

Software scoring approaches provide an attractive alternative to human evaluation of CDMAM images from digital mammography systems, particularly for annual quality control testing as recommended by the European Protocol for the Quality Control of the Physical and Technical Aspects of Mammography Screening (EPQCM). Methods for correlating CDCOM-based results with human observer performance have been proposed. A common feature of all methods is the use of a small number (at most eight) of CDMAM images to evaluate the system. This study focuses on the potential variability in the estimated system performance that is associated with these methods. Sets of 36 CDMAM images were acquired under carefully controlled conditions from three different digital mammography systems. The threshold visibility thickness (TVT) for each disk diameter was determined using previously reported post-analysis methods from the CDCOM scorings for a randomly selected group of eight images for one measurement trial. This random selection process was repeated 3000 times to estimate the variability in the resulting TVT values for each disk diameter. The results from using different post-analysis methods, different random selection strategies and different digital systems were compared. Additional variability of the 0.1 mm disk diameter was explored by comparing the results from two different image data sets acquired under the same conditions from the same system. The magnitude and the type of error estimated for experimental data was explained through modeling. The modeled results also suggest a limitation in the current phantom design for the 0.1 mm diameter disks. Through modeling, it was also found that, because of the binomial statistic nature of the CDMAM test, the true variability of the test could be underestimated by the commonly used method of random re-sampling.

Cerebral Laterality and Handedness in Aviation: Performance and Selection Implications

DTIC Science & Technology

1989-01-01

population; orangutans , rhesus monkeys, and mice demonstrated this seemingly random pattern (253). Chimpanzees have recently been tested for...higher right Sylvian point In the brains of chimpanzees and orangutans (as in humans) (144), a larger right frontal lobe in the baboon (34), and the

Antitumor Efficacy Testing in Rodents

PubMed Central

2008-01-01

The preclinical research and human clinical trials necessary for developing anticancer therapeutics are costly. One contributor to these costs is preclinical rodent efficacy studies, which, in addition to the costs associated with conducting them, often guide the selection of agents for clinical development. If inappropriate or inaccurate recommendations are made on the basis of these preclinical studies, then additional costs are incurred. In this commentary, I discuss the issues associated with preclinical rodent efficacy studies. These include the identification of proper preclinical efficacy models, the selection of appropriate experimental endpoints, and the correct statistical evaluation of the resulting data. I also describe important experimental design considerations, such as selecting the drug vehicle, optimizing the therapeutic treatment plan, properly powering the experiment by defining appropriate numbers of replicates in each treatment arm, and proper randomization. Improved preclinical selection criteria can aid in reducing unnecessary human studies, thus reducing the overall costs of anticancer drug development. PMID:18957675

Inequity of Human Services: The Rural Tennessee Dilemma.

ERIC Educational Resources Information Center

Tennessee State Univ., Nashville.

Davidson, Williamson, Rutherford, and Cheatham counties of Tennessee were the setting for a study that sought to determine the types of health and social services provided to residents of rural areas and to assess the present status of the service delivery system. Interviews with both agency representatives and randomly selected household…

Availability of arsenic in human milk in women and its correlation with arsenic in urine of breastfed children living in arsenic contaminated areas in Bangladesh.

PubMed

Islam, Md Rafiqul; Attia, John; Alauddin, Mohammad; McEvoy, Mark; McElduff, Patrick; Slater, Christine; Islam, Md Monirul; Akhter, Ayesha; d'Este, Catherine; Peel, Roseanne; Akter, Shahnaz; Smith, Wayne; Begg, Stephen; Milton, Abul Hasnat

2014-12-04

Early life exposure to inorganic arsenic may be related to adverse health effects in later life. However, there are few data on postnatal arsenic exposure via human milk. In this study, we aimed to determine arsenic levels in human milk and the correlation between arsenic in human milk and arsenic in mothers and infants urine. Between March 2011 and March 2012, this prospective study identified a total of 120 new mother-baby pairs from Kashiani (subdistrict), Bangladesh. Of these, 30 mothers were randomly selected for human milk samples at 1, 6 and 9 months post-natally; the same mother baby pairs were selected for urine sampling at 1 and 6 months. Twelve urine samples from these 30 mother baby pairs were randomly selected for arsenic speciation. Arsenic concentration in human milk was low and non-normally distributed. The median arsenic concentration in human milk at all three time points remained at 0.5 μg/L. In the mixed model estimates, arsenic concentration in human milk was non-significantly reduced by -0.035 μg/L (95% CI: -0.09 to 0.02) between 1 and 6 months and between 6 and 9 months. With the progression of time, arsenic concentration in infant's urine increased non-significantly by 0.13 μg/L (95% CI: -1.27 to 1.53). Arsenic in human milk at 1 and 6 months was not correlated with arsenic in the infant's urine at the same time points (r = -0.13 at 1 month and r = -0.09 at 6 month). Arsenite (AsIII), arsenate (AsV), monomethyl arsonic acid (MMA), dimethyl arsinic acid (DMA) and arsenobetaine (AsB) were the constituents of total urinary arsenic; DMA was the predominant arsenic metabolite in infant urine. We observed a low arsenic concentration in human milk. The concentration was lower than the World Health Organization's maximum permissible limit (WHO Permissible Limit 15 μg/kg-bw/week). Our findings support the safety of breastfeeding even in arsenic contaminated areas.

The signature of positive selection at randomly chosen loci.

PubMed

Przeworski, Molly

2002-03-01

In Drosophila and humans, there are accumulating examples of loci with a significant excess of high-frequency-derived alleles or high levels of linkage disequilibrium, relative to a neutral model of a random-mating population of constant size. These are features expected after a recent selective sweep. Their prevalence suggests that positive directional selection may be widespread in both species. However, as I show here, these features do not persist long after the sweep ends: The high-frequency alleles drift to fixation and no longer contribute to polymorphism, while linkage disequilibrium is broken down by recombination. As a result, loci chosen without independent evidence of recent selection are not expected to exhibit either of these features, even if they have been affected by numerous sweeps in their genealogical history. How then can we explain the patterns in the data? One possibility is population structure, with unequal sampling from different subpopulations. Alternatively, positive selection may not operate as is commonly modeled. In particular, the rate of fixation of advantageous mutations may have increased in the recent past.

Human cooperation by lethal group competition

PubMed Central

Egas, Martijn; Kats, Ralph; van der Sar, Xander; Reuben, Ernesto; Sabelis, Maurice W.

2013-01-01

Why humans are prone to cooperate puzzles biologists, psychologists and economists alike. Between-group conflict has been hypothesized to drive within-group cooperation. However, such conflicts did not have lasting effects in laboratory experiments, because they were about luxury goods, not needed for survival (“looting”). Here, we find within-group cooperation to last when between-group conflict is implemented as “all-out war” (eliminating the weakest groups). Human subjects invested in helping group members to avoid having the lowest collective pay-off, whereas they failed to cooperate in control treatments with random group elimination or with no subdivision in groups. When the game was repeated, experience was found to promote helping. Thus, not within-group interactions alone, not random group elimination, but pay-off-dependent group elimination was found to drive within-group cooperation in our experiment. We suggest that some forms of human cooperation are maintained by multi-level selection: reciprocity within groups and lethal competition among groups acting together. PMID:23459158

Does time-lapse imaging have favorable results for embryo incubation and selection compared with conventional methods in clinical in vitro fertilization? A meta-analysis and systematic review of randomized controlled trials.

PubMed

Chen, Minghao; Wei, Shiyou; Hu, Junyan; Yuan, Jing; Liu, Fenghua

2017-01-01

The present study aimed to undertake a review of available evidence assessing whether time-lapse imaging (TLI) has favorable outcomes for embryo incubation and selection compared with conventional methods in clinical in vitro fertilization (IVF). Using PubMed, EMBASE, Cochrane library and ClinicalTrial.gov up to February 2017 to search for randomized controlled trials (RCTs) comparing TLI versus conventional methods. Both studies randomized women and oocytes were included. For studies randomized women, the primary outcomes were live birth and ongoing pregnancy, the secondary outcomes were clinical pregnancy and miscarriage; for studies randomized oocytes, the primary outcome was blastocyst rate, the secondary outcome was good quality embryo on Day 2/3. Subgroup analysis was conducted based on different incubation and embryo selection between groups. Ten RCTs were included, four randomized oocytes and six randomized women. For oocyte-based review, the pool-analysis observed no significant difference between TLI group and control group for blastocyst rate [relative risk (RR) 1.08, 95% CI 0.94-1.25, I2 = 0%, two studies, including 1154 embryos]. The quality of evidence was moderate for all outcomes in oocyte-based review. For woman-based review, only one study provided live birth rate (RR 1,23, 95% CI 1.06-1.44,I2 N/A, one study, including 842 women), the pooled result showed no significant difference in ongoing pregnancy rate (RR 1.04, 95% CI 0.80-1.36, I2 = 59%, four studies, including 1403 women) between two groups. The quality of the evidence was low or very low for all outcomes in woman-based review. Currently there is insufficient evidence to support that TLI is superior to conventional methods for human embryo incubation and selection. In consideration of the limitations and flaws of included studies, more well designed RCTs are still in need to comprehensively evaluate the effectiveness of clinical TLI use.

Fast Human Detection for Intelligent Monitoring Using Surveillance Visible Sensors

PubMed Central

Ko, Byoung Chul; Jeong, Mira; Nam, JaeYeal

2014-01-01

Human detection using visible surveillance sensors is an important and challenging work for intruder detection and safety management. The biggest barrier of real-time human detection is the computational time required for dense image scaling and scanning windows extracted from an entire image. This paper proposes fast human detection by selecting optimal levels of image scale using each level's adaptive region-of-interest (ROI). To estimate the image-scaling level, we generate a Hough windows map (HWM) and select a few optimal image scales based on the strength of the HWM and the divide-and-conquer algorithm. Furthermore, adaptive ROIs are arranged per image scale to provide a different search area. We employ a cascade random forests classifier to separate candidate windows into human and nonhuman classes. The proposed algorithm has been successfully applied to real-world surveillance video sequences, and its detection accuracy and computational speed show a better performance than those of other related methods. PMID:25393782

Many States Include Evolution Questions on Assessments

ERIC Educational Resources Information Center

Cavanagh, Sean

2005-01-01

The theory of evolution, pioneered most famously by Charles Darwin, posits that humans and other living creatures have descended from common ancestors over time through a process of random mutation and natural selection. It is widely considered to be a pillar of modern biology. Over the past year, however, public education has been roiled by…

1989 Student Survey Results: HIV-Related Knowledge, Attitudes, and Behaviors. Summary.

ERIC Educational Resources Information Center

Colorado State Dept. of Education, Denver.

In 1989, the Colorado Department of Education, in cooperation with the Centers for Disease Control, administered the Acquired Immune Deficiency Syndrome/Human Immunodeficiency Virus (AIDS/HIV) Student Survey to randomly selected Colorado students (1,851), excluding the Denver Public Schools, grades 9-12. The sample was fairly equally divided by…

Goal selection versus process control while learning to use a brain-computer interface

NASA Astrophysics Data System (ADS)

Royer, Audrey S.; Rose, Minn L.; He, Bin

2011-06-01

A brain-computer interface (BCI) can be used to accomplish a task without requiring motor output. Two major control strategies used by BCIs during task completion are process control and goal selection. In process control, the user exerts continuous control and independently executes the given task. In goal selection, the user communicates their goal to the BCI and then receives assistance executing the task. A previous study has shown that goal selection is more accurate and faster in use. An unanswered question is, which control strategy is easier to learn? This study directly compares goal selection and process control while learning to use a sensorimotor rhythm-based BCI. Twenty young healthy human subjects were randomly assigned either to a goal selection or a process control-based paradigm for eight sessions. At the end of the study, the best user from each paradigm completed two additional sessions using all paradigms randomly mixed. The results of this study were that goal selection required a shorter training period for increased speed, accuracy, and information transfer over process control. These results held for the best subjects as well as in the general subject population. The demonstrated characteristics of goal selection make it a promising option to increase the utility of BCIs intended for both disabled and able-bodied users.

Control of highly pathogenic avian influenza in Quang Tri province, Vietnam: voices from the human-animal interface.

PubMed

Farrell, Penny C; Hunter, Cynthia; Truong, Bui; Bunning, Michel

2015-01-01

Highly pathogenic avian influenza (HPAI) is caused by the haemagglutinin 5, neuraminidase 1 (H5N1) influenza A virus. Around 80% of households in rural Vietnam raise poultry, which provides food security and nutrition to their households and beyond. Of these, around 15-20% are semi-commercial producers, producing at least 28% of the country's chicken. Through learning the experiences of these semi-commercial farmers, this study aimed to explore the local understandings and sociocultural aspects of HPAI's impact, particularly the aetiology, diagnosis, and the prevention and control methods in one Vietnamese rural province. This study was conducted in Quang Tri province, Vietnam. Quang Tri province has eight districts. Five of these districts were at high risk of HPAI during the study period, of which three were selected for the present study. Within these three districts, six communes were randomly selected for the study from the list of intervention communes in Quang Tri province. Six out of the 26 intervention communes in Quang Tri were therefore selected. Participants were randomly selected and recruited from lists of semi-commercial farmers, village animal health workers, village human health workers and local authorities so that the study population (representative population) included an amount of variability similar to that of the wider population. A key benefit of this village-level control program was the residential proximity of animal and human health professionals. Participants were well aware of the typical clinical signs for avian influenza and of the reporting process for suspect cases. However there was extensive room for improvement in Quang Tri province regarding access to the HPAI vaccine, essential medical equipment for animal use, and available financial support. This qualitative research study provided an important insight for in-country policy makers and international stakeholders. It is vital that there are continued efforts to prevent and control highly pathogenic avian influenza through support programs that provide locally appropriate information and resources to those at the human-animal interface.

Kennard-Stone combined with least square support vector machine method for noncontact discriminating human blood species

NASA Astrophysics Data System (ADS)

Zhang, Linna; Li, Gang; Sun, Meixiu; Li, Hongxiao; Wang, Zhennan; Li, Yingxin; Lin, Ling

2017-11-01

Identifying whole bloods to be either human or nonhuman is an important responsibility for import-export ports and inspection and quarantine departments. Analytical methods and DNA testing methods are usually destructive. Previous studies demonstrated that visible diffuse reflectance spectroscopy method can realize noncontact human and nonhuman blood discrimination. An appropriate method for calibration set selection was very important for a robust quantitative model. In this paper, Random Selection (RS) method and Kennard-Stone (KS) method was applied in selecting samples for calibration set. Moreover, proper stoichiometry method can be greatly beneficial for improving the performance of classification model or quantification model. Partial Least Square Discrimination Analysis (PLSDA) method was commonly used in identification of blood species with spectroscopy methods. Least Square Support Vector Machine (LSSVM) was proved to be perfect for discrimination analysis. In this research, PLSDA method and LSSVM method was used for human blood discrimination. Compared with the results of PLSDA method, this method could enhance the performance of identified models. The overall results convinced that LSSVM method was more feasible for identifying human and animal blood species, and sufficiently demonstrated LSSVM method was a reliable and robust method for human blood identification, and can be more effective and accurate.

Deficiencies of effectiveness of intervention studies in veterinary medicine: a cross-sectional survey of ten leading veterinary and medical journals

PubMed Central

Meursinge Reynders, Reint

2016-01-01

The validity of studies that assess the effectiveness of an intervention (EoI) depends on variables such as the type of study design, the quality of their methodology, and the participants enrolled. Five leading veterinary journals and 5 leading human medical journals were hand-searched for EoI studies for the year 2013. We assessed (1) the prevalence of randomized controlled trials (RCTs) among EoI studies, (2) the type of participants enrolled, and (3) the methodological quality of the selected studies. Of 1707 eligible articles, 590 were EoI articles and 435 RCTs. Random allocation to the intervention was performed in 52% (114/219; 95%CI:45.2–58.8%) of veterinary EoI articles, against 87% (321/371; 82.5–89.7%) of human EoI articles (adjusted OR:9.2; 3.4–24.8). Veterinary RCTs were smaller (median: 26 animals versus 465 humans) and less likely to enroll real patients, compared with human RCTs (OR:331; 45–2441). Only 2% of the veterinary RCTs, versus 77% of the human RCTs, reported power calculations, primary outcomes, random sequence generation, allocation concealment and estimation methods. Currently, internal and external validity of veterinary EoI studies is limited compared to human medical ones. To address these issues, veterinary interventional research needs to improve its methodology, increase the number of published RCTs and enroll real clinical patients. PMID:26835187

Ecogeography, genetics, and the evolution of human body form.

PubMed

Roseman, Charles C; Auerbach, Benjamin M

2015-01-01

Genetic resemblances among groups are non-randomly distributed in humans. This population structure may influence the correlations between traits and environmental drivers of natural selection thus complicating the interpretation of the fossil record when modern human variation is used as a referential model. In this paper, we examine the effects of population structure and natural selection on postcranial traits that reflect body size and shape with application to the more general issue of how climate - using latitude as a proxy - has influenced hominin morphological variation. We compare models that include terms reflecting population structure, ascertained from globally distributed microsatellite data, and latitude on postcranial phenotypes derived from skeletal dimensions taken from a large global sample of modern humans. We find that models with a population structure term fit better than a model of natural selection along a latitudinal cline in all cases. A model including both latitude and population structure terms is a good fit to distal limb element lengths and bi-iliac breadth, indicating that multiple evolutionary forces shaped these morphologies. In contrast, a model that included only a population structure term best explained femoral head diameter and the crural index. The results demonstrate that population structure is an important part of human postcranial variation, and that clinally distributed natural selection is not sufficient to explain among-group differentiation. The distribution of human body form is strongly influenced by the contingencies of modern human origins, which calls for new ways to approach problems in the evolution of human variation, past and present. Copyright © 2014 Elsevier Ltd. All rights reserved.

The Responsiveness of Biological Motion Processing Areas to Selective Attention Towards Goals

PubMed Central

Herrington, John; Nymberg, Charlotte; Faja, Susan; Price, Elinora; Schultz, Robert

2012-01-01

A growing literature indicates that visual cortex areas viewed as primarily responsive to exogenous stimuli are susceptible to top-down modulation by selective attention. The present study examines whether brain areas involved in biological motion perception are among these areas – particularly with respect to selective attention towards human movement goals. Fifteen participants completed a point-light biological motion study following a two-by-two factorial design, with one factor representing an exogenous manipulation of human movement goals (goal-directed versus random movement), and the other an endogenous manipulation (a goal identification task versus an ancillary color-change task). Both manipulations yielded increased activation in the human homologue of motion-sensitive area MT+ (hMT+) as well as the extrastriate body area (EBA). The endogenous manipulation was associated with increased right posterior superior temporal sulcus (STS) activation, whereas the exogenous manipulation was associated with increased activation in left posterior STS. Selective attention towards goals activated portion of left hMT+/EBA only during the perception of purposeful movement consistent with emerging theories associating this area with the matching of visual motion input to known goal-directed actions. The overall pattern of results indicates that attention towards the goals of human movement activates biological motion areas. Ultimately, selective attention may explain why some studies examining biological motion show activation in hMT+ and EBA, even when using control stimuli with comparable motion properties. PMID:22796987

The Causal Effect of Tracing by Peer Health Workers on Return to Clinic Among Patients Who Were Lost to Follow-up From Antiretroviral Therapy in Eastern Africa: A "Natural Experiment" Arising From Surveillance of Lost Patients.

PubMed

Bershetyn, Anna; Odeny, Thomas A; Lyamuya, Rita; Nakiwogga-Muwanga, Alice; Diero, Lameck; Bwana, Mwebesa; Braitstein, Paula; Somi, Geoffrey; Kambugu, Andrew; Bukusi, Elizabeth; Hartogensis, Wendy; Glidden, David V; Wools-Kaloustian, Kara; Yiannoutsos, Constantin; Martin, Jeffrey; Geng, Elvin H

2017-06-01

The effect of tracing human immunodeficiency virus (HIV)-infected patients who are lost to follow-up (LTFU) on reengagement has not been rigorously assessed. We carried out an ex post analysis of a surveillance study in which LTFU patients were randomly selected for tracing to identify the effect of tracing on reengagement. We evaluated HIV-infected adults on antiretroviral therapy who were LTFU (>90 days late for last visit) at 14 clinics in Uganda, Kenya, and Tanzania. A random sample of LTFU patients was selected for tracing by peer health workers. We assessed the effect of selection for tracing using Kaplan-Meier estimates of reengagement among all patients as well as the subset of LTFU patients who were alive, contacted in person by the tracer, and out of care. Of 5781 eligible patients, 991 (17%) were randomly selected for tracing. One year after selection for tracing, 13.3% (95% confidence interval [CI], 11.1%-15.3%) of those selected for tracing returned compared with 10.0% (95% CI, 9.1%-10.8%) of those not randomly selected, an adjusted risk difference of 3.0% (95% CI, .7%-5.3%). Among patients found to be alive, personally contacted, and out of care, tracing increased the absolute probability of return at 1 year by 22% (95% CI, 7.1%-36.2%). The effect of tracing on rate of return to clinic decayed with a half-life of 7.0 days after tracing (95% CI, 2.6 %-12.9%). Tracing interventions increase reengagement, but developing methods for targeting LTFU patients most likely to benefit can make this practice more efficient. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Objective Model Selection for Identifying the Human Feedforward Response in Manual Control.

PubMed

Drop, Frank M; Pool, Daan M; van Paassen, Marinus Rene M; Mulder, Max; Bulthoff, Heinrich H

2018-01-01

Realistic manual control tasks typically involve predictable target signals and random disturbances. The human controller (HC) is hypothesized to use a feedforward control strategy for target-following, in addition to feedback control for disturbance-rejection. Little is known about human feedforward control, partly because common system identification methods have difficulty in identifying whether, and (if so) how, the HC applies a feedforward strategy. In this paper, an identification procedure is presented that aims at an objective model selection for identifying the human feedforward response, using linear time-invariant autoregressive with exogenous input models. A new model selection criterion is proposed to decide on the model order (number of parameters) and the presence of feedforward in addition to feedback. For a range of typical control tasks, it is shown by means of Monte Carlo computer simulations that the classical Bayesian information criterion (BIC) leads to selecting models that contain a feedforward path from data generated by a pure feedback model: "false-positive" feedforward detection. To eliminate these false-positives, the modified BIC includes an additional penalty on model complexity. The appropriate weighting is found through computer simulations with a hypothesized HC model prior to performing a tracking experiment. Experimental human-in-the-loop data will be considered in future work. With appropriate weighting, the method correctly identifies the HC dynamics in a wide range of control tasks, without false-positive results.

Large-scale randomized clinical trials of bioactives and nutrients in relation to human health and disease prevention - Lessons from the VITAL and COSMOS trials.

PubMed

Rautiainen, Susanne; Sesso, Howard D; Manson, JoAnn E

2017-12-29

Several bioactive compounds and nutrients in foods have physiological properties that are beneficial for human health. While nutrients typically have clear definitions with established levels of recommended intakes, bioactive compounds often lack such a definition. Although a food-based approach is often the optimal approach to ensure adequate intake of bioactives and nutrients, these components are also often produced as dietary supplements. However, many of these supplements are not sufficiently studied and have an unclear role in chronic disease prevention. Randomized trials are considered the gold standard of study designs, but have not been fully applied to understand the effects of bioactives and nutrients. We review the specific role of large-scale trials to test whether bioactives and nutrients have an effect on health outcomes through several crucial components of trial design, including selection of intervention, recruitment, compliance, outcome selection, and interpretation and generalizability of study findings. We will discuss these components in the context of two randomized clinical trials, the VITamin D and OmegA-3 TriaL (VITAL) and the COcoa Supplement and Multivitamin Outcomes Study (COSMOS). We will mainly focus on dietary supplements of bioactives and nutrients while also emphasizing the need for translation and integration with food-based trials that are of vital importance within nutritional research. Copyright © 2017. Published by Elsevier Ltd.

Counterfactual thinking affects the excitability of the motor cortex.

PubMed

Vicario, Carmelo M; Rafal, Robert D; Avenanti, Alessio

2015-04-01

Evidence suggests that monetary reward and affective experiences induce activity in the cortical motor system. Nevertheless, it is unclear whether counterfactual thinking related to wrong choices that lead to monetary loss and regret affects motor excitability. Using transcranial magnetic stimulation (TMS) of the motor cortex, we measured corticospinal excitability of 2 groups of healthy humans asked to actively guess the winning key among two possible alternatives (choice group); or passively assist to monetary outcomes randomly selected by the computer program (follow group). Results document a selective increment of the corticospinal excitability when a monetary loss outcome followed the key selection (i.e., in the choice group). On the other hand, no change in corticospinal excitability was found when participants passively assisted to a monetary loss randomly selected by the computer program (i.e., follow group). These findings suggest that counterfactual thinking and the negative emotional experiences arising from choices causing monetary loss--i.e., "I would have won instead of lost money if I'd made a different choice"--are mapped in the motor system. Copyright © 2015 Elsevier Ltd. All rights reserved.

Influences of human and livestock density on winter habitat selection of Mongolian gazelle (Procapra gutturosa).

PubMed

Luo, Zhenhua; Liu, Bingwan; Liu, Songtao; Jiang, Zhigang; Halbrook, Richard S

2014-01-01

Human and livestock related disturbances of habitat selection by ungulates are topics of global concern, as they have profound impacts on ungulate survival, population density, fitness, and management; however, differences in ungulate habitat use under different human and livestock densities are not fully understood. Mongolian gazelle (Procapra gutturosa), an endemic ungulate species on the Asia-European steppe, faces varying intensities of human and livestock disturbances in the area around Dalai Lake, China. To investigate how habitat selection strategies vary as disturbance intensity changes, we randomly set 20 transects containing 1486 plots, on which we conducted repeated surveys of 21 ecological factors during the winters in the period of 2005-2008. We aimed to: 1) determine the critical factors underlying habitat selection of the gazelles; 2) determine the gazelles' habitat preferences in this area; 3) determine how habitat selection varies with disturbance intensity and explore the primary underlying mechanism. We used binary-logistic regressions and information theoretic approaches to build best-fit habitat selection models, and calculated resource selection functions. Sixty-six herds, 522 individuals, and 499 tracks were recorded. Our results indicate that snow depth and aboveground biomass are the main factors affecting habitat selection by Mongolian gazelle throughout the district in winter. Thin snow cover and abundant aboveground biomass are preferred. Avoiding disturbance was the primary factor accounting for habitat selection in low disturbance areas, although with increasing human or live-stock-related disturbance, gazelle maintained a reduced distance to the source of the disturbance. Presumably owing to that shift, movement costs were more important as disturbance increased. In addition, Mongolian gazelle selected habitats based on topographical features promoting greater visibility where disturbance was lower. We suggest several management implications of our findings for this ungulate species will contribute to the effective conservation of Mongolian gazelle in the Dalai Lake area.

Estimating Sampling Selection Bias in Human Genetics: A Phenomenological Approach

PubMed Central

Risso, Davide; Taglioli, Luca; De Iasio, Sergio; Gueresi, Paola; Alfani, Guido; Nelli, Sergio; Rossi, Paolo; Paoli, Giorgio; Tofanelli, Sergio

2015-01-01

This research is the first empirical attempt to calculate the various components of the hidden bias associated with the sampling strategies routinely-used in human genetics, with special reference to surname-based strategies. We reconstructed surname distributions of 26 Italian communities with different demographic features across the last six centuries (years 1447–2001). The degree of overlapping between "reference founding core" distributions and the distributions obtained from sampling the present day communities by probabilistic and selective methods was quantified under different conditions and models. When taking into account only one individual per surname (low kinship model), the average discrepancy was 59.5%, with a peak of 84% by random sampling. When multiple individuals per surname were considered (high kinship model), the discrepancy decreased by 8–30% at the cost of a larger variance. Criteria aimed at maximizing locally-spread patrilineages and long-term residency appeared to be affected by recent gene flows much more than expected. Selection of the more frequent family names following low kinship criteria proved to be a suitable approach only for historically stable communities. In any other case true random sampling, despite its high variance, did not return more biased estimates than other selective methods. Our results indicate that the sampling of individuals bearing historically documented surnames (founders' method) should be applied, especially when studying the male-specific genome, to prevent an over-stratification of ancient and recent genetic components that heavily biases inferences and statistics. PMID:26452043

Estimating Sampling Selection Bias in Human Genetics: A Phenomenological Approach.

PubMed

Risso, Davide; Taglioli, Luca; De Iasio, Sergio; Gueresi, Paola; Alfani, Guido; Nelli, Sergio; Rossi, Paolo; Paoli, Giorgio; Tofanelli, Sergio

2015-01-01

This research is the first empirical attempt to calculate the various components of the hidden bias associated with the sampling strategies routinely-used in human genetics, with special reference to surname-based strategies. We reconstructed surname distributions of 26 Italian communities with different demographic features across the last six centuries (years 1447-2001). The degree of overlapping between "reference founding core" distributions and the distributions obtained from sampling the present day communities by probabilistic and selective methods was quantified under different conditions and models. When taking into account only one individual per surname (low kinship model), the average discrepancy was 59.5%, with a peak of 84% by random sampling. When multiple individuals per surname were considered (high kinship model), the discrepancy decreased by 8-30% at the cost of a larger variance. Criteria aimed at maximizing locally-spread patrilineages and long-term residency appeared to be affected by recent gene flows much more than expected. Selection of the more frequent family names following low kinship criteria proved to be a suitable approach only for historically stable communities. In any other case true random sampling, despite its high variance, did not return more biased estimates than other selective methods. Our results indicate that the sampling of individuals bearing historically documented surnames (founders' method) should be applied, especially when studying the male-specific genome, to prevent an over-stratification of ancient and recent genetic components that heavily biases inferences and statistics.

Development and validation of novel AAV2 random libraries displaying peptides of diverse lengths and at diverse capsid positions.

PubMed

Naumer, Matthias; Ying, Ying; Michelfelder, Stefan; Reuter, Antje; Trepel, Martin; Müller, Oliver J; Kleinschmidt, Jürgen A

2012-05-01

Libraries based on the insertion of random peptide ligands into the capsid of adeno-associated virus type 2 (AAV2) have been widely used to improve the efficiency and selectivity of the AAV vector system. However, so far only libraries of 7-mer peptide ligands have been inserted at one well-characterized capsid position. Here, we expanded the combinatorial AAV2 display system to a panel of novel AAV libraries, displaying peptides of 5, 7, 12, 19, or 26 amino acids in length at capsid position 588 or displaying 7-mer peptides at position 453, the most prominently exposed region of the viral capsid. Library selections on two unrelated cell types-human coronary artery endothelial cells and rat cardiomyoblasts-revealed the isolation of cell type-characteristic peptides of different lengths mediating strongly improved target-cell transduction, except for the 26-mer peptide ligands. Characterization of vector selectivity by transduction of nontarget cells and comparative gene-transduction analysis using a panel of 44 human tumor cell lines revealed that insertion of different-length peptides allows targeting of distinct cellular receptors for cell entry with similar efficiency, but with different selectivity. The application of such novel AAV2 libraries broadens the spectrum of targetable receptors by capsid-modified AAV vectors and provides the opportunity to choose the best suited targeting ligand for a certain application from a number of different candidates.

Artificial genetic selection for an efficient translation initiation site for expression of human RACK1 gene in Escherichia coli

PubMed Central

Zhelyabovskaya, Olga B.; Berlin, Yuri A.; Birikh, Klara R.

2004-01-01

In bacterial expression systems, translation initiation is usually the rate limiting and the least predictable stage of protein synthesis. Efficiency of a translation initiation site can vary dramatically depending on the sequence context. This is why many standard expression vectors provide very poor expression levels of some genes. This notion persuaded us to develop an artificial genetic selection protocol, which allows one to find for a given target gene an individual efficient ribosome binding site from a random pool. In order to create Darwinian pressure necessary for the genetic selection, we designed a system based on translational coupling, in which microorganism survival in the presence of antibiotic depends on expression of the target gene, while putting no special requirements on this gene. Using this system we obtained superproducing constructs for the human protein RACK1 (receptor for activated C kinase). PMID:15034151

Can Random Mutation Mimic Design?: A Guided Inquiry Laboratory for Undergraduate Students

PubMed Central

Kalinowski, Steven T.; Taper, Mark L.; Metz, Anneke M.

2006-01-01

Complex biological structures, such as the human eye, have been interpreted as evidence for a creator for over three centuries. This raises the question of whether random mutation can create such adaptations. In this article, we present an inquiry-based laboratory experiment that explores this question using paper airplanes as a model organism. The main task for students in this investigation is to figure out how to simulate paper airplane evolution (including reproduction, inheritance, mutation, and selection). In addition, the lab requires students to practice analytic thinking and to carefully delineate the implications of their results. PMID:16951065

Lost human capital from early-onset chronic depression.

PubMed

Berndt, E R; Koran, L M; Finkelstein, S N; Gelenberg, A J; Kornstein, S G; Miller, I M; Thase, M E; Trapp, G A; Keller, M B

2000-06-01

Chronic depression starts at an early age for many individuals and could affect their accumulation of "human capital" (i.e., education, higher amounts of which can broaden occupational choice and increase earnings potential). The authors examined the impact, by gender, of early- (before age 22) versus late-onset major depressive disorder on educational attainment. They also determined whether the efficacy and sustainability of antidepressant treatments and psychosocial outcomes vary by age at onset and quantified the impact of early- versus late-onset, as well as never-occurring, major depressive disorder on expected lifetime earnings. The authors used logistic and multivariate regression methods to analyze data from a three-phase, multicenter, double-blind, randomized trial that compared sertraline and imipramine treatment of 531 patients with chronic depression aged 30 years and older. These data were integrated with U.S. Census Bureau data on 1995 earnings by age, educational attainment, and gender. Early-onset major depressive disorder adversely affected the educational attainment of women but not of men. No significant difference in treatment responsiveness by age at onset was observed after 12 weeks of acute treatment or, for subjects rated as having responded, after 76 weeks of maintenance treatment. A randomly selected 21-year-old woman with early-onset major depressive disorder in 1995 could expect future annual earnings that were 12%-18% lower than those of a randomly selected 21-year-old woman whose onset of major depressive disorder occurred after age 21 or not at all. Early-onset major depressive disorder causes substantial human capital loss, particularly for women. Detection and effective treatment of early-onset major depressive disorder may have substantial economic benefits.

Applications of step-selection functions in ecology and conservation.

PubMed

Thurfjell, Henrik; Ciuti, Simone; Boyce, Mark S

2014-01-01

Recent progress in positioning technology facilitates the collection of massive amounts of sequential spatial data on animals. This has led to new opportunities and challenges when investigating animal movement behaviour and habitat selection. Tools like Step Selection Functions (SSFs) are relatively new powerful models for studying resource selection by animals moving through the landscape. SSFs compare environmental attributes of observed steps (the linear segment between two consecutive observations of position) with alternative random steps taken from the same starting point. SSFs have been used to study habitat selection, human-wildlife interactions, movement corridors, and dispersal behaviours in animals. SSFs also have the potential to depict resource selection at multiple spatial and temporal scales. There are several aspects of SSFs where consensus has not yet been reached such as how to analyse the data, when to consider habitat covariates along linear paths between observations rather than at their endpoints, how many random steps should be considered to measure availability, and how to account for individual variation. In this review we aim to address all these issues, as well as to highlight weak features of this modelling approach that should be developed by further research. Finally, we suggest that SSFs could be integrated with state-space models to classify behavioural states when estimating SSFs.

47 CFR 1.1602 - Designation for random selection.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 1 2010-10-01 2010-10-01 false Designation for random selection. 1.1602 Section 1.1602 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL PRACTICE AND PROCEDURE Random Selection Procedures for Mass Media Services General Procedures § 1.1602 Designation for random selection...

47 CFR 1.1602 - Designation for random selection.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 1 2011-10-01 2011-10-01 false Designation for random selection. 1.1602 Section 1.1602 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL PRACTICE AND PROCEDURE Random Selection Procedures for Mass Media Services General Procedures § 1.1602 Designation for random selection...

Does time-lapse imaging have favorable results for embryo incubation and selection compared with conventional methods in clinical in vitro fertilization? A meta-analysis and systematic review of randomized controlled trials

PubMed Central

Yuan, Jing; Liu, Fenghua

2017-01-01

Objective The present study aimed to undertake a review of available evidence assessing whether time-lapse imaging (TLI) has favorable outcomes for embryo incubation and selection compared with conventional methods in clinical in vitro fertilization (IVF). Methods Using PubMed, EMBASE, Cochrane library and ClinicalTrial.gov up to February 2017 to search for randomized controlled trials (RCTs) comparing TLI versus conventional methods. Both studies randomized women and oocytes were included. For studies randomized women, the primary outcomes were live birth and ongoing pregnancy, the secondary outcomes were clinical pregnancy and miscarriage; for studies randomized oocytes, the primary outcome was blastocyst rate, the secondary outcome was good quality embryo on Day 2/3. Subgroup analysis was conducted based on different incubation and embryo selection between groups. Results Ten RCTs were included, four randomized oocytes and six randomized women. For oocyte-based review, the pool-analysis observed no significant difference between TLI group and control group for blastocyst rate [relative risk (RR) 1.08, 95% CI 0.94–1.25, I2 = 0%, two studies, including 1154 embryos]. The quality of evidence was moderate for all outcomes in oocyte-based review. For woman-based review, only one study provided live birth rate (RR 1,23, 95% CI 1.06–1.44,I2 N/A, one study, including 842 women), the pooled result showed no significant difference in ongoing pregnancy rate (RR 1.04, 95% CI 0.80–1.36, I2 = 59%, four studies, including 1403 women) between two groups. The quality of the evidence was low or very low for all outcomes in woman-based review. Conclusions Currently there is insufficient evidence to support that TLI is superior to conventional methods for human embryo incubation and selection. In consideration of the limitations and flaws of included studies, more well designed RCTs are still in need to comprehensively evaluate the effectiveness of clinical TLI use. PMID:28570713

47 CFR 1.1603 - Conduct of random selection.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 1 2010-10-01 2010-10-01 false Conduct of random selection. 1.1603 Section 1.1603 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL PRACTICE AND PROCEDURE Random Selection Procedures for Mass Media Services General Procedures § 1.1603 Conduct of random selection. The...

47 CFR 1.1603 - Conduct of random selection.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 1 2011-10-01 2011-10-01 false Conduct of random selection. 1.1603 Section 1.1603 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL PRACTICE AND PROCEDURE Random Selection Procedures for Mass Media Services General Procedures § 1.1603 Conduct of random selection. The...

The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)

PubMed Central

2004-01-01

The National Institutes of Health's Mammalian Gene Collection (MGC) project was designed to generate and sequence a publicly accessible cDNA resource containing a complete open reading frame (ORF) for every human and mouse gene. The project initially used a random strategy to select clones from a large number of cDNA libraries from diverse tissues. Candidate clones were chosen based on 5′-EST sequences, and then fully sequenced to high accuracy and analyzed by algorithms developed for this project. Currently, more than 11,000 human and 10,000 mouse genes are represented in MGC by at least one clone with a full ORF. The random selection approach is now reaching a saturation point, and a transition to protocols targeted at the missing transcripts is now required to complete the mouse and human collections. Comparison of the sequence of the MGC clones to reference genome sequences reveals that most cDNA clones are of very high sequence quality, although it is likely that some cDNAs may carry missense variants as a consequence of experimental artifact, such as PCR, cloning, or reverse transcriptase errors. Recently, a rat cDNA component was added to the project, and ongoing frog (Xenopus) and zebrafish (Danio) cDNA projects were expanded to take advantage of the high-throughput MGC pipeline. PMID:15489334

Human Papillomavirus Vaccine and Pap Tests on College Campuses: How Do Historically Black Colleges and Universities (HSBCUs) Measure Up?

ERIC Educational Resources Information Center

Barnett, Kierra S.; Shoben, Abigail B.; McRee, Annie-Laurie; Reiter, Paul L.; Paskett, Electra D.; Katz, Mira L.

2016-01-01

Objective: The availability of cervical cancer prevention services at college health centers was compared between historically black colleges and universities (HBCUs) and non-HBCUs. Methods: Four-year, non-primarily distant learning colleges, matching HBCUs with randomly selected non-HBCUs within the same states (N = 136) were examined. Data were…

The responsiveness of biological motion processing areas to selective attention towards goals.

PubMed

Herrington, John; Nymberg, Charlotte; Faja, Susan; Price, Elinora; Schultz, Robert

2012-10-15

A growing literature indicates that visual cortex areas viewed as primarily responsive to exogenous stimuli are susceptible to top-down modulation by selective attention. The present study examines whether brain areas involved in biological motion perception are among these areas-particularly with respect to selective attention towards human movement goals. Fifteen participants completed a point-light biological motion study following a two-by-two factorial design, with one factor representing an exogenous manipulation of human movement goals (goal-directed versus random movement), and the other an endogenous manipulation (a goal identification task versus an ancillary color-change task). Both manipulations yielded increased activation in the human homologue of motion-sensitive area MT+ (hMT+) as well as the extrastriate body area (EBA). The endogenous manipulation was associated with increased right posterior superior temporal sulcus (STS) activation, whereas the exogenous manipulation was associated with increased activation in left posterior STS. Selective attention towards goals activated a portion of left hMT+/EBA only during the perception of purposeful movement-consistent with emerging theories associating this area with the matching of visual motion input to known goal-directed actions. The overall pattern of results indicates that attention towards the goals of human movement activates biological motion areas. Ultimately, selective attention may explain why some studies examining biological motion show activation in hMT+ and EBA, even when using control stimuli with comparable motion properties. Copyright © 2012 Elsevier Inc. All rights reserved.

A simple rule for the evolution of cooperation on graphs and social networks.

PubMed

Ohtsuki, Hisashi; Hauert, Christoph; Lieberman, Erez; Nowak, Martin A

2006-05-25

A fundamental aspect of all biological systems is cooperation. Cooperative interactions are required for many levels of biological organization ranging from single cells to groups of animals. Human society is based to a large extent on mechanisms that promote cooperation. It is well known that in unstructured populations, natural selection favours defectors over cooperators. There is much current interest, however, in studying evolutionary games in structured populations and on graphs. These efforts recognize the fact that who-meets-whom is not random, but determined by spatial relationships or social networks. Here we describe a surprisingly simple rule that is a good approximation for all graphs that we have analysed, including cycles, spatial lattices, random regular graphs, random graphs and scale-free networks: natural selection favours cooperation, if the benefit of the altruistic act, b, divided by the cost, c, exceeds the average number of neighbours, k, which means b/c > k. In this case, cooperation can evolve as a consequence of 'social viscosity' even in the absence of reputation effects or strategic complexity.

Stability-Diversity Tradeoffs Impose Fundamental Constraints on Selection of Synthetic Human VH/VL Single-Domain Antibodies from In Vitro Display Libraries

PubMed Central

Henry, Kevin A.; Kim, Dae Young; Kandalaft, Hiba; Lowden, Michael J.; Yang, Qingling; Schrag, Joseph D.; Hussack, Greg; MacKenzie, C. Roger; Tanha, Jamshid

2017-01-01

Human autonomous VH/VL single-domain antibodies (sdAbs) are attractive therapeutic molecules, but often suffer from suboptimal stability, solubility and affinity for cognate antigens. Most commonly, human sdAbs have been isolated from in vitro display libraries constructed via synthetic randomization of rearranged VH/VL domains. Here, we describe the design and characterization of three novel human VH/VL sdAb libraries through a process of: (i) exhaustive biophysical characterization of 20 potential VH/VL sdAb library scaffolds, including assessment of expression yield, aggregation resistance, thermostability and tolerance to complementarity-determining region (CDR) substitutions; (ii) in vitro randomization of the CDRs of three VH/VL sdAb scaffolds, with tailored amino acid representation designed to promote solubility and expressibility; and (iii) systematic benchmarking of the three VH/VL libraries by panning against five model antigens. We isolated ≥1 antigen-specific human sdAb against four of five targets (13 VHs and 7 VLs in total); these were predominantly monomeric, had antigen-binding affinities ranging from 5 nM to 12 µM (average: 2–3 µM), but had highly variable expression yields (range: 0.1–19 mg/L). Despite our efforts to identify the most stable VH/VL scaffolds, selection of antigen-specific binders from these libraries was unpredictable (overall success rate for all library-target screens: ~53%) with a high attrition rate of sdAbs exhibiting false positive binding by ELISA. By analyzing VH/VL sdAb library sequence composition following selection for monomeric antibody expression (binding to protein A/L followed by amplification in bacterial cells), we found that some VH/VL sdAbs had marked growth advantages over others, and that the amino acid composition of the CDRs of this set of sdAbs was dramatically restricted (bias toward Asp and His and away from aromatic and hydrophobic residues). Thus, CDR sequence clearly dramatically impacts the stability of human autonomous VH/VL immunoglobulin domain folds, and sequence-stability tradeoffs must be taken into account during the design of such libraries. PMID:29375542

Athletic equipment microbiota are shaped by interactions with human skin

DOE PAGES

Wood, Mariah; Gibbons, Sean M.; Lax, Simon; ...

2015-06-19

Background: Americans spend the vast majority of their lives in built environments. Even traditionally outdoor pursuits, such as exercising, are often now performed indoors. Bacteria that colonize these indoor ecosystems are primarily derived from the human microbiome. The modes of human interaction with indoor surfaces and the physical conditions associated with each surface type determine the steady-state ecology of the microbial community. Results: Bacterial assemblages associated with different surfaces in three athletic facilities, including floors, mats, benches, free weights, and elliptical handles, were sampled every other hour (8 am to 6 pm) for 2 days. Surface and equipment type hadmore » a stronger influence on bacterial community composition than the facility in which they were housed. Surfaces that were primarily in contact with human skin exhibited highly dynamic bacterial community composition and non-random co-occurrence patterns, suggesting that different host microbiomes—shaped by selective forces—were being deposited on these surfaces through time. Bacterial assemblages found on the floors and mats changed less over time, and species co-occurrence patterns appeared random, suggesting more neutral community assembly. Conclusions: These longitudinal patterns highlight the dramatic turnover of microbial communities on surfaces in regular contact with human skin. By uncovering these longitudinal patterns, this study promotes a better understanding of microbe-human interactions within the built environment.« less

Sampling designs for HIV molecular epidemiology with application to Honduras.

PubMed

Shepherd, Bryan E; Rossini, Anthony J; Soto, Ramon Jeremias; De Rivera, Ivette Lorenzana; Mullins, James I

2005-11-01

Proper sampling is essential to characterize the molecular epidemiology of human immunodeficiency virus (HIV). HIV sampling frames are difficult to identify, so most studies use convenience samples. We discuss statistically valid and feasible sampling techniques that overcome some of the potential for bias due to convenience sampling and ensure better representation of the study population. We employ a sampling design called stratified cluster sampling. This first divides the population into geographical and/or social strata. Within each stratum, a population of clusters is chosen from groups, locations, or facilities where HIV-positive individuals might be found. Some clusters are randomly selected within strata and individuals are randomly selected within clusters. Variation and cost help determine the number of clusters and the number of individuals within clusters that are to be sampled. We illustrate the approach through a study designed to survey the heterogeneity of subtype B strains in Honduras.

Combined glyco- and protein-Fc engineering simultaneously enhance cytotoxicity and half-life of a therapeutic antibody.

PubMed

Monnet, Céline; Jorieux, Sylvie; Souyris, Nathalie; Zaki, Ouafa; Jacquet, Alexandra; Fournier, Nathalie; Crozet, Fabien; de Romeuf, Christophe; Bouayadi, Khalil; Urbain, Rémi; Behrens, Christian K; Mondon, Philippe; Fontayne, Alexandre

2014-01-01

While glyco-engineered monoclonal antibodies (mAbs) with improved antibody-dependent cell-mediated cytotoxicity (ADCC) are reaching the market, extensive efforts have also been made to improve their pharmacokinetic properties to generate biologically superior molecules. Most therapeutic mAbs are human or humanized IgG molecules whose half-life is dependent on the neonatal Fc receptor FcRn. FcRn reduces IgG catabolism by binding to the Fc domain of endocytosed IgG in acidic lysosomal compartments, allowing them to be recycled into the blood. Fc-engineered mAbs with increased FcRn affinity resulted in longer in vivo half-life in animal models, but also in healthy humans. These Fc-engineered mAbs were obtained by alanine scanning, directed mutagenesis or in silico approach of the FcRn binding site. In our approach, we applied a random mutagenesis technology (MutaGen™) to generate mutations evenly distributed over the whole Fc sequence of human IgG1. IgG variants with improved FcRn-binding were then isolated from these Fc-libraries using a pH-dependent phage display selection process. Two successive rounds of mutagenesis and selection were performed to identify several mutations that dramatically improve FcRn binding. Notably, many of these mutations were unpredictable by rational design as they were located distantly from the FcRn binding site, validating our random molecular approach. When produced on the EMABling(®) platform allowing effector function increase, our IgG variants retained both higher ADCC and higher FcRn binding. Moreover, these IgG variants exhibited longer half-life in human FcRn transgenic mice. These results clearly demonstrate that glyco-engineering to improve cytotoxicity and protein-engineering to increase half-life can be combined to further optimize therapeutic mAbs.

Conserving Critical Sites for Biodiversity Provides Disproportionate Benefits to People

PubMed Central

Larsen, Frank W.; Turner, Will R.; Brooks, Thomas M.

2012-01-01

Protecting natural habitats in priority areas is essential to halt the loss of biodiversity. Yet whether these benefits for biodiversity also yield benefits for human well-being remains controversial. Here we assess the potential human well-being benefits of safeguarding a global network of sites identified as top priorities for the conservation of threatened species. Conserving these sites would yield benefits – in terms of a) climate change mitigation through avoidance of CO2 emissions from deforestation; b) freshwater services to downstream human populations; c) retention of option value; and d) benefits to maintenance of human cultural diversity – significantly exceeding those anticipated from randomly selected sites within the same countries and ecoregions. Results suggest that safeguarding sites important for biodiversity conservation provides substantial benefits to human well-being. PMID:22666337

De novo selection of oncogenes.

PubMed

Chacón, Kelly M; Petti, Lisa M; Scheideman, Elizabeth H; Pirazzoli, Valentina; Politi, Katerina; DiMaio, Daniel

2014-01-07

All cellular proteins are derived from preexisting ones by natural selection. Because of the random nature of this process, many potentially useful protein structures never arose or were discarded during evolution. Here, we used a single round of genetic selection in mouse cells to isolate chemically simple, biologically active transmembrane proteins that do not contain any amino acid sequences from preexisting proteins. We screened a retroviral library expressing hundreds of thousands of proteins consisting of hydrophobic amino acids in random order to isolate four 29-aa proteins that induced focus formation in mouse and human fibroblasts and tumors in mice. These proteins share no amino acid sequences with known cellular or viral proteins, and the simplest of them contains only seven different amino acids. They transformed cells by forming a stable complex with the platelet-derived growth factor β receptor transmembrane domain and causing ligand-independent receptor activation. We term this approach de novo selection and suggest that it can be used to generate structures and activities not observed in nature, create prototypes for novel research reagents and therapeutics, and provide insight into cell biology, transmembrane protein-protein interactions, and possibly virus evolution and the origin of life.

Persistence of Lactobacillus fermentum RC-14 and Lactobacillus rhamnosus GR-1 but Not L. rhamnosus GG in the Human Vagina as Demonstrated by Randomly Amplified Polymorphic DNA

PubMed Central

Gardiner, Gillian E.; Heinemann, Christine; Bruce, Andrew W.; Beuerman, Dee; Reid, Gregor

2002-01-01

Lactobacillus rhamnosus GR-1 and L. fermentum RC-14 are well-characterized probiotic strains with efficacy in the prevention and treatment of urogenital infections in women. The aim of the present study was to apply a molecular biology-based methodology for the detection of these strains and L. rhamnosus GG (a commercially available intestinal probiotic) in the human vagina in order to assess probiotic persistence at this site. Ten healthy women inserted vaginally a capsule containing either a combination of strains GR-1 and RC-14 or the GG strain for 3 consecutive nights. Vaginal swabs taken before and at various time points after probiotic insertion were analyzed, and the Lactobacillus flora was assessed by randomly amplified polymorphic DNA (RAPD) analysis. This method generated discrete DNA fingerprints for GR-1, RC-14, and GG and enabled successful detection of these strains in the vagina. Strain GR-1 and/or strain RC-14 was found to persist in the vaginal tract for up to 19 days after vaginal instillation, while L. rhamnosus GG was detectable for up to 5 days postadministration. In conclusion, the fates of probiotic L. rhamnosus and L. fermentum strains were successfully monitored in the human vagina by RAPD analysis. This technique provides molecular biology-based evidence that RC-14 and GR-1, strains selected as urogenital probiotics, persist in the human vagina and may be more suited to vaginal colonization than L. rhamnosus GG. This highlights the importance of proper selection of strains for urogenital probiotic applications. PMID:11777835

A Descriptive Analysis of the Community College Liberal Arts Curriculum. ERIC Digest.

ERIC Educational Resources Information Center

ERIC Clearinghouse for Junior Colleges, Los Angeles, CA.

In spring 1986, the Center for the Study of Community Colleges analyzed the class schedules of 95 randomly selected two-year colleges to determine the types of liberal arts courses offered by the colleges and to spot changes in the curriculum over the past 11 years. Study findings included the following: (1) the humanities made up 48% of the total…

Acknowledging and Appreciating the Full Spectrum of the Human Condition: School Psychology's (Limited) Focus on Positive Psychological Functioning

ERIC Educational Resources Information Center

Froh, Jeffrey J.; Huebner, E. Scott; Youssef, Al-Jameela; Conte, Vincent

2011-01-01

This study is a content analysis of a random selection of 20% (N = 1,168) of articles from "School Psychology Quarterly", "Psychology in the Schools", the "Journal of School Psychology", and "School Psychology Review". Across the four journals, 27% of the articles had a positive focus, and the percentage of articles focused on the positive has…

A randomized, first-in-human, healthy volunteer trial of BIVV009, a humanized antibody for the specific inhibition of the classical complement pathway.

PubMed

Bartko, Johann; Schoergenhofer, Christian; Schwameis, Michael; Firbas, Christa; Beliveau, Martin; Chang, Colin; Marier, Jean-Francois; Nix, Darrell; Gilbert, James C; Panicker, Sandip; Jilma, Bernd

2018-05-08

Aberrant activation of the classical complement pathway is the common underlying pathophysiology of orphan diseases such as bullous pemphigoid, antibody-mediated rejection of organ transplants, cold agglutinin disease and warm autoimmune haemolytic anaemia. Therapeutic options for these complement-mediated disorders are limited and BIVV009, a humanized monoclonal antibody directed against complement factor C1s, may be potentially useful for inhibition of the classical complement pathway. A phase-1, first-in-human, double-blind, randomized, placebo-controlled, dose-escalation trial of single and multiple doses of BIVV009 or placebo was conducted in 64 volunteers to evaluate safety, tolerability, pharmacokinetic, and pharmacodynamic profiles. Single and multiple infusions of BIVV009 were well tolerated without any safety concerns. BIVV009 exhibited a steep concentration-effect relationship with a Hill coefficient of 2.4, and an IC90 of 15.5 µg/mL. This study establishes the foundation for using BIVV009 as a highly selective inhibitor of the classical complement pathway in different diseases. This article is protected by copyright. All rights reserved. © 2018 American Society for Clinical Pharmacology and Therapeutics.

Press releases by academic medical centers: not so academic?

PubMed

Woloshin, Steven; Schwartz, Lisa M; Casella, Samuel L; Kennedy, Abigail T; Larson, Robin J

2009-05-05

The news media are often criticized for exaggerated coverage of weak science. Press releases, a source of information for many journalists, might be a source of those exaggerations. To characterize research press releases from academic medical centers. Content analysis. Press releases from 10 medical centers at each extreme of U.S. News & World Report's rankings for medical research. Press release quality. Academic medical centers issued a mean of 49 press releases annually. Among 200 randomly selected releases analyzed in detail, 87 (44%) promoted animal or laboratory research, of which 64 (74%) explicitly claimed relevance to human health. Among 95 releases about primary human research, 22 (23%) omitted study size and 32 (34%) failed to quantify results. Among all 113 releases about human research, few (17%) promoted studies with the strongest designs (randomized trials or meta-analyses). Forty percent reported on the most limited human studies--those with uncontrolled interventions, small samples (<30 participants), surrogate primary outcomes, or unpublished data--yet 58% lacked the relevant cautions. The effects of press release quality on media coverage were not directly assessed. Press releases from academic medical centers often promote research that has uncertain relevance to human health and do not provide key facts or acknowledge important limitations. National Cancer Institute.

The Nature and Meaning of Body Concepts in Everyday Language and Theoretical Discourse.

PubMed

Pollio, Howard R; Finn, Mike; Custer, Morgun

2016-06-01

Within phenomenological philosophy four topics, (1) Body, (2) Time, (3) Others and the Social Order and (4) World serve as the major contexts in which human perception, action and reflection take place. At present only three of these domains have been studied from an empirical perspective, leaving Body as the one domain requiring further analysis. Given this state of affairs, the purpose of the present study is to determine the everyday and theoretical meanings of body. To accomplish this task participants coded randomly selected body- related words into groups on the basis of having similar meanings. Once these groupings were established they were then evaluated by statistical clustering and multidimensional scaling procedures. Results indicated that it was possible to define the everyday meaning of the human experience of the human body in terms of the following set of themes: (1) inside/outside, (2) visible/not visible, (3) vitality and activity, (4) instrument and object and (5) appearance and self-expression. Concerns about the representativeness of the words studied led to the development and use of individual word pools from which a set of 50 partially different words was randomly selected for each participant. Results indicated little difference between themes produced in the present study when compared with those of an earlier study. The specific themes derived from the present study were then related to embodiment issues as reflected in the philosophical writings of Merleau-Ponty, the psycholinguistic analyses of Lakoff and Johnson and experimental psychology.

Learning what matters: A neural explanation for the sparsity bias.

PubMed

Hassall, Cameron D; Connor, Patrick C; Trappenberg, Thomas P; McDonald, John J; Krigolson, Olave E

2018-05-01

The visual environment is filled with complex, multi-dimensional objects that vary in their value to an observer's current goals. When faced with multi-dimensional stimuli, humans may rely on biases to learn to select those objects that are most valuable to the task at hand. Here, we show that decision making in a complex task is guided by the sparsity bias: the focusing of attention on a subset of available features. Participants completed a gambling task in which they selected complex stimuli that varied randomly along three dimensions: shape, color, and texture. Each dimension comprised three features (e.g., color: red, green, yellow). Only one dimension was relevant in each block (e.g., color), and a randomly-chosen value ranking determined outcome probabilities (e.g., green > yellow > red). Participants were faster to respond to infrequent probe stimuli that appeared unexpectedly within stimuli that possessed a more valuable feature than to probes appearing within stimuli possessing a less valuable feature. Event-related brain potentials recorded during the task provided a neurophysiological explanation for sparsity as a learning-dependent increase in optimal attentional performance (as measured by the N2pc component of the human event-related potential) and a concomitant learning-dependent decrease in prediction errors (as measured by the feedback-elicited reward positivity). Together, our results suggest that the sparsity bias guides human reinforcement learning in complex environments. Copyright © 2018 Elsevier B.V. All rights reserved.

Maternal and fetal effects of chocolate consumption during pregnancy: a systematic review.

PubMed

Latif, Rabia

2018-03-13

The purpose of this review is to explore the effects of chocolate consumption during pregnancy on fetus and mother herself. Randomized controlled trials/quasi-experimental/observational/controlled before and after studies involving chocolate/cocoa/cacao consumption (irrespective of type or dose, composition, exposure period, and method of administration) among pregnant women/animals; and measuring any outcome (beneficial or harmful) related to fetus or mother after chocolate exposure were included. Databases searched were PubMed, Web of Science and Scopus; between April and May 2017. Risk of bias within each human randomized controlled trial (RCT) and animals' experimental studies was evaluated by "The Cochrane Collaboration's tool" and SYRCLE's tool respectively. Fourteen human studies including a total of 6639 participants and nine animal studies were selected. Outcome variables investigated in human studies were maternal blood pressure, fetal heart rate, and striae gravidarum. Animal studies explored chocolate-induced teratogenicity and fetal metabolic derangements. Ten out of these 23 studies reported chocolate to be "beneficial"; five studies reported adverse effects, whereas eight studies declared chocolate as "neutral". Maternal chocolate intake has acute stimulatory effects on fetal reactivity and chronic blood pressure reducing effect in mothers. Chocolate is nonteratogenic and does not affect reproductive indices. Metabolic derangements in offsprings born to chocolate fed dams have been reported. Pregnant females must be careful about consumption of cocoa and chocolate. Future studies should be planned, keeping in view heterogeneities identified across the selected studies in this review.

Constraint, natural selection, and the evolution of human body form

PubMed Central

Savell, Kristen R. R.; Auerbach, Benjamin M.; Roseman, Charles C.

2016-01-01

Variation in body form among human groups is structured by a blend of natural selection driven by local climatic conditions and random genetic drift. However, attempts to test ecogeographic hypotheses have not distinguished between adaptive traits (i.e., those that evolved as a result of selection) and those that evolved as a correlated response to selection on other traits (i.e., nonadaptive traits), complicating our understanding of the relationship between climate and morphological distinctions among populations. Here, we use evolutionary quantitative methods to test if traits previously identified as supporting ecogeographic hypotheses were actually adaptive by estimating the force of selection on individual traits needed to drive among-group differentiation. Our results show that not all associations between trait means and latitude were caused by selection acting directly on each individual trait. Although radial and tibial length and biiliac and femoral head breadth show signs of responses to directional selection matching ecogeographic hypotheses, the femur was subject to little or no directional selection despite having shorter values by latitude. Additionally, in contradiction to ecogeographic hypotheses, the humerus was under directional selection for longer values by latitude. Responses to directional selection in the tibia and radius induced a nonadaptive correlated response in the humerus that overwhelmed its own trait-specific response to selection. This result emphasizes that mean differences between groups are not good indicators of which traits are adaptations in the absence of information about covariation among characteristics. PMID:27482101

Constraint, natural selection, and the evolution of human body form.

PubMed

Savell, Kristen R R; Auerbach, Benjamin M; Roseman, Charles C

2016-08-23

Variation in body form among human groups is structured by a blend of natural selection driven by local climatic conditions and random genetic drift. However, attempts to test ecogeographic hypotheses have not distinguished between adaptive traits (i.e., those that evolved as a result of selection) and those that evolved as a correlated response to selection on other traits (i.e., nonadaptive traits), complicating our understanding of the relationship between climate and morphological distinctions among populations. Here, we use evolutionary quantitative methods to test if traits previously identified as supporting ecogeographic hypotheses were actually adaptive by estimating the force of selection on individual traits needed to drive among-group differentiation. Our results show that not all associations between trait means and latitude were caused by selection acting directly on each individual trait. Although radial and tibial length and biiliac and femoral head breadth show signs of responses to directional selection matching ecogeographic hypotheses, the femur was subject to little or no directional selection despite having shorter values by latitude. Additionally, in contradiction to ecogeographic hypotheses, the humerus was under directional selection for longer values by latitude. Responses to directional selection in the tibia and radius induced a nonadaptive correlated response in the humerus that overwhelmed its own trait-specific response to selection. This result emphasizes that mean differences between groups are not good indicators of which traits are adaptations in the absence of information about covariation among characteristics.

Genetic considerations in human sex-mate selection: partners share human leukocyte antigen but not short-tandem-repeat identity markers.

PubMed

Israeli, Moshe; Kristt, Don; Nardi, Yuval; Klein, Tirza

2014-05-01

Previous studies support a role for MHC on mating preference, yet it remains unsettled as to whether mating occurs preferentially between individuals sharing human leukocyte antigen (HLA) determinants or not. Investigating sex-mate preferences in the contemporary Israeli population is of further curiosity being a population with distinct genetic characteristics, where multifaceted cultural considerations influence mate selection. Pairs of male-female sex partners were evaluated in three groups. Two groups represented unmarried (n = 1002) or married (n = 308) couples and a control group of fictitious male-female couples. HLA and short-tandem-repeat (STR) genetic identification markers were assessed for the frequency of shared antigens and alleles. Human leukocyte antigen results showed that Class I and/ or Class II single antigen as well as double antigen sharing was more common in sex partners than in control group couples (P < 0.001). Married versus unmarried pairs were not distinguishable. In contrast, STR-DNA markers failed to differentiate between sex-mates and controls (P = 0.78). Sex partnerships shared HLA determinants more frequently than randomly constituted male-female pairs. The observed phenomenon does not reflect a syngenetic background between sex-mates as STR markers were not selectively shared. Thus, sex-mate selection in man may contravene the evolutionary pressure for genetic diversity in regard to HLA. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Incidence and effects of endemic populations of forest pests in young mixed-conifer forests of the Sierra Nevada

Treesearch

Carroll B. Williams; David L. Azuma; George T. Ferrell

1992-01-01

Approximately 3.200 trees in young mixed-conifer stands were examined for pest activity and human-caused or mechanical injuries, and approximately 25 percent of these trees were randomly selected for stem analyses. The examination of trees felled for stem analyses showed that 409 (47 percent) were free of pests and 466 (53 percent) had one or more pest categories....

Information Memory Processing and Retrieval: Relationships of the Intellect with the Processing of a Learning and Cognition Task.

ERIC Educational Resources Information Center

Moser, Gene W.

Reported is one of a series of investigations of the Project on an Information Memory Model. This study was done to test an information memory model for identifying the unit of information structure involved in task cognitions by humans. Four groups of 30 randomly selected subjects (ages 7, 9, 11 and 15 years) performed a sorting task of 14…

The Fair Labor Standards Act. Enforcement of Child Labor Provisions in Massachusetts. Report to the Chairman, Committee on Labor and Human Resources, U.S. Senate.

ERIC Educational Resources Information Center

General Accounting Office, Washington, DC. Div. of Human Resources.

During 1987, investigations of 113 cases of alleged or suspected child labor violations at Massachusetts business establishments were conducted. Thirteen (38 percent) of these were randomly selected for review. Compliance officers in the Department of Labor's Wage and Hour Division substantiated child labor violations in 9 of the 13 cases. A total…

DHSpred: support-vector-machine-based human DNase I hypersensitive sites prediction using the optimal features selected by random forest.

PubMed

Manavalan, Balachandran; Shin, Tae Hwan; Lee, Gwang

2018-01-05

DNase I hypersensitive sites (DHSs) are genomic regions that provide important information regarding the presence of transcriptional regulatory elements and the state of chromatin. Therefore, identifying DHSs in uncharacterized DNA sequences is crucial for understanding their biological functions and mechanisms. Although many experimental methods have been proposed to identify DHSs, they have proven to be expensive for genome-wide application. Therefore, it is necessary to develop computational methods for DHS prediction. In this study, we proposed a support vector machine (SVM)-based method for predicting DHSs, called DHSpred (DNase I Hypersensitive Site predictor in human DNA sequences), which was trained with 174 optimal features. The optimal combination of features was identified from a large set that included nucleotide composition and di- and trinucleotide physicochemical properties, using a random forest algorithm. DHSpred achieved a Matthews correlation coefficient and accuracy of 0.660 and 0.871, respectively, which were 3% higher than those of control SVM predictors trained with non-optimized features, indicating the efficiency of the feature selection method. Furthermore, the performance of DHSpred was superior to that of state-of-the-art predictors. An online prediction server has been developed to assist the scientific community, and is freely available at: http://www.thegleelab.org/DHSpred.html.

DHSpred: support-vector-machine-based human DNase I hypersensitive sites prediction using the optimal features selected by random forest

PubMed Central

Manavalan, Balachandran; Shin, Tae Hwan; Lee, Gwang

2018-01-01

DNase I hypersensitive sites (DHSs) are genomic regions that provide important information regarding the presence of transcriptional regulatory elements and the state of chromatin. Therefore, identifying DHSs in uncharacterized DNA sequences is crucial for understanding their biological functions and mechanisms. Although many experimental methods have been proposed to identify DHSs, they have proven to be expensive for genome-wide application. Therefore, it is necessary to develop computational methods for DHS prediction. In this study, we proposed a support vector machine (SVM)-based method for predicting DHSs, called DHSpred (DNase I Hypersensitive Site predictor in human DNA sequences), which was trained with 174 optimal features. The optimal combination of features was identified from a large set that included nucleotide composition and di- and trinucleotide physicochemical properties, using a random forest algorithm. DHSpred achieved a Matthews correlation coefficient and accuracy of 0.660 and 0.871, respectively, which were 3% higher than those of control SVM predictors trained with non-optimized features, indicating the efficiency of the feature selection method. Furthermore, the performance of DHSpred was superior to that of state-of-the-art predictors. An online prediction server has been developed to assist the scientific community, and is freely available at: http://www.thegleelab.org/DHSpred.html PMID:29416743

Different ranking of avian colors predicted by modeling of retinal function in humans and birds.

PubMed

Håstad, Olle; Odeen, Anders

2008-06-01

Abstract: Only during the past decade have vision-system-neutral methods become common practice in studies of animal color signals. Consequently, much of the current knowledge on sexual selection is based directly or indirectly on human vision, which may or may not emphasize spectral information in a signal differently from the intended receiver. In an attempt to quantify this discrepancy, we used retinal models to test whether human and bird vision rank plumage colors similarly. Of 67 species, human and bird models disagreed in 26 as to which pair of patches in the plumage provides the strongest color contrast or which male in a random pair is the more colorful. These results were only partly attributable to human UV blindness. Despite confirming a strong correlation between avian and human color discrimination, we conclude that a significant proportion of the information in avian visual signals may be lost in translation.

The surprisingly high human efficiency at learning to recognize faces

PubMed Central

Peterson, Matthew F.; Abbey, Craig K.; Eckstein, Miguel P.

2009-01-01

We investigated the ability of humans to optimize face recognition performance through rapid learning of individual relevant features. We created artificial faces with discriminating visual information heavily concentrated in single features (nose, eyes, chin or mouth). In each of 2500 learning blocks a feature was randomly selected and retained over the course of four trials, during which observers identified randomly sampled, noisy face images. Observers learned the discriminating feature through indirect feedback, leading to large performance gains. Performance was compared to a learning Bayesian ideal observer, resulting in unexpectedly high learning compared to previous studies with simpler stimuli. We explore various explanations and conclude that the higher learning measured with faces cannot be driven by adaptive eye movement strategies but can be mostly accounted for by suboptimalities in human face discrimination when observers are uncertain about the discriminating feature. We show that an initial bias of humans to use specific features to perform the task even though they are informed that each of four features is equally likely to be the discriminatory feature would lead to seemingly supra-optimal learning. We also examine the possibility of inefficient human integration of visual information across the spatially distributed facial features. Together, the results suggest that humans can show large performance improvement effects in discriminating faces as they learn to identify the feature containing the discriminatory information. PMID:19000918

Antibody VH and VL recombination using phage and ribosome display technologies reveals distinct structural routes to affinity improvements with VH-VL interface residues providing important structural diversity

PubMed Central

Groves, Maria AT; Amanuel, Lily; Campbell, Jamie I; Rees, D Gareth; Sridharan, Sudharsan; Finch, Donna K; Lowe, David C; Vaughan, Tristan J

2014-01-01

In vitro selection technologies are an important means of affinity maturing antibodies to generate the optimal therapeutic profile for a particular disease target. Here, we describe the isolation of a parent antibody, KENB061 using phage display and solution phase selections with soluble biotinylated human IL-1R1. KENB061 was affinity matured using phage display and targeted mutagenesis of VH and VL CDR3 using NNS randomization. Affinity matured VHCDR3 and VLCDR3 library blocks were recombined and selected using phage and ribosome display protocol. A direct comparison of the phage and ribosome display antibodies generated was made to determine their functional characteristics. PMID:24256948

Arginine Vasopressin selectively enhances recognition of sexual cues in male humans.

PubMed

Guastella, Adam J; Kenyon, Amanda R; Unkelbach, Christian; Alvares, Gail A; Hickie, Ian B

2011-02-01

Arginine Vasopressin modulates complex social and sexual behavior by enhancing social recognition, pair bonding, and aggression in non-human mammals. The influence of Arginine Vasopressin in human social and sexual behavior is, however, yet to be fully understood. We evaluated whether Arginine Vasopressin nasal spray facilitated recognition of positive and negative social and sexual stimuli over non-social stimuli. We used a recognition task that has already been shown to be sensitive to the influence of Oxytocin nasal spray (Unkelbach et al., 2008). In a double-blind, randomized, placebo-controlled, between-subjects design, 41 healthy male volunteers were administered Arginine Vasopressin (20 IU) or a placebo nasal spray after a 45 min wait period and then completed the recognition task. Results showed that the participants administered Arginine Vasopressin nasal spray were faster to detect sexual words over other types of words. This effect appeared for both positively and negatively valenced words. Results demonstrate for the first time that Arginine Vasopressin selectively enhances human cognition for sexual stimuli, regardless of valence. They further extend animal and human genetic studies linking Arginine Vasopressin to sexual behavior in males. Findings suggest an important cognitive mechanism that could enhance sexual behaviors in humans. Crown Copyright © 2010. Published by Elsevier Ltd. All rights reserved.

Effects of environmental features and sport hunting on caribou migration in northwestern Alaska.

PubMed

Fullman, Timothy J; Joly, Kyle; Ackerman, Andrew

2017-01-01

Ungulate movements are influenced by a variety of biotic and abiotic factors, which may affect connectivity between key resource areas and seasonal ranges. In northwestern Alaska, one important question regarding human impacts on ungulate movement involves caribou ( Rangifer tarandus ) response to autumn hunting and related aircraft activity. While concerns have been voiced by local hunters about the influence of transporter aircraft and non-local sport hunters, there has been little quantitative analysis of the effects of hunter activity on caribou movement. We utilized a novel spatial dataset of commercial aircraft landing locations and sport hunter camps in and around Noatak National Preserve to analyze resource selection of caribou in autumn for non-local hunting activity and environmental features. We combined step selection functions with randomized shortest paths to investigate whether terrain ruggedness, river width, land cover, and hunting activity (in the form of aircraft landings and sport hunter camps) facilitated or impeded caribou movement. By varying a parameter in the randomized shortest path models, we also explored the tradeoff between exploration and exploitation in movement behavior exhibited by traveling caribou. We found that caribou avoided rugged terrain and areas with more river, forest, and tall shrubs while selecting for areas dominated by tussock tundra and dwarf shrubs. Migration of caribou through Noatak does not appear to be inhibited by sport hunting activity, though this does not preclude the possibility of temporary effects altering availability of caribou for individual hunters. Caribou exhibited exploratory movement, following predictions of a random walk model. This behavior may facilitate the location of remaining patches of high-quality forage prior to the onset of winter, especially during mild autumns. Understanding animal movement behavior is fundamental to protecting critical areas of connectivity and to informing management decisions. Our study identifies migratory connectivity and hotspots of potential conflict among user groups, enabling development of policies that balance human access with species conservation.

Application of a haematopoetic progenitor cell-targeted adeno-associated viral (AAV) vector established by selection of an AAV random peptide library on a leukaemia cell line

PubMed Central

Stiefelhagen, Marius; Sellner, Leopold; Kleinschmidt, Jürgen A; Jauch, Anna; Laufs, Stephanie; Wenz, Frederik; Zeller, W Jens; Fruehauf, Stefan; Veldwijk, Marlon R

2008-01-01

Background For many promising target cells (e.g.: haematopoeitic progenitors), the susceptibility to standard adeno-associated viral (AAV) vectors is low. Advancements in vector development now allows the generation of target cell-selected AAV capsid mutants. Methods To determine its suitability, the method was applied on a chronic myelogenous leukaemia (CML) cell line (K562) to obtain a CML-targeted vector and the resulting vectors tested on leukaemia, non-leukaemia, primary human CML and CD34+ peripheral blood progenitor cells (PBPC); standard AAV2 and a random capsid mutant vector served as controls. Results Transduction of CML (BV173, EM3, K562 and Lama84) and AML (HL60 and KG1a) cell lines with the capsid mutants resulted in an up to 36-fold increase in CML transduction efficiency (K562: 2-fold, 60% ± 2% green fluorescent protein (GFP)+ cells; BV173: 9-fold, 37% ± 2% GFP+ cells; Lama84: 36-fold, 29% ± 2% GFP+ cells) compared to controls. For AML (KG1a, HL60) and one CML cell line (EM3), no significant transduction (<1% GFP+ cells) was observed for any vector. Although the capsid mutant clone was established on a cell line, proof-of-principle experiments using primary human cells were performed. For CML (3.2-fold, mutant: 1.75% ± 0.45% GFP+ cells, p = 0.03) and PBPC (3.5-fold, mutant: 4.21% ± 3.40% GFP+ cells) a moderate increase in gene transfer of the capsid mutant compared to control vectors was observed. Conclusion Using an AAV random peptide library on a CML cell line, we were able to generate a capsid mutant, which transduced CML cell lines and primary human haematopoietic progenitor cells with higher efficiency than standard recombinant AAV vectors. PMID:18789140

Neuronal effects of nicotine during auditory selective attention.

PubMed

Smucny, Jason; Olincy, Ann; Eichman, Lindsay S; Tregellas, Jason R

2015-06-01

Although the attention-enhancing effects of nicotine have been behaviorally and neurophysiologically well-documented, its localized functional effects during selective attention are poorly understood. In this study, we examined the neuronal effects of nicotine during auditory selective attention in healthy human nonsmokers. We hypothesized to observe significant effects of nicotine in attention-associated brain areas, driven by nicotine-induced increases in activity as a function of increasing task demands. A single-blind, prospective, randomized crossover design was used to examine neuronal response associated with a go/no-go task after 7 mg nicotine or placebo patch administration in 20 individuals who underwent functional magnetic resonance imaging at 3T. The task design included two levels of difficulty (ordered vs. random stimuli) and two levels of auditory distraction (silence vs. noise). Significant treatment × difficulty × distraction interaction effects on neuronal response were observed in the hippocampus, ventral parietal cortex, and anterior cingulate. In contrast to our hypothesis, U and inverted U-shaped dependencies were observed between the effects of nicotine on response and task demands, depending on the brain area. These results suggest that nicotine may differentially affect neuronal response depending on task conditions. These results have important theoretical implications for understanding how cholinergic tone may influence the neurobiology of selective attention.

Staphylococcus nepalensis in the guano of bats (Mammalia).

PubMed

Vandžurová, A; Bačkor, P; Javorský, P; Pristaš, P

2013-05-31

Thirty randomly selected mesophilic isolates from the six years old guano sample from mixed Myotis myotis and M. blythii summer roosts colony were isolated and identified as Staphylococcus nepalensis using MALDI TOF analysis. 16S rRNA gene sequencing of selected five isolates and subsequent phylogenetic analysis confirmed that all sequences showed the highest similarity to S. nepalensis sequences. Several virulence factors were produced by tested isolates, mainly capsule formation and resistance to tetracycline, ampicillin, gentamycin, and chloramphenicol antibiotics. Our experiments show that the majority of cultivable mesophilic bacteria from the guano of bats belong to the S. nepalensis species. This is the first report on the occurrence of this species in the guano of bats and our results indicate that the guano accumulated near or directly in human dwellings and buildings may represent a significant risk for human health. Copyright © 2013 Elsevier B.V. All rights reserved.

Enantioseparation of thalidomide and its hydroxylated metabolites using capillary electrophoresis with various cyclodextrins and their combinations as chiral buffer additives.

PubMed

Meyring, M; Chankvetadze, B; Blaschke, G

1999-09-01

The separation of thalidomide (TD) and its hydroxylated metabolites including their simultaneous enantioseparation was studied in capillary electrophoresis (CE) using four different randomly substituted charged cyclodextrin (CD) derivatives, the combinations of some of them with each other, and beta-CD. TD, as well as two metabolites recently found in incubations of human liver microsomes and human blood, 5-hydroxythalidomide (5-OH-TD) and one of the diastereomeric 5'-hydroxythalidomides (5'-OH-TD), are neutral compounds. Therefore, they were resolved using charged chiral selectors in CE. Two different separation modes (normal polarity and carrier mode) and two different capillaries (fused-silica and polyacrylamide-coated) were tested. Based on the behavior of the individual CDs, their designed combinations were selected in order to improve the separation selectivity and enantioselectivity. Under optimized conditions all three chiral compounds and their enantiomers were resolved simultaneously.

Identification of polypeptides with selective affinity to intact mouse cerebellar granule neurons from a random peptide-presenting phage library.

PubMed

Hou, Sheng T; Dove, Mike; Anderson, Erica; Zhang, Jiangbing; MacKenzie, C Roger

2004-09-30

Targeting of postmitotic neurons selectively for gene delivery poses a challenge. One way to achieve such a selective targeting is to link the gene delivery vector with small ligand-binding polypeptides which have selective affinity to intact neurons. In order to identify such novel neuron selective polypeptides, we screened a phage-display library displaying random 12-mer polypeptides and subtractively bio-panned for clones having selectivity towards cultured mouse cerebellar granule neurons. The selected phage clones were amplified and sequenced. Affinities of these clones to neurons were determined by the visible presence or absence of fluorescence of phage particles as detected by immunocytochemistry using an antibody to M-13 phage. This affinity was further qualified by how much phage was bound, and where in or on the cell it tended to accumulate. The selectivity of binding to neurons was determined by the negative binding of these clones to several cultured non-neuronal cells, including, primary glial cells, NT2 cells, human embryonic kidney 293 cells, neuroblastoma cells, and mouse 3T3 cells. Among the 46 clones that we have sequenced and characterized, four clones appeared to have excellent selectivity in binding to neurons. Homology comparison of these polypeptides revealed that three of them contained a consensus D(E)-W(F)-I(N)-D-W motif. This motif was also present in the Bdm1 gene product which was predominantly expressed in postnatal brains. Further characterizations of these polypeptides are required to reveal the utilities of these peptides to function as an effective linker to facilitate gene transfer selectively to neurons.

Stability-Diversity Tradeoffs Impose Fundamental Constraints on Selection of Synthetic Human VH/VL Single-Domain Antibodies from In Vitro Display Libraries.

PubMed

Henry, Kevin A; Kim, Dae Young; Kandalaft, Hiba; Lowden, Michael J; Yang, Qingling; Schrag, Joseph D; Hussack, Greg; MacKenzie, C Roger; Tanha, Jamshid

2017-01-01

Human autonomous V H /V L single-domain antibodies (sdAbs) are attractive therapeutic molecules, but often suffer from suboptimal stability, solubility and affinity for cognate antigens. Most commonly, human sdAbs have been isolated from in vitro display libraries constructed via synthetic randomization of rearranged V H /V L domains. Here, we describe the design and characterization of three novel human V H /V L sdAb libraries through a process of: (i) exhaustive biophysical characterization of 20 potential V H /V L sdAb library scaffolds, including assessment of expression yield, aggregation resistance, thermostability and tolerance to complementarity-determining region (CDR) substitutions; (ii) in vitro randomization of the CDRs of three V H /V L sdAb scaffolds, with tailored amino acid representation designed to promote solubility and expressibility; and (iii) systematic benchmarking of the three V H /V L libraries by panning against five model antigens. We isolated ≥1 antigen-specific human sdAb against four of five targets (13 V H s and 7 V L s in total); these were predominantly monomeric, had antigen-binding affinities ranging from 5 nM to 12 µM (average: 2-3 µM), but had highly variable expression yields (range: 0.1-19 mg/L). Despite our efforts to identify the most stable V H /V L scaffolds, selection of antigen-specific binders from these libraries was unpredictable (overall success rate for all library-target screens: ~53%) with a high attrition rate of sdAbs exhibiting false positive binding by ELISA. By analyzing V H /V L sdAb library sequence composition following selection for monomeric antibody expression (binding to protein A/L followed by amplification in bacterial cells), we found that some V H /V L sdAbs had marked growth advantages over others, and that the amino acid composition of the CDRs of this set of sdAbs was dramatically restricted (bias toward Asp and His and away from aromatic and hydrophobic residues). Thus, CDR sequence clearly dramatically impacts the stability of human autonomous V H /V L immunoglobulin domain folds, and sequence-stability tradeoffs must be taken into account during the design of such libraries.

Genome-wide prediction and analysis of human tissue-selective genes using microarray expression data

PubMed Central

2013-01-01

Background Understanding how genes are expressed specifically in particular tissues is a fundamental question in developmental biology. Many tissue-specific genes are involved in the pathogenesis of complex human diseases. However, experimental identification of tissue-specific genes is time consuming and difficult. The accurate predictions of tissue-specific gene targets could provide useful information for biomarker development and drug target identification. Results In this study, we have developed a machine learning approach for predicting the human tissue-specific genes using microarray expression data. The lists of known tissue-specific genes for different tissues were collected from UniProt database, and the expression data retrieved from the previously compiled dataset according to the lists were used for input vector encoding. Random Forests (RFs) and Support Vector Machines (SVMs) were used to construct accurate classifiers. The RF classifiers were found to outperform SVM models for tissue-specific gene prediction. The results suggest that the candidate genes for brain or liver specific expression can provide valuable information for further experimental studies. Our approach was also applied for identifying tissue-selective gene targets for different types of tissues. Conclusions A machine learning approach has been developed for accurately identifying the candidate genes for tissue specific/selective expression. The approach provides an efficient way to select some interesting genes for developing new biomedical markers and improve our knowledge of tissue-specific expression. PMID:23369200

COMPARISON OF RANDOM AND SYSTEMATIC SITE SELECTION FOR ASSESSING ATTAINMENT OF AQUATIC LIFE USES IN SEGMENTS OF THE OHIO RIVER

EPA Science Inventory

This report is a description of field work and data analysis results comparing a design comparable to systematic site selection with one based on random selection of sites. The report is expected to validate the use of random site selection in the bioassessment program for the O...

Human Centred Design Considerations for Connected Health Devices for the Older Adult

PubMed Central

Harte, Richard P.; Glynn, Liam G.; Broderick, Barry J.; Rodriguez-Molinero, Alejandro; Baker, Paul M. A.; McGuiness, Bernadette; O’Sullivan, Leonard; Diaz, Marta; Quinlan, Leo R.; ÓLaighin, Gearóid

2014-01-01

Connected health devices are generally designed for unsupervised use, by non-healthcare professionals, facilitating independent control of the individuals own healthcare. Older adults are major users of such devices and are a population significantly increasing in size. This group presents challenges due to the wide spectrum of capabilities and attitudes towards technology. The fit between capabilities of the user and demands of the device can be optimised in a process called Human Centred Design. Here we review examples of some connected health devices chosen by random selection, assess older adult known capabilities and attitudes and finally make analytical recommendations for design approaches and design specifications. PMID:25563225

Game, cloud architecture and outreach for The BIG Bell Test

NASA Astrophysics Data System (ADS)

Abellan, Carlos; Tura, Jordi; Garcia, Marta; Beduini, Federica; Hirschmann, Alina; Pruneri, Valerio; Acin, Antonio; Marti, Maria; Mitchell, Morgan

The BIG Bell test uses the input from the Bellsters, self-selected human participants introducing zeros and ones through an online videogame, to perform a suite of quantum physics experiments. In this talk, we will explore the videogame, the data infrastructure and the outreach efforts of the BIG Bell test collaboration. First, we will discuss how the game was designed so as to eliminate possible feedback mechanisms that could influence people's behavior. Second, we will discuss the cloud architecture design for scalability as well as explain how we sent each individual bit from the users to the labs. Also, and using all the bits collected via the BIG Bell test interface, we will show a data analysis on human randomness, e.g. are younger Bellsters more random than older Bellsters? Finally, we will talk about the outreach and communication efforts of the BIG Bell test collaboration, exploring both the social media campaigns as well as the close interaction with teachers and educators to bring the project into classrooms.

Role of re-screening of cervical smears in internal quality control.

PubMed Central

Baker, A; Melcher, D; Smith, R

1995-01-01

AIMS--To investigate the use of rapid re-screening as a quality control method for previously screened cervical slides; to compare this method with 10% random re-screening and clinically indicated double screening. METHODS--Between June 1990 and December 1994, 117,890 negative smears were subjected to rapid re-screening. RESULTS--This study shows that rapid re-screening detects far greater numbers of false negative cases when compared with both 10% random re-screening and clinically indicated double screening, with no additional demand on human resources. The technique also identifies variation in the performance of screening personnel as an additional benefit. CONCLUSION--Rapid re-screening is an effective method of quality control. Although less sensitive, rapid re-screening should replace 10% random re-screening and selected re-screening as greater numbers of false negative results are detected while consuming less resources. PMID:8543619

Randomizing Roaches: Exploring the "Bugs" of Randomization in Experimental Design

ERIC Educational Resources Information Center

Wagler, Amy; Wagler, Ron

2014-01-01

Understanding the roles of random selection and random assignment in experimental design is a central learning objective in most introductory statistics courses. This article describes an activity, appropriate for a high school or introductory statistics course, designed to teach the concepts, values and pitfalls of random selection and assignment…

Analysis of internal structure changes in black human hair keratin fibers with aging using Raman spectroscopy.

PubMed

Kuzuhara, Akio; Fujiwara, Nobuki; Hori, Teruo

To investigate the internal structure changes in virgin black human hair keratin fibers due to aging, the structure of cross-sections at various depths of virgin black human hair (sections of new growth hair: 2 mm from the scalp) from a group of eight Japanese females in their twenties and another group of eight Japanese females in their fifties were analyzed using Raman spectroscopy. For the first time, we have succeeded in recording the Raman spectra of virgin black human hair, which had been impossible due to high melanin granule content. The key points of this method are to cross-section hair samples to a thickness of 1.50-microm, to select points at various depths of the cortex with the fewest possible melanin granules, and to optimize laser power, cross slit width as well as total acquisition time. The reproducibility of the Raman bands, namely the alpha-helix (alpha) content, the beta-sheet and/or random coil (beta/R) content, the disulfide (--SS--) content, and random coil content of two adjoining cross-sections of a single hair keratin fiber was clearly good. The --SS-- content of virgin black human hair from the Japanese females in their fifties for the cortex region decreased compared with that of the Japanese females in their twenties. On the other hand, the beta/R and alpha contents of the cortex region did not change.

[Effects of rare earth compounds on human peripheral mononuclear cell telomerase and apoptosis].

PubMed

Yu, Li; Dai, Yu-Cheng; Yuan, Zhao-Kang; Li, Jie

2004-07-01

To study the effects of rare earth exposure on human telomerase and apoptosis of human peripheral mononuclear cells (PBMNs). Rare earth mine lot in Xunwu county, the biggest ion absorptive rare earth mine lot of China, was selected as the study site. Another village of Xunwu county, with comparable geological structure and social environment was selected as the control site. Thirty healthy adults were randomly selected from the study site as exposure group and another 30 healthy adults randomly selected from the control site as control group. The blood content of 15 rare earth elements, including La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu and Y, were determined by inductive coupled plasma-source mass spectrometry (ICP-MS). The total contents of rare earth elements in the blood were calculated. The TRAP and FCM assays were carried out to analyse the telomerase and apoptosis of human PBMNCs respectively. In the exposure group, the concentration of La, Ce, Dy and Y were significantly higher (P<0.001), and Pr, Nd, Sm, Gd and Yb were higher than those in the control group (P<0.05). The total content of rare earth in the blood of exposure group showed significant difference compared with control group (P<0.001). Telomerase activity in PBMNs of the exposure group was higher than that in the control group (P<0.05); there were 11 adults in the exposure group (30 adults) and 5 adults in control group (30 adults) showed positive telomerase activity. The average age of the exposure group was (38.69 +/- 8.02) years-old, while the control group was (40.45 +/- 9.02) years-old (P >0.05). It was found that there was a significant relationship between telomerase activity and the total content of rare earth elements (P <0.01). 3. The proportion of apoptosis was not different between the two groups (P >0.05), but the cells in the S-phase and G2-M phase were increased (P <0.01) in the exposed group. The telomerase activity of PBMNs in the rare earth elements exposed group was higher than that of the control group, and there is no effect on apoptotic rate of PBMNs, but may promote the diploid DNA replication, and increase the percentage of G2/M and S phase cells.

Selection Gradients, the Opportunity for Selection, and the Coefficient of Determination

PubMed Central

Moorad, Jacob A.; Wade, Michael J.

2013-01-01

We derive the relationship between R2 (the coefficient of determination), selection gradients, and the opportunity for selection for univariate and multivariate cases. Our main result is to show that the portion of the opportunity for selection that is caused by variation for any trait is equal to the product of its selection gradient and its selection differential. This relationship is a corollary of the first and second fundamental theorems of natural selection, and it permits one to investigate the portions of the total opportunity for selection that are involved in directional selection, stabilizing (and diversifying) selection, and correlational selection, which is important to morphological integration. It also allows one to determine the fraction of fitness variation not explained by variation in measured phenotypes and therefore attributable to random (or, at least, unknown) influences. We apply our methods to a human data set to show how sex-specific mating success as a component of fitness variance can be decoupled from that owing to prereproductive mortality. By quantifying linear sources of sexual selection and quadratic sources of sexual selection, we illustrate that the former is stronger in males, while the latter is stronger in females. PMID:23448880

Selection gradients, the opportunity for selection, and the coefficient of determination.

PubMed

Moorad, Jacob A; Wade, Michael J

2013-03-01

Abstract We derive the relationship between R(2) (the coefficient of determination), selection gradients, and the opportunity for selection for univariate and multivariate cases. Our main result is to show that the portion of the opportunity for selection that is caused by variation for any trait is equal to the product of its selection gradient and its selection differential. This relationship is a corollary of the first and second fundamental theorems of natural selection, and it permits one to investigate the portions of the total opportunity for selection that are involved in directional selection, stabilizing (and diversifying) selection, and correlational selection, which is important to morphological integration. It also allows one to determine the fraction of fitness variation not explained by variation in measured phenotypes and therefore attributable to random (or, at least, unknown) influences. We apply our methods to a human data set to show how sex-specific mating success as a component of fitness variance can be decoupled from that owing to prereproductive mortality. By quantifying linear sources of sexual selection and quadratic sources of sexual selection, we illustrate that the former is stronger in males, while the latter is stronger in females.

Evaluation of Medical Students' Attitudes and Performance of Basic Surgery Skills in a Training Program Using Fresh Human skin, Excised During Body Contouring Surgeries.

PubMed

Rothenberger, Jens; Seyed Jafari, Seyed Morteza; Schnabel, Kai P; Tschumi, Christian; Angermeier, Sarina; Shafighi, Maziar

2015-01-01

Learning surgical skills in the operating room may be a challenge for medical students. Therefore, more approaches using simulation to enable students to develop their practical skills are required. We hypothesized that (1) there would be a need for additional surgical training for medical students in the pre-final year, and (2) our basic surgery skills training program using fresh human skin would improve medical students' surgical skills. We conducted a preliminary survey of medical students to clarify the need for further training in basic surgery procedures. A new approach using simulation to teach surgical skills on human skin was set up. The procedural skills of 15 randomly selected students were assessed in the operating room before and after participation in the simulation, using Objective Structured Assessment of Technical Skills. Furthermore, subjective assessment was performed based on students' self-evaluation. The data were analyzed using SPSS, version 21 (SPSS, Inc., Chicago, IL). The study took place at the Inselspital, Bern University Hospital. A total of 186 pre-final-year medical students were enrolled into the preliminary survey; 15 randomly selected medical students participated in the basic surgical skills training course on the fresh human skin operating room. The preliminary survey revealed the need for a surgical skills curriculum. The simulation approach we developed showed significant (p < 0.001) improvement for all 12 surgical skills, with mean cumulative precourse and postcourse values of 31.25 ± 5.013 and 45.38 ± 3.557, respectively. The self-evaluation contained positive feedback as well. Simulation of surgery using human tissue samples could help medical students become more proficient in handling surgical instruments before stepping into a real surgical situation. We suggest further studies evaluating our proposed teaching method and the possibility of integrating this simulation approach into the medical school curriculum. Copyright © 2015 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.

Selection bias in studies of human reproduction-longevity trade-offs.

PubMed

Helle, Samuli

2017-12-13

A shorter lifespan as a potential cost of high reproductive effort in humans has intrigued researchers for more than a century. However, the results have been inconclusive so far and despite strong theoretical expectations we do not currently have compelling evidence for the longevity costs of reproduction. Using Monte Carlo simulation, it is shown here that a common practice in human reproduction-longevity studies using historical data (the most relevant data sources for this question), the omission of women who died prior to menopausal age from the analysis, results in severe underestimation of the potential underlying trade-off between reproduction and lifespan. In other words, assuming that such a trade-off is expressed also during reproductive years, the strength of the trade-off between reproduction and lifespan is progressively weakened when women dying during reproductive ages are sequentially and non-randomly excluded from the analysis. In cases of small sample sizes (e.g. few hundreds of observations), this selection bias by reducing statistical power may even partly explain the null results commonly found in this field. Future studies in this field should thus apply statistical approaches that account for or avoid selection bias in order to recover reliable effect size estimates between reproduction and longevity. © 2017 The Author(s).

Application of random effects to the study of resource selection by animals

USGS Publications Warehouse

Gillies, C.S.; Hebblewhite, M.; Nielsen, S.E.; Krawchuk, M.A.; Aldridge, Cameron L.; Frair, J.L.; Saher, D.J.; Stevens, C.E.; Jerde, C.L.

2006-01-01

1. Resource selection estimated by logistic regression is used increasingly in studies to identify critical resources for animal populations and to predict species occurrence.2. Most frequently, individual animals are monitored and pooled to estimate population-level effects without regard to group or individual-level variation. Pooling assumes that both observations and their errors are independent, and resource selection is constant given individual variation in resource availability.3. Although researchers have identified ways to minimize autocorrelation, variation between individuals caused by differences in selection or available resources, including functional responses in resource selection, have not been well addressed.4. Here we review random-effects models and their application to resource selection modelling to overcome these common limitations. We present a simple case study of an analysis of resource selection by grizzly bears in the foothills of the Canadian Rocky Mountains with and without random effects.5. Both categorical and continuous variables in the grizzly bear model differed in interpretation, both in statistical significance and coefficient sign, depending on how a random effect was included. We used a simulation approach to clarify the application of random effects under three common situations for telemetry studies: (a) discrepancies in sample sizes among individuals; (b) differences among individuals in selection where availability is constant; and (c) differences in availability with and without a functional response in resource selection.6. We found that random intercepts accounted for unbalanced sample designs, and models with random intercepts and coefficients improved model fit given the variation in selection among individuals and functional responses in selection. Our empirical example and simulations demonstrate how including random effects in resource selection models can aid interpretation and address difficult assumptions limiting their generality. This approach will allow researchers to appropriately estimate marginal (population) and conditional (individual) responses, and account for complex grouping, unbalanced sample designs and autocorrelation.

Application of random effects to the study of resource selection by animals.

PubMed

Gillies, Cameron S; Hebblewhite, Mark; Nielsen, Scott E; Krawchuk, Meg A; Aldridge, Cameron L; Frair, Jacqueline L; Saher, D Joanne; Stevens, Cameron E; Jerde, Christopher L

2006-07-01

1. Resource selection estimated by logistic regression is used increasingly in studies to identify critical resources for animal populations and to predict species occurrence. 2. Most frequently, individual animals are monitored and pooled to estimate population-level effects without regard to group or individual-level variation. Pooling assumes that both observations and their errors are independent, and resource selection is constant given individual variation in resource availability. 3. Although researchers have identified ways to minimize autocorrelation, variation between individuals caused by differences in selection or available resources, including functional responses in resource selection, have not been well addressed. 4. Here we review random-effects models and their application to resource selection modelling to overcome these common limitations. We present a simple case study of an analysis of resource selection by grizzly bears in the foothills of the Canadian Rocky Mountains with and without random effects. 5. Both categorical and continuous variables in the grizzly bear model differed in interpretation, both in statistical significance and coefficient sign, depending on how a random effect was included. We used a simulation approach to clarify the application of random effects under three common situations for telemetry studies: (a) discrepancies in sample sizes among individuals; (b) differences among individuals in selection where availability is constant; and (c) differences in availability with and without a functional response in resource selection. 6. We found that random intercepts accounted for unbalanced sample designs, and models with random intercepts and coefficients improved model fit given the variation in selection among individuals and functional responses in selection. Our empirical example and simulations demonstrate how including random effects in resource selection models can aid interpretation and address difficult assumptions limiting their generality. This approach will allow researchers to appropriately estimate marginal (population) and conditional (individual) responses, and account for complex grouping, unbalanced sample designs and autocorrelation.

Variance Component Selection With Applications to Microbiome Taxonomic Data.

PubMed

Zhai, Jing; Kim, Juhyun; Knox, Kenneth S; Twigg, Homer L; Zhou, Hua; Zhou, Jin J

2018-01-01

High-throughput sequencing technology has enabled population-based studies of the role of the human microbiome in disease etiology and exposure response. Microbiome data are summarized as counts or composition of the bacterial taxa at different taxonomic levels. An important problem is to identify the bacterial taxa that are associated with a response. One method is to test the association of specific taxon with phenotypes in a linear mixed effect model, which incorporates phylogenetic information among bacterial communities. Another type of approaches consider all taxa in a joint model and achieves selection via penalization method, which ignores phylogenetic information. In this paper, we consider regression analysis by treating bacterial taxa at different level as multiple random effects. For each taxon, a kernel matrix is calculated based on distance measures in the phylogenetic tree and acts as one variance component in the joint model. Then taxonomic selection is achieved by the lasso (least absolute shrinkage and selection operator) penalty on variance components. Our method integrates biological information into the variable selection problem and greatly improves selection accuracies. Simulation studies demonstrate the superiority of our methods versus existing methods, for example, group-lasso. Finally, we apply our method to a longitudinal microbiome study of Human Immunodeficiency Virus (HIV) infected patients. We implement our method using the high performance computing language Julia. Software and detailed documentation are freely available at https://github.com/JingZhai63/VCselection.

Molecular Population Genetics of Human CYP3A Locus: Signatures of Positive Selection and Implications for Evolutionary Environmental Medicine

PubMed Central

Chen, Xiaoping; Wang, Haijian; Zhou, Gangqiao; Zhang, Xiumei; Dong, Xiaojia; Zhi, Lianteng; Jin, Li; He, Fuchu

2009-01-01

Background The human CYP3A gene cluster codes for cytochrome P450 (CYP) subfamily enzymes that catalyze the metabolism of various exogenous and endogenous chemicals and is an obvious candidate for evolutionary and environmental genomic study. Functional variants in the CYP3A locus may have undergone a selective sweep in response to various environmental conditions. Objective The goal of this study was to profile the allelic structure across the human CYP3A locus and investigate natural selection on that locus. Methods From the CYP3A locus spanning 231 kb, we resequenced 54 genomic DNA fragments (a total of 43,675 bases) spanning four genes (CYP3A4, CYP3A5, CYP3A7, and CYP3A43) and two pseudogenes (CYP3AP1 and CYP3AP2), and randomly selected intergenic regions at the CYP3A locus in Africans (24 individuals), Caucasians (24 individuals), and Chinese (29 individuals). We comprehensively investigated the nucleotide diversity and haplotype structure and examined the possible role of natural selection in shaping the sequence variation throughout the gene cluster. Results Neutrality tests with Tajima’s D, Fu and Li’s D* and F*, and Fay and Wu’s H indicated possible roles of positive selection on the entire CYP3A locus in non-Africans. Sliding-window analyses of nucleotide diversity and frequency spectrum, as well as haplotype diversity and phylogenetically inferred haplotype structure, revealed that CYP3A4 and CYP3A7 had recently undergone or were undergoing a selective sweep in all three populations, whereas CYP3A43 and CYP3A5 were undergoing a selective sweep in non-Africans and Caucasians, respectively. Conclusion The refined allelic architecture and selection spectrum for the human CYP3A locus highlight that evolutionary dynamics of molecular adaptation may underlie the phenotypic variation of the xenobiotic disposition system and varied predisposition to complex disorders in which xenobiotics play a role. PMID:20019904

CrowdPhase: crowdsourcing the phase problem

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

Jorda, Julien; Sawaya, Michael R.; Yeates, Todd O., E-mail: yeates@mbi.ucla.edu

The idea of attacking the phase problem by crowdsourcing is introduced. Using an interactive, multi-player, web-based system, participants work simultaneously to select phase sets that correspond to better electron-density maps in order to solve low-resolution phasing problems. The human mind innately excels at some complex tasks that are difficult to solve using computers alone. For complex problems amenable to parallelization, strategies can be developed to exploit human intelligence in a collective form: such approaches are sometimes referred to as ‘crowdsourcing’. Here, a first attempt at a crowdsourced approach for low-resolution ab initio phasing in macromolecular crystallography is proposed. A collaborativemore » online game named CrowdPhase was designed, which relies on a human-powered genetic algorithm, where players control the selection mechanism during the evolutionary process. The algorithm starts from a population of ‘individuals’, each with a random genetic makeup, in this case a map prepared from a random set of phases, and tries to cause the population to evolve towards individuals with better phases based on Darwinian survival of the fittest. Players apply their pattern-recognition capabilities to evaluate the electron-density maps generated from these sets of phases and to select the fittest individuals. A user-friendly interface, a training stage and a competitive scoring system foster a network of well trained players who can guide the genetic algorithm towards better solutions from generation to generation via gameplay. CrowdPhase was applied to two synthetic low-resolution phasing puzzles and it was shown that players could successfully obtain phase sets in the 30° phase error range and corresponding molecular envelopes showing agreement with the low-resolution models. The successful preliminary studies suggest that with further development the crowdsourcing approach could fill a gap in current crystallographic methods by making it possible to extract meaningful information in cases where limited resolution might otherwise prevent initial phasing.« less

Feature-selective attention enhances color signals in early visual areas of the human brain.

PubMed

Müller, M M; Andersen, S; Trujillo, N J; Valdés-Sosa, P; Malinowski, P; Hillyard, S A

2006-09-19

We used an electrophysiological measure of selective stimulus processing (the steady-state visual evoked potential, SSVEP) to investigate feature-specific attention to color cues. Subjects viewed a display consisting of spatially intermingled red and blue dots that continually shifted their positions at random. The red and blue dots flickered at different frequencies and thereby elicited distinguishable SSVEP signals in the visual cortex. Paying attention selectively to either the red or blue dot population produced an enhanced amplitude of its frequency-tagged SSVEP, which was localized by source modeling to early levels of the visual cortex. A control experiment showed that this selection was based on color rather than flicker frequency cues. This signal amplification of attended color items provides an empirical basis for the rapid identification of feature conjunctions during visual search, as proposed by "guided search" models.

Synthetic single domain antibodies for the conformational trapping of membrane proteins

PubMed Central

Arnold, Fabian M; Stohler, Peter; Bocquet, Nicolas; Hug, Melanie N; Huber, Sylwia; Siegrist, Martin; Hetemann, Lisa; Gera, Jennifer; Gmür, Samira; Spies, Peter; Gygax, Daniel

2018-01-01

Mechanistic and structural studies of membrane proteins require their stabilization in specific conformations. Single domain antibodies are potent reagents for this purpose, but their generation relies on immunizations, which impedes selections in the presence of ligands typically needed to populate defined conformational states. To overcome this key limitation, we developed an in vitro selection platform based on synthetic single domain antibodies named sybodies. To target the limited hydrophilic surfaces of membrane proteins, we designed three sybody libraries that exhibit different shapes and moderate hydrophobicity of the randomized surface. A robust binder selection cascade combining ribosome and phage display enabled the generation of conformation-selective, high affinity sybodies against an ABC transporter and two previously intractable human SLC transporters, GlyT1 and ENT1. The platform does not require access to animal facilities and builds exclusively on commercially available reagents, thus enabling every lab to rapidly generate binders against challenging membrane proteins. PMID:29792401

High efficiency family shuffling based on multi-step PCR and in vivo DNA recombination in yeast: statistical and functional analysis of a combinatorial library between human cytochrome P450 1A1 and 1A2.

PubMed

Abécassis, V; Pompon, D; Truan, G

2000-10-15

The design of a family shuffling strategy (CLERY: Combinatorial Libraries Enhanced by Recombination in Yeast) associating PCR-based and in vivo recombination and expression in yeast is described. This strategy was tested using human cytochrome P450 CYP1A1 and CYP1A2 as templates, which share 74% nucleotide sequence identity. Construction of highly shuffled libraries of mosaic structures and reduction of parental gene contamination were two major goals. Library characterization involved multiprobe hybridization on DNA macro-arrays. The statistical analysis of randomly selected clones revealed a high proportion of chimeric genes (86%) and a homogeneous representation of the parental contribution among the sequences (55.8 +/- 2.5% for parental sequence 1A2). A microtiter plate screening system was designed to achieve colorimetric detection of polycyclic hydrocarbon hydroxylation by transformed yeast cells. Full sequences of five randomly picked and five functionally selected clones were analyzed. Results confirmed the shuffling efficiency and allowed calculation of the average length of sequence exchange and mutation rates. The efficient and statistically representative generation of mosaic structures by this type of family shuffling in a yeast expression system constitutes a novel and promising tool for structure-function studies and tuning enzymatic activities of multicomponent eucaryote complexes involving non-soluble enzymes.

A pragmatic trial to improve adherence with scheduled appointments in an inner-city pain clinic by human phone calls in the patient's preferred language.

PubMed

Andreae, Michael H; Nair, Singh; Gabry, Jonah S; Goodrich, Ben; Hall, Charles; Shaparin, Naum

2017-11-01

We investigated if human reminder phone calls in the patient's preferred language increase adherence with scheduled appointments in an inner-city chronic pain clinic. We hypothesized that language and cultural incongruence is the underlying mechanism to explain poor attendance at clinic appointments in underserved Hispanic populations. Pragmatic randomized controlled clinical trial SETTING: Innercity academic chronic pain clinic with a diverse, predominantly African-American and Hispanic population PATIENTS: All (n=963) adult patients with a scheduled first appointment between October 2014 and October 2015 at the Montefiore Pain Center in the Bronx, New York were enrolled. Patients were randomized to receive a human reminder call in their preferred language before their appointment, or no contact. We recorded patients' demographic characteristics and as primary outcome attendance as scheduled, failure to attend and/or cancellation calls. We fit Bayesian and classical multinomial logistic regression models to test if the intervention improved adherence with scheduled appointments. Among the 953 predominantly African American and Hispanic/Latino patients, 475 patients were randomly selected to receive a language-congruent, human reminder call, while 478 were assigned to receive no prior contact, (after we excluded 10 patients, scheduled for repeat appointments). In the experimental group, 275 patients adhered to their scheduled appointment, while 84 cancelled and 116 failed to attend. In the control group, 249 patients adhered to their scheduled appointment, 31 cancelled and 198 failed to attend. Human phone reminders in the preferred language increased adherence (RR 1.89, CI95% [1.42, 1.42], (p<0.01). The intervention seemed particularly effective in Hispanic patients, supporting our hypothesis of cultural congruence as possible underlying mechanism. Human reminder phone calls prior in the patient's preferred language increased adherence with scheduled appointments. The intervention facilitated access to much needed care in an ethnically diverse, resource poor population, presumably by overcoming language barriers. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of multiple spreaders in community networks

NASA Astrophysics Data System (ADS)

Hu, Zhao-Long; Ren, Zhuo-Ming; Yang, Guang-Yong; Liu, Jian-Guo

2014-12-01

Human contact networks exhibit the community structure. Understanding how such community structure affects the epidemic spreading could provide insights for preventing the spreading of epidemics between communities. In this paper, we explore the spreading of multiple spreaders in community networks. A network based on the clustering preferential mechanism is evolved, whose communities are detected by the Girvan-Newman (GN) algorithm. We investigate the spreading effectiveness by selecting the nodes as spreaders in the following ways: nodes with the largest degree in each community (community hubs), the same number of nodes with the largest degree from the global network (global large-degree) and randomly selected one node within each community (community random). The experimental results on the SIR model show that the spreading effectiveness based on the global large-degree and community hubs methods is the same in the early stage of the infection and the method of community random is the worst. However, when the infection rate exceeds the critical value, the global large-degree method embodies the worst spreading effectiveness. Furthermore, the discrepancy of effectiveness for the three methods will decrease as the infection rate increases. Therefore, we should immunize the hubs in each community rather than those hubs in the global network to prevent the outbreak of epidemics.

Oral Administration of Lactobacillus plantarum 299v Reduces Cortisol Levels in Human Saliva during Examination Induced Stress: A Randomized, Double-Blind Controlled Trial.

PubMed

Andersson, Hannah; Tullberg, Cecilia; Ahrné, Siv; Hamberg, Kristina; Lazou Ahrén, Irini; Molin, Göran; Sonesson, Mikael; Håkansson, Åsa

2016-01-01

Objective . To clarify the effect of Lactobacillus plantarum 299v on the salivary cortisol and salivary IgA levels in young adults under examination stress. Design . Forty-one students with an upcoming academic exam were included in a randomized double-blind, placebo-controlled study. The probiotic bacteria or the placebo product was administered in capsules once a day during 14 days. Saliva was collected and a perceived stress test was filled out at each sampling occasion. Saliva was collected for cortisol analysis by Electrochemiluminescence Immunoassay (ECLI) and salivary IgA was analysed by Enzyme-Linked Immunosorbent Assay (ELISA). Abundance of lactobacilli was evaluated by cultivation of saliva on selective medium and identification of L. plantarum 299v was done on randomly selected colonies by a random amplification of polymorphic DNA (RAPD) typing. Results . A significant difference in cortisol levels was found between the treatment group and the placebo group ( P < 0.05), together with a significant increase in levels of lactobacilli in the treatment group compared with the placebo group ( P < 0.001). No significant changes were found for salivary IgA. Conclusion . A probiotic bacterium with ability to reduce symptoms of irritable bowel syndrome (IBS) prohibited increased levels of the stress marker cortisol during the examination period. The registration number of the study is NCT02974894, and the study is registered at ClinicalTrials.gov.

Oral Administration of Lactobacillus plantarum 299v Reduces Cortisol Levels in Human Saliva during Examination Induced Stress: A Randomized, Double-Blind Controlled Trial

PubMed Central

Andersson, Hannah; Tullberg, Cecilia; Ahrné, Siv; Hamberg, Kristina; Lazou Ahrén, Irini; Molin, Göran; Sonesson, Mikael

2016-01-01

Objective. To clarify the effect of Lactobacillus plantarum 299v on the salivary cortisol and salivary IgA levels in young adults under examination stress. Design. Forty-one students with an upcoming academic exam were included in a randomized double-blind, placebo-controlled study. The probiotic bacteria or the placebo product was administered in capsules once a day during 14 days. Saliva was collected and a perceived stress test was filled out at each sampling occasion. Saliva was collected for cortisol analysis by Electrochemiluminescence Immunoassay (ECLI) and salivary IgA was analysed by Enzyme-Linked Immunosorbent Assay (ELISA). Abundance of lactobacilli was evaluated by cultivation of saliva on selective medium and identification of L. plantarum 299v was done on randomly selected colonies by a random amplification of polymorphic DNA (RAPD) typing. Results. A significant difference in cortisol levels was found between the treatment group and the placebo group (P < 0.05), together with a significant increase in levels of lactobacilli in the treatment group compared with the placebo group (P < 0.001). No significant changes were found for salivary IgA. Conclusion. A probiotic bacterium with ability to reduce symptoms of irritable bowel syndrome (IBS) prohibited increased levels of the stress marker cortisol during the examination period. The registration number of the study is NCT02974894, and the study is registered at ClinicalTrials.gov. PMID:28101105

Marked antigiardial activity of Yucca baccata extracts: a potential natural alternative for treating protozoan infections.

PubMed

Quihui-Cota, Luis; León-Trujillo, Rocio; Astiazarán-García, Humberto; Esparza-Romero, Julián; del Refugio Robles, María; Robles-Zepeda, Ramón E; Canett, Rafael; Sánchez-Escalante, Jesús

2014-01-01

Human giardiosis is a public health problem in Mexico, where the national prevalence was estimated to be up to 68%. Misuse of antiprotozoal drugs may result in low effectiveness and undesirable side effects. Research on natural products is a good strategy for discovering more effective antiparasitic compounds. This study evaluated the antigiardial activity of extracts of Yucca baccata, which is native to northwestern Mexico. Forty-two gerbils (females) were weighed and orally inoculated with 5 × 10(6) Giardia trophozoites. Two gerbils were selected at random to confirm infection. Forty living gerbils were randomly allocated into 5 treatment groups (8 per group). Gerbils were randomly assigned to be treated with 24.4 mg/mL, 12.2 mg/mL, and 6.1 mg/mL of extracts, metronidazole (2 mg/mL) or PBS, which were intragastrically administered once per day for 3 days. Nine gerbils died during the study course. On day 10 postinfection, gerbils were euthanized and trophozoites were quantified. Yucca extracts reduced, albeit not significantly, the trophozoite counts in the duodenum segment. Only the high-extract concentration significantly reduced the trophozoite counts in the proximal segment and it was similar to that of metronidazole. Extracts of Y. baccata may represent an effective and natural therapeutic alternative for human giardiosis.

Pseudo CT estimation from MRI using patch-based random forest

NASA Astrophysics Data System (ADS)

Yang, Xiaofeng; Lei, Yang; Shu, Hui-Kuo; Rossi, Peter; Mao, Hui; Shim, Hyunsuk; Curran, Walter J.; Liu, Tian

2017-02-01

Recently, MR simulators gain popularity because of unnecessary radiation exposure of CT simulators being used in radiation therapy planning. We propose a method for pseudo CT estimation from MR images based on a patch-based random forest. Patient-specific anatomical features are extracted from the aligned training images and adopted as signatures for each voxel. The most robust and informative features are identified using feature selection to train the random forest. The well-trained random forest is used to predict the pseudo CT of a new patient. This prediction technique was tested with human brain images and the prediction accuracy was assessed using the original CT images. Peak signal-to-noise ratio (PSNR) and feature similarity (FSIM) indexes were used to quantify the differences between the pseudo and original CT images. The experimental results showed the proposed method could accurately generate pseudo CT images from MR images. In summary, we have developed a new pseudo CT prediction method based on patch-based random forest, demonstrated its clinical feasibility, and validated its prediction accuracy. This pseudo CT prediction technique could be a useful tool for MRI-based radiation treatment planning and attenuation correction in a PET/MRI scanner.

Factors Associated With Time to Site Activation, Randomization, and Enrollment Performance in a Stroke Prevention Trial.

PubMed

Demaerschalk, Bart M; Brown, Robert D; Roubin, Gary S; Howard, Virginia J; Cesko, Eldina; Barrett, Kevin M; Longbottom, Mary E; Voeks, Jenifer H; Chaturvedi, Seemant; Brott, Thomas G; Lal, Brajesh K; Meschia, James F; Howard, George

2017-09-01

Multicenter clinical trials attempt to select sites that can move rapidly to randomization and enroll sufficient numbers of patients. However, there are few assessments of the success of site selection. In the CREST-2 (Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trials), we assess factors associated with the time between site selection and authorization to randomize, the time between authorization to randomize and the first randomization, and the average number of randomizations per site per month. Potential factors included characteristics of the site, specialty of the principal investigator, and site type. For 147 sites, the median time between site selection to authorization to randomize was 9.9 months (interquartile range, 7.7, 12.4), and factors associated with early site activation were not identified. The median time between authorization to randomize and a randomization was 4.6 months (interquartile range, 2.6, 10.5). Sites with authorization to randomize in only the carotid endarterectomy study were slower to randomize, and other factors examined were not significantly associated with time-to-randomization. The recruitment rate was 0.26 (95% confidence interval, 0.23-0.28) patients per site per month. By univariate analysis, factors associated with faster recruitment were authorization to randomize in both trials, principal investigator specialties of interventional radiology and cardiology, pre-trial reported performance >50 carotid angioplasty and stenting procedures per year, status in the top half of recruitment in the CREST trial, and classification as a private health facility. Participation in StrokeNet was associated with slower recruitment as compared with the non-StrokeNet sites. Overall, selection of sites with high enrollment rates will likely require customization to align the sites selected to the factor under study in the trial. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02089217. © 2017 American Heart Association, Inc.

Random integration of SV40 in SV40-transformed, immortalized human fibroblasts.

PubMed

Hara, H; Kaji, H

1987-02-01

We have studied the relationship between immortalization of SV40-transformed human embryonic fibroblasts and their SV40 integration sites. From several independently transformed cell pools, we have isolated clones which do not harbor unintegrated SV40 DNA. We have analysed whole-cell DNA from these clones, using the Southern blot method. Our results suggest that no specific integration sites in the cellular genome exist which are a prerequisite for the immortalization process. Although some integration sites were found to be predominant in pre-crisis clones, they could not be detected in the post-crisis clones. This suggests that none of these predominating sites is selected for during the crisis period.

On random field Completely Automated Public Turing Test to Tell Computers and Humans Apart generation.

PubMed

Kouritzin, Michael A; Newton, Fraser; Wu, Biao

2013-04-01

Herein, we propose generating CAPTCHAs through random field simulation and give a novel, effective and efficient algorithm to do so. Indeed, we demonstrate that sufficient information about word tests for easy human recognition is contained in the site marginal probabilities and the site-to-nearby-site covariances and that these quantities can be embedded directly into certain conditional probabilities, designed for effective simulation. The CAPTCHAs are then partial random realizations of the random CAPTCHA word. We start with an initial random field (e.g., randomly scattered letter pieces) and use Gibbs resampling to re-simulate portions of the field repeatedly using these conditional probabilities until the word becomes human-readable. The residual randomness from the initial random field together with the random implementation of the CAPTCHA word provide significant resistance to attack. This results in a CAPTCHA, which is unrecognizable to modern optical character recognition but is recognized about 95% of the time in a human readability study.

An HPLC method for the determination of selected amino acids in human embryo culture medium.

PubMed

Drábková, Petra; Andrlová, Lenka; Kanďár, Roman

2017-02-01

A method for the determination of selected amino acids in culture medium using HPLC with fluorescence detection is described. Twenty hours after intra-cytoplasmic sperm injection, one randomly selected zygote was transferred to the culture medium. After incubation (72 h after fertilization), the culture medium in which the embryo was incubated and blank medium was immediately stored at -80°C. Filtered medium samples were derivatized with ortho-phthalaldehyde (naphthalene-2,3-dicarboxaldehyde), forming highly fluorescent amino acids derivatives. Reverse-phase columns (LichroCART, Purospher STAR RP 18e or Ascentis Express C 18 ) were used for the separation. The derivatives were analyzed by gradient elution with a mobile phase containing ethanol and sodium dihydrogen phosphate. The analytical performance of this method is satisfactory for all amino acids; the intra-assay coefficients of variation were <10% and quantitative recoveries were between 95.5 and 104.4%. Changes in the levels of selected amino acids before and after human embryo cultivation were observed. After embryo incubation, the levels of all amino acids in the medium were increased, apart from aspartate and asparagine. After the cultivation of some embryos, amino acids which were not part of the medium were detected. Low amino acids turnover was observed in some embryos. Copyright © 2016 John Wiley & Sons, Ltd.

Are mutagenic non D-loop direct repeat motifs in mitochondrial DNA under a negative selection pressure?

PubMed Central

Lakshmanan, Lakshmi Narayanan; Gruber, Jan; Halliwell, Barry; Gunawan, Rudiyanto

2015-01-01

Non D-loop direct repeats (DRs) in mitochondrial DNA (mtDNA) have been commonly implicated in the mutagenesis of mtDNA deletions associated with neuromuscular disease and ageing. Further, these DRs have been hypothesized to put a constraint on the lifespan of mammals and are under a negative selection pressure. Using a compendium of 294 mammalian mtDNA, we re-examined the relationship between species lifespan and the mutagenicity of such DRs. Contradicting the prevailing hypotheses, we found no significant evidence that long-lived mammals possess fewer mutagenic DRs than short-lived mammals. By comparing DR counts in human mtDNA with those in selectively randomized sequences, we also showed that the number of DRs in human mtDNA is primarily determined by global mtDNA properties, such as the bias in synonymous codon usage (SCU) and nucleotide composition. We found that SCU bias in mtDNA positively correlates with DR counts, where repeated usage of a subset of codons leads to more frequent DR occurrences. While bias in SCU and nucleotide composition has been attributed to nucleotide mutational bias, mammalian mtDNA still exhibit higher SCU bias and DR counts than expected from such mutational bias, suggesting a lack of negative selection against non D-loop DRs. PMID:25855815

Prediction of human disease-associated phosphorylation sites with combined feature selection approach and support vector machine.

PubMed

Xu, Xiaoyi; Li, Ao; Wang, Minghui

2015-08-01

Phosphorylation is a crucial post-translational modification, which regulates almost all cellular processes in life. It has long been recognised that protein phosphorylation has close relationship with diseases, and therefore many researches are undertaken to predict phosphorylation sites for disease treatment and drug design. However, despite the success achieved by these approaches, no method focuses on disease-associated phosphorylation sites prediction. Herein, for the first time the authors propose a novel approach that is specially designed to identify associations between phosphorylation sites and human diseases. To take full advantage of local sequence information, a combined feature selection method-based support vector machine (CFS-SVM) that incorporates minimum-redundancy-maximum-relevance filtering process and forward feature selection process is developed. Performance evaluation shows that CFS-SVM is significantly better than the widely used classifiers including Bayesian decision theory, k nearest neighbour and random forest. With the extremely high specificity of 99%, CFS-SVM can still achieve a high sensitivity. Besides, tests on extra data confirm the effectiveness and general applicability of CFS-SVM approach on a variety of diseases. Finally, the analysis of selected features and corresponding kinases also help the understanding of the potential mechanism of disease-phosphorylation relationships and guide further experimental validations.

Partial characterization of normal and Haemophilus influenzae-infected mucosal complementary DNA libraries in chinchilla middle ear mucosa.

PubMed

Kerschner, Joseph E; Erdos, Geza; Hu, Fen Ze; Burrows, Amy; Cioffi, Joseph; Khampang, Pawjai; Dahlgren, Margaret; Hayes, Jay; Keefe, Randy; Janto, Benjamin; Post, J Christopher; Ehrlich, Garth D

2010-04-01

We sought to construct and partially characterize complementary DNA (cDNA) libraries prepared from the middle ear mucosa (MEM) of chinchillas to better understand pathogenic aspects of infection and inflammation, particularly with respect to leukotriene biogenesis and response. Chinchilla MEM was harvested from controls and after middle ear inoculation with nontypeable Haemophilus influenzae. RNA was extracted to generate cDNA libraries. Randomly selected clones were subjected to sequence analysis to characterize the libraries and to provide DNA sequence for phylogenetic analyses. Reverse transcription-polymerase chain reaction of the RNA pools was used to generate cDNA sequences corresponding to genes associated with leukotriene biosynthesis and metabolism. Sequence analysis of 921 randomly selected clones from the uninfected MEM cDNA library produced approximately 250,000 nucleotides of almost entirely novel sequence data. Searches of the GenBank database with the Basic Local Alignment Search Tool provided for identification of 515 unique genes expressed in the MEM and not previously described in chinchillas. In almost all cases, the chinchilla cDNA sequences displayed much greater homology to human or other primate genes than with rodent species. Genes associated with leukotriene metabolism were present in both normal and infected MEM. Based on both phylogenetic comparisons and gene expression similarities with humans, chinchilla MEM appears to be an excellent model for the study of middle ear inflammation and infection. The higher degree of sequence similarity between chinchillas and humans compared to chinchillas and rodents was unexpected. The cDNA libraries from normal and infected chinchilla MEM will serve as useful molecular tools in the study of otitis media and should yield important information with respect to middle ear pathogenesis.

Partial Characterization of Normal and Haemophilus influenzae–Infected Mucosal Complementary DNA Libraries in Chinchilla Middle Ear Mucosa

PubMed Central

Kerschner, Joseph E.; Erdos, Geza; Hu, Fen Ze; Burrows, Amy; Cioffi, Joseph; Khampang, Pawjai; Dahlgren, Margaret; Hayes, Jay; Keefe, Randy; Janto, Benjamin; Post, J. Christopher; Ehrlich, Garth D.

2010-01-01

Objectives We sought to construct and partially characterize complementary DNA (cDNA) libraries prepared from the middle ear mucosa (MEM) of chinchillas to better understand pathogenic aspects of infection and inflammation, particularly with respect to leukotriene biogenesis and response. Methods Chinchilla MEM was harvested from controls and after middle ear inoculation with nontypeable Haemophilus influenzae. RNA was extracted to generate cDNA libraries. Randomly selected clones were subjected to sequence analysis to characterize the libraries and to provide DNA sequence for phylogenetic analyses. Reverse transcription–polymerase chain reaction of the RNA pools was used to generate cDNA sequences corresponding to genes associated with leukotriene biosynthesis and metabolism. Results Sequence analysis of 921 randomly selected clones from the uninfected MEM cDNA library produced approximately 250,000 nucleotides of almost entirely novel sequence data. Searches of the GenBank database with the Basic Local Alignment Search Tool provided for identification of 515 unique genes expressed in the MEM and not previously described in chinchillas. In almost all cases, the chinchilla cDNA sequences displayed much greater homology to human or other primate genes than with rodent species. Genes associated with leukotriene metabolism were present in both normal and infected MEM. Conclusions Based on both phylogenetic comparisons and gene expression similarities with humans, chinchilla MEM appears to be an excellent model for the study of middle ear inflammation and infection. The higher degree of sequence similarity between chinchillas and humans compared to chinchillas and rodents was unexpected. The cDNA libraries from normal and infected chinchilla MEM will serve as useful molecular tools in the study of otitis media and should yield important information with respect to middle ear pathogenesis. PMID:20433028

CrowdPhase: crowdsourcing the phase problem

PubMed Central

Jorda, Julien; Sawaya, Michael R.; Yeates, Todd O.

2014-01-01

The human mind innately excels at some complex tasks that are difficult to solve using computers alone. For complex problems amenable to parallelization, strategies can be developed to exploit human intelligence in a collective form: such approaches are sometimes referred to as ‘crowdsourcing’. Here, a first attempt at a crowdsourced approach for low-resolution ab initio phasing in macromolecular crystallography is proposed. A collaborative online game named CrowdPhase was designed, which relies on a human-powered genetic algorithm, where players control the selection mechanism during the evolutionary process. The algorithm starts from a population of ‘individuals’, each with a random genetic makeup, in this case a map prepared from a random set of phases, and tries to cause the population to evolve towards individuals with better phases based on Darwinian survival of the fittest. Players apply their pattern-recognition capabilities to evaluate the electron-density maps generated from these sets of phases and to select the fittest individuals. A user-friendly interface, a training stage and a competitive scoring system foster a network of well trained players who can guide the genetic algorithm towards better solutions from generation to generation via gameplay. CrowdPhase was applied to two synthetic low-resolution phasing puzzles and it was shown that players could successfully obtain phase sets in the 30° phase error range and corresponding molecular envelopes showing agreement with the low-resolution models. The successful preliminary studies suggest that with further development the crowdsourcing approach could fill a gap in current crystallographic methods by making it possible to extract meaningful information in cases where limited resolution might otherwise prevent initial phasing. PMID:24914965

Selective intra-dinucleotide interactions and periodicities of bases separated by K sites: a new vision and tool for phylogeny analyses.

PubMed

Valenzuela, Carlos Y

2017-02-13

Direct tests of the random or non-random distribution of nucleotides on genomes have been devised to test the hypothesis of neutral, nearly-neutral or selective evolution. These tests are based on the direct base distribution and are independent of the functional (coding or non-coding) or structural (repeated or unique sequences) properties of the DNA. The first approach described the longitudinal distribution of bases in tandem repeats under the Bose-Einstein statistics. A huge deviation from randomness was found. A second approach was the study of the base distribution within dinucleotides whose bases were separated by 0, 1, 2… K nucleotides. Again an enormous difference from the random distribution was found with significances out of tables and programs. These test values were periodical and included the 16 dinucleotides. For example a high "positive" (more observed than expected dinucleotides) value, found in dinucleotides whose bases were separated by (3K + 2) sites, was preceded by two smaller "negative" (less observed than expected dinucleotides) values, whose bases were separated by (3K) or (3K + 1) sites. We examined mtDNAs, prokaryote genomes and some eukaryote chromosomes and found that the significant non-random interactions and periodicities were present up to 1000 or more sites of base separation and in human chromosome 21 until separations of more than 10 millions sites. Each nucleotide has its own significant value of its distance to neutrality; this yields 16 hierarchical significances. A three dimensional table with the number of sites of separation between the bases and the 16 significances (the third dimension is the dinucleotide, individual or taxon involved) gives directly an evolutionary state of the analyzed genome that can be used to obtain phylogenies. An example is provided.

Chemokine CCR3 ligands-binding peptides derived from a random phage-epitope library.

PubMed

Houimel, Mehdi; Mazzucchelli, Luca

2013-01-01

Eosinophils are major effectors cells implicated in a number of chronic inflammatory diseases in humans, particularly bronchial asthma and allergic rhinitis. The human chemokine receptor C-C receptor 3 (hCCR3) provides a mechanism for the recruitment of eosinophils into tissue and thus has recently become an attractive biological target for therapeutic intervention. In order to develop peptides antagonists of hCCR3-hCCL11 (human eotaxin) interactions, a random bacteriophage hexapeptide library was used to map structural features of hCCR3 by determining the epitopes of neutralizing anti-hCCR3 mAb 7B11. This mAb t is selective for hCCR3 and exhibit potent antagonist activity in receptor binding and functional assays. After three rounds of biopanning, four mAb7B11-binding peptides were identified from a 6-mer linear peptide library. The phage bearing the peptides showed specific binding to immobilized mAb 7B11 with over 94% of phages bound being competitively inhibited by free synthetic peptides. In FACScan analysis all selected phage peptides were able to strongly inhibit the binding of mAb 7B11 to hCCR3-transfected preB-300-19 murine cells. Furthermore, synthetic peptides of the corresponding phage epitopes were effective in blocking the antibody-hCCR3 interactions and to inhibit the binding of hCCL11 to hCCR3 transfectants. Chemically synthesized peptides CKGERF, FERKGK, SSMKVK and RHVSSQ, effectively competed for (125)I-hCCL11 binding to hCCR3 with IC(50) ranging from 3.5 to 9.7μM. Calcium release and chemotaxis of hCCR3 transfectants or human eosinophils were inhibited by all peptides in a dose-dependent manner. Furthermore, they showed inhibitory effects on chemotaxis of human eosinophils induced by hCCL11, hCCL5, hCCL7, hCCL8, and hCCL24. Specificities of all selected peptides were assessed with hCXCR1, hCXCR2, hCXCR3, and hCCR5 receptors. Peptides CKGERF and FERKGK showed inhibitory effects on eosinophil chemotaxis in a murine model of mCCL11-induced peritoneal eosinophilia. The development of peptides inhibiting the interactions between hCCR3 and its chemokine ligands will facilitate the development of small peptides antagonists with the hope of ameliorating chronic inflammatory diseases in humans. Copyright © 2012 Elsevier B.V. All rights reserved.

47 CFR 1.1604 - Post-selection hearings.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 1 2010-10-01 2010-10-01 false Post-selection hearings. 1.1604 Section 1.1604 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL PRACTICE AND PROCEDURE Random Selection Procedures for Mass Media Services General Procedures § 1.1604 Post-selection hearings. (a) Following the random...

47 CFR 1.1604 - Post-selection hearings.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 1 2011-10-01 2011-10-01 false Post-selection hearings. 1.1604 Section 1.1604 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL PRACTICE AND PROCEDURE Random Selection Procedures for Mass Media Services General Procedures § 1.1604 Post-selection hearings. (a) Following the random...

Ion channel gene expression predicts survival in glioma patients

PubMed Central

Wang, Rong; Gurguis, Christopher I.; Gu, Wanjun; Ko, Eun A; Lim, Inja; Bang, Hyoweon; Zhou, Tong; Ko, Jae-Hong

2015-01-01

Ion channels are important regulators in cell proliferation, migration, and apoptosis. The malfunction and/or aberrant expression of ion channels may disrupt these important biological processes and influence cancer progression. In this study, we investigate the expression pattern of ion channel genes in glioma. We designate 18 ion channel genes that are differentially expressed in high-grade glioma as a prognostic molecular signature. This ion channel gene expression based signature predicts glioma outcome in three independent validation cohorts. Interestingly, 16 of these 18 genes were down-regulated in high-grade glioma. This signature is independent of traditional clinical, molecular, and histological factors. Resampling tests indicate that the prognostic power of the signature outperforms random gene sets selected from human genome in all the validation cohorts. More importantly, this signature performs better than the random gene signatures selected from glioma-associated genes in two out of three validation datasets. This study implicates ion channels in brain cancer, thus expanding on knowledge of their roles in other cancers. Individualized profiling of ion channel gene expression serves as a superior and independent prognostic tool for glioma patients. PMID:26235283

The applications of regenerative medicine in sinus lift procedures: A systematic review.

PubMed

Correia, Francisco; Pozza, Daniel Humberto; Gouveia, Sónia; Felino, António; Faria E Almeida, Ricardo

2018-04-01

Findings in regenerative medicine applied to the sinus lift procedures. Evaluate the effectiveness of regenerative medicine in sinus lift. An extensive search for manuscripts were performed by using different combinations of keywords and MeSH terms (Pub-med; Embase; Scopus; Web of Science Core Collection; Medline; Current Contents Connect; Derwent Innovations Index; Scielo Citation Index; Cochrane library). The full text selected articles are written in English, Portuguese, Spanish, Italian, German, or French, and published until 28 of November 2016. Inclusion criteria were: implant osteointegration, radiographic, histologic, and/or histomorphometric analysis, clinical studies in humans using of regenerative medicine. This systematic review was performed by selecting only randomized controlled clinical trials and controlled clinical trials. Eighteen published studies (11 CT and 7 RCT) were considered eligible for inclusion in the present systematic review. These studies demonstrated considerable variation of biomaterial and cell technics used, study design, sinus lift technic, outcomes, follow-up, and results. Only few studies have demonstrated potential of regenerative medicine in sinus lift; further randomized clinical trials are needed to achieve more accurate results. © 2017 Wiley Periodicals, Inc.

Mobile access to virtual randomization for investigator-initiated trials.

PubMed

Deserno, Thomas M; Keszei, András P

2017-08-01

Background/aims Randomization is indispensable in clinical trials in order to provide unbiased treatment allocation and a valid statistical inference. Improper handling of allocation lists can be avoided using central systems, for example, human-based services. However, central systems are unaffordable for investigator-initiated trials and might be inaccessible from some places, where study subjects need allocations. We propose mobile access to virtual randomization, where the randomization lists are non-existent and the appropriate allocation is computed on demand. Methods The core of the system architecture is an electronic data capture system or a clinical trial management system, which is extended by an R interface connecting the R server using the Java R Interface. Mobile devices communicate via the representational state transfer web services. Furthermore, a simple web-based setup allows configuring the appropriate statistics by non-statisticians. Our comprehensive R script supports simple randomization, restricted randomization using a random allocation rule, block randomization, and stratified randomization for un-blinded, single-blinded, and double-blinded trials. For each trial, the electronic data capture system or the clinical trial management system stores the randomization parameters and the subject assignments. Results Apps are provided for iOS and Android and subjects are randomized using smartphones. After logging onto the system, the user selects the trial and the subject, and the allocation number and treatment arm are displayed instantaneously and stored in the core system. So far, 156 subjects have been allocated from mobile devices serving five investigator-initiated trials. Conclusion Transforming pre-printed allocation lists into virtual ones ensures the correct conduct of trials and guarantees a strictly sequential processing in all trial sites. Covering 88% of all randomization models that are used in recent trials, virtual randomization becomes available for investigator-initiated trials and potentially for large multi-center trials.

Workplace violence and gender discrimination in Rwanda's health workforce: Increasing safety and gender equality.

PubMed

Newman, Constance J; de Vries, Daniel H; d'Arc Kanakuze, Jeanne; Ngendahimana, Gerard

2011-07-19

Workplace violence has been documented in all sectors, but female-dominated sectors such as health and social services are at particular risk. In 2007-2008, IntraHealth International assisted the Rwanda Ministries of Public Service and Labor and Health to study workplace violence in Rwanda's health sector. This article reexamines a set of study findings that directly relate to the influence of gender on workplace violence, synthesizes these findings with other research from Rwanda, and examines the subsequent impact of the study on Rwanda's policy environment. Fifteen out of 30 districts were selected at random. Forty-four facilities at all levels were randomly selected in these districts. From these facilities, 297 health workers were selected at random, of whom 205 were women and 92 were men. Researchers used a utilization-focused approach and administered health worker survey, facility audits, key informant and health facility manager interviews and focus groups to collect data in 2007. After the study was disseminated in 2008, stakeholder recommendations were documented and three versions of the labor law were reviewed to assess study impact. Thirty-nine percent of health workers had experienced some form of workplace violence in year prior to the study. The study identified gender-related patterns of perpetration, victimization and reactions to violence. Negative stereotypes of women, discrimination based on pregnancy, maternity and family responsibilities and the 'glass ceiling' affected female health workers' experiences and career paths and contributed to a context of violence. Gender equality lowered the odds of health workers experiencing violence. Rwandan stakeholders used study results to formulate recommendations to address workplace violence gender discrimination through policy reform and programs. Gender inequality influences workplace violence. Addressing gender discrimination and violence simultaneously should be a priority in workplace violence research, workforce policies, strategies, laws and human resources management training. This will go a long way in making workplaces safer and fairer for the health workforce. This is likely to improve workforce productivity and retention and the enjoyment of human rights at work. Finally, studies that involve stakeholders throughout the research process are likely to improve the utilization of results and policy impact.

Workplace violence and gender discrimination in Rwanda's health workforce: Increasing safety and gender equality

PubMed Central

2011-01-01

Background Workplace violence has been documented in all sectors, but female-dominated sectors such as health and social services are at particular risk. In 2007-2008, IntraHealth International assisted the Rwanda Ministries of Public Service and Labor and Health to study workplace violence in Rwanda's health sector. This article reexamines a set of study findings that directly relate to the influence of gender on workplace violence, synthesizes these findings with other research from Rwanda, and examines the subsequent impact of the study on Rwanda's policy environment. Methods Fifteen out of 30 districts were selected at random. Forty-four facilities at all levels were randomly selected in these districts. From these facilities, 297 health workers were selected at random, of whom 205 were women and 92 were men. Researchers used a utilization-focused approach and administered health worker survey, facility audits, key informant and health facility manager interviews and focus groups to collect data in 2007. After the study was disseminated in 2008, stakeholder recommendations were documented and three versions of the labor law were reviewed to assess study impact. Results Thirty-nine percent of health workers had experienced some form of workplace violence in year prior to the study. The study identified gender-related patterns of perpetration, victimization and reactions to violence. Negative stereotypes of women, discrimination based on pregnancy, maternity and family responsibilities and the 'glass ceiling' affected female health workers' experiences and career paths and contributed to a context of violence. Gender equality lowered the odds of health workers experiencing violence. Rwandan stakeholders used study results to formulate recommendations to address workplace violence gender discrimination through policy reform and programs. Conclusions Gender inequality influences workplace violence. Addressing gender discrimination and violence simultaneously should be a priority in workplace violence research, workforce policies, strategies, laws and human resources management training. This will go a long way in making workplaces safer and fairer for the health workforce. This is likely to improve workforce productivity and retention and the enjoyment of human rights at work. Finally, studies that involve stakeholders throughout the research process are likely to improve the utilization of results and policy impact. PMID:21767411

Kin groups and trait groups: population structure and epidemic disease selection.

PubMed

Fix, A G

1984-10-01

A Monte Carlo simulation based on the population structure of a small-scale human population, the Semai Senoi of Malaysia, has been developed to study the combined effects of group, kin, and individual selection. The population structure resembles D.S. Wilson's structured deme model in that local breeding populations (Semai settlements) are subdivided into trait groups (hamlets) that may be kin-structured and are not themselves demes. Additionally, settlement breeding populations are connected by two-dimensional stepping-stone migration approaching 30% per generation. Group and kin-structured group selection occur among hamlets the survivors of which then disperse to breed within the settlement population. Genetic drift is modeled by the process of hamlet formation; individual selection as a deterministic process, and stepping-stone migration as either random or kin-structured migrant groups. The mechanism for group selection is epidemics of infectious disease that can wipe out small hamlets particularly if most adults become sick and social life collapses. Genetic resistance to a disease is an individual attribute; however, hamlet groups with several resistant adults are less likely to disintegrate and experience high social mortality. A specific human gene, hemoglobin E, which confers resistance to malaria, is studied as an example of the process. The results of the simulations show that high genetic variance among hamlet groups may be generated by moderate degrees of kin-structuring. This strong microdifferentiation provides the potential for group selection. The effect of group selection in this case is rapid increase in gene frequencies among the total set of populations. In fact, group selection in concert with individual selection produced a faster rate of gene frequency increase among a set of 25 populations than the rate within a single unstructured population subject to deterministic individual selection. Such rapid evolution with plausible rates of extinction, individual selection, and migration and a population structure realistic in its general form, has implications for specific human polymorphisms such as hemoglobin variants and for the more general problem of the tempo of evolution as well.

[Randomized controlled study: Sophora flavescens gel in treatment of cervical HPV infection].

PubMed

Zhao, Hong-da; Feng, Xiao-Ling; Zhao, Yan; Li, Na

2016-11-01

This study aimed to evaluate the efficacy of Sophora flavescens gel in treatment of cervical HPV infection. 120 patients with cervical HPV infections were selected from department of gynecology, the first affiliated hospital, Heilongjiang university of Chinese medicine. They were randomly divided into three groups: test group(S. flavescens gel, 40 cases), control group(human recombinant interferon α-2b gel, 40 cases) and combined application group(combination of the above two, 40 cases). The treatment course was three months in all three groups. Before and after treatment, the changes of HPV viral load and the changes of viral load for different HPV types were observed.The results could provide guidance for clinical application of S. flavescens gel. Copyright© by the Chinese Pharmaceutical Association.

A Controlled Study of Funding for Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome as Resource Capacity Building in the Health System in Rwanda

PubMed Central

Shepard, Donald S.; Zeng, Wu; Amico, Peter; Rwiyereka, Angelique K.; Avila-Figueroa, Carlos

2012-01-01

Because human inmmunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) receives more donor funding globally than that for all other diseases combined, some critics allege this support undermines general health care. This empirical study evaluates the impact of HIV/AIDS funding on the primary health care system in Rwanda. Using a quasi-experimental design, we randomly selected 25 rural health centers (HCs) that started comprehensive HIV/AIDS services from 2002 through 2006 as the intervention group. Matched HCs with no HIV/AIDS services formed the control group. The analysis compared growth in inputs and services between intervention and control HCs with a difference-in-difference analysis in a random-effects model. Intervention HCs performed better than control HCs in most services (seven of nine), although only one of these improvements (Bacille Calmette-Guérin vaccination) reached or approached statistical significance. In conclusion, this six-year controlled study found no adverse effects of the expansion of HIV/AIDS services on non-HIV services among rural health centers in Rwanda. PMID:22556094

A controlled study of funding for human immunodeficiency virus/acquired immunodeficiency syndrome as resource capacity building in the health system in Rwanda.

PubMed

Shepard, Donald S; Zeng, Wu; Amico, Peter; Rwiyereka, Angelique K; Avila-Figueroa, Carlos

2012-05-01

Because human inmmunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) receives more donor funding globally than that for all other diseases combined, some critics allege this support undermines general health care. This empirical study evaluates the impact of HIV/AIDS funding on the primary health care system in Rwanda. Using a quasi-experimental design, we randomly selected 25 rural health centers (HCs) that started comprehensive HIV/AIDS services from 2002 through 2006 as the intervention group. Matched HCs with no HIV/AIDS services formed the control group. The analysis compared growth in inputs and services between intervention and control HCs with a difference-in-difference analysis in a random-effects model. Intervention HCs performed better than control HCs in most services (seven of nine), although only one of these improvements (Bacille Calmette-Guérin vaccination) reached or approached statistical significance. In conclusion, this six-year controlled study found no adverse effects of the expansion of HIV/AIDS services on non-HIV services among rural health centers in Rwanda.

The use of crop rotation for mapping soil organic content in farmland

NASA Astrophysics Data System (ADS)

Yang, Lin; Song, Min; Zhu, A.-Xing; Qin, Chengzhi

2017-04-01

Most of the current digital soil mapping uses natural environmental covariates. However, human activities have significantly impacted the development of soil properties since half a century, and therefore become an important factor affecting soil spatial variability. Many researches have done field experiments to show how soil properties are impacted and changed by human activities, however, spatial variation data of human activities as environmental covariates have been rarely used in digital soil mapping. In this paper, we took crop rotation as an example of agricultural activities, and explored its effectiveness in characterizing and mapping the spatial variability of soil. The cultivated area of Xuanzhou city and Langxi County in Anhui Province was chosen as the study area. Three main crop rotations,including double-rice, wheat-rice,and oilseed rape-cotton were observed through field investigation in 2010. The spatial distribution of the three crop rotations in the study area was obtained by multi-phase remote sensing image interpretation using a supervised classification method. One-way analysis of variance (ANOVA) for topsoil organic content in the three crop rotation groups was performed. Factor importance of seven natural environmental covariates, crop rotation, Land use and NDVI were generated by variable importance criterion of Random Forest. Different combinations of environmental covariates were selected according to the importance rankings of environmental covariates for predicting SOC using Random Forest and Soil Landscape Inference Model (SOLIM). A cross validation was generated to evaluated the mapping accuracies. The results showed that there were siginificant differences of topsoil organic content among the three crop rotation groups. The crop rotation is more important than parent material, land use or NDVI according to the importance ranking calculated by Random Forest. In addition, crop rotation improved the mapping accuracy, especially for the flat clutivated area. This study demonstrates the usefulness of human activities in digital soil mapping and thus indicates the necessity for human activity factors in digital soil mapping studies.

The scarcity heuristic impacts reward processing within the medial-frontal cortex.

PubMed

Williams, Chad C; Saffer, Boaz Y; McCulloch, Robert B; Krigolson, Olave E

2016-05-04

Objects that are rare are often perceived to be inherently more valuable than objects that are abundant - a bias brought about in part by the scarcity heuristic. In the present study, we sought to test whether perception of rarity impacted reward evaluation within the human medial-frontal cortex. Here, participants played a gambling game in which they flipped rare and abundant 'cards' on a computer screen to win financial rewards while electroencephalographic data were recorded. Unbeknownst to participants, reward outcome and frequency was random and equivalent for both rare and abundant cards; thus, only a perception of scarcity was true. Analysis of the electroencephalographic data indicated that the P300 component of the event-related brain potential differed in amplitude for wins and losses following the selection of rare cards, but not following the selection of abundant cards. Importantly, then, we found that the perception of card rarity impacted reward processing even though reward feedback was independent of and subsequent to card selection. Our data indicate a top-down influence of the scarcity heuristic on reward evaluation, and specifically the processing of reward magnitude, within the human medial-frontal cortex.

Modulation of human extrastriate visual processing by selective attention to colours and words.

PubMed

Nobre, A C; Allison, T; McCarthy, G

1998-07-01

The present study investigated the effect of visual selective attention upon neural processing within functionally specialized regions of the human extrastriate visual cortex. Field potentials were recorded directly from the inferior surface of the temporal lobes in subjects with epilepsy. The experimental task required subjects to focus attention on words from one of two competing texts. Words were presented individually and foveally. Texts were interleaved randomly and were distinguishable on the basis of word colour. Focal field potentials were evoked by words in the posterior part of the fusiform gyrus. Selective attention strongly modulated long-latency potentials evoked by words. The attention effect co-localized with word-related potentials in the posterior fusiform gyrus, and was independent of stimulus colour. The results demonstrated that stimuli receive differential processing within specialized regions of the extrastriate cortex as a function of attention. The late onset of the attention effect and its co-localization with letter string-related potentials but not with colour-related potentials recorded from nearby regions of the fusiform gyrus suggest that the attention effect is due to top-down influences from downstream regions involved in word processing.

Clomiphene citrate versus letrozole with gonadotropins in intrauterine insemination cycles: A randomized trial.

PubMed

Pourali, Leila; Ayati, Sedigheh; Tavakolizadeh, Shirin; Soleimani, Hourieh; Teimouri Sani, Fatemeh

2017-01-01

Clomiphene citrate is one of the effective drugs for infertility treatment due to oligo-ovulation or anovulation. Intrauterine insemination (IUI) is one of more adherent methods for treatment of infertile cases which is followed by controlled ovarian hyperstimulation (COH). the aim of this study was to evaluate Clomiphene citrate versus letrozole with gonadotropins in IUI cycles. In this prospective randomized trial, 180 infertile women who were referred to Milad Hospital were selected. The first group received 5 mg/day letrozole on day 3-7 of menstrual cycle. The second group received 100 mg/day Clomiphene in the same way as letrozole. In both groups, human menopausal gonadotropin was administered every day starting on day between 6-8 of cycle. Ovulation was triggered with urinary Human Chorionic Gonadotropin (5000 IU) when have two follicles of ≥16 mm. IUI was performed 36 hr later. The number of matured follicles, cycle cancellation, and abortion were the same in both groups. Endometrial thickness was higher at the time of human menopausal gonadotropin administration in letrozole group. Chemical and clinical pregnancy rates were much higher in letrozole group. Ovarian hyperstimulation was significantly higher in clomiphene group. Letrozole appears to be a good alternative to clomiphene citrate with fewer side effects.

Human tracking in thermal images using adaptive particle filters with online random forest learning

NASA Astrophysics Data System (ADS)

Ko, Byoung Chul; Kwak, Joon-Young; Nam, Jae-Yeal

2013-11-01

This paper presents a fast and robust human tracking method to use in a moving long-wave infrared thermal camera under poor illumination with the existence of shadows and cluttered backgrounds. To improve the human tracking performance while minimizing the computation time, this study proposes an online learning of classifiers based on particle filters and combination of a local intensity distribution (LID) with oriented center-symmetric local binary patterns (OCS-LBP). Specifically, we design a real-time random forest (RF), which is the ensemble of decision trees for confidence estimation, and confidences of the RF are converted into a likelihood function of the target state. First, the target model is selected by the user and particles are sampled. Then, RFs are generated using the positive and negative examples with LID and OCS-LBP features by online learning. The learned RF classifiers are used to detect the most likely target position in the subsequent frame in the next stage. Then, the RFs are learned again by means of fast retraining with the tracked object and background appearance in the new frame. The proposed algorithm is successfully applied to various thermal videos as tests and its tracking performance is better than those of other methods.

Links between fear of humans, stress and survival support a non-random distribution of birds among urban and rural habitats

PubMed Central

Rebolo-Ifrán, Natalia; Carrete, Martina; Sanz-Aguilar, Ana; Rodríguez-Martínez, Sol; Cabezas, Sonia; Marchant, Tracy A.; Bortolotti, Gary R.; Tella, José L.

2015-01-01

Urban endocrine ecology aims to understand how organisms cope with new sources of stress and maintain allostatic load to thrive in an increasingly urbanized world. Recent research efforts have yielded controversial results based on short-term measures of stress, without exploring its fitness effects. We measured feather corticosterone (CORTf, reflecting the duration and amplitude of glucocorticoid secretion over several weeks) and subsequent annual survival in urban and rural burrowing owls. This species shows high individual consistency in fear of humans (i.e., flight initiation distance, FID), allowing us to hypothesize that individuals distribute among habitats according to their tolerance to human disturbance. FIDs were shorter in urban than in rural birds, but CORTf levels did not differ, nor were correlated to FIDs. Survival was twice as high in urban as in rural birds and links with CORTf varied between habitats: while a quadratic relationship supports stabilizing selection in urban birds, high predation rates may have masked CORTf-survival relationship in rural ones. These results evidence that urban life does not constitute an additional source of stress for urban individuals, as shown by their near identical CORTf values compared with rural conspecifics supporting the non-random distribution of individuals among habitats according to their behavioural phenotypes. PMID:26348294

Links between fear of humans, stress and survival support a non-random distribution of birds among urban and rural habitats.

PubMed

Rebolo-Ifrán, Natalia; Carrete, Martina; Sanz-Aguilar, Ana; Rodríguez-Martínez, Sol; Cabezas, Sonia; Marchant, Tracy A; Bortolotti, Gary R; Tella, José L

2015-09-08

Urban endocrine ecology aims to understand how organisms cope with new sources of stress and maintain allostatic load to thrive in an increasingly urbanized world. Recent research efforts have yielded controversial results based on short-term measures of stress, without exploring its fitness effects. We measured feather corticosterone (CORTf, reflecting the duration and amplitude of glucocorticoid secretion over several weeks) and subsequent annual survival in urban and rural burrowing owls. This species shows high individual consistency in fear of humans (i.e., flight initiation distance, FID), allowing us to hypothesize that individuals distribute among habitats according to their tolerance to human disturbance. FIDs were shorter in urban than in rural birds, but CORTf levels did not differ, nor were correlated to FIDs. Survival was twice as high in urban as in rural birds and links with CORTf varied between habitats: while a quadratic relationship supports stabilizing selection in urban birds, high predation rates may have masked CORTf-survival relationship in rural ones. These results evidence that urban life does not constitute an additional source of stress for urban individuals, as shown by their near identical CORTf values compared with rural conspecifics supporting the non-random distribution of individuals among habitats according to their behavioural phenotypes.

Assessment of the geoavailability of trace elements from minerals in mine wastes: analytical techniques and assessment of selected copper minerals

USGS Publications Warehouse

Driscoll, Rhonda; Hageman, Phillip L.; Benzel, William M.; Diehl, Sharon F.; Adams, David T.; Morman, Suzette; Choate, LaDonna M.

2012-01-01

In this study, four randomly selected copper-bearing minerals were examined—azurite, malachite, bornite, and chalcopyrite. The objectives were to examine and enumerate the crystalline and chemical properties of each of the minerals, to determine which, if any, of the Cu-bearing minerals might adversely affect systems biota, and to provide a multi-procedure reference. Laboratory work included use of computational software for quantifying crystalline and amorphous material and optical and electron imaging instruments to model and project crystalline structures. Chemical weathering, human fluid, and enzyme simulation studies were also conducted. The analyses were conducted systematically: X-ray diffraction and microanalytical studies followed by a series of chemical, bio-leaching, and toxicity experiments.

Randomization in clinical trials in orthodontics: its significance in research design and methods to achieve it.

PubMed

Pandis, Nikolaos; Polychronopoulou, Argy; Eliades, Theodore

2011-12-01

Randomization is a key step in reducing selection bias during the treatment allocation phase in randomized clinical trials. The process of randomization follows specific steps, which include generation of the randomization list, allocation concealment, and implementation of randomization. The phenomenon in the dental and orthodontic literature of characterizing treatment allocation as random is frequent; however, often the randomization procedures followed are not appropriate. Randomization methods assign, at random, treatment to the trial arms without foreknowledge of allocation by either the participants or the investigators thus reducing selection bias. Randomization entails generation of random allocation, allocation concealment, and the actual methodology of implementing treatment allocation randomly and unpredictably. Most popular randomization methods include some form of restricted and/or stratified randomization. This article introduces the reasons, which make randomization an integral part of solid clinical trial methodology, and presents the main randomization schemes applicable to clinical trials in orthodontics.

Double-Blind, Placebo-Controlled, Randomized Phase III Trial Evaluating Pertuzumab Combined With Chemotherapy for Low Tumor Human Epidermal Growth Factor Receptor 3 mRNA-Expressing Platinum-Resistant Ovarian Cancer (PENELOPE).

PubMed

Kurzeder, Christian; Bover, Isabel; Marmé, Frederik; Rau, Joern; Pautier, Patricia; Colombo, Nicoletta; Lorusso, Domenica; Ottevanger, Petronella; Bjurberg, Maria; Marth, Christian; Barretina-Ginesta, Pilar; Vergote, Ignace; Floquet, Anne; Del Campo, Josep M; Mahner, Sven; Bastière-Truchot, Lydie; Martin, Nicolas; Oestergaard, Mikkel Z; Kiermaier, Astrid; Schade-Brittinger, Carmen; Polleis, Sandra; du Bois, Andreas; Gonzalez-Martin, Antonio

2016-07-20

The AGO-OVAR 2.29/ENGOT-ov14/PENELOPE prospectively randomized phase III trial evaluated the addition of pertuzumab to chemotherapy in patients with platinum-resistant ovarian carcinoma with low tumor human epidermal growth factor receptor 3 (HER3) mRNA expression. We report the results of the primary efficacy analysis. Eligible patients had ovarian carcinoma that progressed during or within 6 months of completing four or more platinum cycles, centrally tested low tumor HER3 mRNA expression (concentration ratio ≤ 2.81 by quantitative reverse transcriptase polymerase chain reaction on cobas z480 [Roche Molecular Diagnostics, Pleasanton, CA]), and no more than two prior lines of chemotherapy. After investigators' selection of the chemotherapy backbone (single-agent topotecan, weekly paclitaxel, or gemcitabine), patients were randomly assigned to also receive either placebo or pertuzumab (840-mg loading dose followed by 420 mg every 3 weeks). Stratification factors were selected chemotherapy, prior antiangiogenic therapy, and platinum-free interval. The primary end point was independent review committee-assessed progression-free survival (PFS). Additional end points included overall survival, investigator-assessed PFS, objective response rate, safety, patient-reported outcomes, and translational research. Overall, 156 patients were randomly assigned. Adding pertuzumab to chemotherapy did not significantly improve independent review committee-assessed PFS for the primary analysis (stratified hazard ratio, 0.74; 95% CI, 0.50 to 1.11; P = .14; median PFS, 4.3 months for pertuzumab plus chemotherapy v 2.6 months for placebo plus chemotherapy). Sensitivity analyses and secondary efficacy end point results were consistent with the primary analysis. The effect on PFS favoring pertuzumab was more pronounced in the gemcitabine and paclitaxel cohorts. No new safety signals were seen. Although the primary objective was not met, subgroup analyses showed trends in PFS favoring pertuzumab in the gemcitabine and paclitaxel cohorts, meriting further exploration of pertuzumab in ovarian cancer. © 2016 by American Society of Clinical Oncology.

Gas chromatography and ultra high performance liquid chromatography tandem mass spectrometry methods for the determination of selected endocrine disrupting chemicals in human breast milk after stir-bar sorptive extraction.

PubMed

Rodríguez-Gómez, R; Zafra-Gómez, A; Camino-Sánchez, F J; Ballesteros, O; Navalón, A

2014-07-04

In the present work, two specific, accurate and sensitive methods for the determination of endocrine disrupting chemicals (EDCs) in human breast milk are developed and validated. Bisphenol A and its main chlorinated derivatives, five benzophenone-UV filters and four parabens were selected as target analytes. The method involves a stir-bar sorptive extraction (SBSE) procedure followed by a solvent desorption prior to GC-MS/MS or UHPLC-MS/MS analysis. A derivatization step is also necessary when GC analysis is performed. The GC column used was a capillary HP-5MS with a run time of 26min. For UHPLC analysis, the stationary phase was a non-polar Acquity UPLC(®) BEH C18 column and the run time was 10min. In both cases, the analytes were detected and quantified using a triple quadrupole mass spectrometer (QqQ). Quality parameters such as linearity, accuracy (trueness and precision), sensitivity and selectivity were examined and yielded good results. The limits of quantification (LOQs) ranged from 0.3 to 5.0ngmL(-1) for GC and from 0.2 to 1.0ngmL(-1) for LC. The relative standard deviation (RSD) was lower than 15% and the recoveries ranged from 92 to 114% in all cases, being slightly unfavorable the results obtained with LC. The methods were satisfactorily applied for the determination of target compounds in human milk samples from 10 randomly selected women. Copyright © 2014 Elsevier B.V. All rights reserved.

Improving virtual screening predictive accuracy of Human kallikrein 5 inhibitors using machine learning models.

PubMed

Fang, Xingang; Bagui, Sikha; Bagui, Subhash

2017-08-01

The readily available high throughput screening (HTS) data from the PubChem database provides an opportunity for mining of small molecules in a variety of biological systems using machine learning techniques. From the thousands of available molecular descriptors developed to encode useful chemical information representing the characteristics of molecules, descriptor selection is an essential step in building an optimal quantitative structural-activity relationship (QSAR) model. For the development of a systematic descriptor selection strategy, we need the understanding of the relationship between: (i) the descriptor selection; (ii) the choice of the machine learning model; and (iii) the characteristics of the target bio-molecule. In this work, we employed the Signature descriptor to generate a dataset on the Human kallikrein 5 (hK 5) inhibition confirmatory assay data and compared multiple classification models including logistic regression, support vector machine, random forest and k-nearest neighbor. Under optimal conditions, the logistic regression model provided extremely high overall accuracy (98%) and precision (90%), with good sensitivity (65%) in the cross validation test. In testing the primary HTS screening data with more than 200K molecular structures, the logistic regression model exhibited the capability of eliminating more than 99.9% of the inactive structures. As part of our exploration of the descriptor-model-target relationship, the excellent predictive performance of the combination of the Signature descriptor and the logistic regression model on the assay data of the Human kallikrein 5 (hK 5) target suggested a feasible descriptor/model selection strategy on similar targets. Copyright © 2017 Elsevier Ltd. All rights reserved.

Development of a 'mouse and human cross-reactive' affinity-matured exosite inhibitory human antibody specific to TACE (ADAM17) for cancer immunotherapy.

PubMed

Kwok, Hang Fai; Botkjaer, Kenneth A; Tape, Christopher J; Huang, Yanchao; McCafferty, John; Murphy, Gillian

2014-06-01

We previously showed that a human anti-TACE antibody, D1(A12), is a potent inhibitor of TNF-α converting enzyme (TACE) ectodomain proteolysis and has pharmacokinetic properties suitable for studies of the inhibition of TACE-dependent growth factor shedding in relation to possible therapeutic applications. However, the lack of murine TACE immunoreactivity limits pre-clinical in vivo studies to human xenograft models which are poor analogies to in situ pathology and are not considered clinically predictive. Here, to overcome these limitations, we set out to develop a 'mouse and human cross-reactive' specific anti-TACE antibody. We first re-investigated the originally selected anti-TACE ectodomain phage-display clones, and isolated a lead 'mouse-human cross-reactive' anti-TACE scFv, clone A9. We reformatted scFv-A9 into an IgG2 framework for comprehensive biochemical and cellular characterization and further demonstrated that A9 is an exosite TACE inhibitor. However, surface plasmon resonance analysis and quenched-fluorescent (QF) peptide assay indicated that IgG reformatting of A9 caused low binding affinity and an 80-fold reduction in TACE ectodomain inhibition, severely limiting its efficacy. To address this, we constructed second generation phage-display randomization libraries focused on the complementarity-determining region 3, and carried out affinity selections shuffling between human and mouse TACE ectodomain as antigen in addition to an off-rate selection to increase the chance of affinity improvement. The bespoke 'three-step' selections enabled a 100-fold affinity enhancement of A9 IgG, and also improved its IC50 in a QF peptide assay to 0.2 nM. In human and mouse cancer cell assays, matured A9 IgG showed significant cell-surface TACE inhibition as a monotherapy or combination therapy with chemotherapeutic agent. Collectively, these data suggest that we successfully developed an exosite inhibitor of TACE with sub-nanomolar affinity, which possesses both murine and human immunoreactive properties that can be used for in vivo application in murine pre-clinical cancer models. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Different functional classes of genes are characterized by different compositional properties.

PubMed

D'Onofrio, Giuseppe; Ghosh, Tapash Chandra; Saccone, Salvatore

2007-12-22

A compositional analysis on a set of human genes classified in several functional classes was performed. We found out that the GC3, i.e. the GC level at the third codon positions, of the genes involved in cellular metabolism was significantly higher than those involved in information storage and processing. Analyses of human/Xenopus ortologous genes showed that: (i) the GC3 increment of the genes involved in cellular metabolism was significantly higher than those involved in information storage and processing; and (ii) a strong correlation between the GC3 and the corresponding GCi, i.e. the GC level of introns, was found in each functional class. The non-randomness of the GC increments favours the selective hypothesis of gene/genome evolution.

Identification and selection of cases and controls in the Pneumonia Etiology Research for Child Health project.

PubMed

Deloria-Knoll, Maria; Feikin, Daniel R; Scott, J Anthony G; O'Brien, Katherine L; DeLuca, Andrea N; Driscoll, Amanda J; Levine, Orin S

2012-04-01

Methods for the identification and selection of patients (cases) with severe or very severe pneumonia and controls for the Pneumonia Etiology Research for Child Health (PERCH) project were needed. Issues considered include eligibility criteria and sampling strategies, whether to enroll hospital or community controls, whether to exclude controls with upper respiratory tract infection (URTI) or nonsevere pneumonia, and matching criteria, among others. PERCH ultimately decided to enroll community controls and an additional human immunodeficiency virus (HIV)-infected control group at high HIV-prevalence sites matched on age and enrollment date of cases; controls with symptoms of URTI or nonsevere pneumonia will not be excluded. Systematic sampling of cases (when necessary) and random sampling of controls will be implemented. For each issue, we present the options that were considered, the advantages and disadvantages of each, the rationale for the methods selected for PERCH, and remaining implications and limitations.

Searching for patterns in remote sensing image databases using neural networks

NASA Technical Reports Server (NTRS)

Paola, Justin D.; Schowengerdt, Robert A.

1995-01-01

We have investigated a method, based on a successful neural network multispectral image classification system, of searching for single patterns in remote sensing databases. While defining the pattern to search for and the feature to be used for that search (spectral, spatial, temporal, etc.) is challenging, a more difficult task is selecting competing patterns to train against the desired pattern. Schemes for competing pattern selection, including random selection and human interpreted selection, are discussed in the context of an example detection of dense urban areas in Landsat Thematic Mapper imagery. When applying the search to multiple images, a simple normalization method can alleviate the problem of inconsistent image calibration. Another potential problem, that of highly compressed data, was found to have a minimal effect on the ability to detect the desired pattern. The neural network algorithm has been implemented using the PVM (Parallel Virtual Machine) library and nearly-optimal speedups have been obtained that help alleviate the long process of searching through imagery.

Planckian Information (Ip): A New Measure of Order in Atoms, Enzymes, Cells, Brains, Human Societies, and the Cosmos

NASA Astrophysics Data System (ADS)

Ji, Sungchul

A new mathematical formula referred to as the Planckian distribution equation (PDE) has been found to fit long-tailed histograms generated in various fields of studies, ranging from atomic physics to single-molecule enzymology, cell biology, brain neurobiology, glottometrics, econophysics, and to cosmology. PDE can be derived from a Gaussian-like equation (GLE) by non-linearly transforming its variable, x, while keeping the y coordinate constant. Assuming that GLE represents a random distribution (due to its symmetry), it is possible to define a binary logarithm of the ratio between the areas under the curves of PDE and GLE as a measure of the non-randomness (or order) underlying the biophysicochemical processes generating long-tailed histograms that fit PDE. This new function has been named the Planckian information, IP, which (i) may be a new measure of order that can be applied widely to both natural and human sciences and (ii) can serve as the opposite of the Boltzmann-Gibbs entropy, S, which is a measure of disorder. The possible rationales for the universality of PDE may include (i) the universality of the wave-particle duality embedded in PDE, (ii) the selection of subsets of random processes (thereby breaking the symmetry of GLE) as the basic mechanism of generating order, organization, and function, and (iii) the quantity-quality complementarity as the connection between PDE and Peircean semiotics.

Marked Antigiardial Activity of Yucca baccata Extracts: A Potential Natural Alternative for Treating Protozoan Infections

PubMed Central

Quihui-Cota, Luis; León-Trujillo, Rocio; Astiazarán-García, Humberto; Esparza-Romero, Julián; Robles, María del Refugio; Robles-Zepeda, Ramón E.; Canett, Rafael; Sánchez-Escalante, Jesús

2014-01-01

Human Giardiosis is a public health problem in Mexico, where the national prevalence was estimated to be up to 68%. Misuse of antiprotozoal drugs may result in low effectiveness and undesirable side effects. Research on natural products is a good strategy for discovering more effective antiparasitic compounds. This study evaluated the antigiardial activity of extracts of Yucca baccata, which is native to northwestern Mexico. Forty-two gerbils (females) were weighed and orally inoculated with 5 × 106 Giardia trophozoites. Two gerbils were selected at random to confirm infection. Forty living gerbils were randomly allocated into 5 treatment groups (8 per group). Gerbils were randomly assigned to be treated with 24.4 mg/mL, 12.2 mg/mL, and 6.1 mg/mL of extracts, metronidazole (2 mg/mL) or PBS, which were intragastrically administered once per day for 3 days. Nine gerbils died during the study course. On day 10 postinfection, gerbils were euthanized and trophozoites were quantified. Yucca extracts reduced, albeit not significantly, the trophozoite counts in the duodenum segment. Only the high-extract concentration significantly reduced the trophozoite counts in the proximal segment and it was similar to that of metronidazole. Extracts of Y. baccata may represent an effective and natural therapeutic alternative for human giardiosis. PMID:25250335

Evidence of dengue virus transmission and factors associated with the presence of anti-dengue virus antibodies in humans in three major towns in Cameroon.

PubMed

Demanou, Maurice; Pouillot, Régis; Grandadam, Marc; Boisier, Pascal; Kamgang, Basile; Hervé, Jean Pierre; Rogier, Christophe; Rousset, Dominique; Paupy, Christophe

2014-07-01

Dengue is not well documented in Africa. In Cameroon, data are scarce, but dengue infection has been confirmed in humans. We conducted a study to document risk factors associated with anti-dengue virus Immunoglobulin G seropositivity in humans in three major towns in Cameroon. A cross sectional survey was conducted in Douala, Garoua and Yaounde, using a random cluster sampling design. Participants underwent a standardized interview and were blood sampled. Environmental and housing characteristics were recorded. Randomized houses were prospected to record all water containers, and immature stages of Aedes mosquitoes were collected. Sera were screened for anti-dengue virus IgG and IgM antibodies. Risk factors of seropositivity were tested using logistic regression methods with random effects. Anti-dengue IgG were found from 61.4% of sera in Douala (n = 699), 24.2% in Garoua (n = 728) and 9.8% in Yaounde (n = 603). IgM were found from 0.3% of Douala samples, 0.1% of Garoua samples and 0.0% of Yaounde samples. Seroneutralization on randomly selected IgG positive sera showed that 72% (n = 100) in Douala, 80% (n = 94) in Garoua and 77% (n = 66) in Yaounde had antibodies specific for dengue virus serotype 2 (DENV-2). Age, temporary house walls materials, having water-storage containers, old tires or toilets in the yard, having no TV, having no air conditioning and having travelled at least once outside the city were independently associated with anti-dengue IgG positivity in Douala. Age, having uncovered water containers, having no TV, not being born in Garoua and not breeding pigs were significant risk factors in Garoua. Recent history of malaria, having banana trees and stagnant water in the yard were independent risk factors in Yaounde. In this survey, most identified risk factors of dengue were related to housing conditions. Poverty and underdevelopment are central to the dengue epidemiology in Cameroon.

Melatonin increases reactive aggression in humans.

PubMed

Liu, Jinting; Zhong, Ru; Xiong, Wei; Liu, Haibo; Eisenegger, Christoph; Zhou, Xiaolin

2017-10-01

Melatonin, a hormone released preferentially by the pineal gland during the night, affects circadian rhythms and aging processes. As animal studies have shown that melatonin increases resident-intruder aggression, this study aimed to investigate the impact of melatonin treatment on human aggression. In a double-blind, randomized, placebo-controlled between-participant design, 63 healthy male volunteers completed the Taylor Aggression Paradigm (TAP) after oral administration of melatonin or placebo. We found that when given the opportunity to administer high or low punishments to an opponent, participants who ingested melatonin selected the high punishment more often than those who ingested placebo. The increased reactive aggression under melatonin administration remained after controlling for inhibitory ability, trait aggression, trait impulsiveness, circadian preference, perceptual sensibility to noise, and changes in subjective sleepiness and emotional states. This study provides novel and direct evidence for the involvement of melatonin in human social processes.

Antimalarial drug discovery: screening of Brazilian medicinal plants and purified compounds.

PubMed

Krettli, Antoniana Ursine

2009-02-01

Malaria is the most important parasitic disease and its control depends on specific chemotherapy, now complicated by Plasmodium falciparum that has become resistant to most commonly available antimalarials. Treatment of the disease requires quinine or drug combinations of artemisinin derivatives and other antimalarials. Further drug resistance is expected. New active compounds need to be discovered. To find new antimalarials from medicinal and randomly collected plants, crude extracts are screened against P. falciparum in cultures and in malaria animal models, following bioassays of purified fractions, and cytotoxicity tests. For antimalarial research, screening medicinal plants is more efficient than screening randomly chosen plants. Biomonitored fractionation allows selection of new active molecules identified as potential antimalarials in multidisciplinary projects in Brazil; no new molecule is available for human testing. The advantages of projects based on ethnopharmacology are discussed.

An Overview of Randomization and Minimization Programs for Randomized Clinical Trials

PubMed Central

Saghaei, Mahmoud

2011-01-01

Randomization is an essential component of sound clinical trials, which prevents selection biases and helps in blinding the allocations. Randomization is a process by which subsequent subjects are enrolled into trial groups only by chance, which essentially eliminates selection biases. A serious consequence of randomization is severe imbalance among the treatment groups with respect to some prognostic factors, which invalidate the trial results or necessitate complex and usually unreliable secondary analysis to eradicate the source of imbalances. Minimization on the other hand tends to allocate in such a way as to minimize the differences among groups, with respect to prognostic factors. Pure minimization is therefore completely deterministic, that is, one can predict the allocation of the next subject by knowing the factor levels of a previously enrolled subject and having the properties of the next subject. To eliminate the predictability of randomization, it is necessary to include some elements of randomness in the minimization algorithms. In this article brief descriptions of randomization and minimization are presented followed by introducing selected randomization and minimization programs. PMID:22606659

The relationship between environmental exposure to cadmium and lead and blood selenium concentration in randomly selected population of children inhabiting industrial regions of Silesian Voivodship (Poland).

PubMed

Gać, P; Pawlas, N; Poręba, R; Poręba, M; Pawlas, K

2014-06-01

This study aimed at determining the relationship between environmental exposure to lead (Pb) and cadmium (Cd) and blood selenium (Se) concentration in randomly selected population of children inhabiting the industrial regions of Silesian Voivodship, Poland. The study was conducted on a group of consecutive randomly selected 349 children aged below 15 years and inhabiting the industrial regions in Upper Silesia. The examined variables included whole blood Cd concentration (Cd-B), whole blood Pb concentration (Pb-B) and whole blood Se concentration (Se-B). The concentration of Cd-B, Pb-B and Se-B in the studied group of children amounted to 0.26 ± 0.14, 37.62 ± 25.30 and 78.31 ± 12.82 μg/L, respectively. In the entire examined group a statistically significant negative linear relationship was noted between Pb-B and Se-B (r = -0.12, p < 0.05). Also, a statistically insignificant negative correlation was detected between Cd-B and Se-B (r = -0.02, p > 0.05) and a statistically insignificant positive correlation between Pb-B and Cd-B (r = 0.08, p > 0.05). A multivariate backward stepwise regression analysis demonstrated that in the studied group of children higher Pb-B and a more advanced age-represented independent risk factors for a decreased Se-B. Environmental exposure to Pb may represent an independent risk factor for Se deficit in blood of the studied population of children. In children, the lowered Se-B may create one of the mechanisms in which Pb unfavourably affects human body. © The Author(s) 2014.

A prediction of templates in the auditory cortex system

NASA Astrophysics Data System (ADS)

Ghanbeigi, Kimia

In this study variation of human auditory evoked mismatch field amplitudes in response to complex tones as a function of the removal in single partials in the onset period was investigated. It was determined: 1-A single frequency elimination in a sound stimulus plays a significant role in human brain sound recognition. 2-By comparing the mismatches of the brain response due to a single frequency elimination in the "Starting Transient" and "Sustain Part" of the sound stimulus, it is found that the brain is more sensitive to frequency elimination in the Starting Transient. This study involves 4 healthy subjects with normal hearing. Neural activity was recorded with stimulus whole-head MEG. Verification of spatial location in the auditory cortex was determined by comparing with MRI images. In the first set of stimuli, repetitive ('standard') tones with five selected onset frequencies were randomly embedded in the string of rare ('deviant') tones with randomly varying inter stimulus intervals. In the deviant tones one of the frequency components was omitted relative to the deviant tones during the onset period. The frequency of the test partial of the complex tone was intentionally selected to preclude its reinsertion by generation of harmonics or combination tones due to either the nonlinearity of the ear, the electronic equipment or the brain processing. In the second set of stimuli, time structured as above, repetitive ('standard') tones with five selected sustained frequency components were embedded in the string of rare '(deviant') tones for which one of these selected frequencies was omitted in the sustained tone. In both measurements, the carefully frequency selection precluded their reinsertion by generation of harmonics or combination tones due to the nonlinearity of the ear, the electronic equipment and brain processing. The same considerations for selecting the test frequency partial were applied. Results. By comparing MMN of the two data sets, the relative contribution to sound recognition of the omitted partial frequency components in the onset and sustained regions has been determined. Conclusion. The presence of significant mismatch negativity, due to neural activity of auditory cortex, emphasizes that the brain recognizes the elimination of a single frequency of carefully chosen anharmonic frequencies. It was shown this mismatch is more significant if the single frequency elimination occurs in the onset period.

Algorithms for selecting informative marker panels for population assignment.

PubMed

Rosenberg, Noah A

2005-11-01

Given a set of potential source populations, genotypes of an individual of unknown origin at a collection of markers can be used to predict the correct source population of the individual. For improved efficiency, informative markers can be chosen from a larger set of markers to maximize the accuracy of this prediction. However, selecting the loci that are individually most informative does not necessarily produce the optimal panel. Here, using genotypes from eight species--carp, cat, chicken, dog, fly, grayling, human, and maize--this univariate accumulation procedure is compared to new multivariate "greedy" and "maximin" algorithms for choosing marker panels. The procedures generally suggest similar panels, although the greedy method often recommends inclusion of loci that are not chosen by the other algorithms. In seven of the eight species, when applied to five or more markers, all methods achieve at least 94% assignment accuracy on simulated individuals, with one species--dog--producing this level of accuracy with only three markers, and the eighth species--human--requiring approximately 13-16 markers. The new algorithms produce substantial improvements over use of randomly selected markers; where differences among the methods are noticeable, the greedy algorithm leads to slightly higher probabilities of correct assignment. Although none of the approaches necessarily chooses the panel with optimal performance, the algorithms all likely select panels with performance near enough to the maximum that they all are suitable for practical use.

Randomized trial of exclusive human milk versus preterm formula diets in extremely premature infants

USDA-ARS?s Scientific Manuscript database

Our objective was to compare the duration of parenteral nutrition, growth, and morbidity in extremely premature infants fed exclusive diets of either bovine milk-based preterm formula (BOV) or donor human milk and human milk-based human milk fortifier (HUM), in a randomized trial of formula vs human...

The RANDOM computer program: A linear congruential random number generator

NASA Technical Reports Server (NTRS)

Miles, R. F., Jr.

1986-01-01

The RANDOM Computer Program is a FORTRAN program for generating random number sequences and testing linear congruential random number generators (LCGs). The linear congruential form of random number generator is discussed, and the selection of parameters of an LCG for a microcomputer described. This document describes the following: (1) The RANDOM Computer Program; (2) RANDOM.MOD, the computer code needed to implement an LCG in a FORTRAN program; and (3) The RANCYCLE and the ARITH Computer Programs that provide computational assistance in the selection of parameters for an LCG. The RANDOM, RANCYCLE, and ARITH Computer Programs are written in Microsoft FORTRAN for the IBM PC microcomputer and its compatibles. With only minor modifications, the RANDOM Computer Program and its LCG can be run on most micromputers or mainframe computers.

A Randomized Controlled Trial of Interventions to Impede Date Palm Sap Contamination by Bats to Prevent Nipah Virus Transmission in Bangladesh

PubMed Central

Khan, Salah Uddin; Gurley, Emily S.; Hossain, M. Jahangir; Nahar, Nazmun; Sharker, M. A. Yushuf; Luby, Stephen P.

2012-01-01

Background Drinking raw date palm sap is a risk factor for human Nipah virus (NiV) infection. Fruit bats, the natural reservoir of NiV, commonly contaminate raw sap with saliva by licking date palm’s sap producing surface. We evaluated four types of physical barriers that may prevent bats from contacting sap. Methods During 2009, we used a crossover design and randomly selected 20 date palm sap producing trees and observed each tree for 2 nights: one night with a bamboo skirt intervention applied and one night without the intervention. During 2010, we selected 120 trees and randomly assigned four types of interventions to 15 trees each: bamboo, dhoincha (local plant), jute stick and polythene skirts covering the shaved part, sap stream, tap and collection pot. We enrolled the remaining 60 trees as controls. We used motion sensor activated infrared cameras to examine bat contact with sap. Results During 2009 bats contacted date palm sap in 85% of observation nights when no intervention was used compared with 35% of nights when the intervention was used [p<0.001]. Bats were able to contact the sap when the skirt did not entirely cover the sap producing surface. Therefore, in 2010 we requested the sap harvesters to use larger skirts. During 2010 bats contacted date palm sap [2% vs. 83%, p<0.001] less frequently in trees protected with skirts compared to control trees. No bats contacted sap in trees with bamboo (p<0.001 compared to control), dhoincha skirt (p<0.001) or polythene covering (p<0.001), but bats did contact sap during one night (7%) with the jute stick skirt (p<0.001). Conclusion Bamboo, dhoincha, jute stick and polythene skirts covering the sap producing areas of a tree effectively prevented bat-sap contact. Community interventions should promote applying these skirts to prevent occasional Nipah spillovers to human. PMID:22905160

Asynchronous Replication and Autosome-Pair Non-Equivalence in Human Embryonic Stem Cells

PubMed Central

Dutta, Devkanya; Ensminger, Alexander W.; Zucker, Jacob P.; Chess, Andrew

2009-01-01

A number of mammalian genes exhibit the unusual properties of random monoallelic expression and random asynchronous replication. Such exceptional genes include genes subject to X inactivation and autosomal genes including odorant receptors, immunoglobulins, interleukins, pheromone receptors, and p120 catenin. In differentiated cells, random asynchronous replication of interspersed autosomal genes is coordinated at the whole chromosome level, indicative of chromosome-pair non-equivalence. Here we have investigated the replication pattern of the random asynchronously replicating genes in undifferentiated human embryonic stem cells, using fluorescence in situ hybridization based assay. We show that allele-specific replication of X-linked genes and random monoallelic autosomal genes occur in human embryonic stem cells. The direction of replication is coordinated at the whole chromosome level and can cross the centromere, indicating the existence of autosome-pair non-equivalence in human embryonic stem cells. These results suggest that epigenetic mechanism(s) that randomly distinguish between two parental alleles are emerging in the cells of the inner cell mass, the source of human embryonic stem cells. PMID:19325893

Effects of prey abundance, distribution, visual contrast and morphology on selection by a pelagic piscivore

USGS Publications Warehouse

Hansen, Adam G.; Beauchamp, David A.

2014-01-01

Most predators eat only a subset of possible prey. However, studies evaluating diet selection rarely measure prey availability in a manner that accounts for temporal–spatial overlap with predators, the sensory mechanisms employed to detect prey, and constraints on prey capture.We evaluated the diet selection of cutthroat trout (Oncorhynchus clarkii) feeding on a diverse planktivore assemblage in Lake Washington to test the hypothesis that the diet selection of piscivores would reflect random (opportunistic) as opposed to non-random (targeted) feeding, after accounting for predator–prey overlap, visual detection and capture constraints.Diets of cutthroat trout were sampled in autumn 2005, when the abundance of transparent, age-0 longfin smelt (Spirinchus thaleichthys) was low, and 2006, when the abundance of smelt was nearly seven times higher. Diet selection was evaluated separately using depth-integrated and depth-specific (accounted for predator–prey overlap) prey abundance. The abundance of different prey was then adjusted for differences in detectability and vulnerability to predation to see whether these factors could explain diet selection.In 2005, cutthroat trout fed non-randomly by selecting against the smaller, transparent age-0 longfin smelt, but for the larger age-1 longfin smelt. After adjusting prey abundance for visual detection and capture, cutthroat trout fed randomly. In 2006, depth-integrated and depth-specific abundance explained the diets of cutthroat trout well, indicating random feeding. Feeding became non-random after adjusting for visual detection and capture. Cutthroat trout selected strongly for age-0 longfin smelt, but against similar sized threespine stickleback (Gasterosteus aculeatus) and larger age-1 longfin smelt in 2006. Overlap with juvenile sockeye salmon (O. nerka) was minimal in both years, and sockeye salmon were rare in the diets of cutthroat trout.The direction of the shift between random and non-random selection depended on the presence of a weak versus a strong year class of age-0 longfin smelt. These fish were easy to catch, but hard to see. When their density was low, poor detection could explain their rarity in the diet. When their density was high, poor detection was compensated by higher encounter rates with cutthroat trout, sufficient to elicit a targeted feeding response. The nature of the feeding selectivity of a predator can be highly dependent on fluctuations in the abundance and suitability of key prey.

Group Counseling With Emotionally Disturbed School Children in Taiwan.

ERIC Educational Resources Information Center

Chiu, Peter

The application of group counseling to emotionally disturbed school children in Chinese culture was examined. Two junior high schools located in Tao-Yuan Province were randomly selected with two eighth-grade classes randomly selected from each school. Ten emotionally disturbed students were chosen from each class and randomly assigned to two…

Sample Selection in Randomized Experiments: A New Method Using Propensity Score Stratified Sampling

ERIC Educational Resources Information Center

Tipton, Elizabeth; Hedges, Larry; Vaden-Kiernan, Michael; Borman, Geoffrey; Sullivan, Kate; Caverly, Sarah

2014-01-01

Randomized experiments are often seen as the "gold standard" for causal research. Despite the fact that experiments use random assignment to treatment conditions, units are seldom selected into the experiment using probability sampling. Very little research on experimental design has focused on how to make generalizations to well-defined…

On Measuring and Reducing Selection Bias with a Quasi-Doubly Randomized Preference Trial

ERIC Educational Resources Information Center

Joyce, Ted; Remler, Dahlia K.; Jaeger, David A.; Altindag, Onur; O'Connell, Stephen D.; Crockett, Sean

2017-01-01

Randomized experiments provide unbiased estimates of treatment effects, but are costly and time consuming. We demonstrate how a randomized experiment can be leveraged to measure selection bias by conducting a subsequent observational study that is identical in every way except that subjects choose their treatment--a quasi-doubly randomized…

Dissecting protein:protein interactions between transcription factors with an RNA aptamer.

PubMed Central

Tian, Y; Adya, N; Wagner, S; Giam, C Z; Green, M R; Ellington, A D

1995-01-01

Nucleic acid aptamers isolated from random sequence pools have generally proven useful at inhibiting the interactions of nucleic acid binding proteins with their cognate nucleic acids. In order to develop reagents that could also be used to study protein:protein interactions, we have used in vitro selection to search for RNA aptamers that could interact with the transactivating protein Tax from human T-cell leukemia virus. Tax does not normally bind to nucleic acids, but instead stimulates transcription by interacting with a variety of cellular transcription factors, including the cyclic AMP-response element binding protein (CREB), NF-kappa B, and the serum response factor (SRF). Starting from a pool of greater than 10(13) different RNAs with a core of 120 random sequence positions, RNAs were selected for their ability to be co-retained on nitrocellulose filters with Tax. After five cycles of selection and amplification, a single nucleic acid species remained. This aptamer was found to bind Tax with high affinity and specificity, and could disrupt complex formation between Tax and NF-kappa B, but not with SRF. The differential effects of our aptamer probe on protein:protein interactions suggest a model for how the transcription factor binding sites on the surface of the Tax protein are organized. This model is consistent with data from a variety of other studies. PMID:7489503

Isolation of expressed sequences from the region commonly deleted in Velo-cardio-facial syndrome

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

Sirotkin, H.; Morrow, B.; DasGupta, R.

Velo-cardio-facial syndrome (VCFS) is a relatively common autosomal dominant genetic disorder characterized by cleft palate, cardiac abnormalities, learning disabilities and a characteristic facial dysmorphology. Most VCFS patients have interstitial deletions of 22q11 of 1-2 mb. In an effort to isolate the gene(s) responsible for VCFS we have utilized a hybrid selection protocol to recover expressed sequences from three non-overlapping YACs comprising almost 1 mb of the commonly deleted region. Total yeast genomic DNA or isolated YAC DNA was immobilized on Hybond-N filters, blocked with yeast and human ribosomal and human repetitive sequences and hybridized with a mixture of random primedmore » short fragment cDNA libraries. Six human short fragment libraries derived from total fetus, fetal brain, adult brain, testes, thymus and spleen have been used for the selections. Short fragment cDNAs retained on the filter were passed through a second round of selection and cloned into lambda gt10. cDNAs shown to originate from the YACs and from chromosome 22 are being used to isolate full length cDNAs. Three genes known to be present on these YACs, catechol-O-methyltransferase, tuple 1 and clathrin heavy chain have been recovered. Additionally, a gene related to the murine p120 gene and a number of novel short cDNAs have been isolated. The role of these genes in VCFS is being investigated.« less

SNP selection and classification of genome-wide SNP data using stratified sampling random forests.

PubMed

Wu, Qingyao; Ye, Yunming; Liu, Yang; Ng, Michael K

2012-09-01

For high dimensional genome-wide association (GWA) case-control data of complex disease, there are usually a large portion of single-nucleotide polymorphisms (SNPs) that are irrelevant with the disease. A simple random sampling method in random forest using default mtry parameter to choose feature subspace, will select too many subspaces without informative SNPs. Exhaustive searching an optimal mtry is often required in order to include useful and relevant SNPs and get rid of vast of non-informative SNPs. However, it is too time-consuming and not favorable in GWA for high-dimensional data. The main aim of this paper is to propose a stratified sampling method for feature subspace selection to generate decision trees in a random forest for GWA high-dimensional data. Our idea is to design an equal-width discretization scheme for informativeness to divide SNPs into multiple groups. In feature subspace selection, we randomly select the same number of SNPs from each group and combine them to form a subspace to generate a decision tree. The advantage of this stratified sampling procedure can make sure each subspace contains enough useful SNPs, but can avoid a very high computational cost of exhaustive search of an optimal mtry, and maintain the randomness of a random forest. We employ two genome-wide SNP data sets (Parkinson case-control data comprised of 408 803 SNPs and Alzheimer case-control data comprised of 380 157 SNPs) to demonstrate that the proposed stratified sampling method is effective, and it can generate better random forest with higher accuracy and lower error bound than those by Breiman's random forest generation method. For Parkinson data, we also show some interesting genes identified by the method, which may be associated with neurological disorders for further biological investigations.

Evolution in fluctuating environments: decomposing selection into additive components of the Robertson-Price equation.

PubMed

Engen, Steinar; Saether, Bernt-Erik

2014-03-01

We analyze the stochastic components of the Robertson-Price equation for the evolution of quantitative characters that enables decomposition of the selection differential into components due to demographic and environmental stochasticity. We show how these two types of stochasticity affect the evolution of multivariate quantitative characters by defining demographic and environmental variances as components of individual fitness. The exact covariance formula for selection is decomposed into three components, the deterministic mean value, as well as stochastic demographic and environmental components. We show that demographic and environmental stochasticity generate random genetic drift and fluctuating selection, respectively. This provides a common theoretical framework for linking ecological and evolutionary processes. Demographic stochasticity can cause random variation in selection differentials independent of fluctuating selection caused by environmental variation. We use this model of selection to illustrate that the effect on the expected selection differential of random variation in individual fitness is dependent on population size, and that the strength of fluctuating selection is affected by how environmental variation affects the covariance in Malthusian fitness between individuals with different phenotypes. Thus, our approach enables us to partition out the effects of fluctuating selection from the effects of selection due to random variation in individual fitness caused by demographic stochasticity. © 2013 The Author(s). Evolution © 2013 The Society for the Study of Evolution.

Discovery of an artificial peptide agonist to the fibroblast growth factor receptor 1c/βKlotho complex from random peptide T7 phage display.

PubMed

Sakamoto, Kotaro; Kawata, Yayoi; Masuda, Yasushi; Umemoto, Tadashi; Ito, Takashi; Asami, Taiji; Takekawa, Shiro; Ohtaki, Tetsuya; Inooka, Hiroshi

2016-11-04

Fibroblast growth factor receptor-1c (FGFR1c)/βKlotho (KLB) complex is a receptor of fibroblast growth factor 21 (FGF21). Pharmacologically, FGF21 shows anti-obesity and anti-diabetic effects upon peripheral administration. Here, we report the development of an artificial peptide agonist to the FGFR1c/KLB heterodimer complex. The peptide, F91-8A07 (LPGRTCREYPDLWWVRCY), was discovered from random peptide T7 phage display and selectively bound to the FGFR1c/KLB complex, but not to FGFR1c and KLB individually. After subsequent peptide dimerization using a short polyethyleneglycol (PEG) linker, the dimeric F91-8A07 peptide showed higher potent agonist activity than that of FGF21 in cultured primary human adipocytes. Moreover, the dimeric peptide led to an expression of the early growth response protein-1 (Egr-1) mRNA in vivo, which is a target gene of FGFR1c. To the best of our knowledge, this is the first report of a FGFR1c/KLB complex-selective artificial peptide agonist. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Phage display of the serpin alpha-1 proteinase inhibitor randomized at consecutive residues in the reactive centre loop and biopanned with or without thrombin.

PubMed

Scott, Benjamin M; Matochko, Wadim L; Gierczak, Richard F; Bhakta, Varsha; Derda, Ratmir; Sheffield, William P

2014-01-01

In spite of the power of phage display technology to identify variant proteins with novel properties in large libraries, it has only been previously applied to one member of the serpin superfamily. Here we describe phage display of human alpha-1 proteinase inhibitor (API) in a T7 bacteriophage system. API M358R fused to the C-terminus of T7 capsid protein 10B was directly shown to form denaturation-resistant complexes with thrombin by electrophoresis and immunoblotting following exposure of intact phages to thrombin. We therefore developed a biopanning protocol in which thrombin-reactive phages were selected using biotinylated anti-thrombin antibodies and streptavidin-coated magnetic beads. A library consisting of displayed API randomized at residues 357 and 358 (P2-P1) yielded predominantly Pro-Arg at these positions after five rounds of thrombin selection; in contrast the same degree of mock selection yielded only non-functional variants. A more diverse library of API M358R randomized at residues 352-356 (P7-P3) was also probed, yielding numerous variants fitting a loose consensus of DLTVS as judged by sequencing of the inserts of plaque-purified phages. The thrombin-selected sequences were transferred en masse into bacterial expression plasmids, and lysates from individual colonies were screening for API-thrombin complexing. The most active candidates from this sixth round of screening contained DITMA and AAFVS at P7-P3 and inhibited thrombin 2.1-fold more rapidly than API M358R with no change in reaction stoichiometry. Deep sequencing using the Ion Torrent platform confirmed that over 800 sequences were significantly enriched in the thrombin-panned versus naïve phage display library, including some detected using the combined phage display/bacterial lysate screening approach. Our results show that API joins Plasminogen Activator Inhibitor-1 (PAI-1) as a serpin amenable to phage display and suggest the utility of this approach for the selection of "designer serpins" with novel reactivity and/or specificity.

Phage Display of the Serpin Alpha-1 Proteinase Inhibitor Randomized at Consecutive Residues in the Reactive Centre Loop and Biopanned with or without Thrombin

PubMed Central

Scott, Benjamin M.; Matochko, Wadim L.; Gierczak, Richard F.; Bhakta, Varsha; Derda, Ratmir; Sheffield, William P.

2014-01-01

In spite of the power of phage display technology to identify variant proteins with novel properties in large libraries, it has only been previously applied to one member of the serpin superfamily. Here we describe phage display of human alpha-1 proteinase inhibitor (API) in a T7 bacteriophage system. API M358R fused to the C-terminus of T7 capsid protein 10B was directly shown to form denaturation-resistant complexes with thrombin by electrophoresis and immunoblotting following exposure of intact phages to thrombin. We therefore developed a biopanning protocol in which thrombin-reactive phages were selected using biotinylated anti-thrombin antibodies and streptavidin-coated magnetic beads. A library consisting of displayed API randomized at residues 357 and 358 (P2–P1) yielded predominantly Pro-Arg at these positions after five rounds of thrombin selection; in contrast the same degree of mock selection yielded only non-functional variants. A more diverse library of API M358R randomized at residues 352–356 (P7–P3) was also probed, yielding numerous variants fitting a loose consensus of DLTVS as judged by sequencing of the inserts of plaque-purified phages. The thrombin-selected sequences were transferred en masse into bacterial expression plasmids, and lysates from individual colonies were screening for API-thrombin complexing. The most active candidates from this sixth round of screening contained DITMA and AAFVS at P7–P3 and inhibited thrombin 2.1-fold more rapidly than API M358R with no change in reaction stoichiometry. Deep sequencing using the Ion Torrent platform confirmed that over 800 sequences were significantly enriched in the thrombin-panned versus naïve phage display library, including some detected using the combined phage display/bacterial lysate screening approach. Our results show that API joins Plasminogen Activator Inhibitor-1 (PAI-1) as a serpin amenable to phage display and suggest the utility of this approach for the selection of “designer serpins” with novel reactivity and/or specificity. PMID:24427287

Impact of heterogeneous activity and community structure on the evolutionary success of cooperators in social networks

NASA Astrophysics Data System (ADS)

Wu, Zhi-Xi; Rong, Zhihai; Yang, Han-Xin

2015-01-01

Recent empirical studies suggest that heavy-tailed distributions of human activities are universal in real social dynamics [L. Muchnik, S. Pei, L. C. Parra, S. D. S. Reis, J. S. Andrade Jr., S. Havlin, and H. A. Makse, Sci. Rep. 3, 1783 (2013), 10.1038/srep01783]. On the other hand, community structure is ubiquitous in biological and social networks [M. E. J. Newman, Nat. Phys. 8, 25 (2012), 10.1038/nphys2162]. Motivated by these facts, we here consider the evolutionary prisoner's dilemma game taking place on top of a real social network to investigate how the community structure and the heterogeneity in activity of individuals affect the evolution of cooperation. In particular, we account for a variation of the birth-death process (which can also be regarded as a proportional imitation rule from a social point of view) for the strategy updating under both weak and strong selection (meaning the payoffs harvested from games contribute either slightly or heavily to the individuals' performance). By implementing comparative studies, where the players are selected either randomly or in terms of their actual activities to play games with their immediate neighbors, we figure out that heterogeneous activity benefits the emergence of collective cooperation in a harsh environment (the action for cooperation is costly) under strong selection, whereas it impairs the formation of altruism under weak selection. Moreover, we find that the abundance of communities in the social network can evidently foster the formation of cooperation under strong selection, in contrast to the games evolving on randomized counterparts. Our results are therefore helpful for us to better understand the evolution of cooperation in real social systems.

Effects of feature-selective and spatial attention at different stages of visual processing.

PubMed

Andersen, Søren K; Fuchs, Sandra; Müller, Matthias M

2011-01-01

We investigated mechanisms of concurrent attentional selection of location and color using electrophysiological measures in human subjects. Two completely overlapping random dot kinematograms (RDKs) of two different colors were presented on either side of a central fixation cross. On each trial, participants attended one of these four RDKs, defined by its specific combination of color and location, in order to detect coherent motion targets. Sustained attentional selection while monitoring for targets was measured by means of steady-state visual evoked potentials (SSVEPs) elicited by the frequency-tagged RDKs. Attentional selection of transient targets and distractors was assessed by behavioral responses and by recording event-related potentials to these stimuli. Spatial attention and attention to color had independent and largely additive effects on the amplitudes of SSVEPs elicited in early visual areas. In contrast, behavioral false alarms and feature-selective modulation of P3 amplitudes to targets and distractors were limited to the attended location. These results suggest that feature-selective attention produces an early, global facilitation of stimuli having the attended feature throughout the visual field, whereas the discrimination of target events takes place at a later stage of processing that is only applied to stimuli at the attended position.

The reinterpretation of dreams: an evolutionary hypothesis of the function of dreaming.

PubMed

Revonsuo, A

2000-12-01

Several theories claim that dreaming is a random by-product of REM sleep physiology and that it does not serve any natural function. Phenomenal dream content, however, is not as disorganized as such views imply. The form and content of dreams is not random but organized and selective: during dreaming, the brain constructs a complex model of the world in which certain types of elements, when compared to waking life, are underrepresented whereas others are over represented. Furthermore, dream content is consistently and powerfully modulated by certain types of waking experiences. On the basis of this evidence, I put forward the hypothesis that the biological function of dreaming is to simulate threatening events, and to rehearse threat perception and threat avoidance. To evaluate this hypothesis, we need to consider the original evolutionary context of dreaming and the possible traces it has left in the dream content of the present human population. In the ancestral environment human life was short and full of threats. Any behavioral advantage in dealing with highly dangerous events would have increased the probability of reproductive success. A dream-production mechanism that tends to select threatening waking events and simulate them over and over again in various combinations would have been valuable for the development and maintenance of threat-avoidance skills. Empirical evidence from normative dream content, children's dreams, recurrent dreams, nightmares, post traumatic dreams, and the dreams of hunter-gatherers indicates that our dream-production mechanisms are in fact specialized in the simulation of threatening events, and thus provides support to the threat simulation hypothesis of the function of dreaming.

Identifying Human Papillomavirus Vaccination Practices Among Primary Care Providers of Minority, Low-Income and Immigrant Patient Populations

PubMed Central

Bruno, Denise M.; Wilson, Tracey E.; Gany, Francesca; Aragones, Abraham

2014-01-01

Objective Minority populations in the United States are disproportionally affected by Human Papillomavirus (HPV) infection and HPV-related cancer. We sought to understand physician practices, knowledge and beliefs that affect utilization of the HPV vaccine in primary care settings serving large minority populations in areas with increased rates of HPV-related cancer. Study Design Cross-sectional survey of randomly selected primary care providers, including pediatricians, family practice physicians and internists, serving large minority populations in Brooklyn, N.Y. and in areas with higher than average cervical cancer rates. Results Of 156 physicians randomly selected, 121 eligible providers responded to the survey; 64% were pediatricians, 19% were internists and 17% were family practitioners. Thirty-four percent of respondents reported that they routinely offered HPV vaccine to their eligible patients. Seventy percent of physicians reported that the lack of preventive care visits for patients in the eligible age group limited their ability to recommend the HPV vaccine and 70% of those who reported this barrier do not routinely recommend HPV vaccine. The lack of time to educate parents about the HPV vaccine and cost of the vaccine to their patients were two commonly reported barriers that affected whether providers offered the vaccine. Conclusions Our study found that the majority of providers serving the highest risk populations for HPV infection and HPV-related cancers are not routinely recommending the HPV vaccine to their patients. Reasons for providers' failure to recommend the HPV vaccine routinely are identified and possible areas for targeted interventions to increase HPV vaccination rates are discussed. PMID:24886959

Jacques Monod and Chance and Necessity.

PubMed

Ribatti, Domenico

2015-01-01

Charles Darwin proposed the theory that evolution of live organisms is based on random variation and natural selection. Jacques Monod, in his classic book Chance and Necessity, published 45 years ago, presented his thesis that the biosphere does not contain a predictable class of objects or events, but constitutes a particular occurrence, compatible indeed with the first principles but not deducible from those principles. The biosphere is therefore essentially unpredictable. In his book, Monod expounded at length on the conflict between science and religion. He saw religion as a collection of primitive myths that had been blown to shreds by science. At every turn, Monod emphasized the role of chance in human existence, an idea that is antithetical to essentially every religious doctrine that places humans as some inevitable intention of a Creator.

External validity of randomized controlled trials in older adults, a systematic review.

PubMed

van Deudekom, Floor J; Postmus, Iris; van der Ham, Danielle J; Pothof, Alexander B; Broekhuizen, Karen; Blauw, Gerard J; Mooijaart, Simon P

2017-01-01

To critically assess the external validity of randomized controlled trials (RCTs) it is important to know what older adults have been enrolled in the trials. The aim of this systematic review is to study what proportion of trials specifically designed for older patients report on somatic status, physical and mental functioning, social environment and frailty in the patient characteristics. PubMed was searched for articles published in 2012 and only RCTs were included. Articles were further excluded if not conducted with humans or only secondary analyses were reported. A random sample of 10% was drawn. The current review analyzed this random sample and further selected trials when the reported mean age was ≥ 60 years. We extracted geriatric assessments from the population descriptives or the in- and exclusion criteria. In total 1396 trials were analyzed and 300 trials included. The median of the reported mean age was 66 (IQR 63-70) and the median percentage of men in the trials was 60 (IQR 45-72). In 34% of the RCTs specifically designed for older patients somatic status, physical and mental functioning, social environment or frailty were reported in the population descriptives or the in- and exclusion criteria. Physical and mental functioning was reported most frequently (22% and 14%). When selecting RCTs on a mean age of 70 or 80 years the report of geriatric assessments in the patient characteristics was 46% and 85% respectively but represent only 5% and 1% of the trials. Somatic status, physical and mental functioning, social environment and frailty are underreported even in RCTs specifically designed for older patients published in 2012. Therefore, it is unclear for clinicians to which older patients the results can be applied. We recommend systematic to transparently report these relevant characteristics of older participants included in RCTs.

Applying a weighted random forests method to extract karst sinkholes from LiDAR data

NASA Astrophysics Data System (ADS)

Zhu, Junfeng; Pierskalla, William P.

2016-02-01

Detailed mapping of sinkholes provides critical information for mitigating sinkhole hazards and understanding groundwater and surface water interactions in karst terrains. LiDAR (Light Detection and Ranging) measures the earth's surface in high-resolution and high-density and has shown great potentials to drastically improve locating and delineating sinkholes. However, processing LiDAR data to extract sinkholes requires separating sinkholes from other depressions, which can be laborious because of the sheer number of the depressions commonly generated from LiDAR data. In this study, we applied the random forests, a machine learning method, to automatically separate sinkholes from other depressions in a karst region in central Kentucky. The sinkhole-extraction random forest was grown on a training dataset built from an area where LiDAR-derived depressions were manually classified through a visual inspection and field verification process. Based on the geometry of depressions, as well as natural and human factors related to sinkholes, 11 parameters were selected as predictive variables to form the dataset. Because the training dataset was imbalanced with the majority of depressions being non-sinkholes, a weighted random forests method was used to improve the accuracy of predicting sinkholes. The weighted random forest achieved an average accuracy of 89.95% for the training dataset, demonstrating that the random forest can be an effective sinkhole classifier. Testing of the random forest in another area, however, resulted in moderate success with an average accuracy rate of 73.96%. This study suggests that an automatic sinkhole extraction procedure like the random forest classifier can significantly reduce time and labor costs and makes its more tractable to map sinkholes using LiDAR data for large areas. However, the random forests method cannot totally replace manual procedures, such as visual inspection and field verification.

Some practical problems in implementing randomization.

PubMed

Downs, Matt; Tucker, Kathryn; Christ-Schmidt, Heidi; Wittes, Janet

2010-06-01

While often theoretically simple, implementing randomization to treatment in a masked, but confirmable, fashion can prove difficult in practice. At least three categories of problems occur in randomization: (1) bad judgment in the choice of method, (2) design and programming errors in implementing the method, and (3) human error during the conduct of the trial. This article focuses on these latter two types of errors, dealing operationally with what can go wrong after trial designers have selected the allocation method. We offer several case studies and corresponding recommendations for lessening the frequency of problems in allocating treatment or for mitigating the consequences of errors. Recommendations include: (1) reviewing the randomization schedule before starting a trial, (2) being especially cautious of systems that use on-demand random number generators, (3) drafting unambiguous randomization specifications, (4) performing thorough testing before entering a randomization system into production, (5) maintaining a dataset that captures the values investigators used to randomize participants, thereby allowing the process of treatment allocation to be reproduced and verified, (6) resisting the urge to correct errors that occur in individual treatment assignments, (7) preventing inadvertent unmasking to treatment assignments in kit allocations, and (8) checking a sample of study drug kits to allow detection of errors in drug packaging and labeling. Although we performed a literature search of documented randomization errors, the examples that we provide and the resultant recommendations are based largely on our own experience in industry-sponsored clinical trials. We do not know how representative our experience is or how common errors of the type we have seen occur. Our experience underscores the importance of verifying the integrity of the treatment allocation process before and during a trial. Clinical Trials 2010; 7: 235-245. http://ctj.sagepub.com.

The Coalescent Process in Models with Selection

PubMed Central

Kaplan, N. L.; Darden, T.; Hudson, R. R.

1988-01-01

Statistical properties of the process describing the genealogical history of a random sample of genes are obtained for a class of population genetics models with selection. For models with selection, in contrast to models without selection, the distribution of this process, the coalescent process, depends on the distribution of the frequencies of alleles in the ancestral generations. If the ancestral frequency process can be approximated by a diffusion, then the mean and the variance of the number of segregating sites due to selectively neutral mutations in random samples can be numerically calculated. The calculations are greatly simplified if the frequencies of the alleles are tightly regulated. If the mutation rates between alleles maintained by balancing selection are low, then the number of selectively neutral segregating sites in a random sample of genes is expected to substantially exceed the number predicted under a neutral model. PMID:3066685

Preliminary investigation of human exhaled breath for tuberculosis diagnosis by multidimensional gas chromatography - Time of flight mass spectrometry and machine learning.

PubMed

Beccaria, Marco; Mellors, Theodore R; Petion, Jacky S; Rees, Christiaan A; Nasir, Mavra; Systrom, Hannah K; Sairistil, Jean W; Jean-Juste, Marc-Antoine; Rivera, Vanessa; Lavoile, Kerline; Severe, Patrice; Pape, Jean W; Wright, Peter F; Hill, Jane E

2018-02-01

Tuberculosis (TB) remains a global public health malady that claims almost 1.8 million lives annually. Diagnosis of TB represents perhaps one of the most challenging aspects of tuberculosis control. Gold standards for diagnosis of active TB (culture and nucleic acid amplification) are sputum-dependent, however, in up to a third of TB cases, an adequate biological sputum sample is not readily available. The analysis of exhaled breath, as an alternative to sputum-dependent tests, has the potential to provide a simple, fast, and non-invasive, and ready-available diagnostic service that could positively change TB detection. Human breath has been evaluated in the setting of active tuberculosis using thermal desorption-comprehensive two-dimensional gas chromatography-time of flight mass spectrometry methodology. From the entire spectrum of volatile metabolites in breath, three random forest machine learning models were applied leading to the generation of a panel of 46 breath features. The twenty-two common features within each random forest model used were selected as a set that could distinguish subjects with confirmed pulmonary M. tuberculosis infection and people with other pathologies than TB. Copyright © 2018 Elsevier B.V. All rights reserved.

Effects of Selected Meditative Asanas on Kinaesthetic Perception and Speed of Movement

ERIC Educational Resources Information Center

Singh, Kanwaljeet; Bal, Baljinder S.; Deol, Nishan S.

2009-01-01

Study aim: To assess the effects of selected meditative "asanas" on kinesthetic perception and movement speed. Material and methods: Thirty randomly selected male students aged 18-24 years volunteered to participate in the study. They were randomly assigned into two groups: A (medidative) and B (control). The Nelson's movement speed and…

Model Selection with the Linear Mixed Model for Longitudinal Data

ERIC Educational Resources Information Center

Ryoo, Ji Hoon

2011-01-01

Model building or model selection with linear mixed models (LMMs) is complicated by the presence of both fixed effects and random effects. The fixed effects structure and random effects structure are codependent, so selection of one influences the other. Most presentations of LMM in psychology and education are based on a multilevel or…

Random one-of-N selector

DOEpatents

Kronberg, J.W.

1993-04-20

An apparatus for selecting at random one item of N items on the average comprising counter and reset elements for counting repeatedly between zero and N, a number selected by the user, a circuit for activating and deactivating the counter, a comparator to determine if the counter stopped at a count of zero, an output to indicate an item has been selected when the count is zero or not selected if the count is not zero. Randomness is provided by having the counter cycle very often while varying the relatively longer duration between activation and deactivation of the count. The passive circuit components of the activating/deactivating circuit and those of the counter are selected for the sensitivity of their response to variations in temperature and other physical characteristics of the environment so that the response time of the circuitry varies. Additionally, the items themselves, which may be people, may vary in shape or the time they press a pushbutton, so that, for example, an ultrasonic beam broken by the item or person passing through it will add to the duration of the count and thus to the randomness of the selection.

Random one-of-N selector

DOEpatents

Kronberg, James W.

1993-01-01

An apparatus for selecting at random one item of N items on the average comprising counter and reset elements for counting repeatedly between zero and N, a number selected by the user, a circuit for activating and deactivating the counter, a comparator to determine if the counter stopped at a count of zero, an output to indicate an item has been selected when the count is zero or not selected if the count is not zero. Randomness is provided by having the counter cycle very often while varying the relatively longer duration between activation and deactivation of the count. The passive circuit components of the activating/deactivating circuit and those of the counter are selected for the sensitivity of their response to variations in temperature and other physical characteristics of the environment so that the response time of the circuitry varies. Additionally, the items themselves, which may be people, may vary in shape or the time they press a pushbutton, so that, for example, an ultrasonic beam broken by the item or person passing through it will add to the duration of the count and thus to the randomness of the selection.

A multiresidue method for the determination of selected endocrine disrupting chemicals in human breast milk based on a simple extraction procedure.

PubMed

Rodríguez-Gómez, R; Jiménez-Díaz, I; Zafra-Gómez, A; Ballesteros, O; Navalón, A

2014-12-01

In recent decades, in parallel to industrial development, a large amount of new chemicals have emerged that are able to produce disorders in human endocrine system. These groups of substances, so-called endocrine disrupting chemicals (EDCs), include many families of compounds, such as parabens, benzophenone-UV filters and bisphenols. Given the demonstrated biological activity of those compounds, it is necessary to develop new analytical procedures to evaluate the exposure with the final objective of establishing, in an accurate way, relationships between EDCs concentrations and the harmful health effects observed in population. In the present work, a method based on a simplified sample treatment involving steps of precipitation, evaporation and clean-up of the extracts with C18 followed by ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) analysis for the determination of bisphenol A and its chlorinated derivatives (monochloro-, dichloro-, trichloro- and tetrachlorobisphenol A), parabens (methyl-, ethyl-, propyl- and butylparaben) and benzophenone-UV filters (benzophenone -1,-2, -3, -6, -8 and 4-hydroxybenzophenone) in human breast milk samples is proposed and validated. The limits of detections found ranged from 0.02 to 0.05 ng mL(-1). The method was validated using matrix-matched standard calibration followed by a recovery assay with spiked samples. Recovery rates ranged from 91% to 110% and the precision (evaluated as relative standard deviation) was lower than 15% for all compounds, being within the acceptable limits for the selected bioanalytical method validation guide. The method was satisfactorily applied for the determination of these compounds in human breast milk samples collected from 10 randomly selected women. Copyright © 2014 Elsevier B.V. All rights reserved.

Acute and chronic effects of noradrenergic enhancement on transcranial direct current stimulation-induced neuroplasticity in humans.

PubMed

Kuo, Hsiao-I; Paulus, Walter; Batsikadze, Giorgi; Jamil, Asif; Kuo, Min-Fang; Nitsche, Michael A

2017-02-15

Chronic administration of the selective noradrenaline reuptake inhibitor (NRI) reboxetine (RBX) increased and prolonged the long-term potentiation-like plasticity induced by anodal transcranial direct current stimulation (tDCS) for over 24 h. Chronic administration of RBX converted cathodal tDCS-induced long-term depression-like plasticity into facilitation for 120 min. Chronic noradrenergic activity enhancement on plasticity of the human brain might partially explain the delayed therapeutic impact of selective NRIs in depression and other neuropsychiatric diseases. Noradrenaline affects cognition and motor learning processes via its impact on long-term potentiation (LTP) and depression (LTD). We aimed to explore the impact of single dose and chronic administration of the selective noradrenaline reuptake inhibitor (NRI) reboxetine (RBX) on plasticity induced by transcranial direct current stimulation (tDCS) in healthy humans via a double-blinded, placebo-controlled, randomized crossover study. Sixteen healthy volunteers received placebo or single dose RBX (8 mg) before anodal or cathodal tDCS of the primary motor cortex. Afterwards, the same subjects took RBX (8 mg day -1 ) consecutively for 21 days. During this period, two additional interventions were performed (RBX with anodal or cathodal tDCS), to explore the impact of chronic RBX treatment on plasticity. Plasticity was monitored by motor-evoked potential amplitudes elicited by transcranial magnetic stimulation. Chronic administration of RBX increased and prolonged the LTP-like plasticity induced by anodal tDCS for over 24 h. Chronic RBX significantly converted cathodal tDCS-induced LTD-like plasticity into facilitation, as compared to the single dose condition, for 120 min after stimulation. The results show a prominent impact of chronic noradrenergic enhancement on plasticity of the human brain that might partially explain the delayed therapeutic impact of selective NRIs in depression and other neuropsychiatric diseases. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

PrimerStation: a highly specific multiplex genomic PCR primer design server for the human genome

PubMed Central

Yamada, Tomoyuki; Soma, Haruhiko; Morishita, Shinichi

2006-01-01

PrimerStation () is a web service that calculates primer sets guaranteeing high specificity against the entire human genome. To achieve high accuracy, we used the hybridization ratio of primers in liquid solution. Calculating the status of sequence hybridization in terms of the stringent hybridization ratio is computationally costly, and no web service checks the entire human genome and returns a highly specific primer set calculated using a precise physicochemical model. To shorten the response time, we precomputed candidates for specific primers using a massively parallel computer with 100 CPUs (SunFire 15 K) about 3 months in advance. This enables PrimerStation to search and output qualified primers interactively. PrimerStation can select highly specific primers suitable for multiplex PCR by seeking a wider temperature range that minimizes the possibility of cross-reaction. It also allows users to add heuristic rules to the primer design, e.g. the exclusion of single nucleotide polymorphisms (SNPs) in primers, the avoidance of poly(A) and CA-repeats in the PCR products, and the elimination of defective primers using the secondary structure prediction. We performed several tests to verify the PCR amplification of randomly selected primers for ChrX, and we confirmed that the primers amplify specific PCR products perfectly. PMID:16845094

Transmutation of human glutathione transferase A2-2 with peroxidase activity into an efficient steroid isomerase.

PubMed

Pettersson, Par L; Johansson, Ann-Sofie; Mannervik, Bengt

2002-08-16

A major goal in protein engineering is the tailor-making of enzymes for specified chemical reactions. Successful attempts have frequently been based on directed molecular evolution involving libraries of random mutants in which variants with desired properties were identified. For the engineering of enzymes with novel functions, it would be of great value if the necessary changes of the active site could be predicted and implemented. Such attempts based on the comparison of similar structures with different substrate selectivities have previously met with limited success. However, the present work shows that the knowledge-based redesign restricted to substrate-binding residues in human glutathione transferase A2-2 can introduce high steroid double-bond isomerase activity into the enzyme originally characterized by glutathione peroxidase activity. Both the catalytic center activity (k(cat)) and catalytic efficiency (k(cat)/K(m)) match the values of the naturally evolved glutathione transferase A3-3, the most active steroid isomerase known in human tissues. The substrate selectivity of the mutated glutathione transferase was changed 7000-fold by five point mutations. This example demonstrates the functional plasticity of the glutathione transferase scaffold as well as the potential of rational active-site directed mutagenesis as a complement to DNA shuffling and other stochastic methods for the redesign of proteins with novel functions.

Efficiency of extracting stereo-driven object motions

PubMed Central

Jain, Anshul; Zaidi, Qasim

2013-01-01

Most living things and many nonliving things deform as they move, requiring observers to separate object motions from object deformations. When the object is partially occluded, the task becomes more difficult because it is not possible to use two-dimensional (2-D) contour correlations (Cohen, Jain, & Zaidi, 2010). That leaves dynamic depth matching across the unoccluded views as the main possibility. We examined the role of stereo cues in extracting motion of partially occluded and deforming three-dimensional (3-D) objects, simulated by disk-shaped random-dot stereograms set at randomly assigned depths and placed uniformly around a circle. The stereo-disparities of the disks were temporally oscillated to simulate clockwise or counterclockwise rotation of the global shape. To dynamically deform the global shape, random disparity perturbation was added to each disk's depth on each stimulus frame. At low perturbation, observers reported rotation directions consistent with the global shape, even against local motion cues, but performance deteriorated at high perturbation. Using 3-D global shape correlations, we formulated an optimal Bayesian discriminator for rotation direction. Based on rotation discrimination thresholds, human observers were 75% as efficient as the optimal model, demonstrating that global shapes derived from stereo cues facilitate inferences of object motions. To complement reports of stereo and motion integration in extrastriate cortex, our results suggest the possibilities that disparity selectivity and feature tracking are linked, or that global motion selective neurons can be driven purely from disparity cues. PMID:23325345

Semiparametric Bayesian classification with longitudinal markers

PubMed Central

De la Cruz-Mesía, Rolando; Quintana, Fernando A.; Müller, Peter

2013-01-01

Summary We analyse data from a study involving 173 pregnant women. The data are observed values of the β human chorionic gonadotropin hormone measured during the first 80 days of gestational age, including from one up to six longitudinal responses for each woman. The main objective in this study is to predict normal versus abnormal pregnancy outcomes from data that are available at the early stages of pregnancy. We achieve the desired classification with a semiparametric hierarchical model. Specifically, we consider a Dirichlet process mixture prior for the distribution of the random effects in each group. The unknown random-effects distributions are allowed to vary across groups but are made dependent by using a design vector to select different features of a single underlying random probability measure. The resulting model is an extension of the dependent Dirichlet process model, with an additional probability model for group classification. The model is shown to perform better than an alternative model which is based on independent Dirichlet processes for the groups. Relevant posterior distributions are summarized by using Markov chain Monte Carlo methods. PMID:24368871

Population differentiation in Pacific salmon: local adaptation, genetic drift, or the environment?

USGS Publications Warehouse

Adkison, Milo D.

1995-01-01

Morphological, behavioral, and life-history differences between Pacific salmon (Oncorhynchus spp.) populations are commonly thought to reflect local adaptation, and it is likewise common to assume that salmon populations separated by small distances are locally adapted. Two alternatives to local adaptation exist: random genetic differentiation owing to genetic drift and founder events, and genetic homogeneity among populations, in which differences reflect differential trait expression in differing environments. Population genetics theory and simulations suggest that both alternatives are possible. With selectively neutral alleles, genetic drift can result in random differentiation despite many strays per generation. Even weak selection can prevent genetic drift in stable populations; however, founder effects can result in random differentiation despite selective pressures. Overlapping generations reduce the potential for random differentiation. Genetic homogeneity can occur despite differences in selective regimes when straying rates are high. In sum, localized differences in selection should not always result in local adaptation. Local adaptation is favored when population sizes are large and stable, selection is consistent over large areas, selective diffeentials are large, and straying rates are neither too high nor too low. Consideration of alternatives to local adaptation would improve both biological research and salmon conservation efforts.

Do Vascular Networks Branch Optimally or Randomly across Spatial Scales?

PubMed Central

Newberry, Mitchell G.; Savage, Van M.

2016-01-01

Modern models that derive allometric relationships between metabolic rate and body mass are based on the architectural design of the cardiovascular system and presume sibling vessels are symmetric in terms of radius, length, flow rate, and pressure. Here, we study the cardiovascular structure of the human head and torso and of a mouse lung based on three-dimensional images processed via our software Angicart. In contrast to modern allometric theories, we find systematic patterns of asymmetry in vascular branching, potentially explaining previously documented mismatches between predictions (power-law or concave curvature) and observed empirical data (convex curvature) for the allometric scaling of metabolic rate. To examine why these systematic asymmetries in vascular branching might arise, we construct a mathematical framework to derive predictions based on local, junction-level optimality principles that have been proposed to be favored in the course of natural selection and development. The two most commonly used principles are material-cost optimizations (construction materials or blood volume) and optimization of efficient flow via minimization of power loss. We show that material-cost optimization solutions match with distributions for asymmetric branching across the whole network but do not match well for individual junctions. Consequently, we also explore random branching that is constrained at scales that range from local (junction-level) to global (whole network). We find that material-cost optimizations are the strongest predictor of vascular branching in the human head and torso, whereas locally or intermediately constrained random branching is comparable to material-cost optimizations for the mouse lung. These differences could be attributable to developmentally-programmed local branching for larger vessels and constrained random branching for smaller vessels. PMID:27902691

Long-range correlations and charge transport properties of DNA sequences

NASA Astrophysics Data System (ADS)

Liu, Xiao-liang; Ren, Yi; Xie, Qiong-tao; Deng, Chao-sheng; Xu, Hui

2010-04-01

By using Hurst's analysis and transfer approach, the rescaled range functions and Hurst exponents of human chromosome 22 and enterobacteria phage lambda DNA sequences are investigated and the transmission coefficients, Landauer resistances and Lyapunov coefficients of finite segments based on above genomic DNA sequences are calculated. In a comparison with quasiperiodic and random artificial DNA sequences, we find that λ-DNA exhibits anticorrelation behavior characterized by a Hurst exponent 0.5

Genetic relatedness between oral and intestinal isolates of Porphyromonas endodontalis by analysis of random amplified polymorphic DNA.

PubMed

Gonçalves, R B; Väisänen, M L; Van Steenbergen, T J; Sundqvist, G; Mouton, C

1999-01-01

Genomic fingerprints from the DNA of 27 strains of Porphyromonas endodontalis from diverse clinical and geographic origins were generated as random amplified polymorphic DNA (RAPD) using the technique of PCR amplification with a single primer of arbitrary sequence. Cluster analysis of the combined RAPD data obtained with three selected 9- or 10-mer-long primers identified 25 distinct RAPD types which clustered as three main groups identifying three genogroups. Genogroups I and II included exclusively P. endodontalis isolates of oral origin, while 7/9 human intestinal strains of genogroup III which linked at a similarity level of 52% constituted the most homogeneous group in our study. Genotypic diversity within P. endodontalis, as shown by RAPD analysis, suggests that the taxon is composed of two oral genogroups and one intestinal genogroup. This hypothesis remains to be confirmed.

Effect of expanding medicaid for parents on children's health insurance coverage: lessons from the Oregon experiment.

PubMed

DeVoe, Jennifer E; Marino, Miguel; Angier, Heather; O'Malley, Jean P; Crawford, Courtney; Nelson, Christine; Tillotson, Carrie J; Bailey, Steffani R; Gallia, Charles; Gold, Rachel

2015-01-01

In the United States, health insurance is not universal. Observational studies show an association between uninsured parents and children. This association persisted even after expansions in child-only public health insurance. Oregon's randomized Medicaid expansion for adults, known as the Oregon Experiment, created a rare opportunity to assess causality between parent and child coverage. To estimate the effect on a child's health insurance coverage status when (1) a parent randomly gains access to health insurance and (2) a parent obtains coverage. Oregon Experiment randomized natural experiment assessing the results of Oregon's 2008 Medicaid expansion. We used generalized estimating equation models to examine the longitudinal effect of a parent randomly selected to apply for Medicaid on their child's Medicaid or Children's Health Insurance Program (CHIP) coverage (intent-to-treat analyses). We used per-protocol analyses to understand the impact on children's coverage when a parent was randomly selected to apply for and obtained Medicaid. Participants included 14409 children aged 2 to 18 years whose parents participated in the Oregon Experiment. For intent-to-treat analyses, the date a parent was selected to apply for Medicaid was considered the date the child was exposed to the intervention. In per-protocol analyses, exposure was defined as whether a selected parent obtained Medicaid. Children's Medicaid or CHIP coverage, assessed monthly and in 6-month intervals relative to their parent's selection date. In the immediate period after selection, children whose parents were selected to apply significantly increased from 3830 (61.4%) to 4152 (66.6%) compared with a nonsignificant change from 5049 (61.8%) to 5044 (61.7%) for children whose parents were not selected to apply. Children whose parents were randomly selected to apply for Medicaid had 18% higher odds of being covered in the first 6 months after parent's selection compared with children whose parents were not selected (adjusted odds ratio [AOR]=1.18; 95% CI, 1.10-1.27). The effect remained significant during months 7 to 12 (AOR=1.11; 95% CI, 1.03-1.19); months 13 to 18 showed a positive but not significant effect (AOR=1.07; 95% CI, 0.99-1.14). Children whose parents were selected and obtained coverage had more than double the odds of having coverage compared with children whose parents were not selected and did not gain coverage (AOR=2.37; 95% CI, 2.14-2.64). Children's odds of having Medicaid or CHIP coverage increased when their parents were randomly selected to apply for Medicaid. Children whose parents were selected and subsequently obtained coverage benefited most. This study demonstrates a causal link between parents' access to Medicaid coverage and their children's coverage.

3D statistical shape models incorporating 3D random forest regression voting for robust CT liver segmentation

NASA Astrophysics Data System (ADS)

Norajitra, Tobias; Meinzer, Hans-Peter; Maier-Hein, Klaus H.

2015-03-01

During image segmentation, 3D Statistical Shape Models (SSM) usually conduct a limited search for target landmarks within one-dimensional search profiles perpendicular to the model surface. In addition, landmark appearance is modeled only locally based on linear profiles and weak learners, altogether leading to segmentation errors from landmark ambiguities and limited search coverage. We present a new method for 3D SSM segmentation based on 3D Random Forest Regression Voting. For each surface landmark, a Random Regression Forest is trained that learns a 3D spatial displacement function between the according reference landmark and a set of surrounding sample points, based on an infinite set of non-local randomized 3D Haar-like features. Landmark search is then conducted omni-directionally within 3D search spaces, where voxelwise forest predictions on landmark position contribute to a common voting map which reflects the overall position estimate. Segmentation experiments were conducted on a set of 45 CT volumes of the human liver, of which 40 images were randomly chosen for training and 5 for testing. Without parameter optimization, using a simple candidate selection and a single resolution approach, excellent results were achieved, while faster convergence and better concavity segmentation were observed, altogether underlining the potential of our approach in terms of increased robustness from distinct landmark detection and from better search coverage.

The analgesic effects of exogenous melatonin in humans.

PubMed

Andersen, Lars Peter Holst

2016-10-01

The hormone, melatonin is produced with circadian rhythm by the pineal gland in humans. The melatonin rhythm provides an endogenous synchronizer, modulating e.g. blood pressure, body temperature, cortisol rhythm, sleep-awake-cycle, immune function and anti-oxidative defence. Interestingly, a number of experimental animal studies demonstrate significant dose-dependent anti-nociceptive effects of exogenous melatonin. Similarly, recent experimental- and clinical studies in humans indicate significant analgesic effects. In study I, we systematically reviewed all randomized studies investigating clinical effects of perioperative melatonin. Meta-analyses demonstrated significant analgesic and anxiolytic effects of melatonin in surgical patients, equating reductions of 20 mm and 19 mm, respectively on a VAS, compared with placebo. Profound heterogeneity between the included studies was, however, present. In study II, we aimed to investigate the analgesic, anti-hyperalgesic and anti-inflammatory effects of exogenous melatonin in a validated human inflammatory pain model, the human burn model. The study was performed as a randomized, double blind placebo-controlled crossover study. Primary outcomes were pain during the burn injury and areas of secondary hyperalgesia. No significant effects of exogenous melatonin were observed with respect to primary or secondary outcomes, compared to placebo. Study III and IV estimated the pharmacokinetic variables of exogenous melatonin. Oral melatonin demonstrated a t max value of 41 minutes. Bioavailability of oral melatonin was only 3%. Elimination t 1/2 were approximately 45 minutes following both oral and intravenous administration, respectively. High-dose intravenous melatonin was not associated with increased sedation, in terms of simple reaction times, compared to placebo. Similarly, no other adverse effects were reported. In Study V, we aimed to re-analyse data obtained from a randomized analgesic drug trial by a selection of standard statistical test. Furthermore, we presented an integrated assessment method of longitudinally measured pain intensity and opioid consumption. Our analyses documented that the employed statistical method impacted the statistical significance of post-operative analgesic outcomes. Furthermore, the novel integrated assessment method combines two interdependent outcomes, lowers the risk of type 2 errors, increases the statistical power, and provides a more accurate description of post-operative analgesic efficacy. Exogenous melatonin may offer an effective and safe analgesic drug. At this moment, however, the results of human studies have been contradictory. High-quality randomized experimental- and clinical studies are still needed to establish a "genuine" analgesic effect of the drug in humans. Other perioperative effects of exogenous melatonin should also be investigated, before melatonin can be introduced for clinical routine use in surgical patients. Despite promising experimental and clinical findings, several unanswered questions also relate to optimal dosage, timing of administration and administration route of exogenous melatonin.

40 CFR 761.355 - Third level of sample selection.

Code of Federal Regulations, 2012 CFR

2012-07-01

... of sample selection further reduces the size of the subsample to 100 grams which is suitable for the... procedures in § 761.353 of this part into 100 gram portions. (b) Use a random number generator or random number table to select one 100 gram size portion as a sample for a procedure used to simulate leachate...

40 CFR 761.355 - Third level of sample selection.

Code of Federal Regulations, 2011 CFR

2011-07-01

... of sample selection further reduces the size of the subsample to 100 grams which is suitable for the... procedures in § 761.353 of this part into 100 gram portions. (b) Use a random number generator or random number table to select one 100 gram size portion as a sample for a procedure used to simulate leachate...

40 CFR 761.355 - Third level of sample selection.

Code of Federal Regulations, 2013 CFR

2013-07-01

... of sample selection further reduces the size of the subsample to 100 grams which is suitable for the... procedures in § 761.353 of this part into 100 gram portions. (b) Use a random number generator or random number table to select one 100 gram size portion as a sample for a procedure used to simulate leachate...

40 CFR 761.355 - Third level of sample selection.

Code of Federal Regulations, 2010 CFR

2010-07-01

... of sample selection further reduces the size of the subsample to 100 grams which is suitable for the... procedures in § 761.353 of this part into 100 gram portions. (b) Use a random number generator or random number table to select one 100 gram size portion as a sample for a procedure used to simulate leachate...

40 CFR 761.355 - Third level of sample selection.

Code of Federal Regulations, 2014 CFR

2014-07-01

... of sample selection further reduces the size of the subsample to 100 grams which is suitable for the... procedures in § 761.353 of this part into 100 gram portions. (b) Use a random number generator or random number table to select one 100 gram size portion as a sample for a procedure used to simulate leachate...

Evolution of the human immunodeficiency virus envelope gene is dominated by purifying selection.

PubMed

Edwards, C T T; Holmes, E C; Pybus, O G; Wilson, D J; Viscidi, R P; Abrams, E J; Phillips, R E; Drummond, A J

2006-11-01

The evolution of the human immunodeficiency virus (HIV-1) during chronic infection involves the rapid, continuous turnover of genetic diversity. However, the role of natural selection, relative to random genetic drift, in governing this process is unclear. We tested a stochastic model of genetic drift using partial envelope sequences sampled longitudinally in 28 infected children. In each case the Bayesian posterior (empirical) distribution of coalescent genealogies was estimated using Markov chain Monte Carlo methods. Posterior predictive simulation was then used to generate a null distribution of genealogies assuming neutrality, with the null and empirical distributions compared using four genealogy-based summary statistics sensitive to nonneutral evolution. Because both null and empirical distributions were generated within a coalescent framework, we were able to explicitly account for the confounding influence of demography. From the distribution of corrected P-values across patients, we conclude that empirical genealogies are more asymmetric than expected if evolution is driven by mutation and genetic drift only, with an excess of low-frequency polymorphisms in the population. This indicates that although drift may still play an important role, natural selection has a strong influence on the evolution of HIV-1 envelope. A negative relationship between effective population size and substitution rate indicates that as the efficacy of selection increases, a smaller proportion of mutations approach fixation in the population. This suggests the presence of deleterious mutations. We therefore conclude that intrahost HIV-1 evolution in envelope is dominated by purifying selection against low-frequency deleterious mutations that do not reach fixation.

Peculiarities of the statistics of spectrally selected fluorescence radiation in laser-pumped dye-doped random media

NASA Astrophysics Data System (ADS)

Yuvchenko, S. A.; Ushakova, E. V.; Pavlova, M. V.; Alonova, M. V.; Zimnyakov, D. A.

2018-04-01

We consider the practical realization of a new optical probe method of the random media which is defined as the reference-free path length interferometry with the intensity moments analysis. A peculiarity in the statistics of the spectrally selected fluorescence radiation in laser-pumped dye-doped random medium is discussed. Previously established correlations between the second- and the third-order moments of the intensity fluctuations in the random interference patterns, the coherence function of the probe radiation, and the path difference probability density for the interfering partial waves in the medium are confirmed. The correlations were verified using the statistical analysis of the spectrally selected fluorescence radiation emitted by a laser-pumped dye-doped random medium. Water solution of Rhodamine 6G was applied as the doping fluorescent agent for the ensembles of the densely packed silica grains, which were pumped by the 532 nm radiation of a solid state laser. The spectrum of the mean path length for a random medium was reconstructed.

Effect of Methodological and Ecological Approaches on Heterogeneity of Nest-Site Selection of a Long-Lived Vulture

PubMed Central

Moreno-Opo, Rubén; Fernández-Olalla, Mariana; Margalida, Antoni; Arredondo, Ángel; Guil, Francisco

2012-01-01

The application of scientific-based conservation measures requires that sampling methodologies in studies modelling similar ecological aspects produce comparable results making easier their interpretation. We aimed to show how the choice of different methodological and ecological approaches can affect conclusions in nest-site selection studies along different Palearctic meta-populations of an indicator species. First, a multivariate analysis of the variables affecting nest-site selection in a breeding colony of cinereous vulture (Aegypius monachus) in central Spain was performed. Then, a meta-analysis was applied to establish how methodological and habitat-type factors determine differences and similarities in the results obtained by previous studies that have modelled the forest breeding habitat of the species. Our results revealed patterns in nesting-habitat modelling by the cinereous vulture throughout its whole range: steep and south-facing slopes, great cover of large trees and distance to human activities were generally selected. The ratio and situation of the studied plots (nests/random), the use of plots vs. polygons as sampling units and the number of years of data set determined the variability explained by the model. Moreover, a greater size of the breeding colony implied that ecological and geomorphological variables at landscape level were more influential. Additionally, human activities affected in greater proportion to colonies situated in Mediterranean forests. For the first time, a meta-analysis regarding the factors determining nest-site selection heterogeneity for a single species at broad scale was achieved. It is essential to homogenize and coordinate experimental design in modelling the selection of species' ecological requirements in order to avoid that differences in results among studies would be due to methodological heterogeneity. This would optimize best conservation and management practices for habitats and species in a global context. PMID:22413023

Decision-making after continuous wins or losses in a randomized guessing task: implications for how the prior selection results affect subsequent decision-making.

PubMed

Dong, Guangheng; Lin, Xiao; Zhou, Hongli; Du, Xiaoxia

2014-04-03

Human decision-making is often affected by prior selections and their outcomes, even in situations where decisions are independent and outcomes are unpredictable. In this study, we created a task that simulated real-life non-strategic gambling to examine the effect of prior outcomes on subsequent decisions in a group of male college students. Behavioral performance showed that participants needed more time to react after continuous losses (LOSS) than continuous wins (WIN) and discontinuous outcomes (CONTROL). In addition, participants were more likely to repeat their selections in both WIN and LOSS conditions. Functional MRI data revealed that decisions in WINs were associated with increased activation in the mesolimbic pathway, but decreased activation in the inferior frontal gyrus relative to LOSS. Increased prefrontal cortical activation was observed during LOSS relative to WIN and CONTROL conditions. Taken together, the behavioral and neuroimaging findings suggest that participants tended to repeat previous selections during LOSS trials, a pattern resembling the gambler's fallacy. However, during WIN trials, participants tended to follow their previous lucky decisions, like the 'hot hand' fallacy.

Directed evolution: tailoring biocatalysts for industrial applications.

PubMed

Kumar, Ashwani; Singh, Suren

2013-12-01

Current challenges and promises of white biotechnology encourage protein engineers to use a directed evolution approach to generate novel and useful biocatalysts for various sets of applications. Different methods of enzyme engineering have been used in the past in an attempt to produce enzymes with improved functions and properties. Recent advancement in the field of random mutagenesis, screening, selection and computational design increased the versatility and the rapid development of enzymes under strong selection pressure with directed evolution experiments. Techniques of directed evolution improve enzymes fitness without understanding them in great detail and clearly demonstrate its future role in adapting enzymes for use in industry. Despite significant advances to date regarding biocatalyst improvement, there still remains a need to improve mutagenesis strategies and development of easy screening and selection tools without significant human intervention. This review covers fundamental and major development of directed evolution techniques, and highlights the advances in mutagenesis, screening and selection methods with examples of enzymes developed by using these approaches. Several commonly used methods for creating molecular diversity with their advantages and disadvantages including some recently used strategies are also discussed.

Computational problems in autoregressive moving average (ARMA) models

NASA Technical Reports Server (NTRS)

Agarwal, G. C.; Goodarzi, S. M.; Oneill, W. D.; Gottlieb, G. L.

1981-01-01

The choice of the sampling interval and the selection of the order of the model in time series analysis are considered. Band limited (up to 15 Hz) random torque perturbations are applied to the human ankle joint. The applied torque input, the angular rotation output, and the electromyographic activity using surface electrodes from the extensor and flexor muscles of the ankle joint are recorded. Autoregressive moving average models are developed. A parameter constraining technique is applied to develop more reliable models. The asymptotic behavior of the system must be taken into account during parameter optimization to develop predictive models.

Biological cell controllable patch-clamp microchip

NASA Astrophysics Data System (ADS)

Penmetsa, Siva; Nagrajan, Krithika; Gong, Zhongcheng; Mills, David; Que, Long

2010-12-01

A patch-clamp (PC) microchip with cell sorting and positioning functions is reported, which can avoid drawbacks of random cell selection or positioning for a PC microchip. The cell sorting and positioning are enabled by air bubble (AB) actuators. AB actuators are pneumatic actuators, in which air pressure is generated by microheaters within sealed microchambers. The sorting, positioning, and capturing of 3T3 cells by this type of microchip have been demonstrated. Using human breast cancer cells MDA-MB-231 as the model, experiments have been demonstrated by this microchip as a label-free technical platform for real-time monitoring of the cell viability.

CURE-SMOTE algorithm and hybrid algorithm for feature selection and parameter optimization based on random forests.

PubMed

Ma, Li; Fan, Suohai

2017-03-14

The random forests algorithm is a type of classifier with prominent universality, a wide application range, and robustness for avoiding overfitting. But there are still some drawbacks to random forests. Therefore, to improve the performance of random forests, this paper seeks to improve imbalanced data processing, feature selection and parameter optimization. We propose the CURE-SMOTE algorithm for the imbalanced data classification problem. Experiments on imbalanced UCI data reveal that the combination of Clustering Using Representatives (CURE) enhances the original synthetic minority oversampling technique (SMOTE) algorithms effectively compared with the classification results on the original data using random sampling, Borderline-SMOTE1, safe-level SMOTE, C-SMOTE, and k-means-SMOTE. Additionally, the hybrid RF (random forests) algorithm has been proposed for feature selection and parameter optimization, which uses the minimum out of bag (OOB) data error as its objective function. Simulation results on binary and higher-dimensional data indicate that the proposed hybrid RF algorithms, hybrid genetic-random forests algorithm, hybrid particle swarm-random forests algorithm and hybrid fish swarm-random forests algorithm can achieve the minimum OOB error and show the best generalization ability. The training set produced from the proposed CURE-SMOTE algorithm is closer to the original data distribution because it contains minimal noise. Thus, better classification results are produced from this feasible and effective algorithm. Moreover, the hybrid algorithm's F-value, G-mean, AUC and OOB scores demonstrate that they surpass the performance of the original RF algorithm. Hence, this hybrid algorithm provides a new way to perform feature selection and parameter optimization.

Risk factors for human-directed canine aggression in a referral level clinical population.

PubMed

Lord, M; Casey, R A; Loftus, B A; Blackwell, E J

2017-07-07

Risk factors for human-directed aggression were investigated using retrospective analysis of data from a referral-level clinical behaviour population in the UK. A sample of 200 cases involving human-directed canine aggression and 200 control cases involving no instance of human-directed aggression were selected at random from a population of 746 cases. The final model suggested that clinical cases with human-directed aggression were significantly younger than those presenting with other undesired behaviours (P=0.008) and that male dogs were 1.4 times more likely to be aggressive towards human beings than female dogs (P=0.019). Dogs were 1.7 times more likely to be aggressive towards people if they had attended more than five puppy classes than if they had never attended puppy class (P=0.015) and that dogs were 2.8 times more likely to be aggressive towards human beings if there was another dog between 0 months and 24 months of age in the home (P=0.004). These factors only account for 7 per cent to 10 per cent of the variance between the human-directed aggression population and the control population, but factors such as attendance at puppy classes and numbers of dogs in the household suggest the need for longitudinal studies to investigate temporal relationships.

Landscape conditions predisposing grizzly bears to conflicts on private agricultural lands in the western USA

USGS Publications Warehouse

Wilson, S.M.; Madel, M.J.; Mattson, D.J.; Graham, J.M.; Merrill, T.

2006-01-01

We used multiple logistic regression to model how different landscape conditions contributed to the probability of human-grizzly bear conflicts on private agricultural ranch lands. We used locations of livestock pastures, traditional livestock carcass disposal areas (boneyards), beehives, and wetland-riparian associated vegetation to model the locations of 178 reported human-grizzly bear conflicts along the Rocky Mountain East Front, Montana, USA during 1986-2001. We surveyed 61 livestock producers in the upper Teton watershed of north-central Montana, to collect spatial and temporal data on livestock pastures, boneyards, and beehives for the same period, accounting for changes in livestock and boneyard management and beehive location and protection, for each season. We used 2032 random points to represent the null hypothesis of random location relative to potential explanatory landscape features, and used Akaike's Information Criteria (AIC/AICC) and Hosmer-Lemeshow goodness-of-fit statistics for model selection. We used a resulting "best" model to map contours of predicted probabilities of conflict, and used this map for verification with an independent dataset of conflicts to provide additional insights regarding the nature of conflicts. The presence of riparian vegetation and distances to spring, summer, and fall sheep or cattle pastures, calving and sheep lambing areas, unmanaged boneyards, and fenced and unfenced beehives were all associated with the likelihood of human-grizzly bear conflicts. Our model suggests that collections of attractants concentrated in high quality bear habitat largely explain broad patterns of human-grizzly bear conflicts on private agricultural land in our study area. ?? 2005 Elsevier Ltd. All rights reserved.

A highly functional synthetic phage display library containing over 40 billion human antibody clones.

PubMed

Weber, Marcel; Bujak, Emil; Putelli, Alessia; Villa, Alessandra; Matasci, Mattia; Gualandi, Laura; Hemmerle, Teresa; Wulhfard, Sarah; Neri, Dario

2014-01-01

Several synthetic antibody phage display libraries have been created and used for the isolation of human monoclonal antibodies. The performance of antibody libraries, which is usually measured in terms of their ability to yield high-affinity binding specificities against target proteins of interest, depends both on technical aspects (such as library size and quality of cloning) and on design features (which influence the percentage of functional clones in the library and their ability to be used for practical applications). Here, we describe the design, construction and characterization of a combinatorial phage display library, comprising over 40 billion human antibody clones in single-chain fragment variable (scFv) format. The library was designed with the aim to obtain highly stable antibody clones, which can be affinity-purified on protein A supports, even when used in scFv format. The library was found to be highly functional, as >90% of randomly selected clones expressed the corresponding antibody. When selected against more than 15 antigens from various sources, the library always yielded specific and potent binders, at a higher frequency compared to previous antibody libraries. To demonstrate library performance in practical biomedical research projects, we isolated the human antibody G5, which reacts both against human and murine forms of the alternatively spliced BCD segment of tenascin-C, an extracellular matrix component frequently over-expressed in cancer and in chronic inflammation. The new library represents a useful source of binding specificities, both for academic research and for the development of antibody-based therapeutics.

A Highly Functional Synthetic Phage Display Library Containing over 40 Billion Human Antibody Clones

PubMed Central

Weber, Marcel; Bujak, Emil; Putelli, Alessia; Villa, Alessandra; Matasci, Mattia; Gualandi, Laura; Hemmerle, Teresa; Wulhfard, Sarah; Neri, Dario

2014-01-01

Several synthetic antibody phage display libraries have been created and used for the isolation of human monoclonal antibodies. The performance of antibody libraries, which is usually measured in terms of their ability to yield high-affinity binding specificities against target proteins of interest, depends both on technical aspects (such as library size and quality of cloning) and on design features (which influence the percentage of functional clones in the library and their ability to be used for practical applications). Here, we describe the design, construction and characterization of a combinatorial phage display library, comprising over 40 billion human antibody clones in single-chain fragment variable (scFv) format. The library was designed with the aim to obtain highly stable antibody clones, which can be affinity-purified on protein A supports, even when used in scFv format. The library was found to be highly functional, as >90% of randomly selected clones expressed the corresponding antibody. When selected against more than 15 antigens from various sources, the library always yielded specific and potent binders, at a higher frequency compared to previous antibody libraries. To demonstrate library performance in practical biomedical research projects, we isolated the human antibody G5, which reacts both against human and murine forms of the alternatively spliced BCD segment of tenascin-C, an extracellular matrix component frequently over-expressed in cancer and in chronic inflammation. The new library represents a useful source of binding specificities, both for academic research and for the development of antibody-based therapeutics. PMID:24950200

Dihydrofolate-Reductase Mutations in Plasmodium knowlesi Appear Unrelated to Selective Drug Pressure from Putative Human-To-Human Transmission in Sabah, Malaysia.

PubMed

Grigg, Matthew J; Barber, Bridget E; Marfurt, Jutta; Imwong, Mallika; William, Timothy; Bird, Elspeth; Piera, Kim A; Aziz, Ammar; Boonyuen, Usa; Drakeley, Christopher J; Cox, Jonathan; White, Nicholas J; Cheng, Qin; Yeo, Tsin W; Auburn, Sarah; Anstey, Nicholas M

2016-01-01

Malaria caused by zoonotic Plasmodium knowlesi is an emerging threat in Eastern Malaysia. Despite demonstrated vector competency, it is unknown whether human-to-human (H-H) transmission is occurring naturally. We sought evidence of drug selection pressure from the antimalarial sulfadoxine-pyrimethamine (SP) as a potential marker of H-H transmission. The P. knowlesi dihdyrofolate-reductase (pkdhfr) gene was sequenced from 449 P. knowlesi malaria cases from Sabah (Malaysian Borneo) and genotypes evaluated for association with clinical and epidemiological factors. Homology modelling using the pvdhfr template was used to assess the effect of pkdhfr mutations on the pyrimethamine binding pocket. Fourteen non-synonymous mutations were detected, with the most common being at codon T91P (10.2%) and R34L (10.0%), resulting in 21 different genotypes, including the wild-type, 14 single mutants, and six double mutants. One third of the P. knowlesi infections were with pkdhfr mutants; 145 (32%) patients had single mutants and 14 (3%) had double-mutants. In contrast, among the 47 P. falciparum isolates sequenced, three pfdhfr genotypes were found, with the double mutant 108N+59R being fixed and the triple mutants 108N+59R+51I and 108N+59R+164L occurring with frequencies of 4% and 8%, respectively. Two non-random spatio-temporal clusters were identified with pkdhfr genotypes. There was no association between pkdhfr mutations and hyperparasitaemia or malaria severity, both hypothesized to be indicators of H-H transmission. The orthologous loci associated with resistance in P. falciparum were not mutated in pkdhfr. Subsequent homology modelling of pkdhfr revealed gene loci 13, 53, 120, and 173 as being critical for pyrimethamine binding, however, there were no mutations at these sites among the 449 P. knowlesi isolates. Although moderate diversity was observed in pkdhfr in Sabah, there was no evidence this reflected selective antifolate drug pressure in humans.

THE SELECTION OF A NATIONAL RANDOM SAMPLE OF TEACHERS FOR EXPERIMENTAL CURRICULUM EVALUATION.

ERIC Educational Resources Information Center

WELCH, WAYNE W.; AND OTHERS

MEMBERS OF THE EVALUATION SECTION OF HARVARD PROJECT PHYSICS, DESCRIBING WHAT IS SAID TO BE THE FIRST ATTEMPT TO SELECT A NATIONAL RANDOM SAMPLE OF (HIGH SCHOOL PHYSICS) TEACHERS, LIST THE STEPS AS (1) PURCHASE OF A LIST OF PHYSICS TEACHERS FROM THE NATIONAL SCIENCE TEACHERS ASSOCIATION (MOST COMPLETE AVAILABLE), (2) SELECTION OF 136 NAMES BY A…

Unbiased feature selection in learning random forests for high-dimensional data.

PubMed

Nguyen, Thanh-Tung; Huang, Joshua Zhexue; Nguyen, Thuy Thi

2015-01-01

Random forests (RFs) have been widely used as a powerful classification method. However, with the randomization in both bagging samples and feature selection, the trees in the forest tend to select uninformative features for node splitting. This makes RFs have poor accuracy when working with high-dimensional data. Besides that, RFs have bias in the feature selection process where multivalued features are favored. Aiming at debiasing feature selection in RFs, we propose a new RF algorithm, called xRF, to select good features in learning RFs for high-dimensional data. We first remove the uninformative features using p-value assessment, and the subset of unbiased features is then selected based on some statistical measures. This feature subset is then partitioned into two subsets. A feature weighting sampling technique is used to sample features from these two subsets for building trees. This approach enables one to generate more accurate trees, while allowing one to reduce dimensionality and the amount of data needed for learning RFs. An extensive set of experiments has been conducted on 47 high-dimensional real-world datasets including image datasets. The experimental results have shown that RFs with the proposed approach outperformed the existing random forests in increasing the accuracy and the AUC measures.

Applications of random forest feature selection for fine-scale genetic population assignment.

PubMed

Sylvester, Emma V A; Bentzen, Paul; Bradbury, Ian R; Clément, Marie; Pearce, Jon; Horne, John; Beiko, Robert G

2018-02-01

Genetic population assignment used to inform wildlife management and conservation efforts requires panels of highly informative genetic markers and sensitive assignment tests. We explored the utility of machine-learning algorithms (random forest, regularized random forest and guided regularized random forest) compared with F ST ranking for selection of single nucleotide polymorphisms (SNP) for fine-scale population assignment. We applied these methods to an unpublished SNP data set for Atlantic salmon ( Salmo salar ) and a published SNP data set for Alaskan Chinook salmon ( Oncorhynchus tshawytscha ). In each species, we identified the minimum panel size required to obtain a self-assignment accuracy of at least 90% using each method to create panels of 50-700 markers Panels of SNPs identified using random forest-based methods performed up to 7.8 and 11.2 percentage points better than F ST -selected panels of similar size for the Atlantic salmon and Chinook salmon data, respectively. Self-assignment accuracy ≥90% was obtained with panels of 670 and 384 SNPs for each data set, respectively, a level of accuracy never reached for these species using F ST -selected panels. Our results demonstrate a role for machine-learning approaches in marker selection across large genomic data sets to improve assignment for management and conservation of exploited populations.

High-Tg Polynorbornene-Based Block and Random Copolymers for Butanol Pervaporation Membranes

NASA Astrophysics Data System (ADS)

Register, Richard A.; Kim, Dong-Gyun; Takigawa, Tamami; Kashino, Tomomasa; Burtovyy, Oleksandr; Bell, Andrew

Vinyl addition polymers of substituted norbornene (NB) monomers possess desirably high glass transition temperatures (Tg); however, until very recently, the lack of an applicable living polymerization chemistry has precluded the synthesis of such polymers with controlled architecture, or copolymers with controlled sequence distribution. We have recently synthesized block and random copolymers of NB monomers bearing hydroxyhexafluoroisopropyl and n-butyl substituents (HFANB and BuNB) via living vinyl addition polymerization with Pd-based catalysts. Both series of polymers were cast into the selective skin layers of thin film composite (TFC) membranes, and these organophilic membranes investigated for the isolation of n-butanol from dilute aqueous solution (model fermentation broth) via pervaporation. The block copolymers show well-defined microphase-separated morphologies, both in bulk and as the selective skin layers on TFC membranes, while the random copolymers are homogeneous. Both block and random vinyl addition copolymers are effective as n-butanol pervaporation membranes, with the block copolymers showing a better flux-selectivity balance. While polyHFANB has much higher permeability and n-butanol selectivity than polyBuNB, incorporating BuNB units into the polymer (in either a block or random sequence) limits the swelling of the polyHFANB and thereby improves the n-butanol pervaporation selectivity.

Enhanced emotional reactivity after selective REM sleep deprivation in humans: an fMRI study

PubMed Central

Rosales-Lagarde, Alejandra; Armony, Jorge L.; del Río-Portilla, Yolanda; Trejo-Martínez, David; Conde, Ruben; Corsi-Cabrera, Maria

2012-01-01

Converging evidence from animal and human studies suggest that rapid eye movement (REM) sleep modulates emotional processing. The aim of the present study was to explore the effects of selective REM sleep deprivation (REM-D) on emotional responses to threatening visual stimuli and their brain correlates using functional magnetic resonance imaging (fMRI). Twenty healthy subjects were randomly assigned to two groups: selective REM-D, by awakening them at each REM sleep onset, or non-rapid eye movement sleep interruptions (NREM-I) as control for potential non-specific effects of awakenings and lack of sleep. In a within-subject design, a visual emotional reactivity task was performed in the scanner before and 24 h after sleep manipulation. Behaviorally, emotional reactivity was enhanced relative to baseline (BL) in the REM deprived group only. In terms of fMRI signal, there was, as expected, an overall decrease in activity in the NREM-I group when subjects performed the task the second time, particularly in regions involved in emotional processing, such as occipital and temporal areas, as well as in the ventrolateral prefrontal cortex, involved in top-down emotion regulation. In contrast, activity in these areas remained the same level or even increased in the REM-D group, compared to their BL level. Taken together, these results suggest that lack of REM sleep in humans is associated with enhanced emotional reactivity, both at behavioral and neural levels, and thus highlight the specific role of REM sleep in regulating the neural substrates for emotional responsiveness. PMID:22719723

Biomonitoring of 21 endocrine disrupting chemicals in human hair samples using ultra-high performance liquid chromatography-tandem mass spectrometry.

PubMed

Rodríguez-Gómez, R; Martín, J; Zafra-Gómez, A; Alonso, E; Vílchez, J L; Navalón, A

2017-02-01

Rapid industrial growth has increased human exposure to a large variety of chemicals with adverse health effects. These industrial chemicals are usually present in the environment, foods, beverages, clothes and personal care products. Among these compounds, endocrine disrupting chemicals (EDCs) have raised concern over the last years. In the present work, the determination of 21 EDCs in human hair samples is proposed. An analytical method based on the digestion of the samples with a mixture of acetic acid/methanol (20:80, v/v) followed by a solid-liquid microextraction and analysis by ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was developed and validated. The most influential parameters affecting the extraction method were optimized. The method was validated using matrix-matched calibration and recovery assays. Limits of detection ranged from 0.2 to 4 ng g -1 , limits of quantification from 0.5 to 12 ng g -1 , and inter- and intra-day variability was under 15% in all cases. Recovery rates for spiked samples ranged from 92.1 to 113.8%. The method was applied for the determination of the selected compounds in human hair. Samples were collected weekly from six randomly selected volunteers (three men and three women) over a three-month period. All the analyzed samples tested positive for at least one of the analyzed compounds. Copyright © 2016 Elsevier Ltd. All rights reserved.

Dopamine D2/3- and μ-opioid receptor antagonists reduce cue-induced responding and reward impulsivity in humans.

PubMed

Weber, S C; Beck-Schimmer, B; Kajdi, M-E; Müller, D; Tobler, P N; Quednow, B B

2016-07-05

Increased responding to drug-associated stimuli (cue reactivity) and an inability to tolerate delayed gratification (reward impulsivity) have been implicated in the development and maintenance of drug addiction. Whereas data from animal studies suggest that both the dopamine and opioid system are involved in these two reward-related processes, their role in humans is less clear. Moreover, dopaminergic and opioidergic drugs have not been directly compared with regard to these functions, even though a deeper understanding of the underlying mechanisms might inform the development of specific treatments for elevated cue reactivity and reward impulsivity. In a randomized, double-blind, between-subject design we administered the selective dopamine D2/D3 receptor antagonist amisulpride (400 mg, n=41), the unspecific opioid receptor antagonist naltrexone (50 mg, n=40) or placebo (n=40) to healthy humans and measured cue-induced responding with a Pavlovian-instrumental transfer task and reward impulsivity with a delay discounting task. Mood was assessed using a visual analogue scale. Compared with placebo, amisulpride significantly suppressed cue-induced responding and reward impulsivity. The effects of naltrexone were similar, although less pronounced. Both amisulpride and naltrexone decreased average mood ratings compared with placebo. Our results demonstrate that a selective blockade of dopamine D2/D3 receptors reduces cue-induced responding and reward impulsivity in healthy humans. Antagonizing μ-opioid receptors has similar effects for cue-induced responding and to a lesser extent for reward impulsivity.

Robust portfolio selection based on asymmetric measures of variability of stock returns

NASA Astrophysics Data System (ADS)

Chen, Wei; Tan, Shaohua

2009-10-01

This paper addresses a new uncertainty set--interval random uncertainty set for robust optimization. The form of interval random uncertainty set makes it suitable for capturing the downside and upside deviations of real-world data. These deviation measures capture distributional asymmetry and lead to better optimization results. We also apply our interval random chance-constrained programming to robust mean-variance portfolio selection under interval random uncertainty sets in the elements of mean vector and covariance matrix. Numerical experiments with real market data indicate that our approach results in better portfolio performance.

A randomized controlled trial investigating the use of a predictive nomogram for the selection of the FSH starting dose in IVF/ICSI cycles.

PubMed

Allegra, Adolfo; Marino, Angelo; Volpes, Aldo; Coffaro, Francesco; Scaglione, Piero; Gullo, Salvatore; La Marca, Antonio

2017-04-01

The number of oocytes retrieved is a relevant intermediate outcome in women undergoing IVF/intracytoplasmic sperm injection (ICSI). This trial compared the efficiency of the selection of the FSH starting dose according to a nomogram based on multiple biomarkers (age, day 3 FSH, anti-Müllerian hormone) versus an age-based strategy. The primary outcome measure was the proportion of women with an optimal number of retrieved oocytes defined as 8-14. At their first IVF/ICSI cycle, 191 patients underwent a long gonadotrophin-releasing hormone agonist protocol and were randomized to receive a starting dose of recombinant (human) FSH, based on their age (150 IU if ≤35 years, 225 IU if >35 years) or based on the nomogram. Optimal response was observed in 58/92 patients (63%) in the nomogram group and in 42/99 (42%) in the control group (+21%, 95% CI = 0.07 to 0.35, P = 0.0037). No significant differences were found in the clinical pregnancy rate or the number of embryos cryopreserved per patient. The study showed that the FSH starting dose selected according to ovarian reserve is associated with an increase in the proportion of patients with an optimal response: large trials are recommended to investigate any possible effect on the live-birth rate. Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

“Forward Genetics” as a Method to Maximize Power and Cost-Efficiency in Studies of Human Complex Traits

PubMed Central

Derks, E. M.; Dolan, C. V.; Kahn, R. S.; Ophoff, R. A.

2010-01-01

There is increasing interest in methods to disentangle the relationship between genotype and (endo)phenotypes in human complex traits. We present a population-based method of increasing the power and cost-efficiency of studies by selecting random individuals with a particular genotype and then assessing the accompanying quantitative phenotypes. Using statistical derivations, power- and cost graphs we show that such a “forward genetics” approach can lead to a marked reduction in sample size and costs. This approach is particularly apt for implementing in epidemiological studies for which DNA is already available but the phenotyping costs are high. Electronic supplementary material The online version of this article (doi:10.1007/s10519-010-9348-y) contains supplementary material, which is available to authorized users. PMID:20232132

Restriction fragment length polymorphism of the human c-fms gene.

PubMed Central

Xu, D Q; Guilhot, S; Galibert, F

1985-01-01

By using blot hybridization with a v-fms probe, a polymorphism for EcoRI, HindIII, and BamHI restriction endonuclease sites associated with the human c-fms locus was observed in a random adult population. This restriction fragment length polymorphism can be explained on the basis of the existence of two alleles, a and b, and is due to a short (congruent to 500 base pairs) deletion characteristic of allele a. The distribution in the analyzed population (48 unrelated individuals) is 23% heterozygotes ab, 75% homozygotes bb, and 2% homozygotes aa. Though the inheritance of this polymorphism follows a Mendelian pattern, the children from couples ab X bb are of the following genotype: 74% ab and 26% bb. These deviations from the expected frequencies of 50% suggest a selective pressure in favor of heterozygotes. Images PMID:2986142

Adaptive consensus of scale-free multi-agent system by randomly selecting links

NASA Astrophysics Data System (ADS)

Mou, Jinping; Ge, Huafeng

2016-06-01

This paper investigates an adaptive consensus problem for distributed scale-free multi-agent systems (SFMASs) by randomly selecting links, where the degree of each node follows a power-law distribution. The randomly selecting links are based on the assumption that every agent decides to select links among its neighbours according to the received data with a certain probability. Accordingly, a novel consensus protocol with the range of the received data is developed, and each node updates its state according to the protocol. By the iterative method and Cauchy inequality, the theoretical analysis shows that all errors among agents converge to zero, and in the meanwhile, several criteria of consensus are obtained. One numerical example shows the reliability of the proposed methods.

The Influence of Probiotic Lactobacillus casei in Combination with Prebiotic Inulin on the Antioxidant Capacity of Human Plasma

PubMed Central

Kleniewska, Paulina; Hoffmann, Arkadiusz; Pniewska, Ewa

2016-01-01

The aim of the present study was to assess whether probiotic bacteria Lactobacillus casei (4 × 108 CFU) influences the antioxidant properties of human plasma when combined with prebiotic Inulin (400 mg). Experiments were carried out on healthy volunteers (n = 32). Volunteers were divided according to sex (16 male and 16 female) and randomly assigned to synbiotic and control groups. Blood samples were collected before synbiotic supplementation and after 7 weeks, at the end of the study. Catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) activity, and the ferric reducing ability of plasma (FRAP) in human plasma were examined. The administration of synbiotics containing L. casei plus Inulin resulted in a significant increase in FRAP values (p = 0.00008) and CAT activity (p = 0.02) and an insignificant increase in SOD and GPx activity compared to controls. Synbiotics containing L. casei (4 × 108 CFU) with prebiotic Inulin (400 mg) may have a positive influence on human plasma antioxidant capacity and the activity of selected antioxidant enzymes. PMID:27066188

Unbiased split variable selection for random survival forests using maximally selected rank statistics.

PubMed

Wright, Marvin N; Dankowski, Theresa; Ziegler, Andreas

2017-04-15

The most popular approach for analyzing survival data is the Cox regression model. The Cox model may, however, be misspecified, and its proportionality assumption may not always be fulfilled. An alternative approach for survival prediction is random forests for survival outcomes. The standard split criterion for random survival forests is the log-rank test statistic, which favors splitting variables with many possible split points. Conditional inference forests avoid this split variable selection bias. However, linear rank statistics are utilized by default in conditional inference forests to select the optimal splitting variable, which cannot detect non-linear effects in the independent variables. An alternative is to use maximally selected rank statistics for the split point selection. As in conditional inference forests, splitting variables are compared on the p-value scale. However, instead of the conditional Monte-Carlo approach used in conditional inference forests, p-value approximations are employed. We describe several p-value approximations and the implementation of the proposed random forest approach. A simulation study demonstrates that unbiased split variable selection is possible. However, there is a trade-off between unbiased split variable selection and runtime. In benchmark studies of prediction performance on simulated and real datasets, the new method performs better than random survival forests if informative dichotomous variables are combined with uninformative variables with more categories and better than conditional inference forests if non-linear covariate effects are included. In a runtime comparison, the method proves to be computationally faster than both alternatives, if a simple p-value approximation is used. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Block randomization versus complete randomization of human perception stimuli: is there a difference?

NASA Astrophysics Data System (ADS)

Moyer, Steve; Uhl, Elizabeth R.

2015-05-01

For more than 50 years, the U.S. Army RDECOM CERDEC Night Vision and Electronic Sensors Directorate (NVESD) has been studying and modeling the human visual discrimination process as it pertains to military imaging systems. In order to develop sensor performance models, human observers are trained to expert levels in the identification of military vehicles. From 1998 until 2006, the experimental stimuli were block randomized, meaning that stimuli with similar difficulty levels (for example, in terms of distance from target, blur, noise, etc.) were presented together in blocks of approximately 24 images but the order of images within the block was random. Starting in 2006, complete randomization came into vogue, meaning that difficulty could change image to image. It was thought that this would provide a more statistically robust result. In this study we investigated the impact of the two types of randomization on performance in two groups of observers matched for skill to create equivalent groups. It is hypothesized that Soldiers in the Complete Randomized condition will have to shift their decision criterion more frequently than Soldiers in the Block Randomization group and this shifting is expected to impede performance so that Soldiers in the Block Randomized group perform better.

A Prospective, Randomized, Double-blind, Split-face Clinical Trial Comparing the Efficacy of Two Topical Human Growth Factors for the Rejuvenation of the Aging Face

PubMed Central

Goldman, Mitchel P.

2017-01-01

Background: Cosmeceutical products represent an increasingly important therapeutic option for anti-aging and rejuvenation, either used alone or in combination with dermatologic surgical procedures. Among this group of products, topical growth factors have demonstrated efficacy in randomized, controlled clinical trials. However, comparisons between different products remain uncommon. Objective: The objective of this randomized, double-blind, split-face clinical trial was to compare two different topical growth factor formulations derived from either human fibroblasts or human adipose tissue derived mesenchymal stem cells. Methods: This was an institutional review board-approved, randomized, double-blind, split-face clinical trial involving 20 healthy subjects with moderate-to-severe facial wrinkling secondary to photodamage. One half of the face was randomized to receive topical human fibroblast growth factors and the other topical human mesenchymal stem cell growth factors. Treatment was continued for three months, and evaluations were performed in a double-blind fashion. Results: Both growth factor formulations achieved significant improvement in facial wrinkling. Blinded investigator and subject evaluations did not detect any significant differences between the two formulations in terms of efficacy, safety, or tolerability. Conclusion: Both human fibroblast growth factors and human mesenchymal stem cell growth factors are effective at facial rejuvenation. Topical growth factors represent a useful therapeutic modality. PMID:28670356

A Prospective, Randomized, Double-blind, Split-face Clinical Trial Comparing the Efficacy of Two Topical Human Growth Factors for the Rejuvenation of the Aging Face.

PubMed

Wu, Douglas C; Goldman, Mitchel P

2017-05-01

Background: Cosmeceutical products represent an increasingly important therapeutic option for anti-aging and rejuvenation, either used alone or in combination with dermatologic surgical procedures. Among this group of products, topical growth factors have demonstrated efficacy in randomized, controlled clinical trials. However, comparisons between different products remain uncommon. Objective: The objective of this randomized, double-blind, split-face clinical trial was to compare two different topical growth factor formulations derived from either human fibroblasts or human adipose tissue derived mesenchymal stem cells. Methods: This was an institutional review board-approved, randomized, double-blind, split-face clinical trial involving 20 healthy subjects with moderate-to-severe facial wrinkling secondary to photodamage. One half of the face was randomized to receive topical human fibroblast growth factors and the other topical human mesenchymal stem cell growth factors. Treatment was continued for three months, and evaluations were performed in a double-blind fashion. Results: Both growth factor formulations achieved significant improvement in facial wrinkling. Blinded investigator and subject evaluations did not detect any significant differences between the two formulations in terms of efficacy, safety, or tolerability. Conclusion: Both human fibroblast growth factors and human mesenchymal stem cell growth factors are effective at facial rejuvenation. Topical growth factors represent a useful therapeutic modality.

Community perceptions of human excreta as fertilizer in peri-urban agriculture in Ghana.

PubMed

Mariwah, Simon; Drangert, Jan-Olof

2011-08-01

Although human excreta contain the necessary nutrients for plant growth, local authorities in Ghana spend huge sums of money to dispose them as waste. Reusing excreta for agricultural purposes saves expenditure for chemical fertilizers, improves soil fertility, reduces poverty and ensures food security. People's attitudes and perceptions about excreta vary between cultures and even within specific cultures. This study aimed to explore attitudes and perceptions among a peri-urban agricultural community towards sanitized human excreta and its use. The study adopted an exploratory design and collected data from 154 randomly selected households using questionnaires and focus group discussions. It was found that there is a general negative attitude to fresh excreta and the handling of it. However, the residents accept that excreta can be used as fertilizer, but they are not willing to use it on their own crops or consume crops fertilized with excreta. The study recommends open discussions in the community for a successful implementation of ecological sanitation.

Effect of Expanding Medicaid for Parents on Children’s Health Insurance Coverage

PubMed Central

DeVoe, Jennifer E.; Marino, Miguel; Angier, Heather; O’Malley, Jean P.; Crawford, Courtney; Nelson, Christine; Tillotson, Carrie J.; Bailey, Steffani R.; Gallia, Charles; Gold, Rachel

2016-01-01

IMPORTANCE In the United States, health insurance is not universal. Observational studies show an association between uninsured parents and children. This association persisted even after expansions in child-only public health insurance. Oregon’s randomized Medicaid expansion for adults, known as the Oregon Experiment, created a rare opportunity to assess causality between parent and child coverage. OBJECTIVE To estimate the effect on a child’s health insurance coverage status when (1) a parent randomly gains access to health insurance and (2) a parent obtains coverage. DESIGN, SETTING, AND PARTICIPANTS Oregon Experiment randomized natural experiment assessing the results of Oregon’s 2008 Medicaid expansion. We used generalized estimating equation models to examine the longitudinal effect of a parent randomly selected to apply for Medicaid on their child’s Medicaid or Children’s Health Insurance Program (CHIP) coverage (intent-to-treat analyses). We used per-protocol analyses to understand the impact on children’s coverage when a parent was randomly selected to apply for and obtained Medicaid. Participants included 14 409 children aged 2 to 18 years whose parents participated in the Oregon Experiment. EXPOSURES For intent-to-treat analyses, the date a parent was selected to apply for Medicaid was considered the date the child was exposed to the intervention. In per-protocol analyses, exposure was defined as whether a selected parent obtained Medicaid. MAIN OUTCOMES AND MEASURES Children’s Medicaid or CHIP coverage, assessed monthly and in 6-month intervals relative to their parent’s selection date. RESULTS In the immediate period after selection, children whose parents were selected to apply significantly increased from 3830 (61.4%) to 4152 (66.6%) compared with a nonsignificant change from 5049 (61.8%) to 5044 (61.7%) for children whose parents were not selected to apply. Children whose parents were randomly selected to apply for Medicaid had 18% higher odds of being covered in the first 6 months after parent’s selection compared with children whose parents were not selected (adjusted odds ratio [AOR] = 1.18; 95% CI, 1.10–1.27). The effect remained significant during months 7 to 12 (AOR = 1.11; 95% CI, 1.03–1.19); months 13 to 18 showed a positive but not significant effect (AOR = 1.07; 95% CI, 0.99–1.14). Children whose parents were selected and obtained coverage had more than double the odds of having coverage compared with children whose parents were not selected and did not gain coverage (AOR = 2.37; 95% CI, 2.14–2.64). CONCLUSIONS AND RELEVANCE Children’s odds of having Medicaid or CHIP coverage increased when their parents were randomly selected to apply for Medicaid. Children whose parents were selected and subsequently obtained coverage benefited most. This study demonstrates a causal link between parents’ access to Medicaid coverage and their children’s coverage. PMID:25561041

Security under Uncertainty: Adaptive Attackers Are More Challenging to Human Defenders than Random Attackers

PubMed Central

Moisan, Frédéric; Gonzalez, Cleotilde

2017-01-01

Game Theory is a common approach used to understand attacker and defender motives, strategies, and allocation of limited security resources. For example, many defense algorithms are based on game-theoretic solutions that conclude that randomization of defense actions assures unpredictability, creating difficulties for a human attacker. However, many game-theoretic solutions often rely on idealized assumptions of decision making that underplay the role of human cognition and information uncertainty. The consequence is that we know little about how effective these algorithms are against human players. Using a simplified security game, we study the type of attack strategy and the uncertainty about an attacker's strategy in a laboratory experiment where participants play the role of defenders against a simulated attacker. Our goal is to compare a human defender's behavior in three levels of uncertainty (Information Level: Certain, Risky, Uncertain) and three types of attacker's strategy (Attacker's strategy: Minimax, Random, Adaptive) in a between-subjects experimental design. Best defense performance is achieved when defenders play against a minimax and a random attack strategy compared to an adaptive strategy. Furthermore, when payoffs are certain, defenders are as efficient against random attack strategy as they are against an adaptive strategy, but when payoffs are uncertain, defenders have most difficulties defending against an adaptive attacker compared to a random attacker. We conclude that given conditions of uncertainty in many security problems, defense algorithms would be more efficient if they are adaptive to the attacker actions, taking advantage of the attacker's human inefficiencies. PMID:28690557

Estimating the efficacy of Alcoholics Anonymous without self-selection bias: An instrumental variables re-analysis of randomized clinical trials

PubMed Central

Humphreys, Keith; Blodgett, Janet C.; Wagner, Todd H.

2014-01-01

Background Observational studies of Alcoholics Anonymous’ (AA) effectiveness are vulnerable to self-selection bias because individuals choose whether or not to attend AA. The present study therefore employed an innovative statistical technique to derive a selection bias-free estimate of AA’s impact. Methods Six datasets from 5 National Institutes of Health-funded randomized trials (one with two independent parallel arms) of AA facilitation interventions were analyzed using instrumental variables models. Alcohol dependent individuals in one of the datasets (n = 774) were analyzed separately from the rest of sample (n = 1582 individuals pooled from 5 datasets) because of heterogeneity in sample parameters. Randomization itself was used as the instrumental variable. Results Randomization was a good instrument in both samples, effectively predicting increased AA attendance that could not be attributed to self-selection. In five of the six data sets, which were pooled for analysis, increased AA attendance that was attributable to randomization (i.e., free of self-selection bias) was effective at increasing days of abstinence at 3-month (B = .38, p = .001) and 15-month (B = 0.42, p = .04) follow-up. However, in the remaining dataset, in which pre-existing AA attendance was much higher, further increases in AA involvement caused by the randomly assigned facilitation intervention did not affect drinking outcome. Conclusions For most individuals seeking help for alcohol problems, increasing AA attendance leads to short and long term decreases in alcohol consumption that cannot be attributed to self-selection. However, for populations with high pre-existing AA involvement, further increases in AA attendance may have little impact. PMID:25421504

Estimating the efficacy of Alcoholics Anonymous without self-selection bias: an instrumental variables re-analysis of randomized clinical trials.

PubMed

Humphreys, Keith; Blodgett, Janet C; Wagner, Todd H

2014-11-01

Observational studies of Alcoholics Anonymous' (AA) effectiveness are vulnerable to self-selection bias because individuals choose whether or not to attend AA. The present study, therefore, employed an innovative statistical technique to derive a selection bias-free estimate of AA's impact. Six data sets from 5 National Institutes of Health-funded randomized trials (1 with 2 independent parallel arms) of AA facilitation interventions were analyzed using instrumental variables models. Alcohol-dependent individuals in one of the data sets (n = 774) were analyzed separately from the rest of sample (n = 1,582 individuals pooled from 5 data sets) because of heterogeneity in sample parameters. Randomization itself was used as the instrumental variable. Randomization was a good instrument in both samples, effectively predicting increased AA attendance that could not be attributed to self-selection. In 5 of the 6 data sets, which were pooled for analysis, increased AA attendance that was attributable to randomization (i.e., free of self-selection bias) was effective at increasing days of abstinence at 3-month (B = 0.38, p = 0.001) and 15-month (B = 0.42, p = 0.04) follow-up. However, in the remaining data set, in which preexisting AA attendance was much higher, further increases in AA involvement caused by the randomly assigned facilitation intervention did not affect drinking outcome. For most individuals seeking help for alcohol problems, increasing AA attendance leads to short- and long-term decreases in alcohol consumption that cannot be attributed to self-selection. However, for populations with high preexisting AA involvement, further increases in AA attendance may have little impact. Copyright © 2014 by the Research Society on Alcoholism.

Fast Principal-Component Analysis Reveals Convergent Evolution of ADH1B in Europe and East Asia

PubMed Central

Galinsky, Kevin J.; Bhatia, Gaurav; Loh, Po-Ru; Georgiev, Stoyan; Mukherjee, Sayan; Patterson, Nick J.; Price, Alkes L.

2016-01-01

Searching for genetic variants with unusual differentiation between subpopulations is an established approach for identifying signals of natural selection. However, existing methods generally require discrete subpopulations. We introduce a method that infers selection using principal components (PCs) by identifying variants whose differentiation along top PCs is significantly greater than the null distribution of genetic drift. To enable the application of this method to large datasets, we developed the FastPCA software, which employs recent advances in random matrix theory to accurately approximate top PCs while reducing time and memory cost from quadratic to linear in the number of individuals, a computational improvement of many orders of magnitude. We apply FastPCA to a cohort of 54,734 European Americans, identifying 5 distinct subpopulations spanning the top 4 PCs. Using the PC-based test for natural selection, we replicate previously known selected loci and identify three new genome-wide significant signals of selection, including selection in Europeans at ADH1B. The coding variant rs1229984∗T has previously been associated to a decreased risk of alcoholism and shown to be under selection in East Asians; we show that it is a rare example of independent evolution on two continents. We also detect selection signals at IGFBP3 and IGH, which have also previously been associated to human disease. PMID:26924531

Molecular epidemiology of human metapneumovirus in Ireland.

PubMed

Carr, Michael J; Waters, Allison; Fenwick, Fiona; Toms, Geoffrey L; Hall, William W; O'Kelly, Edwin

2008-03-01

Human metapneumovirus (hMPV) is a cause of respiratory illness ranging from wheezing to bronchiolitis and pneumonia in children. A quantitative real-time reverse-transcriptase polymerase chain reaction (RT-PCR) assay was developed for the detection of all four main genetic lineages of hMPV and employed to validate an indirect immunofluorescence (IF) assay to detect hMPV positive specimens. The IF assay detected 24 positives from a screen of 625 randomly selected pediatric respiratory specimens collected (3.8% prevalence). From this cohort of 625 specimens, 229 were also tested by real-time RT-PCR assay. This included the 24 IF positive specimens and 205 randomly selected specimens from both study periods. In addition to confirming all the IF positives, the real-time assay detected an additional six hMPV positive specimens giving rise to a combined prevalence of 4.8%. Phylogenetic analysis showed that hMPV subtypes A2b and B2 to be the most prevalent genotypes circulating in our population and surprisingly no hMPV subgroups A1 or B1 were detected during this study period. Based on this phylogenetic analysis, we propose the existence of sub-clusters of hMPV genotype B2 present in our population which we term subtypes B2a and B2b. The mean log 10 copies/ml of quantitative RT-PCR determinations from these 30 hMPV positive respiratory specimens was 6.35 (range = 4.44-8.15). Statistical analysis of quantitative RT-PCR determinations of viral load from these 30 respiratory specimens suggests that hMPV genotype B specimens have a higher viral load than hMPV genotype A isolates (P < 0.03).

Optimization of protease-inhibitor interactions by randomizing adventitious contacts

PubMed Central

Komiyama, Tomoko; VanderLugt, Bryan; Fugère, Martin; Day, Robert; Kaufman, Randal J.; Fuller, Robert S.

2003-01-01

Polypeptide protease inhibitors are often found to inhibit targets with which they did not coevolve, as in the case of high-affinity inhibition of bacterial subtilisin by the leech inhibitor eglin c. Two kinds of contacts exist in such complexes: (i) reactive site loop-active site contacts and (ii) interactions outside of these that form the broader enzyme-inhibitor interface. We hypothesized that the second class of “adventitious” contacts could be optimized to generate significant increases in affinity for a target enzyme or discrimination of an inhibitor for closely related target proteases. We began with a modified eglin c, Arg-42–Arg-45–eglin, in which the reactive site loop had been optimized for subtilisin-related processing proteases of the Kex2/furin family. We randomized 10 potential adventitious contact residues and screened for inhibition of soluble human furin. Substitutions at one of these sites, Y49, were also screened against yeast Kex2 and human PC7. These screens identified not only variants that exhibited increased affinity (up to 20-fold), but also species that exhibited enhanced selectivity, that is, increased discrimination between the target enzymes (up to 41-fold for furin versus PC7 and 20-fold for PC7 versus furin). One variant, Asp-49–Arg-42–Arg-45–eglin, exhibited a Ki of 310 pM for furin and blocked furin-dependent processing of von Willebrand factor in COS-1 cells when added to the culture medium of the cells. The exploitation of adventitious contact sites may provide a versatile technique for developing potent, selective inhibitors for newly discovered proteases and could in principle be applied to optimize numerous protein–protein interactions. PMID:12832612

Extensively Parameterized Mutation-Selection Models Reliably Capture Site-Specific Selective Constraint.

PubMed

Spielman, Stephanie J; Wilke, Claus O

2016-11-01

The mutation-selection model of coding sequence evolution has received renewed attention for its use in estimating site-specific amino acid propensities and selection coefficient distributions. Two computationally tractable mutation-selection inference frameworks have been introduced: One framework employs a fixed-effects, highly parameterized maximum likelihood approach, whereas the other employs a random-effects Bayesian Dirichlet Process approach. While both implementations follow the same model, they appear to make distinct predictions about the distribution of selection coefficients. The fixed-effects framework estimates a large proportion of highly deleterious substitutions, whereas the random-effects framework estimates that all substitutions are either nearly neutral or weakly deleterious. It remains unknown, however, how accurately each method infers evolutionary constraints at individual sites. Indeed, selection coefficient distributions pool all site-specific inferences, thereby obscuring a precise assessment of site-specific estimates. Therefore, in this study, we use a simulation-based strategy to determine how accurately each approach recapitulates the selective constraint at individual sites. We find that the fixed-effects approach, despite its extensive parameterization, consistently and accurately estimates site-specific evolutionary constraint. By contrast, the random-effects Bayesian approach systematically underestimates the strength of natural selection, particularly for slowly evolving sites. We also find that, despite the strong differences between their inferred selection coefficient distributions, the fixed- and random-effects approaches yield surprisingly similar inferences of site-specific selective constraint. We conclude that the fixed-effects mutation-selection framework provides the more reliable software platform for model application and future development. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Some Aspects of the Investigation of Random Vibration Influence on Ride Comfort

NASA Astrophysics Data System (ADS)

DEMIĆ, M.; LUKIĆ, J.; MILIĆ, Ž.

2002-05-01

Contemporary vehicles must satisfy high ride comfort criteria. This paper attempts to develop criteria for ride comfort improvement. The highest loading levels have been found to be in the vertical direction and the lowest in lateral direction in passenger cars and trucks. These results have formed the basis for further laboratory and field investigations. An investigation of the human body behaviour under random vibrations is reported in this paper. The research included two phases; biodynamic research and ride comfort investigation. A group of 30 subjects was tested. The influence of broadband random vibrations on the human body was examined through the seat-to-head transmissibility function (STHT). Initially, vertical and fore and aft vibrations were considered. Multi-directional vibration was also investigated. In the biodynamic research, subjects were exposed to 0·55, 1·75 and 2·25 m/s2 r.m.s. vibration levels in the 0·5- 40 Hz frequency domain. The influence of sitting position on human body behaviour under two axial vibrations was also examined. Data analysis showed that the human body behaviour under two-directional random vibrations could not be approximated by superposition of one-directional random vibrations. Non-linearity of the seated human body in the vertical and fore and aft directions was observed. Seat-backrest angle also influenced STHT. In the second phase of experimental research, a new method for the assessment of the influence of narrowband random vibration on the human body was formulated and tested. It included determination of equivalent comfort curves in the vertical and fore and aft directions under one- and two-directional narrowband random vibrations. Equivalent comfort curves for durations of 2·5, 4 and 8 h were determined.

Spatial Analysis of “Crazy Quilts”, a Class of Potentially Random Aesthetic Artefacts

PubMed Central

Westphal-Fitch, Gesche; Fitch, W. Tecumseh

2013-01-01

Human artefacts in general are highly structured and often display ordering principles such as translational, reflectional or rotational symmetry. In contrast, human artefacts that are intended to appear random and non symmetrical are very rare. Furthermore, many studies show that humans find it extremely difficult to recognize or reproduce truly random patterns or sequences. Here, we attempt to model two-dimensional decorative spatial patterns produced by humans that show no obvious order. “Crazy quilts” represent a historically important style of quilt making that became popular in the 1870s, and lasted about 50 years. Crazy quilts are unusual because unlike most human artefacts, they are specifically intended to appear haphazard and unstructured. We evaluate the degree to which this intention was achieved by using statistical techniques of spatial point pattern analysis to compare crazy quilts with regular quilts from the same region and era and to evaluate the fit of various random distributions to these two quilt classes. We found that the two quilt categories exhibit fundamentally different spatial characteristics: The patch areas of crazy quilts derive from a continuous random distribution, while area distributions of regular quilts consist of Gaussian mixtures. These Gaussian mixtures derive from regular pattern motifs that are repeated and we suggest that such a mixture is a distinctive signature of human-made visual patterns. In contrast, the distribution found in crazy quilts is shared with many other naturally occurring spatial patterns. Centroids of patches in the two quilt classes are spaced differently and in general, crazy quilts but not regular quilts are well-fitted by a random Strauss process. These results indicate that, within the constraints of the quilt format, Victorian quilters indeed achieved their goal of generating random structures. PMID:24066095

Spatial analysis of "crazy quilts", a class of potentially random aesthetic artefacts.

PubMed

Westphal-Fitch, Gesche; Fitch, W Tecumseh

2013-01-01

Human artefacts in general are highly structured and often display ordering principles such as translational, reflectional or rotational symmetry. In contrast, human artefacts that are intended to appear random and non symmetrical are very rare. Furthermore, many studies show that humans find it extremely difficult to recognize or reproduce truly random patterns or sequences. Here, we attempt to model two-dimensional decorative spatial patterns produced by humans that show no obvious order. "Crazy quilts" represent a historically important style of quilt making that became popular in the 1870s, and lasted about 50 years. Crazy quilts are unusual because unlike most human artefacts, they are specifically intended to appear haphazard and unstructured. We evaluate the degree to which this intention was achieved by using statistical techniques of spatial point pattern analysis to compare crazy quilts with regular quilts from the same region and era and to evaluate the fit of various random distributions to these two quilt classes. We found that the two quilt categories exhibit fundamentally different spatial characteristics: The patch areas of crazy quilts derive from a continuous random distribution, while area distributions of regular quilts consist of Gaussian mixtures. These Gaussian mixtures derive from regular pattern motifs that are repeated and we suggest that such a mixture is a distinctive signature of human-made visual patterns. In contrast, the distribution found in crazy quilts is shared with many other naturally occurring spatial patterns. Centroids of patches in the two quilt classes are spaced differently and in general, crazy quilts but not regular quilts are well-fitted by a random Strauss process. These results indicate that, within the constraints of the quilt format, Victorian quilters indeed achieved their goal of generating random structures.

Search Algorithms as a Framework for the Optimization of Drug Combinations

PubMed Central

Coquin, Laurence; Schofield, Jennifer; Feala, Jacob D.; Reed, John C.; McCulloch, Andrew D.; Paternostro, Giovanni

2008-01-01

Combination therapies are often needed for effective clinical outcomes in the management of complex diseases, but presently they are generally based on empirical clinical experience. Here we suggest a novel application of search algorithms—originally developed for digital communication—modified to optimize combinations of therapeutic interventions. In biological experiments measuring the restoration of the decline with age in heart function and exercise capacity in Drosophila melanogaster, we found that search algorithms correctly identified optimal combinations of four drugs using only one-third of the tests performed in a fully factorial search. In experiments identifying combinations of three doses of up to six drugs for selective killing of human cancer cells, search algorithms resulted in a highly significant enrichment of selective combinations compared with random searches. In simulations using a network model of cell death, we found that the search algorithms identified the optimal combinations of 6–9 interventions in 80–90% of tests, compared with 15–30% for an equivalent random search. These findings suggest that modified search algorithms from information theory have the potential to enhance the discovery of novel therapeutic drug combinations. This report also helps to frame a biomedical problem that will benefit from an interdisciplinary effort and suggests a general strategy for its solution. PMID:19112483

Evolving artificial metalloenzymes via random mutagenesis

NASA Astrophysics Data System (ADS)

Yang, Hao; Swartz, Alan M.; Park, Hyun June; Srivastava, Poonam; Ellis-Guardiola, Ken; Upp, David M.; Lee, Gihoon; Belsare, Ketaki; Gu, Yifan; Zhang, Chen; Moellering, Raymond E.; Lewis, Jared C.

2018-03-01

Random mutagenesis has the potential to optimize the efficiency and selectivity of protein catalysts without requiring detailed knowledge of protein structure; however, introducing synthetic metal cofactors complicates the expression and screening of enzyme libraries, and activity arising from free cofactor must be eliminated. Here we report an efficient platform to create and screen libraries of artificial metalloenzymes (ArMs) via random mutagenesis, which we use to evolve highly selective dirhodium cyclopropanases. Error-prone PCR and combinatorial codon mutagenesis enabled multiplexed analysis of random mutations, including at sites distal to the putative ArM active site that are difficult to identify using targeted mutagenesis approaches. Variants that exhibited significantly improved selectivity for each of the cyclopropane product enantiomers were identified, and higher activity than previously reported ArM cyclopropanases obtained via targeted mutagenesis was also observed. This improved selectivity carried over to other dirhodium-catalysed transformations, including N-H, S-H and Si-H insertion, demonstrating that ArMs evolved for one reaction can serve as starting points to evolve catalysts for others.

Aspiration dynamics in structured population acts as if in a well-mixed one.

PubMed

Du, Jinming; Wu, Bin; Wang, Long

2015-01-26

Understanding the evolution of human interactive behaviors is important. Recent experimental results suggest that human cooperation in spatial structured population is not enhanced as predicted in previous works, when payoff-dependent imitation updating rules are used. This constraint opens up an avenue to shed light on how humans update their strategies in real life. Studies via simulations show that, instead of comparison rules, self-evaluation driven updating rules may explain why spatial structure does not alter the evolutionary outcome. Though inspiring, there is a lack of theoretical result to show the existence of such evolutionary updating rule. Here we study the aspiration dynamics, and show that it does not alter the evolutionary outcome in various population structures. Under weak selection, by analytical approximation, we find that the favored strategy in regular graphs is invariant. Further, we show that this is because the criterion under which a strategy is favored is the same as that of a well-mixed population. By simulation, we show that this holds for random networks. Although how humans update their strategies is an open question to be studied, our results provide a theoretical foundation of the updating rules that may capture the real human updating rules.

Owls see in stereo much like humans do.

PubMed

van der Willigen, Robert F

2011-06-10

While 3D experiences through binocular disparity sensitivity have acquired special status in the understanding of human stereo vision, much remains to be learned about how binocularity is put to use in animals. The owl provides an exceptional model to study stereo vision as it displays one of the highest degrees of binocular specialization throughout the animal kingdom. In a series of six behavioral experiments, equivalent to hallmark human psychophysical studies, I compiled an extensive body of stereo performance data from two trained owls. Computer-generated, binocular random-dot patterns were used to ensure pure stereo performance measurements. In all cases, I found that owls perform much like humans do, viz.: (1) disparity alone can evoke figure-ground segmentation; (2) selective use of "relative" rather than "absolute" disparity; (3) hyperacute sensitivity; (4) disparity processing allows for the avoidance of monocular feature detection prior to object recognition; (5) large binocular disparities are not tolerated; (6) disparity guides the perceptual organization of 2D shape. The robustness and very nature of these binocular disparity-based perceptual phenomena bear out that owls, like humans, exploit the third dimension to facilitate early figure-ground segmentation of tangible objects.

A bolus/basal multiple injection regimen in type I diabetes. A multicentre trial using a new 'fountain-pen' device for short-acting human insulin as well as long-acting human insulin.

PubMed

Distiller, L A; Robertson, L I; Moore, R; Bonnici, F

1987-06-20

A trial was undertaken to ascertain the effect and acceptability of a multiple insulin injection regimen (MII) in patients with insulin-dependent diabetes mellitus using short-acting monocomponent human soluble insulin (Actrapid HM; Novo) for pre-meal bolus injections with the NovoPen injection device (Novo) and long-acting human insulin (Ultratard HM; Novo) at bedtime. Fifty-four patients, all previously on twice-daily short/intermediate-acting human insulin (Monotard HM; Novo) and Actrapid HM, were randomly selected. There was a significant overall improvement in diabetic control over the 12 weeks of the trial, the glycosylated haemoglobin (Hb A1) dropping from a mean of 9.8 +/- 2.2% to 8.6 +/- 1.7% (P less than 0.05). MII, using the NovoPen, was found to be more convenient than conventional insulin administration by 92% of the subjects. It is concluded that the NovoPen is a useful and convenient means of administering pre-meal boluses in an MII regimen, with a very high rate of acceptance by patients of all ages.

Specific insertions of zinc finger domains into Gag-Pol yield engineered retroviral vectors with selective integration properties

PubMed Central

Lim, Kwang-il; Klimczak, Ryan; Yu, Julie H.; Schaffer, David V.

2010-01-01

Retroviral vectors offer benefits of efficient delivery and stable gene expression; however, their clinical use raises the concerns of insertional mutagenesis and potential oncogenesis due to genomic integration preferences in transcriptional start sites (TSS). We have shifted the integration preferences of retroviral vectors by generating a library of viral variants with a DNA-binding domain inserted at random positions throughout murine leukemia virus Gag-Pol, then selecting for variants that are viable and exhibit altered integration properties. We found seven permissive zinc finger domain (ZFD) insertion sites throughout Gag-Pol, including within p12, reverse transcriptase, and integrase. Comprehensive genome integration analysis showed that several ZFD insertions yielded retroviral vector variants with shifted integration patterns that did not favor TSS. Furthermore, integration site analysis revealed selective integration for numerous mutants. For example, two retroviral variants with a given ZFD at appropriate positions in Gag-Pol strikingly integrated primarily into four common sites out of 3.1 × 109 possible human genome locations (P = 4.6 × 10-29). Our findings demonstrate that insertion of DNA-binding motifs into multiple locations in Gag-Pol can make considerable progress toward engineering safer retroviral vectors that integrate into a significantly narrowed pool of sites on human genome and overcome the preference for TSS. PMID:20616052

Selective protection of cultured human cells from the toxic effects of ultraviolet light by proflavine pretreatment

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

Williams, J.R.; Little, J.B.

1977-10-01

Pretreatment of LICH human cells by nontoxic doses (0.1 to 5.0 ..mu..g/ml) of proflavine protects them from inactivation by ultraviolet light. The protection is acquired rapidly after exposure of cells to proflavine, with 50 percent of maximum protection being afforded within 5 min and cells being maximally protected by 20 min. Loss of protection follows similar kinetics upon removal of proflavine from the culture medium. Protection is selective and cannot be explained on the basis of proflavine absorption of uv light. Cellular survival curves after ultraviolet light for cells protected by 1, 2, 3, 4, or 5 ..mu..g/ml of proflavinemore » show that protection alters only the slope of the survival curve, not altering the quasi-threshold dose, D/sub q/. The D/sub 0/ varies from 4.8 J/m/sup 2/ for untreated cells to 10.5 J/m/sup 2/ for cells pretreated with 5 ..mu..g/ml. These data suggest the D/sub 0/ and D/sub q/ do not represent parameters of a single underlying process, manifested in a random stochastic manner, but may reflect different cellular mechanisms or responses to different DNA damage. Proflavine is selective in mitigating only those which predominate at uv doses greater than the D/sub q/.« less

Effect of a selective chloride channel activator, lubiprostone, on gastrointestinal transit, gastric sensory, and motor functions in healthy volunteers.

PubMed

Camilleri, Michael; Bharucha, Adil E; Ueno, Ryuji; Burton, Duane; Thomforde, George M; Baxter, Kari; McKinzie, Sanna; Zinsmeister, Alan R

2006-05-01

Chloride channels modulate gastrointestinal neuromuscular functions in vitro. Lubiprostone, a selective type 2 chloride channel (ClC-2) activator, induces intestinal secretion and has been shown to relieve constipation in clinical trials; however, the effects of lubiprostone on gastric function and whole gut transit in humans are unclear. Our aim was to compare the effects of the selective ClC-2 activator lubiprostone on maximum tolerated volume (MTV) of a meal, postprandial symptoms, gastric volumes, and gastrointestinal and colonic transit in humans. We performed a randomized, parallel-group, double-blind, placebo-controlled study evaluating the effects of lubiprostone (24 microg bid) in 30 healthy volunteers. Validated methods were used: scintigraphic gastrointestinal and colonic transit, SPECT to measure gastric volumes, and the nutrient drink ("satiation") test to measure MTV and postprandial symptoms. Lubiprostone accelerated small bowel and colonic transit, increased fasting gastric volume, and retarded gastric emptying. MTV values were reduced compared with placebo; however, the MTV was within the normal range for healthy adults in 13 of 14 participants, and there was no significant change compared with baseline measurements. Lubiprostone had no significant effect on postprandial gastric volume or aggregate symptoms but did decrease fullness 30 min after the fully satiating meal. Thus the ClC-2 activator lubiprostone accelerates small intestinal and colonic transit, which confers potential in the treatment of constipation.

No consistent effect of plant diversity on productivity

USGS Publications Warehouse

Huston, M.A.; Aarssen, L.W.; Austin, M.P.; Cade, B.S.; Fridley, J.D.; Garnier, E.; Grime, J.P.; Hodgson, J.; Lauenroth, W.K.; Thompson, K.; Vandermeer, J.H.; Wardle, D.A.

2000-01-01

Hector et al. (1) reported on BIODEPTH, a major international experiment on the response of plant productivity to variation in the number of plant species. They found “an overall log-linear reduction of average aboveground biomass with loss of species,” leading to what the accompanying Perspective (2) described as “a rule of thumb—that each halving of diversity leads to a 10 to 20% reduction in productivity.” These conclusions, if true, imply that the continuing high rate of plant extinction threatens the future productivity of Earth's natural and managed ecosystems and could impair their ability to produce resources essential for human survival and to regulate the concentration of atmospheric CO2.The three sites with proper experimental design (Portugal, Sweden, and Sheffield) all showed significant positive regressions of productivity across two or three doublings of species richness [Fig. 1; (12)]. This is the pattern expected from random selection from a set of objects with different properties (13–15), because the probability of including any specific member of the set—such as a plant species that grows rapidly or fixes nitrogen—increases with the number of objects selected. Such a pattern, found consistently in randomly assembled experimental plant communities but only rarely in natural plant communities (4, 5,13–15), has been identified as a statistical artifact of experimental design (5, 13, 14). Although one study (15) suggested that the pattern constitutes a natural mechanism by which diversity affects productivity, this requires the biologically unrealistic assumption that plant communities are randomly assembled with respect to productivity (5).

Risk of Drug Resistance Among Persons Acquiring HIV Within a Randomized Clinical Trial of Single- or Dual-Agent Preexposure Prophylaxis

PubMed Central

Lehman, Dara A.; Baeten, Jared M.; McCoy, Connor O.; Weis, Julie F.; Peterson, Dylan; Mbara, Gerald; Donnell, Deborah; Thomas, Katherine K.; Hendrix, Craig W.; Marzinke, Mark A.; Frenkel, Lisa; Ndase, Patrick; Mugo, Nelly R.; Celum, Connie; Overbaugh, Julie; Matsen, Frederick A.; Celum, Connie; Baeten, Jared M.; Donnell, Deborah; Coombs, Robert W.; Frenkel, Lisa; Hendrix, Craig W.; Marzinke, Mark A.; Lingappa, Jairam; McElrath, M. Juliana; Fife, Kenneth; Were, Edwin; Tumwesigye, Elioda; Ndase, Patrick; Katabira, Elly; Katabira, Elly; Ronald, Allan; Bukusi, Elizabeth; Cohen, Craig; Wangisi, Jonathan; Campbell, James; Tappero, Jordan; Kiarie, James; Farquhar, Carey; John-Stewart, Grace; Mugo, Nelly Rwamba; Campbell, James; Tappero, Jordan; Wangisi, Jonathan

2015-01-01

Background. Preexposure prophylaxis (PrEP) with emtricitabine plus tenofovir disoproxil fumarate (FTC/TDF) or TDF alone reduces the risk of human immunodeficiency virus (HIV) acquisition. Understanding the risk of antiretroviral resistance selected by PrEP during breakthrough infections is important because of the risk of treatment failure during subsequent antiretroviral use. Methods. Within the largest randomized trial of FTC/TDF versus TDF as PrEP, plasma samples were tested for HIV with resistance mutations associated with FTC (K65R and M184IV) and TDF (K65R and K70E), using 454 sequencing. Results. Of 121 HIV seroconverters, 25 received FTC/TDF, 38 received TDF, and 58 received placebo. Plasma drug levels in 26 individuals indicated PrEP use during or after HIV acquisition, of which 5 had virus with resistance mutations associated with their PrEP regimen. Among those with PrEP drug detected during infection, resistance was more frequent in the FTC/TDF arm (4 of 7 [57%]), compared with the TDF arm (1 of 19 [5.3%]; P = .01), owing to the FTC-associated mutation M184IV. Of these cases, 3 had unrecognized acute infection at PrEP randomization, and 2 were HIV negative at enrollment. Conclusions. These results suggest that resistance selected by PrEP is rare but can occur both with PrEP initiation during acute seronegative HIV infection and in PrEP breakthrough infections and that FTC is associated with a greater frequency of resistance mutations than TDF. PMID:25587020

Observational Research Rigor Alone Does Not Justify Causal Inference

PubMed Central

Ejima, Keisuke; Li, Peng; Smith, Daniel L.; Nagy, Tim R.; Kadish, Inga; van Groen, Thomas; Dawson, John A.; Yang, Yongbin; Patki, Amit; Allison, David B.

2016-01-01

Background Differing opinions exist on whether associations obtained in observational studies can be reliable indicators of a causal effect if the observational study is sufficiently well controlled and executed. Materials and methods To test this, we conducted two animal observational studies that were rigorously controlled and executed beyond what is achieved in studies of humans. In study 1, we randomized 332 genetically identical C57BL/6J mice into three diet groups with differing food energy allotments and recorded individual self-selected daily energy intake and lifespan. In study 2, 60 male mice (CD1) were paired and divided into two groups for a 2-week feeding regimen. We evaluated the association between weight gain and food consumption. Within each pair, one animal was randomly assigned to an S group in which the animals had free access to food. The second paired animal (R group) was provided exactly the same diet that their S partner ate the day before. Results In study 1, across all three groups, we found a significant negative effect of energy intake on lifespan. However, we found a positive association between food intake and lifespan among the ad libitum feeding group: 29.99 (95% CI: 8.2 to 51.7) days per daily kcal. In study 2, we found a significant (P=0.003) group (randomized vs self-selected)-by-food consumption interaction effect on weight gain. Conclusions At least in nutrition research, associations derived from observational studies may not be reliable indicators of causal effects, even with the most rigorous study designs achievable. PMID:27711975

Refernce Conditions for Streams in the Grand Prairie Natural Division of Illinois

NASA Astrophysics Data System (ADS)

Sangunett, B.; Dewalt, R.

2005-05-01

As part of the Critical Trends Assessment Program (CTAP) of the Illinois Department of Natural Resources (IDNR), 12 potential reference quality stream sites in the Grand Prairie Natural Division were evaluated in May 2004. This agriculturally dominated region, located in east central Illinois, is the most highly modified in the state. The quality of these sites was assessed using a modified Hilsenhoff Biotic Index and species richness of Ephemeroptera, Plecoptera, and Trichoptera (EPT) insect orders and a 12 parameter Habitat Quality Index (HQI). Illinois EPA high quality fish stations, Illinois Natural History Survey insect collection data, and best professional knowledge were used to choose which streams to evaluate. For analysis, reference quality streams were compared to 37 randomly selected meandering streams and 26 randomly selected channelized streams which were assessed by CTAP between 1997 and 2001. The results showed that the reference streams exceeded both taxa richness and habitat quality of randomly selected streams in the region. Both random meandering sites and reference quality sites increased in taxa richness and HQI as stream width increased. Randomly selected channelized streams had about the same taxa richness and HQI regardless of width.

Key Aspects of Nucleic Acid Library Design for in Vitro Selection

PubMed Central

Vorobyeva, Maria A.; Davydova, Anna S.; Vorobjev, Pavel E.; Pyshnyi, Dmitrii V.; Venyaminova, Alya G.

2018-01-01

Nucleic acid aptamers capable of selectively recognizing their target molecules have nowadays been established as powerful and tunable tools for biospecific applications, be it therapeutics, drug delivery systems or biosensors. It is now generally acknowledged that in vitro selection enables one to generate aptamers to almost any target of interest. However, the success of selection and the affinity of the resulting aptamers depend to a large extent on the nature and design of an initial random nucleic acid library. In this review, we summarize and discuss the most important features of the design of nucleic acid libraries for in vitro selection such as the nature of the library (DNA, RNA or modified nucleotides), the length of a randomized region and the presence of fixed sequences. We also compare and contrast different randomization strategies and consider computer methods of library design and some other aspects. PMID:29401748

Methods and analysis of realizing randomized grouping.

PubMed

Hu, Liang-Ping; Bao, Xiao-Lei; Wang, Qi

2011-07-01

Randomization is one of the four basic principles of research design. The meaning of randomization includes two aspects: one is to randomly select samples from the population, which is known as random sampling; the other is to randomly group all the samples, which is called randomized grouping. Randomized grouping can be subdivided into three categories: completely, stratified and dynamically randomized grouping. This article mainly introduces the steps of complete randomization, the definition of dynamic randomization and the realization of random sampling and grouping by SAS software.

Differential Natural Selection of Human Zinc Transporter Genes between African and Non-African Populations

PubMed Central

Zhang, Chao; Li, Jing; Tian, Lei; Lu, Dongsheng; Yuan, Kai; Yuan, Yuan; Xu, Shuhua

2015-01-01

Zinc transporters play important roles in all eukaryotes by maintaining the rational zinc concentration in cells. However, the diversity of zinc transporter genes (ZTGs) remains poorly studied. Here, we investigated the genetic diversity of 24 human ZTGs based on the 1000 Genomes data. Some ZTGs show small population differences, such as SLC30A6 with a weighted-average FST (WA-FST = 0.015), while other ZTGs exhibit considerably large population differences, such as SLC30A9 (WA-FST = 0.284). Overall, ZTGs harbor many more highly population-differentiated variants compared with random genes. Intriguingly, we found that SLC30A9 was underlying natural selection in both East Asians (EAS) and Africans (AFR) but in different directions. Notably, a non-synonymous variant (rs1047626) in SLC30A9 is almost fixed with 96.4% A in EAS and 92% G in AFR, respectively. Consequently, there are two different functional haplotypes exhibiting dominant abundance in AFR and EAS, respectively. Furthermore, a strong correlation was observed between the haplotype frequencies of SLC30A9 and distributions of zinc contents in soils or crops. We speculate that the genetic differentiation of ZTGs could directly contribute to population heterogeneity in zinc transporting capabilities and local adaptations of human populations in regard to the local zinc state or diets, which have both evolutionary and medical implications. PMID:25927708

Field-based random sampling without a sampling frame: control selection for a case-control study in rural Africa.

PubMed

Crampin, A C; Mwinuka, V; Malema, S S; Glynn, J R; Fine, P E

2001-01-01

Selection bias, particularly of controls, is common in case-control studies and may materially affect the results. Methods of control selection should be tailored both for the risk factors and disease under investigation and for the population being studied. We present here a control selection method devised for a case-control study of tuberculosis in rural Africa (Karonga, northern Malawi) that selects an age/sex frequency-matched random sample of the population, with a geographical distribution in proportion to the population density. We also present an audit of the selection process, and discuss the potential of this method in other settings.

Gene expression profiling gut microbiota in different races of humans

NASA Astrophysics Data System (ADS)

Chen, Lei; Zhang, Yu-Hang; Huang, Tao; Cai, Yu-Dong

2016-03-01

The gut microbiome is shaped and modified by the polymorphisms of microorganisms in the intestinal tract. Its composition shows strong individual specificity and may play a crucial role in the human digestive system and metabolism. Several factors can affect the composition of the gut microbiome, such as eating habits, living environment, and antibiotic usage. Thus, various races are characterized by different gut microbiome characteristics. In this present study, we studied the gut microbiomes of three different races, including individuals of Asian, European and American races. The gut microbiome and the expression levels of gut microbiome genes were analyzed in these individuals. Advanced feature selection methods (minimum redundancy maximum relevance and incremental feature selection) and four machine-learning algorithms (random forest, nearest neighbor algorithm, sequential minimal optimization, Dagging) were employed to capture key differentially expressed genes. As a result, sequential minimal optimization was found to yield the best performance using the 454 genes, which could effectively distinguish the gut microbiomes of different races. Our analyses of extracted genes support the widely accepted hypotheses that eating habits, living environments and metabolic levels in different races can influence the characteristics of the gut microbiome.

Development of a standardized battery of performance tests for the assessment of noise stress effects

NASA Technical Reports Server (NTRS)

Theologus, G. C.; Wheaton, G. R.; Mirabella, A.; Brahlek, R. E.

1973-01-01

A set of 36 relatively independent categories of human performance were identified. These categories encompass human performance in the cognitive, perceptual, and psychomotor areas, and include diagnostic measures and sensitive performance metrics. Then a prototype standardized test battery was constructed, and research was conducted to obtain information on the sensitivity of the tests to stress, the sensitivity of selected categories of performance degradation, the time course of stress effects on each of the selected tests, and the learning curves associated with each test. A research project utilizing a three factor partially repeated analysis of covariance design was conducted in which 60 male subjects were exposed to variations in noise level and quality during performance testing. Effects of randomly intermittent noise on performance of the reaction time tests were observed, but most of the other performance tests showed consistent stability. The results of 14 analyses of covariance of the data taken from the performance of the 60 subjects on the prototype standardized test battery provided information which will enable the final development and test of a standardized test battery and the associated development of differential sensitivity metrics and diagnostic classificatory system.

Gene expression profiling gut microbiota in different races of humans

PubMed Central

Chen, Lei; Zhang, Yu-Hang; Huang, Tao; Cai, Yu-Dong

2016-01-01

The gut microbiome is shaped and modified by the polymorphisms of microorganisms in the intestinal tract. Its composition shows strong individual specificity and may play a crucial role in the human digestive system and metabolism. Several factors can affect the composition of the gut microbiome, such as eating habits, living environment, and antibiotic usage. Thus, various races are characterized by different gut microbiome characteristics. In this present study, we studied the gut microbiomes of three different races, including individuals of Asian, European and American races. The gut microbiome and the expression levels of gut microbiome genes were analyzed in these individuals. Advanced feature selection methods (minimum redundancy maximum relevance and incremental feature selection) and four machine-learning algorithms (random forest, nearest neighbor algorithm, sequential minimal optimization, Dagging) were employed to capture key differentially expressed genes. As a result, sequential minimal optimization was found to yield the best performance using the 454 genes, which could effectively distinguish the gut microbiomes of different races. Our analyses of extracted genes support the widely accepted hypotheses that eating habits, living environments and metabolic levels in different races can influence the characteristics of the gut microbiome. PMID:26975620

Human Variation in Short Regions Predisposed to Deep Evolutionary Conservation

PubMed Central

Loots, Gabriela G.; Ovcharenko, Ivan

2010-01-01

The landscape of the human genome consists of millions of short islands of conservation that are 100% conserved across multiple vertebrate genomes (termed “bricks”), the majority of which are located in noncoding regions. Several hundred thousand bricks are deeply conserved reaching the genomes of amphibians and fish. Deep phylogenetic conservation of noncoding DNA has been reported to be strongly associated with the presence of gene regulatory elements, introducing bricks as a proxy to the functional noncoding landscape of the human genome. Here, we report a significant overrepresentation of bricks in the promoters of transcription factors and developmental genes, where the high level of phylogenetic conservation correlates with an increase in brick overrepresentation. We also found that the presence of a brick dictates a predisposition to evolutionary constraint, with only 0.7% of the amniota brick central nucleotides being diverged within the primate lineage—an 11-fold reduction in the divergence rate compared with random expectation. Human single-nucleotide polymorphism (SNP) data explains only 3% of primate-specific variation in amniota bricks, thus arguing for a widespread fixation of brick mutations within the primate lineage and prior to human radiation. This variation, in turn, might have been utilized as a driving force for primate- and hominoid-specific adaptation. We also discovered a pronounced deviation from the evolutionary predisposition in the human lineage, with over 20-fold increase in the substitution rate at brick SNP sites over expected values. In addition, contrary to typical brick mutations, brick variation commonly encountered in the human population displays limited, if any, signatures of negative selection as measured by the minor allele frequency and population differentiation (F-statistical measure) measures. These observations argue for the plasticity of gene regulatory mechanisms in vertebrates—with evidence of strong purifying selection acting on the gene regulatory landscape of the human genome, where widespread advantageous mutations in putative regulatory elements are likely utilized in functional diversification and adaptation of species. PMID:20093432

Assessing the accuracy and stability of variable selection methods for random forest modeling in ecology

EPA Science Inventory

Random forest (RF) modeling has emerged as an important statistical learning method in ecology due to its exceptional predictive performance. However, for large and complex ecological datasets there is limited guidance on variable selection methods for RF modeling. Typically, e...

Challenging local realism with human choices.

PubMed

2018-05-01

A Bell test is a randomized trial that compares experimental observations against the philosophical worldview of local realism 1 , in which the properties of the physical world are independent of our observation of them and no signal travels faster than light. A Bell test requires spatially distributed entanglement, fast and high-efficiency detection and unpredictable measurement settings 2,3 . Although technology can satisfy the first two of these requirements 4-7 , the use of physical devices to choose settings in a Bell test involves making assumptions about the physics that one aims to test. Bell himself noted this weakness in using physical setting choices and argued that human 'free will' could be used rigorously to ensure unpredictability in Bell tests 8 . Here we report a set of local-realism tests using human choices, which avoids assumptions about predictability in physics. We recruited about 100,000 human participants to play an online video game that incentivizes fast, sustained input of unpredictable selections and illustrates Bell-test methodology 9 . The participants generated 97,347,490 binary choices, which were directed via a scalable web platform to 12 laboratories on five continents, where 13 experiments tested local realism using photons 5,6 , single atoms 7 , atomic ensembles 10 and superconducting devices 11 . Over a 12-hour period on 30 November 2016, participants worldwide provided a sustained data flow of over 1,000 bits per second to the experiments, which used different human-generated data to choose each measurement setting. The observed correlations strongly contradict local realism and other realistic positions in bipartite and tripartite 12 scenarios. Project outcomes include closing the 'freedom-of-choice loophole' (the possibility that the setting choices are influenced by 'hidden variables' to correlate with the particle properties 13 ), the utilization of video-game methods 14 for rapid collection of human-generated randomness, and the use of networking techniques for global participation in experimental science.

Genetic improvement in mastitis resistance: comparison of selection criteria from cross-sectional and random regression sire models for somatic cell score.

PubMed

Odegård, J; Klemetsdal, G; Heringstad, B

2005-04-01

Several selection criteria for reducing incidence of mastitis were developed from a random regression sire model for test-day somatic cell score (SCS). For comparison, sire transmitting abilities were also predicted based on a cross-sectional model for lactation mean SCS. Only first-crop daughters were used in genetic evaluation of SCS, and the different selection criteria were compared based on their correlation with incidence of clinical mastitis in second-crop daughters (measured as mean daughter deviations). Selection criteria were predicted based on both complete and reduced first-crop daughter groups (261 or 65 daughters per sire, respectively). For complete daughter groups, predicted transmitting abilities at around 30 d in milk showed the best predictive ability for incidence of clinical mastitis, closely followed by average predicted transmitting abilities over the entire lactation. Both of these criteria were derived from the random regression model. These selection criteria improved accuracy of selection by approximately 2% relative to a cross-sectional model. However, for reduced daughter groups, the cross-sectional model yielded increased predictive ability compared with the selection criteria based on the random regression model. This result may be explained by the cross-sectional model being more robust, i.e., less sensitive to precision of (co)variance components estimates and effects of data structure.

Human milk is a source of lactic acid bacteria for the infant gut.

PubMed

Martín, Rocío; Langa, Susana; Reviriego, Carlota; Jimínez, Esther; Marín, María L; Xaus, Jordi; Fernández, Leonides; Rodríguez, Juan M

2003-12-01

To investigate whether human breast milk contains potentially probiotic lactic acid bacteria, and therefore, whether it can be considered a synbiotic food. Study design Lactic acid bacteria were isolated from milk, mammary areola, and breast skin of eight healthy mothers and oral swabs and feces of their respective breast-fed infants. Some isolates (178 from each mother and newborn pair) were randomly selected and submitted to randomly amplified polymorphic DNA (RAPD) polymerase chain reaction analysis, and those that displayed identical RAPD patterns were identified by 16S rDNA sequencing. Within each mother and newborn pair, some rod-shaped lactic acid bacteria isolated from mammary areola, breast milk, and infant oral swabs and feces displayed identical RAPD profiles. All of them, independently from the mother and child pair, were identified as Lactobacillus gasseri. Similarly, among coccoid lactic acid bacteria from these different sources, some shared an identical RAPD pattern and were identified as Enterococcus faecium. In contrast, none of the lactic acid bacteria isolated from breast skin shared RAPD profiles with lactic acid bacteria of the other sources. Breast-feeding can be a significant source of lactic acid bacteria to the infant gut. Lactic acid bacteria present in milk may have an endogenous origin and may not be the result of contamination from the surrounding breast skin.

The Effects of Total Physical Response by Storytelling and the Traditional Teaching Styles of a Foreign Language in a Selected High School

ERIC Educational Resources Information Center

Kariuki, Patrick N. K.; Bush, Elizabeth Danielle

2008-01-01

The purpose of this study was to examine the effects of Total Physical Response by Storytelling and the traditional teaching method on a foreign language in a selected high school. The sample consisted of 30 students who were randomly selected and randomly assigned to experimental and control group. The experimental group was taught using Total…

Most Undirected Random Graphs Are Amplifiers of Selection for Birth-Death Dynamics, but Suppressors of Selection for Death-Birth Dynamics.

PubMed

Hindersin, Laura; Traulsen, Arne

2015-11-01

We analyze evolutionary dynamics on graphs, where the nodes represent individuals of a population. The links of a node describe which other individuals can be displaced by the offspring of the individual on that node. Amplifiers of selection are graphs for which the fixation probability is increased for advantageous mutants and decreased for disadvantageous mutants. A few examples of such amplifiers have been developed, but so far it is unclear how many such structures exist and how to construct them. Here, we show that almost any undirected random graph is an amplifier of selection for Birth-death updating, where an individual is selected to reproduce with probability proportional to its fitness and one of its neighbors is replaced by that offspring at random. If we instead focus on death-Birth updating, in which a random individual is removed and its neighbors compete for the empty spot, then the same ensemble of graphs consists of almost only suppressors of selection for which the fixation probability is decreased for advantageous mutants and increased for disadvantageous mutants. Thus, the impact of population structure on evolutionary dynamics is a subtle issue that will depend on seemingly minor details of the underlying evolutionary process.

Using ArcMap, Google Earth, and Global Positioning Systems to select and locate random households in rural Haiti.

PubMed

Wampler, Peter J; Rediske, Richard R; Molla, Azizur R

2013-01-18

A remote sensing technique was developed which combines a Geographic Information System (GIS); Google Earth, and Microsoft Excel to identify home locations for a random sample of households in rural Haiti. The method was used to select homes for ethnographic and water quality research in a region of rural Haiti located within 9 km of a local hospital and source of health education in Deschapelles, Haiti. The technique does not require access to governmental records or ground based surveys to collect household location data and can be performed in a rapid, cost-effective manner. The random selection of households and the location of these households during field surveys were accomplished using GIS, Google Earth, Microsoft Excel, and handheld Garmin GPSmap 76CSx GPS units. Homes were identified and mapped in Google Earth, exported to ArcMap 10.0, and a random list of homes was generated using Microsoft Excel which was then loaded onto handheld GPS units for field location. The development and use of a remote sensing method was essential to the selection and location of random households. A total of 537 homes initially were mapped and a randomized subset of 96 was identified as potential survey locations. Over 96% of the homes mapped using Google Earth imagery were correctly identified as occupied dwellings. Only 3.6% of the occupants of mapped homes visited declined to be interviewed. 16.4% of the homes visited were not occupied at the time of the visit due to work away from the home or market days. A total of 55 households were located using this method during the 10 days of fieldwork in May and June of 2012. The method used to generate and field locate random homes for surveys and water sampling was an effective means of selecting random households in a rural environment lacking geolocation infrastructure. The success rate for locating households using a handheld GPS was excellent and only rarely was local knowledge required to identify and locate households. This method provides an important technique that can be applied to other developing countries where a randomized study design is needed but infrastructure is lacking to implement more traditional participant selection methods.

Energy parasites trigger oncogene mutation.

PubMed

Pokorný, Jiří; Pokorný, Jan; Jandová, Anna; Kobilková, Jitka; Vrba, Jan; Vrba, Jan

2016-10-01

Cancer initialization can be explained as a result of parasitic virus energy consumption leading to randomized genome chemical bonding. Analysis of experimental data on cell-mediated immunity (CMI) containing about 12,000 cases of healthy humans, cancer patients and patients with precancerous cervical lesions disclosed that the specific cancer and the non-specific lactate dehydrogenase-elevating (LDH) virus antigen elicit similar responses. The specific antigen is effective only in cancer type of its origin but the non-specific antigen in all examined cancers. CMI results of CIN patients display both healthy and cancer state. The ribonucleic acid (RNA) of the LDH virus parasitizing on energy reduces the ratio of coherent/random oscillations. Decreased effect of coherent cellular electromagnetic field on bonding electrons in biological macromolecules leads to elevating probability of random genome reactions. Overlapping of wave functions in biological macromolecules depends on energy of the cellular electromagnetic field which supplies energy to bonding electrons for selective chemical bonds. CMI responses of cancer and LDH virus antigens in all examined healthy, precancerous and cancer cases point to energy mechanism in cancer initiation. Dependence of the rate of biochemical reactions on biological electromagnetic field explains yet unknown mechanism of genome mutation.

Generalizing Evidence From Randomized Clinical Trials to Target Populations

PubMed Central

Cole, Stephen R.; Stuart, Elizabeth A.

2010-01-01

Properly planned and conducted randomized clinical trials remain susceptible to a lack of external validity. The authors illustrate a model-based method to standardize observed trial results to a specified target population using a seminal human immunodeficiency virus (HIV) treatment trial, and they provide Monte Carlo simulation evidence supporting the method. The example trial enrolled 1,156 HIV-infected adult men and women in the United States in 1996, randomly assigned 577 to a highly active antiretroviral therapy and 579 to a largely ineffective combination therapy, and followed participants for 52 weeks. The target population was US people infected with HIV in 2006, as estimated by the Centers for Disease Control and Prevention. Results from the trial apply, albeit muted by 12%, to the target population, under the assumption that the authors have measured and correctly modeled the determinants of selection that reflect heterogeneity in the treatment effect. In simulations with a heterogeneous treatment effect, a conventional intent-to-treat estimate was biased with poor confidence limit coverage, but the proposed estimate was largely unbiased with appropriate confidence limit coverage. The proposed method standardizes observed trial results to a specified target population and thereby provides information regarding the generalizability of trial results. PMID:20547574

The role of color and attention-to-color in mirror-symmetry perception.

PubMed

Gheorghiu, Elena; Kingdom, Frederick A A; Remkes, Aaron; Li, Hyung-Chul O; Rainville, Stéphane

2016-07-11

The role of color in the visual perception of mirror-symmetry is controversial. Some reports support the existence of color-selective mirror-symmetry channels, others that mirror-symmetry perception is merely sensitive to color-correlations across the symmetry axis. Here we test between the two ideas. Stimuli consisted of colored Gaussian-blobs arranged either mirror-symmetrically or quasi-randomly. We used four arrangements: (1) 'segregated' - symmetric blobs were of one color, random blobs of the other color(s); (2) 'random-segregated' - as above but with the symmetric color randomly selected on each trial; (3) 'non-segregated' - symmetric blobs were of all colors in equal proportions, as were the random blobs; (4) 'anti-symmetric' - symmetric blobs were of opposite-color across the symmetry axis. We found: (a) near-chance levels for the anti-symmetric condition, suggesting that symmetry perception is sensitive to color-correlations across the symmetry axis; (b) similar performance for random-segregated and non-segregated conditions, giving no support to the idea that mirror-symmetry is color selective; (c) highest performance for the color-segregated condition, but only when the observer knew beforehand the symmetry color, suggesting that symmetry detection benefits from color-based attention. We conclude that mirror-symmetry detection mechanisms, while sensitive to color-correlations across the symmetry axis and subject to the benefits of attention-to-color, are not color selective.

The role of color and attention-to-color in mirror-symmetry perception

PubMed Central

Gheorghiu, Elena; Kingdom, Frederick A. A.; Remkes, Aaron; Li, Hyung-Chul O.; Rainville, Stéphane

2016-01-01

The role of color in the visual perception of mirror-symmetry is controversial. Some reports support the existence of color-selective mirror-symmetry channels, others that mirror-symmetry perception is merely sensitive to color-correlations across the symmetry axis. Here we test between the two ideas. Stimuli consisted of colored Gaussian-blobs arranged either mirror-symmetrically or quasi-randomly. We used four arrangements: (1) ‘segregated’ – symmetric blobs were of one color, random blobs of the other color(s); (2) ‘random-segregated’ – as above but with the symmetric color randomly selected on each trial; (3) ‘non-segregated’ – symmetric blobs were of all colors in equal proportions, as were the random blobs; (4) ‘anti-symmetric’ – symmetric blobs were of opposite-color across the symmetry axis. We found: (a) near-chance levels for the anti-symmetric condition, suggesting that symmetry perception is sensitive to color-correlations across the symmetry axis; (b) similar performance for random-segregated and non-segregated conditions, giving no support to the idea that mirror-symmetry is color selective; (c) highest performance for the color-segregated condition, but only when the observer knew beforehand the symmetry color, suggesting that symmetry detection benefits from color-based attention. We conclude that mirror-symmetry detection mechanisms, while sensitive to color-correlations across the symmetry axis and subject to the benefits of attention-to-color, are not color selective. PMID:27404804

Ensemble Feature Learning of Genomic Data Using Support Vector Machine

PubMed Central

Anaissi, Ali; Goyal, Madhu; Catchpoole, Daniel R.; Braytee, Ali; Kennedy, Paul J.

2016-01-01

The identification of a subset of genes having the ability to capture the necessary information to distinguish classes of patients is crucial in bioinformatics applications. Ensemble and bagging methods have been shown to work effectively in the process of gene selection and classification. Testament to that is random forest which combines random decision trees with bagging to improve overall feature selection and classification accuracy. Surprisingly, the adoption of these methods in support vector machines has only recently received attention but mostly on classification not gene selection. This paper introduces an ensemble SVM-Recursive Feature Elimination (ESVM-RFE) for gene selection that follows the concepts of ensemble and bagging used in random forest but adopts the backward elimination strategy which is the rationale of RFE algorithm. The rationale behind this is, building ensemble SVM models using randomly drawn bootstrap samples from the training set, will produce different feature rankings which will be subsequently aggregated as one feature ranking. As a result, the decision for elimination of features is based upon the ranking of multiple SVM models instead of choosing one particular model. Moreover, this approach will address the problem of imbalanced datasets by constructing a nearly balanced bootstrap sample. Our experiments show that ESVM-RFE for gene selection substantially increased the classification performance on five microarray datasets compared to state-of-the-art methods. Experiments on the childhood leukaemia dataset show that an average 9% better accuracy is achieved by ESVM-RFE over SVM-RFE, and 5% over random forest based approach. The selected genes by the ESVM-RFE algorithm were further explored with Singular Value Decomposition (SVD) which reveals significant clusters with the selected data. PMID:27304923

C57 mice increase wheel-running behavior following stress: preliminary findings.

PubMed

Sibold, Jeremy S; Hammack, Sayamwong E; Falls, William A

2011-10-01

Exercise has been shown to reduce anxiety in both humans and animals. To date, there are few, if any studies that examine the effect of stress on self-selected exercise using an animal model. This study examined the effect of acute stress on wheel-running distance in mice. Forty 8-week-old, male C57BL/6J mice were randomly assigned to one of three groups: no stress + wheel-running experience, stress + wheel-running experience, or stress with no wheel-running experience. Stressed mice were exposed to foot shock in a brightly lit environment. Following treatment, wheel-running distances were observed for three hours. Stress significantly increased voluntary wheel-running in mice with wheel-running experience as compared to nonstressed controls and stressed mice with no wheel-running experience. These results suggest that mice familiar with wheel-running may self-select this exercise as a modality for the mitigation of accumulated anxiety.

Association between serum magnesium and common complications of diabetes mellitus.

PubMed

Zhang, Yiyan; Li, Qin; Xin, Yi; Lv, Weiqi; Ge, Chuanbin

2018-01-01

Magnesium ion, as important cation in the human body, involved in various enzymatic reactions, glucose transport and insulin release. Now diabetes mellitus and diabetic complications have become important public health problems around the world. This paper explores the association between concentration levels of serum magnesium and common complications and comorbidities of diabetes mellitus and other biochemical indexes. There are 1217 eligible patients selected from 14,317 cases of diabetic hospitalization patients from January 2010 to December 2011. Random forest algorithm was applied to assess the importance of various biochemical indexes and to perform diabetic complications prediction. The research results showed that low concentration of serum magnesium and four common diabetic complications - diabetic retinopathy, diabetic nephropathy, diabetic neuropathy and diabetic macroangiopathy - exists association, but no obvious correlation with other comorbidities like hypertension. The specific factors of four common diabetic complications were selected from the biochemical indexes to provide a reference direction for further research.

The effects of a parenting prime on sex differences in mate selection criteria.

PubMed

Millar, Murray G; Ostlund, Nelse M

2006-11-01

This study tested an evolutionary hypothesis that the mere prospect of caring for a child will increase sex differences in human mate selection criteria. That is, women would adopt a stronger preference for socially dominant men when parenting had been primed and men would adopt a stronger preference for physically attractive women when parenting had been primed. Male and female university students were randomly assigned to be exposed to a parenting prime or a nonparenting prime. Following the priming procedure, participants rated the romantic appeal of a target person of the opposite sex. Exposure to the parenting prime, the target's social dominance, and the target's physical attractiveness were orthogonally manipulated. As predicted, women adopted a stronger mate preference for social dominance when parenting was at the forefront of the mind. Contrary to predictions, the parenting prime had no effect on men's mate preference for physical attractiveness.

Multiple groups of orientation-selective visual mechanisms underlying rapid orientated-line detection.

PubMed Central

Foster, D H; Westland, S

1998-01-01

Visual search for an edge or line element differing in orientation from a background of other edge or line elements can be performed rapidly and effortlessly. In this study, based on psychophysical measurements with ten human observers, threshold values of the angle between a target and background line elements were obtained as functions of background-element orientation, in brief masked displays. A repeated-loess analysis of the threshold functions suggested the existence of several groups of orientation-selective mechanisms contributing to rapid orientated-line detection; specifically, coarse, intermediate and fine mechanisms with preferred orientations spaced at angles of approximately 90 degrees, 35 degrees, and 10 degrees-25 degrees, respectively. The preferred orientations of coarse and some intermediate mechanisms coincided with the vertical or horizontal of the frontoparallel plane, but the preferred orientations of fine mechanisms varied randomly from observer to observer, possibly reflecting individual variations in neuronal sampling characteristics. PMID:9753784

Randomization Methods in Emergency Setting Trials: A Descriptive Review

ERIC Educational Resources Information Center

Corbett, Mark Stephen; Moe-Byrne, Thirimon; Oddie, Sam; McGuire, William

2016-01-01

Background: Quasi-randomization might expedite recruitment into trials in emergency care settings but may also introduce selection bias. Methods: We searched the Cochrane Library and other databases for systematic reviews of interventions in emergency medicine or urgent care settings. We assessed selection bias (baseline imbalances) in prognostic…

Middle Level Practices in European International and Department of Defense Schools.

ERIC Educational Resources Information Center

Waggoner, V. Christine; McEwin, C. Kenneth

1993-01-01

Discusses results of a 1989-90 survey of 70 randomly selected international schools and 70 randomly selected Department of Defense Schools in Europe. Programs and practices surveyed included enrollments, grade organization, curriculum and instructional plans, core subjects, grouping patterns, exploratory courses, advisory programs, and scheduling.…

Variable selection with random forest: Balancing stability, performance, and interpretation in ecological and environmental modeling

EPA Science Inventory

Random forest (RF) is popular in ecological and environmental modeling, in part, because of its insensitivity to correlated predictors and resistance to overfitting. Although variable selection has been proposed to improve both performance and interpretation of RF models, it is u...

Hebbian Learning in a Random Network Captures Selectivity Properties of the Prefrontal Cortex.

PubMed

Lindsay, Grace W; Rigotti, Mattia; Warden, Melissa R; Miller, Earl K; Fusi, Stefano

2017-11-08

Complex cognitive behaviors, such as context-switching and rule-following, are thought to be supported by the prefrontal cortex (PFC). Neural activity in the PFC must thus be specialized to specific tasks while retaining flexibility. Nonlinear "mixed" selectivity is an important neurophysiological trait for enabling complex and context-dependent behaviors. Here we investigate (1) the extent to which the PFC exhibits computationally relevant properties, such as mixed selectivity, and (2) how such properties could arise via circuit mechanisms. We show that PFC cells recorded from male and female rhesus macaques during a complex task show a moderate level of specialization and structure that is not replicated by a model wherein cells receive random feedforward inputs. While random connectivity can be effective at generating mixed selectivity, the data show significantly more mixed selectivity than predicted by a model with otherwise matched parameters. A simple Hebbian learning rule applied to the random connectivity, however, increases mixed selectivity and enables the model to match the data more accurately. To explain how learning achieves this, we provide analysis along with a clear geometric interpretation of the impact of learning on selectivity. After learning, the model also matches the data on measures of noise, response density, clustering, and the distribution of selectivities. Of two styles of Hebbian learning tested, the simpler and more biologically plausible option better matches the data. These modeling results provide clues about how neural properties important for cognition can arise in a circuit and make clear experimental predictions regarding how various measures of selectivity would evolve during animal training. SIGNIFICANCE STATEMENT The prefrontal cortex is a brain region believed to support the ability of animals to engage in complex behavior. How neurons in this area respond to stimuli-and in particular, to combinations of stimuli ("mixed selectivity")-is a topic of interest. Even though models with random feedforward connectivity are capable of creating computationally relevant mixed selectivity, such a model does not match the levels of mixed selectivity seen in the data analyzed in this study. Adding simple Hebbian learning to the model increases mixed selectivity to the correct level and makes the model match the data on several other relevant measures. This study thus offers predictions on how mixed selectivity and other properties evolve with training. Copyright © 2017 the authors 0270-6474/17/3711021-16$15.00/0.

Molecular footprints of domestication and improvement in soybean revealed by whole genome re-sequencing

PubMed Central

2013-01-01

Background Artificial selection played an important role in the origin of modern Glycine max cultivars from the wild soybean Glycine soja. To elucidate the consequences of artificial selection accompanying the domestication and modern improvement of soybean, 25 new and 30 published whole-genome re-sequencing accessions, which represent wild, domesticated landrace, and Chinese elite soybean populations were analyzed. Results A total of 5,102,244 single nucleotide polymorphisms (SNPs) and 707,969 insertion/deletions were identified. Among the SNPs detected, 25.5% were not described previously. We found that artificial selection during domestication led to more pronounced reduction in the genetic diversity of soybean than the switch from landraces to elite cultivars. Only a small proportion (2.99%) of the whole genomic regions appear to be affected by artificial selection for preferred agricultural traits. The selection regions were not distributed randomly or uniformly throughout the genome. Instead, clusters of selection hotspots in certain genomic regions were observed. Moreover, a set of candidate genes (4.38% of the total annotated genes) significantly affected by selection underlying soybean domestication and genetic improvement were identified. Conclusions Given the uniqueness of the soybean germplasm sequenced, this study drew a clear picture of human-mediated evolution of the soybean genomes. The genomic resources and information provided by this study would also facilitate the discovery of genes/loci underlying agronomically important traits. PMID:23984715

High In Vitro Activity of the Novel Spiropyrimidinetrione AZD0914, a DNA Gyrase Inhibitor, against Multidrug-Resistant Neisseria gonorrhoeae Isolates Suggests a New Effective Option for Oral Treatment of Gonorrhea

PubMed Central

Jacobsson, Susanne; Golparian, Daniel; Alm, Richard A.; Huband, Michael; Mueller, John; Jensen, Jorgen Skov; Ohnishi, Makoto

2014-01-01

We evaluated the activity of the novel spiropyrimidinetrione AZD0914 (DNA gyrase inhibitor) against clinical gonococcal isolates and international reference strains (n = 250), including strains with diverse multidrug resistance and extensive drug resistance. The AZD0914 MICs were substantially lower than those of most other currently or previously recommended antimicrobials. AZD0914 should be further evaluated, including in vitro selection, in vivo emergence and mechanisms of resistance, pharmacokinetics/pharmacodynamics in humans, optimal dosing, and performance, in appropriate randomized and controlled clinical trials. PMID:24982070

Human Immunodeficiency Virus Proteins Mimic Human T Cell Receptors Inducing Cross-Reactive Antibodies

PubMed Central

2017-01-01

Human immunodeficiency virus (HIV) hides from the immune system in part by mimicking host antigens, including human leukocyte antigens. It is demonstrated here that HIV also mimics the V-β-D-J-β of approximately seventy percent of about 600 randomly selected human T cell receptors (TCR). This degree of mimicry is greater than any other human pathogen, commensal or symbiotic organism studied. These data suggest that HIV may be evolving into a commensal organism just as simian immunodeficiency virus has done in some types of monkeys. The gp120 envelope protein, Nef protein and Pol protein are particularly similar to host TCR, camouflaging HIV from the immune system and creating serious barriers to the development of safe HIV vaccines. One consequence of HIV mimicry of host TCR is that antibodies against HIV proteins have a significant probability of recognizing the corresponding TCR as antigenic targets, explaining the widespread observation of lymphocytotoxic autoantibodies in acquired immunodeficiency syndrome (AIDS). Quantitative enzyme-linked immunoadsorption assays (ELISA) demonstrated that every HIV antibody tested recognized at least one of twelve TCR, and as many as seven, with a binding constant in the 10−8 to 10−9 m range. HIV immunity also affects microbiome tolerance in ways that correlate with susceptibility to specific opportunistic infections. PMID:28972547

Adaptive Electronic Camouflage Using Texture Synthesis

DTIC Science & Technology

2012-04-01

algorithm begins by computing the GLCMs, GIN and GOUT , of the input image (e.g., image of local environment) and output image (randomly generated...respectively. The algorithm randomly selects a pixel from the output image and cycles its gray-level through all values. For each value, GOUT is updated...The value of the selected pixel is permanently changed to the gray-level value that minimizes the error between GIN and GOUT . Without selecting a

Phylogenetic and phylodynamic analyses of human metapneumovirus in Buenos Aires (Argentina) for a three-year period (2009-2011).

PubMed

Velez Rueda, Ana Julia; Mistchenko, Alicia Susana; Viegas, Mariana

2013-01-01

Human metapneumovirus, which belongs to the Paramyxoviridae family and has been classified as a member of the Pneumovirus genus, is genetically and clinically similar to other family members such as human respiratory syncytial virus. A total of 1146 nasopharyngeal aspirates from pediatric patients with moderate and severe acute lower respiratory tract infections, hospitalized at the Ricardo Gutierrez Childreńs Hospital (Buenos Aires, Argentina), were tested by real time RT-PCR for human metapneumovirus. Results showed that 168 (14.65%) were positive. Thirty-six of these 168 samples were randomly selected to characterize positive cases molecularly. The phylogenetic analysis of the sequences of the G and F genes showed that genotypes A2 and B2 cocirculated during 2009 and 2010 and that only genotype A2 circulated in 2011 in Argentina. Genotype A2 prevailed during the study period, a fact supported by a higher effective population size (Neτ) and higher diversity as compared to that of genotype B2 (10.9% (SE 1.3%) vs. 1.7% (SE 0.4%), respectively). The phylogeographic analysis of the G protein gene sequences showed that this virus has no geographical restrictions and can travel globally harbored in hosts. The selection pressure analysis of the F protein showed that although this protein has regions with polymorphisms, it has vast structural and functional constraints. In addition, the predicted B-linear epitopes and the sites recognized by previously described monoclonal antibodies were conserved in all Argentine sequences. This points out this protein as a potential candidate to be the target of future humanized antibodies or vaccines.

Mice with megabase humanization of their immunoglobulin genes generate antibodies as efficiently as normal mice.

PubMed

Murphy, Andrew J; Macdonald, Lynn E; Stevens, Sean; Karow, Margaret; Dore, Anthony T; Pobursky, Kevin; Huang, Tammy T; Poueymirou, William T; Esau, Lakeisha; Meola, Melissa; Mikulka, Warren; Krueger, Pamela; Fairhurst, Jeanette; Valenzuela, David M; Papadopoulos, Nicholas; Yancopoulos, George D

2014-04-08

Mice genetically engineered to be humanized for their Ig genes allow for human antibody responses within a mouse background (HumAb mice), providing a valuable platform for the generation of fully human therapeutic antibodies. Unfortunately, existing HumAb mice do not have fully functional immune systems, perhaps because of the manner in which their genetic humanization was carried out. Heretofore, HumAb mice have been generated by disrupting the endogenous mouse Ig genes and simultaneously introducing human Ig transgenes at a different and random location; KO-plus-transgenic humanization. As we describe in the companion paper, we attempted to make mice that more efficiently use human variable region segments in their humoral responses by precisely replacing 6 Mb of mouse Ig heavy and kappa light variable region germ-line gene segments with their human counterparts while leaving the mouse constant regions intact, using a unique in situ humanization approach. We reasoned the introduced human variable region gene segments would function indistinguishably in their new genetic location, whereas the retained mouse constant regions would allow for optimal interactions and selection of the resulting antibodies within the mouse environment. We show that these mice, termed VelocImmune mice because they were generated using VelociGene technology, efficiently produce human:mouse hybrid antibodies (that are rapidly convertible to fully human antibodies) and have fully functional humoral immune systems indistinguishable from those of WT mice. The efficiency of the VelocImmune approach is confirmed by the rapid progression of 10 different fully human antibodies into human clinical trials.

Polar stir bars for isolation and preconcentration of perfluoroalkyl substances from human milk samples prior to UHPLC-MS/MS analysis.

PubMed

Martín, Julia; Rodríguez-Gómez, Rocío; Zafra-Gómez, Alberto; Alonso, Esteban; Vílchez, José L; Navalón, Alberto

2016-04-01

A new method for the determination of four perfluoroalkyl carboxylic acids (from C5 to C8) and perfluorooctane sulfonate in human milk samples using stir-bar sorptive extraction-ultra-HPLC-MS/MS has been accurately optimized and validated. Polydimethylsiloxane and polyethyleneglycol modified silicone materials were evaluated. Overall, polyethyleneglycol led to a better sensitivity. After optimizing experimental variables, the method was validated reaching detection limits in the range of 0.05-0.20 ng ml(-1); recovery rates from 81 to 105% and relative standard deviations fewer than 13% in all cases. The method was applied to milk samples from five randomly selected women. All samples were positive for at least one of the target compounds with concentrations ranging between 0.8 and 6.6 ng ml(-1), being the most abundant perfluorooctane sulfonate.

Agricultural use of Burkholderia (Pseudomonas) cepacia: a threat to human health?

PubMed Central

Holmes, A.; Govan, J.; Goldstein, R.

1998-01-01

In the past 2 decades, Burkholderia cepacia has emerged as a human pathogen causing numerous outbreaks, particularly among cystic fibrosis (CF) patients. One highly transmissible strain has spread across North America and Britain, and another between hospitalized CF and non-CF patients. Meanwhile, the organism has been developed as a biopesticide for protecting crops against fungal diseases and has potential as a bioremediation agent for breaking down recalcitrant herbicides and pesticides. However, B. cepacia is inherently resistant to multiple antibiotics; selection of strains "safe" for environmental application is not at present possible phenotypically or genotypically; molecular epidemiology and phylogenetic studies demonstrate that highly transmissible strains emerge randomly; and the organism has a capacity for rapid mutation and adaptation (facilitated by numerous insertion sequences), and a large, complex genome divided into separate chromosomes. Therefore, the widespread agricultural use of B. cepacia should be approached with caution. PMID:9621192

Connectome-harmonic decomposition of human brain activity reveals dynamical repertoire re-organization under LSD.

PubMed

Atasoy, Selen; Roseman, Leor; Kaelen, Mendel; Kringelbach, Morten L; Deco, Gustavo; Carhart-Harris, Robin L

2017-12-15

Recent studies have started to elucidate the effects of lysergic acid diethylamide (LSD) on the human brain but the underlying dynamics are not yet fully understood. Here we used 'connectome-harmonic decomposition', a novel method to investigate the dynamical changes in brain states. We found that LSD alters the energy and the power of individual harmonic brain states in a frequency-selective manner. Remarkably, this leads to an expansion of the repertoire of active brain states, suggestive of a general re-organization of brain dynamics given the non-random increase in co-activation across frequencies. Interestingly, the frequency distribution of the active repertoire of brain states under LSD closely follows power-laws indicating a re-organization of the dynamics at the edge of criticality. Beyond the present findings, these methods open up for a better understanding of the complex brain dynamics in health and disease.

Hebbian Learning in a Random Network Captures Selectivity Properties of the Prefrontal Cortex

PubMed Central

Lindsay, Grace W.

2017-01-01

Complex cognitive behaviors, such as context-switching and rule-following, are thought to be supported by the prefrontal cortex (PFC). Neural activity in the PFC must thus be specialized to specific tasks while retaining flexibility. Nonlinear “mixed” selectivity is an important neurophysiological trait for enabling complex and context-dependent behaviors. Here we investigate (1) the extent to which the PFC exhibits computationally relevant properties, such as mixed selectivity, and (2) how such properties could arise via circuit mechanisms. We show that PFC cells recorded from male and female rhesus macaques during a complex task show a moderate level of specialization and structure that is not replicated by a model wherein cells receive random feedforward inputs. While random connectivity can be effective at generating mixed selectivity, the data show significantly more mixed selectivity than predicted by a model with otherwise matched parameters. A simple Hebbian learning rule applied to the random connectivity, however, increases mixed selectivity and enables the model to match the data more accurately. To explain how learning achieves this, we provide analysis along with a clear geometric interpretation of the impact of learning on selectivity. After learning, the model also matches the data on measures of noise, response density, clustering, and the distribution of selectivities. Of two styles of Hebbian learning tested, the simpler and more biologically plausible option better matches the data. These modeling results provide clues about how neural properties important for cognition can arise in a circuit and make clear experimental predictions regarding how various measures of selectivity would evolve during animal training. SIGNIFICANCE STATEMENT The prefrontal cortex is a brain region believed to support the ability of animals to engage in complex behavior. How neurons in this area respond to stimuli—and in particular, to combinations of stimuli (“mixed selectivity”)—is a topic of interest. Even though models with random feedforward connectivity are capable of creating computationally relevant mixed selectivity, such a model does not match the levels of mixed selectivity seen in the data analyzed in this study. Adding simple Hebbian learning to the model increases mixed selectivity to the correct level and makes the model match the data on several other relevant measures. This study thus offers predictions on how mixed selectivity and other properties evolve with training. PMID:28986463

Learning accurate and interpretable models based on regularized random forests regression

PubMed Central

2014-01-01

Background Many biology related research works combine data from multiple sources in an effort to understand the underlying problems. It is important to find and interpret the most important information from these sources. Thus it will be beneficial to have an effective algorithm that can simultaneously extract decision rules and select critical features for good interpretation while preserving the prediction performance. Methods In this study, we focus on regression problems for biological data where target outcomes are continuous. In general, models constructed from linear regression approaches are relatively easy to interpret. However, many practical biological applications are nonlinear in essence where we can hardly find a direct linear relationship between input and output. Nonlinear regression techniques can reveal nonlinear relationship of data, but are generally hard for human to interpret. We propose a rule based regression algorithm that uses 1-norm regularized random forests. The proposed approach simultaneously extracts a small number of rules from generated random forests and eliminates unimportant features. Results We tested the approach on some biological data sets. The proposed approach is able to construct a significantly smaller set of regression rules using a subset of attributes while achieving prediction performance comparable to that of random forests regression. Conclusion It demonstrates high potential in aiding prediction and interpretation of nonlinear relationships of the subject being studied. PMID:25350120

Bioenergetics in human evolution and disease: implications for the origins of biological complexity and the missing genetic variation of common diseases.

PubMed

Wallace, Douglas C

2013-07-19

Two major inconsistencies exist in the current neo-Darwinian evolutionary theory that random chromosomal mutations acted on by natural selection generate new species. First, natural selection does not require the evolution of ever increasing complexity, yet this is the hallmark of biology. Second, human chromosomal DNA sequence variation is predominantly either neutral or deleterious and is insufficient to provide the variation required for speciation or for predilection to common diseases. Complexity is explained by the continuous flow of energy through the biosphere that drives the accumulation of nucleic acids and information. Information then encodes complex forms. In animals, energy flow is primarily mediated by mitochondria whose maternally inherited mitochondrial DNA (mtDNA) codes for key genes for energy metabolism. In mammals, the mtDNA has a very high mutation rate, but the deleterious mutations are removed by an ovarian selection system. Hence, new mutations that subtly alter energy metabolism are continuously introduced into the species, permitting adaptation to regional differences in energy environments. Therefore, the most phenotypically significant gene variants arise in the mtDNA, are regional, and permit animals to occupy peripheral energy environments where rarer nuclear DNA (nDNA) variants can accumulate, leading to speciation. The neutralist-selectionist debate is then a consequence of mammals having two different evolutionary strategies: a fast mtDNA strategy for intra-specific radiation and a slow nDNA strategy for speciation. Furthermore, the missing genetic variation for common human diseases is primarily mtDNA variation plus regional nDNA variants, both of which have been missed by large, inter-population association studies.

Characterization of Pharmacologic and Pharmacokinetic Properties of CCX168, a Potent and Selective Orally Administered Complement 5a Receptor Inhibitor, Based on Preclinical Evaluation and Randomized Phase 1 Clinical Study.

PubMed

Bekker, Pirow; Dairaghi, Daniel; Seitz, Lisa; Leleti, Manmohan; Wang, Yu; Ertl, Linda; Baumgart, Trageen; Shugarts, Sarah; Lohr, Lisa; Dang, Ton; Miao, Shichang; Zeng, Yibin; Fan, Pingchen; Zhang, Penglie; Johnson, Daniel; Powers, Jay; Jaen, Juan; Charo, Israel; Schall, Thomas J

2016-01-01

The complement 5a receptor has been an attractive therapeutic target for many autoimmune and inflammatory disorders. However, development of a selective and potent C5aR antagonist has been challenging. Here we describe the characterization of CCX168 (avacopan), an orally administered selective and potent C5aR inhibitor. CCX168 blocked the C5a binding, C5a-mediated migration, calcium mobilization, and CD11b upregulation in U937 cells as well as in freshly isolated human neutrophils. CCX168 retains high potency when present in human blood. A transgenic human C5aR knock-in mouse model allowed comparison of the in vitro and in vivo efficacy of the molecule. CCX168 effectively blocked migration in in vitro and ex vivo chemotaxis assays, and it blocked the C5a-mediated neutrophil vascular endothelial margination. CCX168 was effective in migration and neutrophil margination assays in cynomolgus monkeys. This thorough in vitro and preclinical characterization enabled progression of CCX168 into the clinic and testing of its safety, tolerability, pharmacokinetic, and pharmacodynamic profiles in a Phase 1 clinical trial in 48 healthy volunteers. CCX168 was shown to be well tolerated across a broad dose range (1 to 100 mg) and it showed dose-dependent pharmacokinetics. An oral dose of 30 mg CCX168 given twice daily blocked the C5a-induced upregulation of CD11b in circulating neutrophils by 94% or greater throughout the entire day, demonstrating essentially complete target coverage. This dose regimen is being tested in clinical trials in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis. Trial Registration ISRCTN registry with trial ID ISRCTN13564773.

Characterization of Pharmacologic and Pharmacokinetic Properties of CCX168, a Potent and Selective Orally Administered Complement 5a Receptor Inhibitor, Based on Preclinical Evaluation and Randomized Phase 1 Clinical Study

PubMed Central

Bekker, Pirow; Dairaghi, Daniel; Seitz, Lisa; Leleti, Manmohan; Wang, Yu; Ertl, Linda; Baumgart, Trageen; Shugarts, Sarah; Lohr, Lisa; Dang, Ton; Miao, Shichang; Zeng, Yibin; Fan, Pingchen; Zhang, Penglie; Johnson, Daniel; Powers, Jay; Jaen, Juan; Charo, Israel; Schall, Thomas J.

2016-01-01

The complement 5a receptor has been an attractive therapeutic target for many autoimmune and inflammatory disorders. However, development of a selective and potent C5aR antagonist has been challenging. Here we describe the characterization of CCX168 (avacopan), an orally administered selective and potent C5aR inhibitor. CCX168 blocked the C5a binding, C5a-mediated migration, calcium mobilization, and CD11b upregulation in U937 cells as well as in freshly isolated human neutrophils. CCX168 retains high potency when present in human blood. A transgenic human C5aR knock-in mouse model allowed comparison of the in vitro and in vivo efficacy of the molecule. CCX168 effectively blocked migration in in vitro and ex vivo chemotaxis assays, and it blocked the C5a-mediated neutrophil vascular endothelial margination. CCX168 was effective in migration and neutrophil margination assays in cynomolgus monkeys. This thorough in vitro and preclinical characterization enabled progression of CCX168 into the clinic and testing of its safety, tolerability, pharmacokinetic, and pharmacodynamic profiles in a Phase 1 clinical trial in 48 healthy volunteers. CCX168 was shown to be well tolerated across a broad dose range (1 to 100 mg) and it showed dose-dependent pharmacokinetics. An oral dose of 30 mg CCX168 given twice daily blocked the C5a-induced upregulation of CD11b in circulating neutrophils by 94% or greater throughout the entire day, demonstrating essentially complete target coverage. This dose regimen is being tested in clinical trials in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis. Trial Registration ISRCTN registry with trial ID ISRCTN13564773. PMID:27768695

HTLV-1 Integration into Transcriptionally Active Genomic Regions Is Associated with Proviral Expression and with HAM/TSP

PubMed Central

Meekings, Kiran N.; Leipzig, Jeremy; Bushman, Frederic D.; Taylor, Graham P.; Bangham, Charles R. M.

2008-01-01

Human T-lymphotropic virus type 1 (HTLV-1) causes leukaemia or chronic inflammatory disease in ∼5% of infected hosts. The level of proviral expression of HTLV-1 differs significantly among infected people, even at the same proviral load (proportion of infected mononuclear cells in the circulation). A high level of expression of the HTLV-1 provirus is associated with a high proviral load and a high risk of the inflammatory disease of the central nervous system known as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). But the factors that control the rate of HTLV-1 proviral expression remain unknown. Here we show that proviral integration sites of HTLV-1 in vivo are not randomly distributed within the human genome but are associated with transcriptionally active regions. Comparison of proviral integration sites between individuals with high and low levels of proviral expression, and between provirus-expressing and provirus non-expressing cells from within an individual, demonstrated that frequent integration into transcription units was associated with an increased rate of proviral expression. An increased frequency of integration sites in transcription units in individuals with high proviral expression was also associated with the inflammatory disease HAM/TSP. By comparing the distribution of integration sites in human lymphocytes infected in short-term cell culture with those from persistent infection in vivo, we infer the action of two selective forces that shape the distribution of integration sites in vivo: positive selection for cells containing proviral integration sites in transcriptionally active regions of the genome, and negative selection against cells with proviral integration sites within transcription units. PMID:18369476

Decision-making after continuous wins or losses in a randomized guessing task: implications for how the prior selection results affect subsequent decision-making

PubMed Central

2014-01-01

Background Human decision-making is often affected by prior selections and their outcomes, even in situations where decisions are independent and outcomes are unpredictable. Methods In this study, we created a task that simulated real-life non-strategic gambling to examine the effect of prior outcomes on subsequent decisions in a group of male college students. Results Behavioral performance showed that participants needed more time to react after continuous losses (LOSS) than continuous wins (WIN) and discontinuous outcomes (CONTROL). In addition, participants were more likely to repeat their selections in both WIN and LOSS conditions. Functional MRI data revealed that decisions in WINs were associated with increased activation in the mesolimbic pathway, but decreased activation in the inferior frontal gyrus relative to LOSS. Increased prefrontal cortical activation was observed during LOSS relative to WIN and CONTROL conditions. Conclusion Taken together, the behavioral and neuroimaging findings suggest that participants tended to repeat previous selections during LOSS trials, a pattern resembling the gambler’s fallacy. However, during WIN trials, participants tended to follow their previous lucky decisions, like the ‘hot hand’ fallacy. PMID:24708897

Quality of human spermatozoa: relationship between high-magnification sperm morphology and DNA integrity.

PubMed

Maettner, R; Sterzik, K; Isachenko, V; Strehler, E; Rahimi, G; Alabart, J L; Sánchez, R; Mallmann, P; Isachenko, E

2014-06-01

The aim of this work is to establish the relationship between the morphology of Intracytoplasmic Morphologically Selected Sperm Injection (IMSI)-selected spermatozoa and their DNA integrity. The 45 ejaculates were randomly distributed into three treatment groups: normozoospermic, oligoasthenozoospermic and oligoasthenotheratozoospermic samples. The evaluation of DNA integrity was performed using the sperm chromatin dispersion test. It was established that DNA integrity of spermatozoa is strongly dependent on ejaculate quality (P < 0.05). The count of spermatozoa with nonfragmented DNA in normozoospermic samples was high and independent from IMSI-morphological classes (Class 1 versus Class 3, respectively) (P > 0.1). With decreased ejaculate quality, the percentage of spermatozoa with nonfragmented DNA decreased significantly (P < 0.05) independent from morphological class. Nevertheless, the rate of IMSI-selected spermatozoa with fragmented DNA within of Class 1 in normozoospermic (Group 1), in oligoasthenozoospermic (Group 2) and in oligoasthenotheratozoospermic (Group 3) samples was 21.1%, 31.8% and 54.1%, respectively. In conclusion, there is a direct relationship between morphological parameters of spermatozoa and their DNA integrity. However, the IMSI technique alone is not enough for the selection of spermatozoa with intact nuclei. © 2013 Blackwell Verlag GmbH.

A multiscale Markov random field model in wavelet domain for image segmentation

NASA Astrophysics Data System (ADS)

Dai, Peng; Cheng, Yu; Wang, Shengchun; Du, Xinyu; Wu, Dan

2017-07-01

The human vision system has abilities for feature detection, learning and selective attention with some properties of hierarchy and bidirectional connection in the form of neural population. In this paper, a multiscale Markov random field model in the wavelet domain is proposed by mimicking some image processing functions of vision system. For an input scene, our model provides its sparse representations using wavelet transforms and extracts its topological organization using MRF. In addition, the hierarchy property of vision system is simulated using a pyramid framework in our model. There are two information flows in our model, i.e., a bottom-up procedure to extract input features and a top-down procedure to provide feedback controls. The two procedures are controlled simply by two pyramidal parameters, and some Gestalt laws are also integrated implicitly. Equipped with such biological inspired properties, our model can be used to accomplish different image segmentation tasks, such as edge detection and region segmentation.

RARtool: A MATLAB Software Package for Designing Response-Adaptive Randomized Clinical Trials with Time-to-Event Outcomes.

PubMed

Ryeznik, Yevgen; Sverdlov, Oleksandr; Wong, Weng Kee

2015-08-01

Response-adaptive randomization designs are becoming increasingly popular in clinical trial practice. In this paper, we present RARtool , a user interface software developed in MATLAB for designing response-adaptive randomized comparative clinical trials with censored time-to-event outcomes. The RARtool software can compute different types of optimal treatment allocation designs, and it can simulate response-adaptive randomization procedures targeting selected optimal allocations. Through simulations, an investigator can assess design characteristics under a variety of experimental scenarios and select the best procedure for practical implementation. We illustrate the utility of our RARtool software by redesigning a survival trial from the literature.

Model Cortical Association Fields Account for the Time Course and Dependence on Target Complexity of Human Contour Perception

PubMed Central

Gintautas, Vadas; Ham, Michael I.; Kunsberg, Benjamin; Barr, Shawn; Brumby, Steven P.; Rasmussen, Craig; George, John S.; Nemenman, Ilya; Bettencourt, Luís M. A.; Kenyon, Garret T.

2011-01-01

Can lateral connectivity in the primary visual cortex account for the time dependence and intrinsic task difficulty of human contour detection? To answer this question, we created a synthetic image set that prevents sole reliance on either low-level visual features or high-level context for the detection of target objects. Rendered images consist of smoothly varying, globally aligned contour fragments (amoebas) distributed among groups of randomly rotated fragments (clutter). The time course and accuracy of amoeba detection by humans was measured using a two-alternative forced choice protocol with self-reported confidence and variable image presentation time (20-200 ms), followed by an image mask optimized so as to interrupt visual processing. Measured psychometric functions were well fit by sigmoidal functions with exponential time constants of 30-91 ms, depending on amoeba complexity. Key aspects of the psychophysical experiments were accounted for by a computational network model, in which simulated responses across retinotopic arrays of orientation-selective elements were modulated by cortical association fields, represented as multiplicative kernels computed from the differences in pairwise edge statistics between target and distractor images. Comparing the experimental and the computational results suggests that each iteration of the lateral interactions takes at least ms of cortical processing time. Our results provide evidence that cortical association fields between orientation selective elements in early visual areas can account for important temporal and task-dependent aspects of the psychometric curves characterizing human contour perception, with the remaining discrepancies postulated to arise from the influence of higher cortical areas. PMID:21998562

Updating the Salivary Gland Transcriptome of Phlebotomus papatasi (Tunisian Strain): The Search for Sand Fly-Secreted Immunogenic Proteins for Humans

PubMed Central

Ben Ahmed, Melika; Zhioua, Elyes; Chelbi, Ifhem; Cherni, Saifedine; Louzir, Hechmi; Ribeiro, José M. C.; Valenzuela, Jesus G.

2012-01-01

Introduction Sand fly saliva plays an important role in both blood feeding and outcome of Leishmania infection. A cellular immune response against a Phlebotomus papatasi salivary protein was shown to protect rodents against Leishmania major infection. In humans, P. papatasi salivary proteins induce a systemic cellular immune response as well as a specific antisaliva humoral immune response, making these salivary proteins attractive targets as markers of exposure for this Leishmania vector. Surprisingly, the repertoire of salivary proteins reported for P. papatasi–a model sand fly for Leishmania-vector-host molecular interactions–is very limited compared with other sand fly species. We hypothesize that a more comprehensive study of the transcripts present in the salivary glands of P. papatasi will provide better knowledge of the repertoire of proteins of this important vector and will aid in selection of potential immunogenic proteins for humans and of those proteins that are highly conserved between different sand fly strains. Methods and Findings A cDNA library from P. papatasi (Tunisian strain) salivary glands was constructed, and randomly selected transcripts were sequenced and analyzed. The most abundant transcripts encoding secreted proteins were identified and compared with previously reported sequences. Importantly, we identified salivary proteins not described before in this sand fly species. Conclusions Comparative analysis between the salivary proteins of P. papatasi from Tunisia and Israel strains shows a high level of identity, suggesting these proteins as potential common targets for markers of vector exposure or inducers of cellular immune responses in humans for different geographic areas. PMID:23139741

Updating the salivary gland transcriptome of Phlebotomus papatasi (Tunisian strain): the search for sand fly-secreted immunogenic proteins for humans.

PubMed

Abdeladhim, Maha; Jochim, Ryan C; Ben Ahmed, Melika; Zhioua, Elyes; Chelbi, Ifhem; Cherni, Saifedine; Louzir, Hechmi; Ribeiro, José M C; Valenzuela, Jesus G

2012-01-01

Sand fly saliva plays an important role in both blood feeding and outcome of Leishmania infection. A cellular immune response against a Phlebotomus papatasi salivary protein was shown to protect rodents against Leishmania major infection. In humans, P. papatasi salivary proteins induce a systemic cellular immune response as well as a specific antisaliva humoral immune response, making these salivary proteins attractive targets as markers of exposure for this Leishmania vector. Surprisingly, the repertoire of salivary proteins reported for P. papatasi-a model sand fly for Leishmania-vector-host molecular interactions-is very limited compared with other sand fly species. We hypothesize that a more comprehensive study of the transcripts present in the salivary glands of P. papatasi will provide better knowledge of the repertoire of proteins of this important vector and will aid in selection of potential immunogenic proteins for humans and of those proteins that are highly conserved between different sand fly strains. A cDNA library from P. papatasi (Tunisian strain) salivary glands was constructed, and randomly selected transcripts were sequenced and analyzed. The most abundant transcripts encoding secreted proteins were identified and compared with previously reported sequences. Importantly, we identified salivary proteins not described before in this sand fly species. Comparative analysis between the salivary proteins of P. papatasi from Tunisia and Israel strains shows a high level of identity, suggesting these proteins as potential common targets for markers of vector exposure or inducers of cellular immune responses in humans for different geographic areas.

Screening and Identification of Peptides Specifically Targeted to Gastric Cancer Cells from a Phage Display Peptide Library

PubMed

Sahin, Deniz; Taflan, Sevket Onur; Yartas, Gizem; Ashktorab, Hassan; Smoot, Duane T

2018-04-25

Background: Gastric cancer is the second most common cancer among the malign cancer types. Inefficiency of traditional techniques both in diagnosis and therapy of the disease makes the development of alternative and novel techniques indispensable. As an alternative to traditional methods, tumor specific targeting small peptides can be used to increase the efficiency of the treatment and reduce the side effects related to traditional techniques. The aim of this study is screening and identification of individual peptides specifically targeted to human gastric cancer cells using a phage-displayed peptide library and designing specific peptide sequences by using experimentally-eluted peptide sequences. Methods: Here, MKN-45 human gastric cancer cells and HFE-145 human normal gastric epithelial cells were used as the target and control cells, respectively. 5 rounds of biopannning with a phage display 12-peptide library were applied following subtraction biopanning with HFE-145 control cells. The selected phage clones were established by enzyme-linked immunosorbent assay and immunofluorescence detection. We first obtain random phage clones after five biopanning rounds, determine the binding levels of each individual clone. Then, we analyze the frequencies of each amino acid in best binding clones to determine positively overexpressed amino acids for designing novel peptide sequences. Results: DE532 (VETSQYFRGTLS) phage clone was screened positive, showing specific binding on MKN-45 gastric cancer cells. DE-Obs (HNDLFPSWYHNY) peptide, which was designed by using amino acid frequencies of experimentally selected peptides in the 5th round of biopanning, showed specific binding in MKN-45 cells. Conclusion: Selection and characterization of individual clones may give us specifically binding peptides, but more importantly, data extracted from eluted phage clones may be used to design theoretical peptides with better binding properties than even experimentally selected ones. Both peptides, experimental and designed, may be potential candidates to be developed as useful diagnostic or therapeutic ligand molecules in gastric cancer research. Creative Commons Attribution License

Nest site selection by Kentish plover suggests a trade-off between nest-crypsis and predator detection strategies.

PubMed

Gómez-Serrano, Miguel Ángel; López-López, Pascual

2014-01-01

Predation is one of the main causes of adult mortality and breeding failure for ground-nesting birds. Micro-habitat structure around nests plays a critical role in minimizing predation risk. Plovers nest in sites with little vegetation cover to maximize the incubating adult visibility, but many studies suggest a trade-off between nest-crypsis and predator detection strategies. However, this trade-off has not been explored in detail because methods used so far do not allow estimating the visibility with regards to critical factors such as slope or plant permeability to vision. Here, we tested the hypothesis that Kentish plovers select exposed sites according to a predator detection strategy, and the hypothesis that more concealed nests survive longer according to a crypsis strategy. To this end, we obtained an accurate estimation of the incubating adult's field of vision through a custom built inverted periscope. Our results showed that plovers selected nest sites with higher visibility than control points randomly selected with regards to humans and dogs, although nests located in sites with higher vegetation cover survived longer. In addition, the flushing distance (i.e., the distance at which incubating adults leave the nest when they detect a potential predator) decreased with vegetation cover. Consequently, the advantages of concealing the nest were limited by the ability to detect predators, thus indirectly supporting the existence of the trade-off between crypsis and predator detection. Finally, human disturbance also constrained nest choice, forcing plovers to move to inland sites that were less suitable because of higher vegetation cover, and modulated flushing behavior, since plovers that were habituated to humans left their nests closer to potential predators. This constraint on the width of suitable breeding habitat is particularly relevant for the conservation of Kentish Plover in sand beaches, especially under the current context of coastal regression and increase of recreational activities.

Nest Site Selection by Kentish Plover Suggests a Trade-Off between Nest-Crypsis and Predator Detection Strategies

PubMed Central

Gómez-Serrano, Miguel Ángel; López-López, Pascual

2014-01-01

Predation is one of the main causes of adult mortality and breeding failure for ground-nesting birds. Micro-habitat structure around nests plays a critical role in minimizing predation risk. Plovers nest in sites with little vegetation cover to maximize the incubating adult visibility, but many studies suggest a trade-off between nest-crypsis and predator detection strategies. However, this trade-off has not been explored in detail because methods used so far do not allow estimating the visibility with regards to critical factors such as slope or plant permeability to vision. Here, we tested the hypothesis that Kentish plovers select exposed sites according to a predator detection strategy, and the hypothesis that more concealed nests survive longer according to a crypsis strategy. To this end, we obtained an accurate estimation of the incubating adult's field of vision through a custom built inverted periscope. Our results showed that plovers selected nest sites with higher visibility than control points randomly selected with regards to humans and dogs, although nests located in sites with higher vegetation cover survived longer. In addition, the flushing distance (i.e., the distance at which incubating adults leave the nest when they detect a potential predator) decreased with vegetation cover. Consequently, the advantages of concealing the nest were limited by the ability to detect predators, thus indirectly supporting the existence of the trade-off between crypsis and predator detection. Finally, human disturbance also constrained nest choice, forcing plovers to move to inland sites that were less suitable because of higher vegetation cover, and modulated flushing behavior, since plovers that were habituated to humans left their nests closer to potential predators. This constraint on the width of suitable breeding habitat is particularly relevant for the conservation of Kentish Plover in sand beaches, especially under the current context of coastal regression and increase of recreational activities. PMID:25208045

A polynomial based model for cell fate prediction in human diseases.

PubMed

Ma, Lichun; Zheng, Jie

2017-12-21

Cell fate regulation directly affects tissue homeostasis and human health. Research on cell fate decision sheds light on key regulators, facilitates understanding the mechanisms, and suggests novel strategies to treat human diseases that are related to abnormal cell development. In this study, we proposed a polynomial based model to predict cell fate. This model was derived from Taylor series. As a case study, gene expression data of pancreatic cells were adopted to test and verify the model. As numerous features (genes) are available, we employed two kinds of feature selection methods, i.e. correlation based and apoptosis pathway based. Then polynomials of different degrees were used to refine the cell fate prediction function. 10-fold cross-validation was carried out to evaluate the performance of our model. In addition, we analyzed the stability of the resultant cell fate prediction model by evaluating the ranges of the parameters, as well as assessing the variances of the predicted values at randomly selected points. Results show that, within both the two considered gene selection methods, the prediction accuracies of polynomials of different degrees show little differences. Interestingly, the linear polynomial (degree 1 polynomial) is more stable than others. When comparing the linear polynomials based on the two gene selection methods, it shows that although the accuracy of the linear polynomial that uses correlation analysis outcomes is a little higher (achieves 86.62%), the one within genes of the apoptosis pathway is much more stable. Considering both the prediction accuracy and the stability of polynomial models of different degrees, the linear model is a preferred choice for cell fate prediction with gene expression data of pancreatic cells. The presented cell fate prediction model can be extended to other cells, which may be important for basic research as well as clinical study of cell development related diseases.

The Effect of CAI on Reading Achievement.

ERIC Educational Resources Information Center

Hardman, Regina

A study determined whether computer assisted instruction (CAI) had an effect on students' reading achievement. Subjects were 21 randomly selected fourth-grade students at D. S. Wentworth Elementary School on the south side of Chicago in a low-income neighborhood who received a year's exposure to a CAI program, and 21 randomly selected students at…

78 FR 57033 - United States Standards for Condition of Food Containers

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-17

... containers during production. Stationary lot sampling is the process of randomly selecting sample units from.... * * * * * Stationary lot sampling. The process of randomly selecting sample units from a lot whose production has been... less than \\1/16\\-inch Stringy seal (excessive plastic threads showing at edge of seal 222 area...

Access to Higher Education by the Luck of the Draw

ERIC Educational Resources Information Center

Stone, Peter

2013-01-01

Random selection is a fair way to break ties between applicants of equal merit seeking admission to institutions of higher education (with "merit" defined here in terms of the intrinsic contribution higher education would make to the applicant's life). Opponents of random selection commonly argue that differences in strength between…

An Evaluation of Information Criteria Use for Correct Cross-Classified Random Effects Model Selection

ERIC Educational Resources Information Center

Beretvas, S. Natasha; Murphy, Daniel L.

2013-01-01

The authors assessed correct model identification rates of Akaike's information criterion (AIC), corrected criterion (AICC), consistent AIC (CAIC), Hannon and Quinn's information criterion (HQIC), and Bayesian information criterion (BIC) for selecting among cross-classified random effects models. Performance of default values for the 5…

1977 Survey of the American Professoriate. Technical Report.

ERIC Educational Resources Information Center

Ladd, Everett Carll, Jr.; And Others

The development and data validation of the 1977 Ladd-Lipset national survey of the American professoriate are described. The respondents were selected from a random sample of colleges and universities and from a random sample of individual faculty members from the universities. The 158 institutions in the 1977 survey were selected from 2,406…

Site Selection in Experiments: A Follow-Up Evaluation of Site Recruitment in Two Scale-Up Studies

ERIC Educational Resources Information Center

Tipton, Elizabeth; Fellers, Lauren; Caverly, Sarah; Vaden-Kiernan, Michael; Borman, Geoffrey; Sullivan, Kate; Ruiz de Castillo, Veronica

2015-01-01

Randomized experiments are commonly used to evaluate if particular interventions improve student achievement. While these experiments can establish that a treatment actually "causes" changes, typically the participants are not randomly selected from a well-defined population and therefore the results do not readily generalize. Three…

Selection dynamic of Escherichia coli host in M13 combinatorial peptide phage display libraries.

PubMed

Zanconato, Stefano; Minervini, Giovanni; Poli, Irene; De Lucrezia, Davide

2011-01-01

Phage display relies on an iterative cycle of selection and amplification of random combinatorial libraries to enrich the initial population of those peptides that satisfy a priori chosen criteria. The effectiveness of any phage display protocol depends directly on library amino acid sequence diversity and the strength of the selection procedure. In this study we monitored the dynamics of the selective pressure exerted by the host organism on a random peptide library in the absence of any additional selection pressure. The results indicate that sequence censorship exerted by Escherichia coli dramatically reduces library diversity and can significantly impair phage display effectiveness.

Feature-selective attention in healthy old age: a selective decline in selective attention?

PubMed

Quigley, Cliodhna; Müller, Matthias M

2014-02-12

Deficient selection against irrelevant information has been proposed to underlie age-related cognitive decline. We recently reported evidence for maintained early sensory selection when older and younger adults used spatial selective attention to perform a challenging task. Here we explored age-related differences when spatial selection is not possible and feature-selective attention must be deployed. We additionally compared the integrity of feedforward processing by exploiting the well established phenomenon of suppression of visual cortical responses attributable to interstimulus competition. Electroencephalogram was measured while older and younger human adults responded to brief occurrences of coherent motion in an attended stimulus composed of randomly moving, orientation-defined, flickering bars. Attention was directed to horizontal or vertical bars by a pretrial cue, after which two orthogonally oriented, overlapping stimuli or a single stimulus were presented. Horizontal and vertical bars flickered at different frequencies and thereby elicited separable steady-state visual-evoked potentials, which were used to examine the effect of feature-based selection and the competitive influence of a second stimulus on ongoing visual processing. Age differences were found in feature-selective attentional modulation of visual responses: older adults did not show consistent modulation of magnitude or phase. In contrast, the suppressive effect of a second stimulus was robust and comparable in magnitude across age groups, suggesting that bottom-up processing of the current stimuli is essentially unchanged in healthy old age. Thus, it seems that visual processing per se is unchanged, but top-down attentional control is compromised in older adults when space cannot be used to guide selection.

Potent and Specific Inhibition of Glycosidases by Small Artificial Binding Proteins (Affitins)

PubMed Central

Mechaly, Ariel E.; Obal, Gonzalo; Béhar, Ghislaine; Mouratou, Barbara; Oppezzo, Pablo; Alzari, Pedro M.; Pecorari, Frédéric

2014-01-01

Glycosidases are associated with various human diseases. The development of efficient and specific inhibitors may provide powerful tools to modulate their activity. However, achieving high selectivity is a major challenge given that glycosidases with different functions can have similar enzymatic mechanisms and active-site architectures. As an alternative approach to small-chemical compounds, proteinaceous inhibitors might provide a better specificity by involving a larger surface area of interaction. We report here the design and characterization of proteinaceous inhibitors that specifically target endoglycosidases representative of the two major mechanistic classes; retaining and inverting glycosidases. These inhibitors consist of artificial affinity proteins, Affitins, selected against the thermophilic CelD from Clostridium thermocellum and lysozyme from hen egg. They were obtained from libraries of Sac7d variants, which involve either the randomization of a surface or the randomization of a surface and an artificially-extended loop. Glycosidase binders exhibited affinities in the nanomolar range with no cross-recognition, with efficient inhibition of lysozyme (Ki = 45 nM) and CelD (Ki = 95 and 111 nM), high expression yields in Escherichia coli, solubility, and thermal stabilities up to 81.1°C. The crystal structures of glycosidase-Affitin complexes validate our library designs. We observed that Affitins prevented substrate access by two modes of binding; covering or penetrating the catalytic site via the extended loop. In addition, Affitins formed salt-bridges with residues essential for enzymatic activity. These results lead us to propose the use of Affitins as versatile selective glycosidase inhibitors and, potentially, as enzymatic inhibitors in general. PMID:24823716

Potent and specific inhibition of glycosidases by small artificial binding proteins (affitins).

PubMed

Correa, Agustín; Pacheco, Sabino; Mechaly, Ariel E; Obal, Gonzalo; Béhar, Ghislaine; Mouratou, Barbara; Oppezzo, Pablo; Alzari, Pedro M; Pecorari, Frédéric

2014-01-01

Glycosidases are associated with various human diseases. The development of efficient and specific inhibitors may provide powerful tools to modulate their activity. However, achieving high selectivity is a major challenge given that glycosidases with different functions can have similar enzymatic mechanisms and active-site architectures. As an alternative approach to small-chemical compounds, proteinaceous inhibitors might provide a better specificity by involving a larger surface area of interaction. We report here the design and characterization of proteinaceous inhibitors that specifically target endoglycosidases representative of the two major mechanistic classes; retaining and inverting glycosidases. These inhibitors consist of artificial affinity proteins, Affitins, selected against the thermophilic CelD from Clostridium thermocellum and lysozyme from hen egg. They were obtained from libraries of Sac7d variants, which involve either the randomization of a surface or the randomization of a surface and an artificially-extended loop. Glycosidase binders exhibited affinities in the nanomolar range with no cross-recognition, with efficient inhibition of lysozyme (Ki = 45 nM) and CelD (Ki = 95 and 111 nM), high expression yields in Escherichia coli, solubility, and thermal stabilities up to 81.1°C. The crystal structures of glycosidase-Affitin complexes validate our library designs. We observed that Affitins prevented substrate access by two modes of binding; covering or penetrating the catalytic site via the extended loop. In addition, Affitins formed salt-bridges with residues essential for enzymatic activity. These results lead us to propose the use of Affitins as versatile selective glycosidase inhibitors and, potentially, as enzymatic inhibitors in general.

Day-roost tree selection by northern long-eared bats—What do non-roost tree comparisons and one year of data really tell us?

USGS Publications Warehouse

Silvis, Alexander; Ford, W. Mark; Britzke, Eric R.

2015-01-01

Bat day-roost selection often is described through comparisons of day-roosts with randomly selected, and assumed unused, trees. Relatively few studies, however, look at patterns of multi-year selection or compare day-roosts used across years. We explored day-roost selection using 2 years of roost selection data for female northern long-eared bats (Myotis septentrionalis) on the Fort Knox Military Reservation, Kentucky, USA. We compared characteristics of randomly selected non-roost trees and day-roosts using a multinomial logistic model and day-roost species selection using chi-squared tests. We found that factors differentiating day-roosts from non-roosts and day-roosts between years varied. Day-roosts differed from non-roosts in the first year of data in all measured factors, but only in size and decay stage in the second year. Between years, day-roosts differed in size and canopy position, but not decay stage. Day-roost species selection was non-random and did not differ between years. Although bats used multiple trees, our results suggest that there were additional unused trees that were suitable as roosts at any time. Day-roost selection pattern descriptions will be inadequate if based only on a single year of data, and inferences of roost selection based only on comparisons of roost to non-roosts should be limited.

Day-roost tree selection by northern long-eared bats - What do non-roost tree comparisons and one year of data really tell us?

USGS Publications Warehouse

Silvis, Alexander; Ford, W. Mark; Britzke, Eric R.

2015-01-01

Bat day-roost selection often is described through comparisons of day-roosts with randomly selected, and assumed unused, trees. Relatively few studies, however, look at patterns of multi-year selection or compare day-roosts used across years. We explored day-roost selection using 2 years of roost selection data for female northern long-eared bats (Myotis septentrionalis) on the Fort Knox Military Reservation, Kentucky, USA. We compared characteristics of randomly selected non-roost trees and day-roosts using a multinomial logistic model and day-roost species selection using chi-squared tests. We found that factors differentiating day-roosts from non-roosts and day-roosts between years varied. Day-roosts differed from non-roosts in the first year of data in all measured factors, but only in size and decay stage in the second year. Between years, day-roosts differed in size and canopy position, but not decay stage. Day-roost species selection was non-random and did not differ between years. Although bats used multiple trees, our results suggest that there were additional unused trees that were suitable as roosts at any time. Day-roost selection pattern descriptions will be inadequate if based only on a single year of data, and inferences of roost selection based only on comparisons of roost to non-roosts should be limited.

Foundational errors in the Neutral and Nearly-Neutral theories of evolution in relation to the Synthetic Theory: is a new evolutionary paradigm necessary?

PubMed

Valenzuela, Carlos Y

2013-01-01

The Neutral Theory of Evolution (NTE) proposes mutation and random genetic drift as the most important evolutionary factors. The most conspicuous feature of evolution is the genomic stability during paleontological eras and lack of variation among taxa; 98% or more of nucleotide sites are monomorphic within a species. NTE explains this homology by random fixation of neutral bases and negative selection (purifying selection) that does not contribute either to evolution or polymorphisms. Purifying selection is insufficient to account for this evolutionary feature and the Nearly-Neutral Theory of Evolution (N-NTE) included negative selection with coefficients as low as mutation rate. These NTE and N-NTE propositions are thermodynamically (tendency to random distributions, second law), biotically (recurrent mutation), logically and mathematically (resilient equilibria instead of fixation by drift) untenable. Recurrent forward and backward mutation and random fluctuations of base frequencies alone in a site make life organization and fixations impossible. Drift is not a directional evolutionary factor, but a directional tendency of matter-energy processes (second law) which threatens the biotic organization. Drift cannot drive evolution. In a site, the mutation rates among bases and selection coefficients determine the resilient equilibrium frequency of bases that genetic drift cannot change. The expected neutral random interaction among nucleotides is zero; however, huge interactions and periodicities were found between bases of dinucleotides separated by 1, 2... and more than 1,000 sites. Every base is co-adapted with the whole genome. Neutralists found that neutral evolution is independent of population size (N); thus neutral evolution should be independent of drift, because drift effect is dependent upon N. Also, chromosome size and shape as well as protein size are far from random.

Computerized stratified random site-selection approaches for design of a ground-water-quality sampling network

USGS Publications Warehouse

Scott, J.C.

1990-01-01

Computer software was written to randomly select sites for a ground-water-quality sampling network. The software uses digital cartographic techniques and subroutines from a proprietary geographic information system. The report presents the approaches, computer software, and sample applications. It is often desirable to collect ground-water-quality samples from various areas in a study region that have different values of a spatial characteristic, such as land-use or hydrogeologic setting. A stratified network can be used for testing hypotheses about relations between spatial characteristics and water quality, or for calculating statistical descriptions of water-quality data that account for variations that correspond to the spatial characteristic. In the software described, a study region is subdivided into areal subsets that have a common spatial characteristic to stratify the population into several categories from which sampling sites are selected. Different numbers of sites may be selected from each category of areal subsets. A population of potential sampling sites may be defined by either specifying a fixed population of existing sites, or by preparing an equally spaced population of potential sites. In either case, each site is identified with a single category, depending on the value of the spatial characteristic of the areal subset in which the site is located. Sites are selected from one category at a time. One of two approaches may be used to select sites. Sites may be selected randomly, or the areal subsets in the category can be grouped into cells and sites selected randomly from each cell.

Automated selection of trabecular bone regions in knee radiographs.

PubMed

Podsiadlo, P; Wolski, M; Stachowiak, G W

2008-05-01

Osteoarthritic (OA) changes in knee joints can be assessed by analyzing the structure of trabecular bone (TB) in the tibia. This analysis is performed on TB regions selected manually by a human operator on x-ray images. Manual selection is time-consuming, tedious, and expensive. Even if a radiologist expert or highly trained person is available to select regions, high inter- and intraobserver variabilities are still possible. A fully automated image segmentation method was, therefore, developed to select the bone regions for numerical analyses of changes in bone structures. The newly developed method consists of image preprocessing, delineation of cortical bone plates (active shape model), and location of regions of interest (ROI). The method was trained on an independent set of 40 x-ray images. Automatically selected regions were compared to the "gold standard" that contains ROIs selected manually by a radiologist expert on 132 x-ray images. All images were acquired from subjects locked in a standardized standing position using a radiography rig. The size of each ROI is 12.8 x 12.8 mm. The automated method results showed a good agreement with the gold standard [similarity index (SI) = 0.83 (medial) and 0.81 (lateral) and the offset =[-1.78, 1.27]x[-0.65,0.26] mm (medial) and [-2.15, 1.59]x[-0.58, 0.52] mm (lateral)]. Bland and Altman plots were constructed for fractal signatures, and changes of fractal dimensions (FD) to region offsets calculated between the gold standard and automatically selected regions were calculated. The plots showed a random scatter and the 95% confidence intervals were (-0.006, 0.008) and (-0.001, 0.011). The changes of FDs to region offsets were less than 0.035. Previous studies showed that differences in FDs between non-OA and OA bone regions were greater than 0.05. ROIs were also selected by a second radiologist and then evaluated. Results indicated that the newly developed method could replace a human operator and produces bone regions with an accuracy that is sufficient for fractal analyses of bone texture.

On grey levels in random CAPTCHA generation

NASA Astrophysics Data System (ADS)

Newton, Fraser; Kouritzin, Michael A.

2011-06-01

A CAPTCHA is an automatically generated test designed to distinguish between humans and computer programs; specifically, they are designed to be easy for humans but difficult for computer programs to pass in order to prevent the abuse of resources by automated bots. They are commonly seen guarding webmail registration forms, online auction sites, and preventing brute force attacks on passwords. In the following, we address the question: How does adding a grey level to random CAPTCHA generation affect the utility of the CAPTCHA? We treat the problem of generating the random CAPTCHA as one of random field simulation: An initial state of background noise is evolved over time using Gibbs sampling and an efficient algorithm for generating correlated random variables. This approach has already been found to yield highly-readable yet difficult-to-crack CAPTCHAs. We detail how the requisite parameters for introducing grey levels are estimated and how we generate the random CAPTCHA. The resulting CAPTCHA will be evaluated in terms of human readability as well as its resistance to automated attacks in the forms of character segmentation and optical character recognition.

The Human Semicircular Canals Orientation Is More Similar to the Bonobos than to the Chimpanzees

PubMed Central

El Khoury, Marwan; Braga, José; Dumoncel, Jean; Nancy, Javotte; Esclassan, Remi; Vaysse, Frederic

2014-01-01

For some traits, the human genome is more closely related to either the bonobo or the chimpanzee genome than they are to each other. Therefore, it becomes crucial to understand whether and how morphostructural differences between humans, chimpanzees and bonobos reflect the well known phylogeny. Here we comparatively investigated intra and extra labyrinthine semicircular canals orientation using 260 computed tomography scans of extant humans (Homo sapiens), bonobos (Pan paniscus) and chimpanzees (Pan troglodytes). Humans and bonobos proved more similarities between themselves than with chimpanzees. This finding did not fit with the well established chimpanzee – bonobo monophyly. One hypothesis was convergent evolution in which bonobos and humans produce independently similar phenotypes possibly in response to similar selective pressures that may be associated with postural adaptations. Another possibility was convergence following a “random walk” (Brownian motion) evolutionary model. A more parsimonious explanation was that the bonobo-human labyrinthine shared morphology more closely retained the ancestral condition with chimpanzees being subsequently derived. Finally, these results might be a consequence of genetic diversity and incomplete lineage sorting. The remarkable symmetry of the Semicircular Canals was the second major finding of this article with possible applications in taphonomy. It has the potential to investigate altered fossils, inferring the probability of post-mortem deformation which can lead to difficulties in understanding taxonomic variation, phylogenetic relationships, and functional morphology. PMID:24710502

Random bit generation at tunable rates using a chaotic semiconductor laser under distributed feedback.

PubMed

Li, Xiao-Zhou; Li, Song-Sui; Zhuang, Jun-Ping; Chan, Sze-Chun

2015-09-01

A semiconductor laser with distributed feedback from a fiber Bragg grating (FBG) is investigated for random bit generation (RBG). The feedback perturbs the laser to emit chaotically with the intensity being sampled periodically. The samples are then converted into random bits by a simple postprocessing of self-differencing and selecting bits. Unlike a conventional mirror that provides localized feedback, the FBG provides distributed feedback which effectively suppresses the information of the round-trip feedback delay time. Randomness is ensured even when the sampling period is commensurate with the feedback delay between the laser and the grating. Consequently, in RBG, the FBG feedback enables continuous tuning of the output bit rate, reduces the minimum sampling period, and increases the number of bits selected per sample. RBG is experimentally investigated at a sampling period continuously tunable from over 16 ns down to 50 ps, while the feedback delay is fixed at 7.7 ns. By selecting 5 least-significant bits per sample, output bit rates from 0.3 to 100 Gbps are achieved with randomness examined by the National Institute of Standards and Technology test suite.

Optimization Of Mean-Semivariance-Skewness Portfolio Selection Model In Fuzzy Random Environment

NASA Astrophysics Data System (ADS)

Chatterjee, Amitava; Bhattacharyya, Rupak; Mukherjee, Supratim; Kar, Samarjit

2010-10-01

The purpose of the paper is to construct a mean-semivariance-skewness portfolio selection model in fuzzy random environment. The objective is to maximize the skewness with predefined maximum risk tolerance and minimum expected return. Here the security returns in the objectives and constraints are assumed to be fuzzy random variables in nature and then the vagueness of the fuzzy random variables in the objectives and constraints are transformed into fuzzy variables which are similar to trapezoidal numbers. The newly formed fuzzy model is then converted into a deterministic optimization model. The feasibility and effectiveness of the proposed method is verified by numerical example extracted from Bombay Stock Exchange (BSE). The exact parameters of fuzzy membership function and probability density function are obtained through fuzzy random simulating the past dates.

The effects of recall errors and of selection bias in epidemiologic studies of mobile phone use and cancer risk.

PubMed

Vrijheid, Martine; Deltour, Isabelle; Krewski, Daniel; Sanchez, Marie; Cardis, Elisabeth

2006-07-01

This paper examines the effects of systematic and random errors in recall and of selection bias in case-control studies of mobile phone use and cancer. These sensitivity analyses are based on Monte-Carlo computer simulations and were carried out within the INTERPHONE Study, an international collaborative case-control study in 13 countries. Recall error scenarios simulated plausible values of random and systematic, non-differential and differential recall errors in amount of mobile phone use reported by study subjects. Plausible values for the recall error were obtained from validation studies. Selection bias scenarios assumed varying selection probabilities for cases and controls, mobile phone users, and non-users. Where possible these selection probabilities were based on existing information from non-respondents in INTERPHONE. Simulations used exposure distributions based on existing INTERPHONE data and assumed varying levels of the true risk of brain cancer related to mobile phone use. Results suggest that random recall errors of plausible levels can lead to a large underestimation in the risk of brain cancer associated with mobile phone use. Random errors were found to have larger impact than plausible systematic errors. Differential errors in recall had very little additional impact in the presence of large random errors. Selection bias resulting from underselection of unexposed controls led to J-shaped exposure-response patterns, with risk apparently decreasing at low to moderate exposure levels. The present results, in conjunction with those of the validation studies conducted within the INTERPHONE study, will play an important role in the interpretation of existing and future case-control studies of mobile phone use and cancer risk, including the INTERPHONE study.

Measuring CAMD technique performance. 2. How "druglike" are drugs? Implications of Random test set selection exemplified using druglikeness classification models.

PubMed

Good, Andrew C; Hermsmeier, Mark A

2007-01-01

Research into the advancement of computer-aided molecular design (CAMD) has a tendency to focus on the discipline of algorithm development. Such efforts are often wrought to the detriment of the data set selection and analysis used in said algorithm validation. Here we highlight the potential problems this can cause in the context of druglikeness classification. More rigorous efforts are applied to the selection of decoy (nondruglike) molecules from the ACD. Comparisons are made between model performance using the standard technique of random test set creation with test sets derived from explicit ontological separation by drug class. The dangers of viewing druglike space as sufficiently coherent to permit simple classification are highlighted. In addition the issues inherent in applying unfiltered data and random test set selection to (Q)SAR models utilizing large and supposedly heterogeneous databases are discussed.

Strong Association between Human and Animal Brucella Seropositivity in a Linked Study in Kenya, 2012–2013

PubMed Central

Osoro, Eric Mogaka; Munyua, Peninah; Omulo, Sylvia; Ogola, Eric; Ade, Fredrick; Mbatha, Peter; Mbabu, Murithi; Ng'ang'a, Zipporah; Kairu, Salome; Maritim, Marybeth; Thumbi, Samuel M.; Bitek, Austine; Gaichugi, Stella; Rubin, Carol; Njenga, Kariuki; Guerra, Marta

2015-01-01

Brucellosis is a common bacterial zoonotic infection but data on the prevalence among humans and animals is limited in Kenya. A cross-sectional survey was conducted in three counties practicing different livestock production systems to simultaneously assess the seroprevalence of, and risk factors for brucellosis among humans and their livestock (cattle, sheep, camels, and goats). A two-stage cluster sampling method with random selection of sublocations and households was conducted. Blood samples were collected from humans and animals and tested for Brucella immunoglobulin G (IgG) antibodies. Human and animal individual seroprevalence was 16% and 8%, respectively. Household and herd seroprevalence ranged from 5% to 73% and 6% to 68%, respectively. There was a 6-fold odds of human seropositivity in households with a seropositive animal compared with those without. Risk factors for human seropositivity included regular ingestion of raw milk (adjusted odds ratio [aOR] = 3.5, 95% confidence interval [CI] = 2.8–4.4), exposure to goats (herding, milking, and feeding) (aOR = 3.1, 95% CI = 2.5–3.8), and handling of animal hides (aOR = 1.8, 95% CI = 1.5–2.2). Attaining at least high school education and above was a protective factor for human seropositivity (aOR = 0.3, 95% CI = 0.3–0.4). This linked study provides evidence of a strong association between human and animal seropositivity at the household level. PMID:26101275

Strong Association Between Human and Animal Brucella Seropositivity in a Linked Study in Kenya, 2012-2013.

PubMed

Osoro, Eric Mogaka; Munyua, Peninah; Omulo, Sylvia; Ogola, Eric; Ade, Fredrick; Mbatha, Peter; Mbabu, Murithi; Ng'ang'a, Zipporah; Kairu, Salome; Maritim, Marybeth; Thumbi, Samuel M; Bitek, Austine; Gaichugi, Stella; Rubin, Carol; Njenga, Kariuki; Guerra, Marta

2015-08-01

Brucellosis is a common bacterial zoonotic infection but data on the prevalence among humans and animals is limited in Kenya. A cross-sectional survey was conducted in three counties practicing different livestock production systems to simultaneously assess the seroprevalence of, and risk factors for brucellosis among humans and their livestock (cattle, sheep, camels, and goats). A two-stage cluster sampling method with random selection of sublocations and households was conducted. Blood samples were collected from humans and animals and tested for Brucella immunoglobulin G (IgG) antibodies. Human and animal individual seroprevalence was 16% and 8%, respectively. Household and herd seroprevalence ranged from 5% to 73% and 6% to 68%, respectively. There was a 6-fold odds of human seropositivity in households with a seropositive animal compared with those without. Risk factors for human seropositivity included regular ingestion of raw milk (adjusted odds ratio [aOR] = 3.5, 95% confidence interval [CI] = 2.8-4.4), exposure to goats (herding, milking, and feeding) (aOR = 3.1, 95% CI = 2.5-3.8), and handling of animal hides (aOR = 1.8, 95% CI = 1.5-2.2). Attaining at least high school education and above was a protective factor for human seropositivity (aOR = 0.3, 95% CI = 0.3-0.4). This linked study provides evidence of a strong association between human and animal seropositivity at the household level. © The American Society of Tropical Medicine and Hygiene.

Conservation challenge: human-herbivore conflict in Chebera Churchura National Park, Ethiopia.

PubMed

Datiko, Demeke; Bekele, Afework

2013-12-01

An investigation on human-herbivore conflict was carried out in CCNP between 2011 and 2012 in seven randomly selected villages (Chebera, Serri, Yora, Shita, Delba, Chuchra, Chewda) around the Park. A total of 312 household samples were identified for interview. Group discussion and field observation were also carried out. Among the respondents, the majority (83.9%) faced crop damage. African elephant (Loxodonta africana), Hippopotamus (Hippopotamus amphibious), African buffalo (Syncerus caffer), Desert warthog (Phacochoerus aethiopicus), Wild pig (Sus scrofa), Porcupine (Hystrix cristata), Vervet monkey (Cercopithecus aethiops) and Anubis baboon (Papio anubis) were identified as the most problematic animals in the area. However, buffalo, monkey and warthog were considered as the notorious pest. Crop damage and threats to human safety were the major problems encountered resulting in conflict between human and wildlife. Most respondents had a negative attitude towards the problem-posing animals. This will lead to a change in public attitude from one that supports wildlife conservation to sees wild herbivores as a threat and a potential negative consequence for wildlife conservation. Active measures have to be implemented to solve the problems and safeguard the future of the wildlife management in the park.

Programming by early nutrition: an experimental approach.

PubMed

Lucas, A

1998-02-01

That events during critical or sensitive periods of development may "program" long-term or life-time structure or function of the organism is well recognized. Evidence for programming by nutrition is established in animals, in whom brief pre- or postnatal nutritional manipulations may program adult size, metabolism, blood lipids, diabetes, blood pressure, obesity, atherosclerosis, learning, behavior and life span. Human epidemiological data link potential markers of early nutrition (size at birth or in infancy) to cardiovascular disease and its risk factors in adulthood. However, these retrospective data cannot prove nutritional cause or underpin health policies. After 16 y, however, of ethical, randomized intervention studies of early nutrition in humans with long-term follow-up to test experimentally the nutritional programming hypothesis, we find that humans, like other species, have sensitive windows for nutrition in terms of later outcomes; for instance, perinatal diet influences neurodevelopment and bone mineralization into mid-childhood. Possible biological mechanisms for storing throughout life the "memory" of early nutritional experience and its expression in adulthood include adaptive changes in gene expression, preferential clonal selection of adapted cells in programmed tissues and programmed differential proliferation of tissue cell types. Animal and human evidence supporting nutritional programming has major potential biological and medical significance.

The Effects of Social Capital Levels in Elementary Schools on Organizational Information Sharing

ERIC Educational Resources Information Center

Ekinci, Abdurrahman

2012-01-01

This study aims to assess the effects of social capital levels at elementary schools on organizational information sharing as reported by teachers. Participants were 267 teachers selected randomly from 16 elementary schools; schools also selected randomly among 42 elementary schools located in the city center of Batman. The data were analyzed by…

The Selection and Prevalence of Natural and Fortified Calcium Food Sources in the Diets of Adolescent Girls

ERIC Educational Resources Information Center

Rafferty, Karen; Watson, Patrice; Lappe, Joan M.

2011-01-01

Objective: To assess the impact of calcium-fortified food and dairy food on selected nutrient intakes in the diets of adolescent girls. Design: Randomized controlled trial, secondary analysis. Setting and Participants: Adolescent girls (n = 149) from a midwestern metropolitan area participated in randomized controlled trials of bone physiology…

A National Survey of Chief Student Personnel Officers at Randomly Selected Institutions of Postsecondary Education in the United States.

ERIC Educational Resources Information Center

Thomas, Henry B.; Kaplan, E. Joseph

A national survey was conducted of randomly selected chief student personnel officers as listed in the 1979 "Education Directory of Colleges and Universities." The survey addressed specific institutional demographics, policy-making authority, reporting structure, and areas of responsibility of the administrators. Over 93 percent of the respondents…

Nonmanufacturing Businesses. U.S. Metric Study Interim Report.

ERIC Educational Resources Information Center

Cornog, June R.; Bunten, Elaine D.

In this fifth interim report on the feasibility of a United States changeover to a metric system stems from the U.S. Metric Study, a primary stratified sample of 2,828 nonmanufacturing firms was randomly selected from 28,184 businesses taken from Social Security files, a secondary sample of 2,258 firms was randomly selected for replacement…

TOC: Table of Contents Practices of Primary Journals--Recommendations for Monolingual, Multilingual and International Journals.

ERIC Educational Resources Information Center

Juhasz, Stephen; And Others

Table of contents (TOC) practices of some 120 primary journals were analyzed. The journals were randomly selected. The method of randomization is described. The samples were selected from a university library with a holding of approximately 12,000 titles published worldwide. A questionnaire was designed. Purpose was to find uniformity and…

Molecular selection in a unified evolutionary sequence

NASA Technical Reports Server (NTRS)

Fox, S. W.

1986-01-01

With guidance from experiments and observations that indicate internally limited phenomena, an outline of unified evolutionary sequence is inferred. Such unification is not visible for a context of random matrix and random mutation. The sequence proceeds from Big Bang through prebiotic matter, protocells, through the evolving cell via molecular and natural selection, to mind, behavior, and society.

Selection of Variables in Cluster Analysis: An Empirical Comparison of Eight Procedures

ERIC Educational Resources Information Center

Steinley, Douglas; Brusco, Michael J.

2008-01-01

Eight different variable selection techniques for model-based and non-model-based clustering are evaluated across a wide range of cluster structures. It is shown that several methods have difficulties when non-informative variables (i.e., random noise) are included in the model. Furthermore, the distribution of the random noise greatly impacts the…

The Relationship between Teachers Commitment and Female Students Academic Achievements in Some Selected Secondary School in Wolaita Zone, Southern Ethiopia

ERIC Educational Resources Information Center

Bibiso, Abyot; Olango, Menna; Bibiso, Mesfin

2017-01-01

The purpose of this study was to investigate the relationship between teacher's commitment and female students academic achievement in selected secondary school of Wolaita zone, Southern Ethiopia. The research method employed was survey study and the sampling techniques were purposive, simple random and stratified random sampling. Questionnaire…

The Social Security Administration's Youth Transition Demonstration Projects: Implementation Lessons from the Original Projects

ERIC Educational Resources Information Center

Martinez, John; Fraker, Thomas; Manno, Michelle; Baird, Peter; Mamun, Arif; O'Day, Bonnie; Rangarajan, Anu; Wittenburg, David

2010-01-01

This report focuses on the seven original Youth Transition Demonstration (YTD) projects selected for funding in 2003. Three of the original seven projects were selected for a national random assignment evaluation in 2005; however, this report only focuses on program operations prior to joining the random assignment evaluation for the three…

Levosimendan for Perioperative Cardioprotection: Myth or Reality?

PubMed

Santillo, Elpidio; Migale, Monica; Massini, Carlo; Incalzi, Raffaele Antonelli

2018-03-21

Levosimendan is a calcium sensitizer drug causing increased contractility in the myocardium and vasodilation in the vascular system. It is mainly used for the therapy of acute decompensated heart failure. Several studies on animals and humans provided evidence of the cardioprotective properties of levosimendan including preconditioning and anti-apoptotic. In view of these favorable effects, levosimendan has been tested in patients undergoing cardiac surgery for the prevention or treatment of low cardiac output syndrome. However, initial positive results from small studies have not been confirmed in three recent large trials. To summarize levosimendan mechanisms of action and clinical use and to review available evidence on its perioperative use in cardiac surgery setting. We searched two electronic medical databases for randomized controlled trials studying levosimendan in cardiac surgery patients, ranging from January 2000 to August 2017. Meta-analyses, consensus documents and retrospective studies were also reviewed. In the selected interval of time, 54 studies on the use of levosimendan in heart surgery have been performed. Early small size studies and meta-analyses have suggested that perioperative levosimendan infusion could diminish mortality and other adverse outcomes (i.e. intensive care unit stay and need for inotropic support). Instead, three recent large randomized controlled trials (LEVO-CTS, CHEETAH and LICORN) showed no significant survival benefits from levosimendan. However, in LEVO-CTS trial, prophylactic levosimendan administration significantly reduced the incidence of low cardiac output syndrome. Based on most recent randomized controlled trials, levosimendan, although effective for the treatment of acute heart failure, can't be recommended as standard therapy for the management of heart surgery patients. Further studies are needed to clarify whether selected subgroups of heart surgery patients may benefit from perioperative levosimendan infusion. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Observational research rigour alone does not justify causal inference.

PubMed

Ejima, Keisuke; Li, Peng; Smith, Daniel L; Nagy, Tim R; Kadish, Inga; van Groen, Thomas; Dawson, John A; Yang, Yongbin; Patki, Amit; Allison, David B

2016-12-01

Differing opinions exist on whether associations obtained in observational studies can be reliable indicators of a causal effect if the observational study is sufficiently well controlled and executed. To test this, we conducted two animal observational studies that were rigorously controlled and executed beyond what is achieved in studies of humans. In study 1, we randomized 332 genetically identical C57BL/6J mice into three diet groups with differing food energy allotments and recorded individual self-selected daily energy intake and lifespan. In study 2, 60 male mice (CD1) were paired and divided into two groups for a 2-week feeding regimen. We evaluated the association between weight gain and food consumption. Within each pair, one animal was randomly assigned to an S group in which the animals had free access to food. The second paired animal (R group) was provided exactly the same diet that their S partner ate the day before. In study 1, across all three groups, we found a significant negative effect of energy intake on lifespan. However, we found a positive association between food intake and lifespan among the ad libitum feeding group: 29·99 (95% CI: 8·2-51·7) days per daily kcal. In study 2, we found a significant (P = 0·003) group (randomized vs. self-selected)-by-food consumption interaction effect on weight gain. At least in nutrition research, associations derived from observational studies may not be reliable indicators of causal effects, even with the most rigorous study designs achievable. © 2016 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.

Enhanced upper respiratory tract airflow and head fanning reduce brain temperature in brain-injured, mechanically ventilated patients: a randomized, crossover, factorial trial.

PubMed

Harris, B A; Andrews, P J D; Murray, G D

2007-01-01

Heat loss from the upper airways and through the skull are physiological mechanisms of brain cooling which have not been fully explored clinically. This randomized, crossover, factorial trial in 12 brain-injured, orally intubated patients investigated the effect of enhanced nasal airflow (high flow unhumidified air with 20 p.p.m. nitric oxide gas) and bilateral head fanning on frontal lobe brain temperature and selective brain cooling. After a 30 min baseline, each patient received the four possible combinations of the interventions--airflow, fanning, both together, no intervention--in randomized order. Each combination was delivered for 30 min and followed by a 30 min washout, the last 5 min of which provided the baseline for the next intervention. The difference in mean brain temperature over the last 5 min of the preceding washout minus the mean over the last 5 min of intervention, was 0.15 degrees C with nasal airflow (P=0.001, 95% CI 0.06-0.23 degrees C) and 0.26 degrees C with head fanning (P<0.001, 95% CI 0.17-0.34 degrees C). The estimate of the combined effect of airflow and fanning on brain temperature was 0.41 degrees C. Selective brain cooling did not occur. Physiologically, this study demonstrates that heat loss through the upper airways and through the skull can reduce parenchymal brain temperature in brain-injured humans and the onset of temperature reduction is rapid. Clinically, in ischaemic stroke, a temperature decrease of 0.27 degrees C may reduce the relative risk of poor outcome by 10-20%. Head fanning may have the potential to achieve a temperature decrease of this order.

Mobile Phone Apps for Smoking Cessation: Quality and Usability Among Smokers With Psychosis.

PubMed

Ferron, Joelle C; Brunette, Mary F; Geiger, Pamela; Marsch, Lisa A; Adachi-Mejia, Anna M; Bartels, Stephen J

2017-03-03

Smoking is one of the top preventable causes of mortality in people with psychotic disorders such as schizophrenia. Cessation treatment improves abstinence outcomes, but access is a barrier. Mobile phone apps are one way to increase access to cessation treatment; however, whether they are usable by people with psychotic disorders, who often have special learning needs, is not known. Researchers reviewed 100 randomly selected apps for smoking cessation to rate them based on US guidelines for nicotine addiction treatment and to categorize them based on app functions. We aimed to test the usability and usefulness of the top-rated apps in 21 smokers with psychotic disorders. We identified 766 smoking cessation apps and randomly selected 100 for review. Two independent reviewers rated each app with the Adherence Index to US Clinical Practice Guideline for Treating Tobacco Use and Dependence. Then, smokers with psychotic disorders evaluated the top 9 apps within a usability testing protocol. We analyzed quantitative results using descriptive statistics and t tests. Qualitative data were open-coded and analyzed for themes. Regarding adherence to practice guidelines, most of the randomly sampled smoking cessation apps scored poorly-66% rated lower than 10 out of 100 on the Adherence Index (Mean 11.47, SD 11.8). Regarding usability, three common usability problems emerged: text-dense content, abstract symbols on the homepage, and subtle directions to edit features. In order for apps to be effective and usable for this population, developers should utilize a balance of text and simple design that facilitate ease of navigation and content comprehension that will help people learn quit smoking skills. ©Joelle C Ferron, Mary F Brunette, Pamela Geiger, Lisa A Marsch, Anna M Adachi-Mejia, Stephen J Bartels. Originally published in JMIR Human Factors (http://humanfactors.jmir.org), 03.03.2017.

Literature review and global consensus on management of acute radiation syndrome affecting nonhematopoietic organ systems.

PubMed

Dainiak, Nicholas; Gent, Robert Nicolas; Carr, Zhanat; Schneider, Rita; Bader, Judith; Buglova, Elena; Chao, Nelson; Coleman, C Norman; Ganser, Arnold; Gorin, Claude; Hauer-Jensen, Martin; Huff, L Andrew; Lillis-Hearne, Patricia; Maekawa, Kazuhiko; Nemhauser, Jeffrey; Powles, Ray; Schünemann, Holger; Shapiro, Alla; Stenke, Leif; Valverde, Nelson; Weinstock, David; White, Douglas; Albanese, Joseph; Meineke, Viktor

2011-10-01

The World Health Organization convened a panel of experts to rank the evidence for medical countermeasures for management of acute radiation syndrome (ARS) in a hypothetical scenario involving the hospitalization of 100 to 200 victims. The goal of this panel was to achieve consensus on optimal management of ARS affecting nonhematopoietic organ systems based upon evidence in the published literature. English-language articles were identified in MEDLINE and PubMed. Reference lists of retrieved articles were distributed to conferees in advance of and updated during the meeting. Published case series and case reports of ARS, publications of randomized controlled trials of relevant interventions used to treat nonirradiated individuals, reports of studies in irradiated animals, and prior recommendations of subject matter experts were selected. Studies were extracted using the Grading of Recommendations Assessment Development and Evaluation system. In cases in which data were limited or incomplete, a narrative review of the observations was made. No randomized controlled trials of medical countermeasures have been completed for individuals with ARS. Reports of countermeasures were often incompletely described, making it necessary to rely on data generated in nonirradiated humans and in experimental animals. A strong recommendation is made for the administration of a serotonin-receptor antagonist prophylactically when the suspected exposure is >2 Gy and topical steroids, antibiotics, and antihistamines for radiation burns, ulcers, or blisters; excision and grafting of radiation ulcers or necrosis with intractable pain; provision of supportive care to individuals with neurovascular syndrome; and administration of electrolyte replacement therapy and sedatives to individuals with significant burns, hypovolemia, and/or shock. A strong recommendation is made against the use of systemic steroids in the absence of a specific indication. A weak recommendation is made for the use of fluoroquinolones, bowel decontamination, loperamide, and enteral nutrition, and for selective oropharyngeal/digestive decontamination, blood glucose maintenance, and stress ulcer prophylaxis in critically ill patients. High-quality studies of therapeutic interventions in humans exposed to nontherapeutic radiation are not available, and because of ethical concerns regarding the conduct of controlled studies in humans, such studies are unlikely to emerge in the near future.

Literature Review and Global Consensus on Management of Acute Radiation Syndrome Affecting Nonhematopoietic Organ Systems

PubMed Central

Dainiak, Nicholas; Gent, Robert Nicolas; Carr, Zhanat; Schneider, Rita; Bader, Judith; Buglova, Elena; Chao, Nelson; Coleman, C. Norman; Ganser, Arnold; Gorin, Claude; Hauer-Jensen, Martin; Huff, L. Andrew; Lillis-Hearne, Patricia; Maekawa, Kazuhiko; Nemhauser, Jeffrey; Powles, Ray; Schünemann, Holger; Shapiro, Alla; Stenke, Leif; Valverde, Nelson; Weinstock, David; White, Douglas; Albanese, Joseph; Meineke, Viktor

2013-01-01

Objectives The World Health Organization convened a panel of experts to rank the evidence for medical countermeasures for management of acute radiation syndrome (ARS) in a hypothetical scenario involving the hospitalization of 100 to 200 victims. The goal of this panel was to achieve consensus on optimal management of ARS affecting nonhematopoietic organ systems based upon evidence in the published literature. Methods English-language articles were identified in MEDLINE and PubMed. Reference lists of retrieved articles were distributed to conferees in advance of and updated during the meeting. Published case series and case reports of ARS, publications of randomized controlled trials of relevant interventions used to treat nonirradiated individuals, reports of studies in irradiated animals, and prior recommendations of subject matter experts were selected. Studies were extracted using the Grading of Recommendations Assessment Development and Evaluation system. In cases in which data were limited or incomplete, a narrative review of the observations was made. Results No randomized controlled trials of medical countermeasures have been completed for individuals with ARS. Reports of countermeasures were often incompletely described, making it necessary to rely on data generated in nonirradiated humans and in experimental animals. A strong recommendation is made for the administration of a serotonin-receptor antagonist prophylactically when the suspected exposure is >2 Gy and topical steroids, antibiotics, and antihistamines for radiation burns, ulcers, or blisters; excision and grafting of radiation ulcers or necrosis with intractable pain; provision of supportive care to individuals with neurovascular syndrome; and administration of electrolyte replacement therapy and sedatives to individuals with significant burns, hypovolemia, and/ orshock. A strong recommendation is made against the use of systemic steroids in the absence of a specific indication. A weak recommendation is made for the use of fluoroquinolones, bowel decontamination, loperamide, and enteral nutrition, and for selective oropharyngeal/digestive decontamination, blood glucose maintenance, and stress ulcer prophylaxis in critically ill patients. Conclusions High-quality studies of therapeutic interventions in humans exposed to nontherapeutic radiation are not available, and because of ethical concerns regarding the conduct of controlled studies in humans, such studies are unlikely to emerge in the near future. PMID:21986999

On the Choice of Adequate Randomization Ranges for Limiting the Use of Unwanted Cues in Same-Different, Dual-Pair, and Oddity Tasks

PubMed Central

Dai, Huanping; Micheyl, Christophe

2010-01-01

A major concern when designing a psychophysical experiment is that participants may use another stimulus feature (“cue”) than that intended by the experimenter. One way to avoid this involves applying random variations to the corresponding feature across stimulus presentations, to make the “unwanted” cue unreliable. An important question facing experimenters who use this randomization (“roving”) technique is: How large should the randomization range be to ensure that participants cannot achieve a certain proportion correct (PC) by using the unwanted cue, while at the same time avoiding unnecessary interference of the randomization with task performance? Previous publications have provided formulas for the selection of adequate randomization ranges in yes-no and multiple-alternative, forced-choice tasks. In this article, we provide figures and tables, which can be used to select randomization ranges that are better suited to experiments involving a same-different, dual-pair, or oddity task. PMID:20139466

American Thoracic Society Member Survey on Climate Change and Health

PubMed Central

Bloodhart, Brittany; Ewart, Gary; Thurston, George D.; Balmes, John R.; Guidotti, Tee L.; Maibach, Edward W.

2015-01-01

The American Thoracic Society (ATS), in collaboration with George Mason University, surveyed a random sample of ATS members to assess their perceptions of, clinical experiences with, and preferred policy responses to climate change. An e-mail containing an invitation from the ATS President and a link to an online survey was sent to 5,500 randomly selected U.S. members; up to four reminder e-mails were sent to nonrespondents. Responses were received from members in 49 states and the District of Columbia (n = 915); the response rate was 17%. Geographic distribution of respondents mirrored that of the sample. Survey estimates’ confidence intervals were ±3.5% or smaller. Results indicate that a large majority of ATS members have concluded that climate change is happening (89%), that it is driven by human activity (68%), and that it is relevant to patient care (“a great deal”/“a moderate amount”) (65%). A majority of respondents indicated they were already observing health impacts of climate change among their patients, most commonly as increases in chronic disease severity from air pollution (77%), allergic symptoms from exposure to plants or mold (58%), and severe weather injuries (57%). A larger majority anticipated seeing these climate-related health impacts in the next 2 decades. Respondents indicated that physicians and physician organizations should play an active role in educating patients, the public, and policy makers on the human health effects of climate change. Overall, ATS members are observing that human health is already adversely affected by climate change and support responses to address this situation. PMID:25535822

Sleep deprivation impairs the accurate recognition of human emotions.

PubMed

van der Helm, Els; Gujar, Ninad; Walker, Matthew P

2010-03-01

Investigate the impact of sleep deprivation on the ability to recognize the intensity of human facial emotions. Randomized total sleep-deprivation or sleep-rested conditions, involving between-group and within-group repeated measures analysis. Experimental laboratory study. Thirty-seven healthy participants, (21 females) aged 18-25 y, were randomly assigned to the sleep control (SC: n = 17) or total sleep deprivation group (TSD: n = 20). Participants performed an emotional face recognition task, in which they evaluated 3 different affective face categories: Sad, Happy, and Angry, each ranging in a gradient from neutral to increasingly emotional. In the TSD group, the task was performed once under conditions of sleep deprivation, and twice under sleep-rested conditions following different durations of sleep recovery. In the SC group, the task was performed twice under sleep-rested conditions, controlling for repeatability. In the TSD group, when sleep-deprived, there was a marked and significant blunting in the recognition of Angry and Happy affective expressions in the moderate (but not extreme) emotional intensity range; differences that were most reliable and significant in female participants. No change in the recognition of Sad expressions was observed. These recognition deficits were, however, ameliorated following one night of recovery sleep. No changes in task performance were observed in the SC group. Sleep deprivation selectively impairs the accurate judgment of human facial emotions, especially threat relevant (Anger) and reward relevant (Happy) categories, an effect observed most significantly in females. Such findings suggest that sleep loss impairs discrete affective neural systems, disrupting the identification of salient affective social cues.

The effect of clustering on perceived quantity in humans (Homo sapiens) and in chicks (Gallus gallus).

PubMed

Bertamini, Marco; Guest, Martin; Vallortigara, Giorgio; Rugani, Rosa; Regolin, Lucia

2018-04-30

Animals can perceive the numerosity of sets of visual elements. Qualitative and quantitative similarities in different species suggest the existence of a shared system (approximate number system). Biases associated with sensory properties are informative about the underlying mechanisms. In humans, regular spacing increases perceived numerosity (regular-random numerosity illusion). This has led to a model that predicts numerosity based on occupancy (a measure that decreases when elements are close together). We used a procedure in which observers selected one of two stimuli and were given feedback with respect to whether the choice was correct. One configuration had 20 elements and the other 40, randomly placed inside a circular region. Participants had to discover the rule based on feedback. Because density and clustering covaried with numerosity, different dimensions could be used. After reaching a criterion, test trials presented two types of configurations with 30 elements. One type had a larger interelement distance than the other (high or low clustering). If observers had adopted a numerosity strategy, they would choose low clustering (if reinforced with 40) and high clustering (if reinforced with 20). A clustering or density strategy predicts the opposite. Human adults used a numerosity strategy. Chicks were tested using a similar procedure. There were two behavioral measures: first approach response and final circumnavigation (walking behind the screen). The prediction based on numerosity was confirmed by the first approach data. For chicks, one clear pattern from both responses was a preference for the configurations with higher clustering. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

American Thoracic Society member survey on climate change and health.

PubMed

Sarfaty, Mona; Bloodhart, Brittany; Ewart, Gary; Thurston, George D; Balmes, John R; Guidotti, Tee L; Maibach, Edward W

2015-02-01

The American Thoracic Society (ATS), in collaboration with George Mason University, surveyed a random sample of ATS members to assess their perceptions of, clinical experiences with, and preferred policy responses to climate change. An e-mail containing an invitation from the ATS President and a link to an online survey was sent to 5,500 randomly selected U.S. members; up to four reminder e-mails were sent to nonrespondents. Responses were received from members in 49 states and the District of Columbia (n = 915); the response rate was 17%. Geographic distribution of respondents mirrored that of the sample. Survey estimates' confidence intervals were ±3.5% or smaller. Results indicate that a large majority of ATS members have concluded that climate change is happening (89%), that it is driven by human activity (68%), and that it is relevant to patient care ("a great deal"/"a moderate amount") (65%). A majority of respondents indicated they were already observing health impacts of climate change among their patients, most commonly as increases in chronic disease severity from air pollution (77%), allergic symptoms from exposure to plants or mold (58%), and severe weather injuries (57%). A larger majority anticipated seeing these climate-related health impacts in the next 2 decades. Respondents indicated that physicians and physician organizations should play an active role in educating patients, the public, and policy makers on the human health effects of climate change. Overall, ATS members are observing that human health is already adversely affected by climate change and support responses to address this situation.

Sampling in health geography: reconciling geographical objectives and probabilistic methods. An example of a health survey in Vientiane (Lao PDR)

PubMed Central

Vallée, Julie; Souris, Marc; Fournet, Florence; Bochaton, Audrey; Mobillion, Virginie; Peyronnie, Karine; Salem, Gérard

2007-01-01

Background Geographical objectives and probabilistic methods are difficult to reconcile in a unique health survey. Probabilistic methods focus on individuals to provide estimates of a variable's prevalence with a certain precision, while geographical approaches emphasise the selection of specific areas to study interactions between spatial characteristics and health outcomes. A sample selected from a small number of specific areas creates statistical challenges: the observations are not independent at the local level, and this results in poor statistical validity at the global level. Therefore, it is difficult to construct a sample that is appropriate for both geographical and probability methods. Methods We used a two-stage selection procedure with a first non-random stage of selection of clusters. Instead of randomly selecting clusters, we deliberately chose a group of clusters, which as a whole would contain all the variation in health measures in the population. As there was no health information available before the survey, we selected a priori determinants that can influence the spatial homogeneity of the health characteristics. This method yields a distribution of variables in the sample that closely resembles that in the overall population, something that cannot be guaranteed with randomly-selected clusters, especially if the number of selected clusters is small. In this way, we were able to survey specific areas while minimising design effects and maximising statistical precision. Application We applied this strategy in a health survey carried out in Vientiane, Lao People's Democratic Republic. We selected well-known health determinants with unequal spatial distribution within the city: nationality and literacy. We deliberately selected a combination of clusters whose distribution of nationality and literacy is similar to the distribution in the general population. Conclusion This paper describes the conceptual reasoning behind the construction of the survey sample and shows that it can be advantageous to choose clusters using reasoned hypotheses, based on both probability and geographical approaches, in contrast to a conventional, random cluster selection strategy. PMID:17543100

Sampling in health geography: reconciling geographical objectives and probabilistic methods. An example of a health survey in Vientiane (Lao PDR).

PubMed

Vallée, Julie; Souris, Marc; Fournet, Florence; Bochaton, Audrey; Mobillion, Virginie; Peyronnie, Karine; Salem, Gérard

2007-06-01

Geographical objectives and probabilistic methods are difficult to reconcile in a unique health survey. Probabilistic methods focus on individuals to provide estimates of a variable's prevalence with a certain precision, while geographical approaches emphasise the selection of specific areas to study interactions between spatial characteristics and health outcomes. A sample selected from a small number of specific areas creates statistical challenges: the observations are not independent at the local level, and this results in poor statistical validity at the global level. Therefore, it is difficult to construct a sample that is appropriate for both geographical and probability methods. We used a two-stage selection procedure with a first non-random stage of selection of clusters. Instead of randomly selecting clusters, we deliberately chose a group of clusters, which as a whole would contain all the variation in health measures in the population. As there was no health information available before the survey, we selected a priori determinants that can influence the spatial homogeneity of the health characteristics. This method yields a distribution of variables in the sample that closely resembles that in the overall population, something that cannot be guaranteed with randomly-selected clusters, especially if the number of selected clusters is small. In this way, we were able to survey specific areas while minimising design effects and maximising statistical precision. We applied this strategy in a health survey carried out in Vientiane, Lao People's Democratic Republic. We selected well-known health determinants with unequal spatial distribution within the city: nationality and literacy. We deliberately selected a combination of clusters whose distribution of nationality and literacy is similar to the distribution in the general population. This paper describes the conceptual reasoning behind the construction of the survey sample and shows that it can be advantageous to choose clusters using reasoned hypotheses, based on both probability and geographical approaches, in contrast to a conventional, random cluster selection strategy.

Selective norepinephrine reuptake inhibition as a human model of orthostatic intolerance

NASA Technical Reports Server (NTRS)

Schroeder, Christoph; Tank, Jens; Boschmann, Michael; Diedrich, Andre; Sharma, Arya M.; Biaggioni, Italo; Luft, Friedrich C.; Jordan, Jens; Robertson, D. (Principal Investigator)

2002-01-01

BACKGROUND: Observations in patients with functional mutations of the norepinephrine transporter (NET) gene suggest that impaired norepinephrine uptake may contribute to idiopathic orthostatic intolerance. METHODS AND RESULTS: We studied the effect of the selective NET blocker reboxetine and placebo in a randomized, double-blind, crossover fashion on cardiovascular responses to cold pressor testing, handgrip testing, and a graded head-up tilt test (HUT) in 18 healthy subjects. In a subset, we determined isoproterenol and phenylephrine sensitivities. Subjects ingested 8 mg reboxetine or placebo 12 hours and 1 hour before testing. In the supine position, heart rate was 65+/-2 bpm with placebo and 71+/-3 bpm with reboxetine. At 75 degrees HUT, heart rate was 84+/-3 and 119+/-4 bpm with placebo and with reboxetine (P<0.0001). Mean arterial pressure was 85+/-2 with placebo and 91+/-2 mm Hg with reboxetine while supine (P<0.01) and 88+/-2 mm Hg and 90+/-3 mm Hg at 75 degrees HUT. Blood pressure responses to cold pressor and handgrip testing were attenuated with reboxetine. Reboxetine increased the sensitivity to the chronotropic effect of isoproterenol and the pressor effect of phenylephrine. Vasovagal reactions occurred in 9 subjects on placebo and in 1 subject on reboxetine. CONCLUSIONS: Selective NET blockade creates a phenotype that resembles idiopathic orthostatic intolerance. This observation supports the hypothesis that disordered norepinephrine uptake mechanisms can contribute to human cardiovascular disease. Our study also suggests that NET inhibition might be useful in preventing vasovagal reactions.

Ultrasonic vocalizations, predictability and sensorimotor gating in the rat

PubMed Central

Webber, Emily S.; Mankin, David E.; McGraw, Justin J.; Beckwith, Travis J.; Cromwell, Howard C.

2013-01-01

Prepulse inhibition (PPI) is a measure of sensorimotor gating in diverse groups of animals including humans. Emotional states can influence PPI in humans both in typical subjects and in individuals with mental illness. Little is known about emotional regulation during PPI in rodents. We used ultrasonic vocalization recording to monitor emotional states in rats during PPI testing. We altered the predictability of the PPI trials to examine any alterations in gating and emotional regulation. We also examined PPI in animals selectively bred for high or low levels of 50 kHz USV emission. Rats emitted high levels of 22 kHz calls consistently throughout the PPI session. USVs were sensitive to prepulses during the PPI session similar to startle. USV rate was sensitive to predictability among the different levels tested and across repeated experiences. Startle and inhibition of startle were not affected by predictability in a similar manner. No significant differences for PPI or startle were found related the different levels of predictability; however, there was a reduction in USV signals and an enhancement of PPI after repeated exposure. Animals selectively bred to emit high levels of USVs emitted significantly higher levels of USVs during the PPI session and a reduced ASR compared to the low and random selective lines. Overall, the results support the idea that PPI tests in rodents induce high levels of negative affect and that manipulating emotional styles of the animals alters the negative impact of the gating session as well as the intensity of the startle response. PMID:23850353

Replication of alpha-satellite DNA arrays in endogenous human centromeric regions and in human artificial chromosome

PubMed Central

Erliandri, Indri; Fu, Haiqing; Nakano, Megumi; Kim, Jung-Hyun; Miga, Karen H.; Liskovykh, Mikhail; Earnshaw, William C.; Masumoto, Hiroshi; Kouprina, Natalay; Aladjem, Mirit I.; Larionov, Vladimir

2014-01-01

In human chromosomes, centromeric regions comprise megabase-size arrays of 171 bp alpha-satellite DNA monomers. The large distances spanned by these arrays preclude their replication from external sites and imply that the repetitive monomers contain replication origins. However, replication within these arrays has not previously been profiled and the role of alpha-satellite DNA in initiation of DNA replication has not yet been demonstrated. Here, replication of alpha-satellite DNA in endogenous human centromeric regions and in de novo formed Human Artificial Chromosome (HAC) was analyzed. We showed that alpha-satellite monomers could function as origins of DNA replication and that replication of alphoid arrays organized into centrochromatin occurred earlier than those organized into heterochromatin. The distribution of inter-origin distances within centromeric alphoid arrays was comparable to the distribution of inter-origin distances on randomly selected non-centromeric chromosomal regions. Depletion of CENP-B, a kinetochore protein that binds directly to a 17 bp CENP-B box motif common to alpha-satellite DNA, resulted in enrichment of alpha-satellite sequences for proteins of the ORC complex, suggesting that CENP-B may have a role in regulating the replication of centromeric regions. Mapping of replication initiation sites in the HAC revealed that replication preferentially initiated in transcriptionally active regions. PMID:25228468

An evaluation of the genetic-matched pair study design using genome-wide SNP data from the European population.

PubMed

Lu, Timothy Tehua; Lao, Oscar; Nothnagel, Michael; Junge, Olaf; Freitag-Wolf, Sandra; Caliebe, Amke; Balascakova, Miroslava; Bertranpetit, Jaume; Bindoff, Laurence Albert; Comas, David; Holmlund, Gunilla; Kouvatsi, Anastasia; Macek, Milan; Mollet, Isabelle; Nielsen, Finn; Parson, Walther; Palo, Jukka; Ploski, Rafal; Sajantila, Antti; Tagliabracci, Adriano; Gether, Ulrik; Werge, Thomas; Rivadeneira, Fernando; Hofman, Albert; Uitterlinden, André Gerardus; Gieger, Christian; Wichmann, Heinz-Erich; Ruether, Andreas; Schreiber, Stefan; Becker, Christian; Nürnberg, Peter; Nelson, Matthew Roberts; Kayser, Manfred; Krawczak, Michael

2009-07-01

Genetic matching potentially provides a means to alleviate the effects of incomplete Mendelian randomization in population-based gene-disease association studies. We therefore evaluated the genetic-matched pair study design on the basis of genome-wide SNP data (309,790 markers; Affymetrix GeneChip Human Mapping 500K Array) from 2457 individuals, sampled at 23 different recruitment sites across Europe. Using pair-wise identity-by-state (IBS) as a matching criterion, we tried to derive a subset of markers that would allow identification of the best overall matching (BOM) partner for a given individual, based on the IBS status for the subset alone. However, our results suggest that, by following this approach, the prediction accuracy is only notably improved by the first 20 markers selected, and increases proportionally to the marker number thereafter. Furthermore, in a considerable proportion of cases (76.0%), the BOM of a given individual, based on the complete marker set, came from a different recruitment site than the individual itself. A second marker set, specifically selected for ancestry sensitivity using singular value decomposition, performed even more poorly and was no more capable of predicting the BOM than randomly chosen subsets. This leads us to conclude that, at least in Europe, the utility of the genetic-matched pair study design depends critically on the availability of comprehensive genotype information for both cases and controls.

Hypoglycemic effects of Acacia nilotica in type II diabetes: a research proposal.

PubMed

Roozbeh, Nasibeh; Darvish, Leili; Abdi, Fatemeh

2017-07-26

Diabetes mellitus is a common metabolic disorder throughout the world which can negatively affect the function of various body organs. Due to their availability and few side effects, herbal medicines have been proposed as suitable alternatives in the management of diabetes. Previous studies have confirmed the anti diabetic properties of Acacia nilotica. The hypoglycemic effects of this plant have been attributed to its role in stimulating the islets of Langerhans to produce more insulin. The present paper describes a systematic review protocol for the assessment of the hypoglycemic effects of A. nilotica. Randomized and non-randomized placebo-controlled clinical trials, performed during 1999-2016 will be included. The outcomes will be measured through FBS, GCT, GTT, and OGTT in all of studies and in addition to these tests, will be measured 2HPP and HbA1c level in human study. Well-known databases will be searched for selected key terms A. nilotica, type II diabetes and hypoglycemia. The quality assessment of the selected papers will be evaluated based on SYRCLE and Cochrane Risk of Bias Tool. We believe that our findings will provide details about difficulties researchers face during the design of protocols or implementation of scientific studies. Ultimately, the publication of our findings will facilitate the development of effective treatment strategies to promote the health of people with type II DM. PROSPERO registration CRD42016053141.

Efficacy of platelet-rich plasma applied to post-extraction retained lower third molar alveoli. A systematic review.

PubMed

Barona-Dorado, C; González-Regueiro, I; Martín-Ares, M; Arias-Irimia, O; Martínez-González, J-M

2014-03-01

Dental retentions have a high prevalence among the general population and their removal can involve multiple complications. The use of platelet rich plasma has been proposed in an attempt to avoid these complications, as it contains high growth factors and stimulates diverse biological functions that facilitate the healing of soft and hard tissues. To evaluate the available scientific evidence related to the application of platelet-rich plasma in the post-extraction alveoli of a retained lower third molars. A systematic review of published literature registered in the Medline, EMBASE, Cochrane and NIH databases. The following categories were included: human randomized clinical studies. Key search words were: platelet rich plasma; platelet rich plasma and oral surgery; platelet rich in growth factors and third molar. Of 101 potentially valid articles, seven were selected, of which four were rejected as they failed to meet quality criteria. Three studies fulfilled all selection and quality criteria: Ogundipe et al.; Rutkowski et al.; Haraji et al. The studies all measured osteoblast activity by means of sintigraphy, and also registered pain, bleeding, inflammation, temperature, numbness as perceived by the patients, radiological bone density and the incidence of alveolar osteitis. Scientific evidence for the use of PRP in retained third molar surgery is poor. For this reason randomized clinical trials are needed before recommendations for the clinical application of PRP can be made.

Identification of Id4 as a regulator of BRCA1 expression by using a ribozyme-library-based inverse genomics approach

PubMed Central

Beger, Carmela; Pierce, Leigh N.; Krüger, Martin; Marcusson, Eric G.; Robbins, Joan M.; Welcsh, Piri; Welch, Peter J.; Welte, Karl; King, Mary-Claire; Barber, Jack R.; Wong-Staal, Flossie

2001-01-01

Expression of the breast and ovarian cancer susceptibility gene BRCA1 is down-regulated in sporadic breast and ovarian cancer cases. Therefore, the identification of genes involved in the regulation of BRCA1 expression might lead to new insights into the pathogenesis and treatment of these tumors. In the present study, an “inverse genomics” approach based on a randomized ribozyme gene library was applied to identify cellular genes regulating BRCA1 expression. A ribozyme gene library with randomized target recognition sequences was introduced into human ovarian cancer-derived cells stably expressing a selectable marker [enhanced green fluorescence protein (EGFP)] under the control of the BRCA1 promoter. Cells in which BRCA1 expression was upregulated by particular ribozymes were selected through their concomitant increase in EGFP expression. The cellular target gene of one ribozyme was identified to be the dominant negative transcriptional regulator Id4. Modulation of Id4 expression resulted in inversely regulated expression of BRCA1. In addition, increase in Id4 expression was associated with the ability of cells to exhibit anchorage-independent growth, demonstrating the biological relevance of this gene. Our data suggest that Id4 is a crucial gene regulating BRCA1 expression and might therefore be important for the BRCA1 regulatory pathway involved in the pathogenesis of sporadic breast and ovarian cancer. PMID:11136250

A High Proportion of Chromosome 21 Promoter Polymorphisms Influence Transcriptional Activity

PubMed Central

Buckland, Paul R.; Coleman, Sharol L.; Hoogendoorn, Bastiaan; Guy, Carol; Smith, S. Kaye; O’Donovan, Michael C.

2004-01-01

We have sought to obtain an unbiased estimate of the proportion of polymorphisms in promoters of human genes that have functional effects. We carried out polymorphism discovery on a randomly selected group of 51 gene promoters mapping to human chromosome 21 and successfully analyzed the effect on transcription of 38 of the sequence variants. To achieve this, a total of 53 different haplotypes from 20 promoters were cloned into a modified pGL3 luciferase reporter gene vector and were tested for their abilities to promote transcription in HEK293t and JEG-3 cells. Up to seven (18%) of the 38 tested variants altered transcription by 1.5-fold, confirming that a surprisingly high proportion of promoter region polymorphisms are likely to be functionally important. The functional variants were distributed across the promoters of CRYAA, IFNAR1, KCNJ15, NCAM2, IGSF5, and B3GALT5. Three of the genes (NCAM2, IFNAR1, and CRYAA) have been previously associated with human phenotypes and the polymorphisms we describe here may therefore play a role in those phenotypes. PMID:15200235

Speed in Information Processing with a Computer Driven Visual Display in a Real-time Digital Simulation. M.S. Thesis - Virginia Polytechnic Inst.

NASA Technical Reports Server (NTRS)

Kyle, R. G.

1972-01-01

Information transfer between the operator and computer-generated display systems is an area where the human factors engineer discovers little useful design data relating human performance to system effectiveness. This study utilized a computer-driven, cathode-ray-tube graphic display to quantify human response speed in a sequential information processing task. The performance criteria was response time to sixteen cell elements of a square matrix display. A stimulus signal instruction specified selected cell locations by both row and column identification. An equal probable number code, from one to four, was assigned at random to the sixteen cells of the matrix and correspondingly required one of four, matched keyed-response alternatives. The display format corresponded to a sequence of diagnostic system maintenance events, that enable the operator to verify prime system status, engage backup redundancy for failed subsystem components, and exercise alternate decision-making judgements. The experimental task bypassed the skilled decision-making element and computer processing time, in order to determine a lower bound on the basic response speed for given stimulus/response hardware arrangement.

Human toxocariasis: a seroepidemiological survey in the municipality of Campinas (SP), Brazil.

PubMed

Anaruma Filho, Francisco; Chieffi, Pedro Paulo; Correa, Carlos Roberto Silveira; Camargo, Eide Dias; Silveira, Edilene P Real da; Aranha, Joana José Brandão; Ribeiro, Manoel Carlos S Almeida

2002-01-01

The occurrence of human Toxocara infection was evaluated in three neighborhoods of the periphery of the Campinas municipality (Jardim Santa Mônica, Jardim São Marcos and Jardim Campineiro) in 1999. Forty residences and 138 residents were randomly selected by drawing lots and were submitted to a seroepidemiological survey, which included blood collection for the immunoenzymatic detection (ELISA) of anti-Toxocara antibodies and a blood count, and the application of a semi-structured questionnaire for the evaluation of epidemiological data. Significant levels of anti-Toxocara antibodies were detected in 23.9% of the 1999 samples. No significant difference in the frequency of infection according to age was observed. Environmental contamination with Toxocara eggs was observed in 12.3 and 14.0% of 57 soil samples collected in the same region in December 1998 and July 1999, respectively. Univariate analysis and multiple logistic regression of the data obtained from the questionnaires and of the results of the serological tests, suggest a significant influence of socioeconomic variables on the frequency of human infection with Toxocara under the conditions prevalent in the study area.

[Comparison of organic component and di-n-butyl phthalate between human milk and cow milk products].

PubMed

Liu, Hui-jie; Cao, Jia; Shu, Wei-qun

2011-01-01

To explore types of organic components and pollution level of di-n-butyl phthalate (DBP) between human milk and cow milk products. Forty healthy postpartum women with an average age of (27.44 ± 3.43) years old were selected, and a 5 ml sample of breast milk were collected. Four different brands of fresh cow milk and 1 brand of milk powder were randomly selected in the market. A total of 15 samples were collected with 3 from each brand, and the qualitative analysis of types of organic components and quantitative analysis of DBP were conducted by gas-chromatography and mass-spectrometry (GC/MS) method. A total of 176 different types of organic components were detected in 40 samples of human milk (averaged at (10.58 ± 4.16) types per sample); 37 different types were detected in 12 samples of fresh cow milk (averaged at (8.67 ± 1.61) types per sample); while 31 types of organic components were detected in 3 samples of milk powder (averaged at (12.67 ± 0.58) types per sample). It was obvious that the types of organic components in milk powder were significantly higher than the other two groups (t = 2.09, 4.00, P < 0.05). The most frequent organic component in human milk and cow milk was 9-octadecenoic acid (45.00% (18/40) in human milk; 53.33% (8/15) in cow milk). DBP concentrations were (57.78 ± 35.42) µg/L, (20.76 ± 6.60) µg/L and (0.45 ± 0.05) mg/kg (equal to (66.78 ± 7.60) µg/L) in human milk, fresh cow milk and milk powder, respectively. The DBP concentration in fresh cow milk was significantly lower than those in human milk and milk powder (t = 37.02, 46.02, P < 0.05). Both human milk and cow milk contain different types of organic pollutants, some of which have toxic effects on reproduction and human development.

Assessment of ambient noise levels in the urban residential streets of Eastern Alexandria, Egypt.

PubMed

Zaki, Gehan R

2012-12-01

Street of Alexandria have numerous unplanned, mixed, and noisy activities that may interfere with public health and comfort. The aim of this study was to assess A-weighted ambient noise levels in urban residential streets of Eastern Alexandria, Egypt, from September 2010 to January 2011, with the objective of recommending corrective actions to minimize high noise levels. A descriptive cross-sectional study was carried out, in which A-weighted ambient noise levels were measured on the basis of 24-h periods, using Ono sokki la-5120--precision integrating sound level meter, from September 2010 to January 2011. The measurements were taken on three streets, which were selected using stratified random sampling. Seven measurement sites, along the three streets under study, were selected by site visits according to predetermined criteria. A-weighted ambient noise levels (LAeq) were the highest [70.7 (24.2) dB] on high-traffic-density and high-human-activity streets followed by streets with moderate and low traffic density and human activity [67.5 (31.3) and 62.8 (38.2) dB], respectively. It varied significantly depending on means of transportation (road traffic, train, and/or tram) and human activities (parking lots, shops, and/or street merchants). The A-weighted ambient noise levels on urban residential streets of Eastern Alexandria, Egypt, exceeded the Egyptian National Standards during the three periods of the day (daytime, evening, and night), except in some relatively quiet locations during the night. Consequently, remedial actions to reduce noise levels were recommended.

Heterogeneity of antibody response to human platelet transfusion.

PubMed Central

Wu, K K; Thompson, J S; Koepke, J A; Hoak, J C; Flink, R

1976-01-01

To study the antibody response to human platelet transfusions, nine thrombocytopenia patients with bone marrow failure were given 6 U (3X10(11)) of random platelet concentrates twice a week. Before transfusion, none of the patients had preexisting antibodies detectable with lymphocytotoxicity, platelet aggregation, or capillary leukoagglutination techniques. After receiving 18-78 U of platelets, they became refractory to further transfusions of random platelets and alloantibodies were detectable. Two patterns of antibody response could be identified. In three patients, the sera were not lymphocytotoxic with a panel of standard cells in which all the known HLA antigens in the first and second series were represented at least once. Yet, they caused platelet aggregation with 30, 24, and 60%, respectively, of a donor population studied. The aggregating activities were inhibited by antihuman IgG but not by antihuman IgA or antihuman IgM antiserum. The aggregating antibodies could be absorbed out with donor platelets but not lymphocytes or granulocytes. Antibodies from two of these patients aggregated platelets of their respective siblings matched for both HLA haplotypes. Transfusion of platelets from these two siblings did not increase the platelet count while platelets obtained from aggregation-negative donors did. The sera from the remaining six patients were lymphocytotoxic with 15-100% of the panel of standard cells. They also had aggregating antibodies, which could be absorbed out by both platelets and lymphocytes, suggesting that they were HLA antibodies. These data suggest that the development of platelet-specific antibodies may play an important role in the immunological rejection of isologous platelets, and should be considered in the selection of donors for patients who are refractory to platelets from random donors. PMID:956376

Immunogenicity and safety of an E. coli-produced bivalent human papillomavirus (type 16 and 18) vaccine: A randomized controlled phase 2 clinical trial.

PubMed

Wu, Ting; Hu, Yue-Mei; Li, Juan; Chu, Kai; Huang, Shou-Jie; Zhao, Hui; Wang, Zhong-Ze; Yang, Chang-Lin; Jiang, Han-Min; Wang, Yi-Jun; Lin, Zhi-Jie; Pan, Hui-Rong; Sheng, Wei; Wei, Fei-Xue; Li, Shao-Wei; Wang, Ying; Zhu, Feng-Cai; Li, Chang-Gui; Zhang, Jun; Xia, Ning-Shao

2015-07-31

This study aimed to investigate the dosage, immunogenicity and safety profile of a novel human papillomavirus (HPV) types 16 and 18 bivalent vaccine produced by E. coli. This randomized, double-blinded, controlled phase 2 trial enrolled women aged 18-25 years in China. Totally 1600 eligible participants were randomized to receive 90μg, 60μg, or 30μg of the recombinant HPV 16/18 bivalent vaccine or the control hepatitis B vaccine on a 0, 1 and 6 month schedule. The designated doses are the combined micrograms of HPV16 and 18 VLPs with dose ratio of 2:1. The immunogenicity of the vaccines was assessed by measuring anti-HPV 16 and 18 neutralizing antibodies and total IgG antibodies. Safety of the vaccine was assessed. All but one of the seronegative participants who received 3 doses of the HPV vaccines seroconverted at month 7 for anti-HPV 16/18 neutralizing antibodies and IgG antibodies. For HPV 16, the geometric mean titers (GMTs) of the neutralizing antibodies were similar between the 60μg (GMT=10,548) and 90μg (GMT=12,505) HPV vaccine groups and were significantly higher than those in the 30μg (GMT=7596) group. For HPV 18, the GMTs of the neutralizing antibodies were similar among the 3 groups. The HPV vaccine was well tolerated. No vaccine-associated serious adverse events were identified. The prokaryotic-expressed HPV vaccine is safe and immunogenic in women aged 18-25 years. The 60μg dosage formulation was selected for further investigation for efficacy. NCT01356823. Copyright © 2015 Elsevier Ltd. All rights reserved.

HUMAN RESPONDING ON RANDOM-INTERVAL SCHEDULES OF RESPONSE-COST PUNISHMENT: THE ROLE OF REDUCED REINFORCEMENT DENSITY

PubMed Central

Pietras, Cynthia J; Brandt, Andrew E; Searcy, Gabriel D

2010-01-01

An experiment with adult humans investigated the effects of response-contingent money loss (response-cost punishment) on monetary-reinforced responding. A yoked-control procedure was used to separate the effects on responding of the response-cost contingency from the effects of reduced reinforcement density. Eight adults pressed buttons for money on a three-component multiple reinforcement schedule. During baseline, responding in all components produced money gains according to a random-interval 20-s schedule. During punishment conditions, responding during the punishment component conjointly produced money losses according to a random-interval schedule. The value of the response-cost schedule was manipulated across conditions to systematically evaluate the effects on responding of response-cost frequency. Participants were assigned to one of two yoked-control conditions. For participants in the Yoked Punishment group, during punishment conditions money losses were delivered in the yoked component response independently at the same intervals that money losses were produced in the punishment component. For participants in the Yoked Reinforcement group, responding in the yoked component produced the same net earnings as produced in the punishment component. In 6 of 8 participants, contingent response cost selectively decreased response rates in the punishment component and the magnitude of the decrease was directly related to the punishment schedule value. Under punishment conditions, for participants in the Yoked Punishment group response rates in the yoked component also decreased, but the decrease was less than that observed in the punishment component, whereas for participants in the Yoked Reinforcement group response rates in the yoked component remained similar to rates in the no-punishment component. These results provide further evidence that contingent response cost functions similarly to noxious punishers in that it appears to suppress responding apart from its effects on reinforcement density. PMID:20676265

Generation of Aptamers from A Primer-Free Randomized ssDNA Library Using Magnetic-Assisted Rapid Aptamer Selection

NASA Astrophysics Data System (ADS)

Tsao, Shih-Ming; Lai, Ji-Ching; Horng, Horng-Er; Liu, Tu-Chen; Hong, Chin-Yih

2017-04-01

Aptamers are oligonucleotides that can bind to specific target molecules. Most aptamers are generated using random libraries in the standard systematic evolution of ligands by exponential enrichment (SELEX). Each random library contains oligonucleotides with a randomized central region and two fixed primer regions at both ends. The fixed primer regions are necessary for amplifying target-bound sequences by PCR. However, these extra-sequences may cause non-specific bindings, which potentially interfere with good binding for random sequences. The Magnetic-Assisted Rapid Aptamer Selection (MARAS) is a newly developed protocol for generating single-strand DNA aptamers. No repeat selection cycle is required in the protocol. This study proposes and demonstrates a method to isolate aptamers for C-reactive proteins (CRP) from a randomized ssDNA library containing no fixed sequences at 5‧ and 3‧ termini using the MARAS platform. Furthermore, the isolated primer-free aptamer was sequenced and binding affinity for CRP was analyzed. The specificity of the obtained aptamer was validated using blind serum samples. The result was consistent with monoclonal antibody-based nephelometry analysis, which indicated that a primer-free aptamer has high specificity toward targets. MARAS is a feasible platform for efficiently generating primer-free aptamers for clinical diagnoses.

Changing friend selection in middle school: A social network analysis of a randomized intervention study designed to prevent adolescent problem behavior

PubMed Central

DeLay, Dawn; Ha, Thao; Van Ryzin, Mark; Winter, Charlotte; Dishion, Thomas J.

2015-01-01

Adolescent friendships that promote problem behavior are often chosen in middle school. The current study examines the unintended impact of a randomized school based intervention on the selection of friends in middle school, as well as on observations of deviant talk with friends five years later. Participants included 998 middle school students (526 boys and 472 girls) recruited at the onset of middle school (age 11-12 years) from three public middle schools participating in the Family Check-up model intervention. The current study focuses only on the effects of the SHAPe curriculum—one level of the Family Check-up model—on friendship choices. Participants nominated friends and completed measures of deviant peer affiliation. Approximately half of the sample (n=500) was randomly assigned to the intervention and the other half (n=498) comprised the control group within each school. The results indicate that the SHAPe curriculum affected friend selection within School 1, but not within Schools 2 or 3. The effects of friend selection in School 1 translated into reductions in observed deviancy training five years later (age 16-17 years). By coupling longitudinal social network analysis with a randomized intervention study the current findings provide initial evidence that a randomized public middle school intervention can disrupt the formation of deviant peer groups and diminish levels of adolescent deviance five years later. PMID:26377235

Preference for point-light human biological motion in newborns: contribution of translational displacement.

PubMed

Bidet-Ildei, Christel; Kitromilides, Elenitsa; Orliaguet, Jean-Pierre; Pavlova, Marina; Gentaz, Edouard

2014-01-01

In human newborns, spontaneous visual preference for biological motion is reported to occur at birth, but the factors underpinning this preference are still in debate. Using a standard visual preferential looking paradigm, 4 experiments were carried out in 3-day-old human newborns to assess the influence of translational displacement on perception of human locomotion. Experiment 1 shows that human newborns prefer a point-light walker display representing human locomotion as if on a treadmill over random motion. However, no preference for biological movement is observed in Experiment 2 when both biological and random motion displays are presented with translational displacement. Experiments 3 and 4 show that newborns exhibit preference for translated biological motion (Experiment 3) and random motion (Experiment 4) displays over the same configurations moving without translation. These findings reveal that human newborns have a preference for the translational component of movement independently of the presence of biological kinematics. The outcome suggests that translation constitutes the first step in development of visual preference for biological motion. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Selective outcome reporting and sponsorship in randomized controlled trials in IVF and ICSI.

PubMed

Braakhekke, M; Scholten, I; Mol, F; Limpens, J; Mol, B W; van der Veen, F

2017-10-01

Are randomized controlled trials (RCTs) on IVF and ICSI subject to selective outcome reporting and is this related to sponsorship? There are inconsistencies, independent from sponsorship, in the reporting of primary outcome measures in the majority of IVF and ICSI trials, indicating selective outcome reporting. RCTs are subject to bias at various levels. Of these biases, selective outcome reporting is particularly relevant to IVF and ICSI trials since there is a wide variety of outcome measures to choose from. An established cause of reporting bias is sponsorship. It is, at present, unknown whether RCTs in IVF/ICSI are subject to selective outcome reporting and whether this is related with sponsorship. We systematically searched RCTs on IVF and ICSI published between January 2009 and March 2016 in MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials and the publisher subset of PubMed. We analysed 415 RCTs. Per included RCT, we extracted data on impact factor of the journal, sample size, power calculation, and trial registry and thereafter data on primary outcome measure, the direction of trial results and sponsorship. Of the 415 identified RCTs, 235 were excluded for our primary analysis, because the sponsorship was not reported. Of the 180 RCTs included in our analysis, 7 trials did not report on any primary outcome measure and 107 of the remaining 173 trials (62%) reported on surrogate primary outcome measures. Of the 114 registered trials, 21 trials (18%) provided primary outcomes in their manuscript that were different from those in the trial registry. This indicates selective outcome reporting. We found no association between selective outcome reporting and sponsorship. We ran additional analyses to include the trials that had not reported sponsorship and found no outcomes that differed from our primary analysis. Since the majority of the trials did not report on sponsorship, there is a risk on sampling bias. IVF and ICSI trials are subject, to a large extent, to selective outcome reporting. Readers should be aware of this to avoid implementation of false or misleading results in clinical practice. No funding received and there are no conflicts of interest. N/A. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Staying on track: a cluster randomized controlled trial of automated reminders aimed at increasing human papillomavirus vaccine completion.

PubMed

Patel, Ashlesha; Stern, Lisa; Unger, Zoe; Debevec, Elie; Roston, Alicia; Hanover, Rita; Morfesis, Johanna

2014-05-01

To evaluate whether automated reminders increase on-time completion of the three-dose human papillomavirus (HPV) vaccine series. Ten reproductive health centers enrolled 365 women aged 19-26 to receive dose one of the HPV vaccine. Health centers were matched and randomized so that participants received either routine follow-up (control) or automated reminder messages for vaccine doses two and three (intervention). Intervention participants selected their preferred method of reminders - text, e-mail, phone, private Facebook message, or standard mail. We compared vaccine completion rates between groups over a period of 32 weeks. The reminder system did not increase completion rates, which overall were low at 17.2% in the intervention group and 18.9% in the control group (p=0.881). Exploratory analyses revealed that participants who completed the series on-time were more likely to be older (OR=1.15, 95% CI 1.01-1.31), report having completed a four-year college degree or more (age-adjusted OR=2.51, 95% CI 1.29-4.90), and report three or more lifetime sexual partners (age-adjusted OR=3.45, 95% CI 1.20-9.92). The study intervention did not increase HPV vaccine series completion. Despite great public health interest in HPV vaccine completion and reminder technologies, completion rates remain low. Copyright © 2014 Elsevier Ltd. All rights reserved.

Investigation of technology needs for avoiding helicopter pilot error related accidents

NASA Technical Reports Server (NTRS)

Chais, R. I.; Simpson, W. E.

1985-01-01

Pilot error which is cited as a cause or related factor in most rotorcraft accidents was examined. Pilot error related accidents in helicopters to identify areas in which new technology could reduce or eliminate the underlying causes of these human errors were investigated. The aircraft accident data base at the U.S. Army Safety Center was studied as the source of data on helicopter accidents. A randomly selected sample of 110 aircraft records were analyzed on a case-by-case basis to assess the nature of problems which need to be resolved and applicable technology implications. Six technology areas in which there appears to be a need for new or increased emphasis are identified.

Potential of Probiotics in Hypercholesterolemia: A Review of In Vitro and In Vivo Findings.

PubMed

Sharma, Smriti; Puri, Seema; Kurpad, Anura V

2017-06-23

Context • Coronary heart disease (CHD) is a major public health problem in developing and developed countries. Elevated cholesterol levels, especially low-density lipoprotein (LDL) cholesterol, and the emergence of CHD, have been positively correlated in many clinical and epidemiological studies. The health benefits of probiotics have received a great deal of attention, including their blood cholesterol-lowering effects on humans. Objective • The research team intended to determine the current state of research examining the effects of various probiotic strains on lipid profiles, including measures in serum of total cholesterol, LDL cholesterol, triglycerides, and high-density lipoprotein (HDL) cholesterol. Design • The review examined studies, in both animal and human models and focused on the potential of various probiotic strains to be dietary adjuncts in lowering levels of serum cholesterol with the aim of reducing the risk of cardiovascular disease (CVD) and CHD. Articles were reviewed systematically from Web search bases including PubMed and Cochrane Clinical Trial Registry. Articles meeting the inclusion search criteria were selected for further review and analysis. Only randomized controlled trials evaluating the effects of probiotics on lipid profiles in animals or humans were considered for inclusion in the review. Setting • The selection of articles and further inclusion in the review was performed in Institute of Home Economics, University of Delhi (New Delhi, India). Results • Some of the studies, in both animal and human models, have revealed that several strains were able to improve at least 1 lipid fraction. Although the results from animal studies have been fairly consistent, the findings from studies on humans have varied. Some strains when evaluated in human studies have shown insignificant effects on lipid fractions. Conclusions • Although several mechanisms for cholesterol removal by probiotics have been proposed, they need further investigation to be validated.

Assessing randomness and complexity in human motion trajectories through analysis of symbolic sequences

PubMed Central

Peng, Zhen; Genewein, Tim; Braun, Daniel A.

2014-01-01

Complexity is a hallmark of intelligent behavior consisting both of regular patterns and random variation. To quantitatively assess the complexity and randomness of human motion, we designed a motor task in which we translated subjects' motion trajectories into strings of symbol sequences. In the first part of the experiment participants were asked to perform self-paced movements to create repetitive patterns, copy pre-specified letter sequences, and generate random movements. To investigate whether the degree of randomness can be manipulated, in the second part of the experiment participants were asked to perform unpredictable movements in the context of a pursuit game, where they received feedback from an online Bayesian predictor guessing their next move. We analyzed symbol sequences representing subjects' motion trajectories with five common complexity measures: predictability, compressibility, approximate entropy, Lempel-Ziv complexity, as well as effective measure complexity. We found that subjects' self-created patterns were the most complex, followed by drawing movements of letters and self-paced random motion. We also found that participants could change the randomness of their behavior depending on context and feedback. Our results suggest that humans can adjust both complexity and regularity in different movement types and contexts and that this can be assessed with information-theoretic measures of the symbolic sequences generated from movement trajectories. PMID:24744716

A management-oriented classification of pinyon-juniper woodlands of the Great Basin

Treesearch

Neil E. West; Robin J. Tausch; Paul T. Tueller

1998-01-01

A hierarchical framework for the classification of Great Basin pinyon-juniper woodlands was based on a systematic sample of 426 stands from a random selection of 66 of the 110 mountain ranges in the region. That is, mountain ranges were randomly selected, but stands were systematically located on mountain ranges. The National Hierarchical Framework of Ecological Units...

School Happiness and School Success: An Investigation across Multiple Grade Levels.

ERIC Educational Resources Information Center

Parish, Joycelyn Gay; Parish, Thomas S.; Batt, Steve

A total of 572 randomly selected sixth-grade students and 908 randomly selected ninth-grade students from a large metropolitan school district in the Midwest were asked to complete a series of survey questions designed to measure the extent to which they were happy while at school, as well as questions concerning the extent to which they treated…

40 CFR 761.306 - Sampling 1 meter square surfaces by random selection of halves.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Sampling 1 meter square surfaces by...(b)(3) § 761.306 Sampling 1 meter square surfaces by random selection of halves. (a) Divide each 1 meter square portion where it is necessary to collect a surface wipe test sample into two equal (or as...

40 CFR 761.308 - Sample selection by random number generation on any two-dimensional square grid.

Code of Federal Regulations, 2013 CFR

2013-07-01

... generation on any two-dimensional square grid. 761.308 Section 761.308 Protection of Environment... § 761.79(b)(3) § 761.308 Sample selection by random number generation on any two-dimensional square grid. (a) Divide the surface area of the non-porous surface into rectangular or square areas having a...

40 CFR 761.306 - Sampling 1 meter square surfaces by random selection of halves.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Sampling 1 meter square surfaces by...(b)(3) § 761.306 Sampling 1 meter square surfaces by random selection of halves. (a) Divide each 1 meter square portion where it is necessary to collect a surface wipe test sample into two equal (or as...

40 CFR 761.308 - Sample selection by random number generation on any two-dimensional square grid.

Code of Federal Regulations, 2011 CFR

2011-07-01

... generation on any two-dimensional square grid. 761.308 Section 761.308 Protection of Environment... § 761.79(b)(3) § 761.308 Sample selection by random number generation on any two-dimensional square grid. (a) Divide the surface area of the non-porous surface into rectangular or square areas having a...

40 CFR 761.306 - Sampling 1 meter square surfaces by random selection of halves.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Sampling 1 meter square surfaces by...(b)(3) § 761.306 Sampling 1 meter square surfaces by random selection of halves. (a) Divide each 1 meter square portion where it is necessary to collect a surface wipe test sample into two equal (or as...

40 CFR 761.308 - Sample selection by random number generation on any two-dimensional square grid.

Code of Federal Regulations, 2010 CFR

2010-07-01

... generation on any two-dimensional square grid. 761.308 Section 761.308 Protection of Environment... § 761.79(b)(3) § 761.308 Sample selection by random number generation on any two-dimensional square grid. (a) Divide the surface area of the non-porous surface into rectangular or square areas having a...

40 CFR 761.306 - Sampling 1 meter square surfaces by random selection of halves.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Sampling 1 meter square surfaces by...(b)(3) § 761.306 Sampling 1 meter square surfaces by random selection of halves. (a) Divide each 1 meter square portion where it is necessary to collect a surface wipe test sample into two equal (or as...

40 CFR 761.308 - Sample selection by random number generation on any two-dimensional square grid.

Code of Federal Regulations, 2014 CFR

2014-07-01

... generation on any two-dimensional square grid. 761.308 Section 761.308 Protection of Environment... § 761.79(b)(3) § 761.308 Sample selection by random number generation on any two-dimensional square grid. (a) Divide the surface area of the non-porous surface into rectangular or square areas having a...

40 CFR 761.306 - Sampling 1 meter square surfaces by random selection of halves.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Sampling 1 meter square surfaces by...(b)(3) § 761.306 Sampling 1 meter square surfaces by random selection of halves. (a) Divide each 1 meter square portion where it is necessary to collect a surface wipe test sample into two equal (or as...

40 CFR 761.308 - Sample selection by random number generation on any two-dimensional square grid.

Code of Federal Regulations, 2012 CFR

2012-07-01

... generation on any two-dimensional square grid. 761.308 Section 761.308 Protection of Environment... § 761.79(b)(3) § 761.308 Sample selection by random number generation on any two-dimensional square grid. (a) Divide the surface area of the non-porous surface into rectangular or square areas having a...

Attitude and Motivation as Predictors of Academic Achievement of Students in Clothing and Textiles

ERIC Educational Resources Information Center

Uwameiye, B. E.; Osho, L. E.

2011-01-01

This study investigated attitude and motivation as predictors of academic achievement of students in clothing and textiles. Three colleges of education in Edo and Delta States were randomly selected for use in this study. From each school, 40 students were selected from Year III using simple random technique yielding a total of 240 students. The…

A morphologic analysis of 'naked' islets of Langerhans in lobular atrophy of the pancreas.

PubMed

Suda, K; Tsukahara, M; Miyake, T; Hirai, S

1994-08-01

The 'naked' islets of Langerhans (NIL) in randomly selected autopsy cases and in cases of chronic alcoholic pancreatitis, cystic fibrosis, and pancreatic carcinoma were studied histopathologically. The NIL were found in 55 of 164 randomly selected cases, with age-related frequency, in 21 of 30 cases of chronic alcoholic pancreatitis, in 2 of 2 cases of cystic fibrosis, and in 25 of 32 cases of pancreatic carcinoma. The NIL were frequently accompanied by ductal alterations: epithelial metaplasia and hyperplasia in randomly selected cases, protein plugs in chronic alcoholic pancreatitis, mucus plugs in cystic fibrosis, and obliterated ducts in pancreatic carcinoma. The NIL in randomly selected cases may have been formed by ductal alterations that caused stenosis of the lumen, those in chronic alcoholic pancreatitis and cystic fibrosis were the result of protein or mucus plugging, and those in pancreatic carcinoma were a result of neoplastic involvement of the distal pancreatic duct. Therefore, the common factor in the development of NIL is thought to be obstruction of the pancreatic duct system, and in cases of NIL that have a multilobular distribution and interinsular fibrosis, a diagnosis of chronic pancreatitis can usually be made.

Does natural selection organize ecosystems for the maintenance of high productivity and diversity?

PubMed Central

Leigh, Egbert Giles; Vermeij, Geerat Jacobus

2002-01-01

Three types of evidence suggest that natural ecosystems are organized for high productivity and diversity: (i) changes not previously experienced by a natural ecosystem, such as novel human disturbances, tend to diminish its productivity and/or diversity, just as 'random' changes in a machine designed for a function usually impair its execution of that function; (ii) humans strive to recreate properties of natural ecosystems to enhance productivity of artificial ones, as farmers try to recreate properties of natural soils in their fields; and (iii) productivity and diversity have increased during the Earth's history as a whole, and after every major biotic crisis. Natural selection results in ecosystems organized to maintain high productivity of organic matter and diversity of species, just as competition among individuals in Adam Smith's ideal economy favours high production of wealth and diversity of occupations. In nature, poorly exploited energy attracts more efficient users. This circumstance favours the opening of new ways of life and more efficient recycling of resources, and eliminates most productivity-reducing 'ecological monopolies'. Ecological dominants tend to be replaced by successors with higher metabolism, which respond to more stimuli and engage in more varied interactions. Finally, increasingly efficient predators and herbivores favour faster turnover of resources. PMID:12079531

Evaluation of maxillary alveolar reconstruction using a resorbable collagen sponge with recombinant human bone morphogenetic protein-2 in cleft lip and palate patients.

PubMed

Alonso, Nivaldo; Tanikawa, Daniela Yukie Sakai; Freitas, Renato da Silva; Canan, Lady; Ozawa, Terumi Okada; Rocha, Diógenes Laércio

2010-10-01

A resorbable collagen matrix with recombinant human bone morphogenetic protein (rhBMP-2) was compared with traditional iliac crest bone graft for the closure of alveolar defects during secondary dental eruption. Sixteen patients with unilateral cleft lip and palate, aged 8 to 12 years, were selected and randomly assigned to group 1 (rhBMP-2) or group 2 (iliac crest bone graft). Computed tomography was performed to assess both groups preoperatively and at months 6 and 12 postoperatively. Bone height and defect volume were calculated through Osirix Dicom Viewer (Pixmeo, Apple Inc.). Overall morbidity was recorded. Preoperative and follow-up examinations revealed progressive alveolar bone union in all patients. For group 1, final completion of the defect with a 65.0% mean bone height was detected 12 months postoperatively. For group 2, final completion of the defect with an 83.8% mean bone height was detected 6 months postoperatively. Dental eruption routinely occurred in both groups. Clinical complications included significant swelling in three group 1 patients (37.5%) and significant donor-site pain in seven group 2 patients (87.5%). For this select group of patients with immature skeleton, rhBMP-2 therapy resulted in satisfactory bone healing and reduced morbidity compared with traditional iliac crest bone grafting.

An efficient system for selectively altering genetic information within mRNAs

PubMed Central

Montiel-González, Maria Fernanda; Vallecillo-Viejo, Isabel C.; Rosenthal, Joshua J. C.

2016-01-01

Site-directed RNA editing (SDRE) is a strategy to precisely alter genetic information within mRNAs. By linking the catalytic domain of the RNA editing enzyme ADAR to an antisense guide RNA, specific adenosines can be converted to inosines, biological mimics for guanosine. Previously, we showed that a genetically encoded iteration of SDRE could target adenosines expressed in human cells, but not efficiently. Here we developed a reporter assay to quantify editing, and used it to improve our strategy. By enhancing the linkage between ADAR's catalytic domain and the guide RNA, and by introducing a mutation in the catalytic domain, the efficiency of converting a UAG premature termination codon (PTC) to tryptophan (UGG) was improved from ∼11 % to ∼70 %. Other PTCs were edited, but less efficiently. Numerous off-target edits were identified in the targeted mRNA, but not in randomly selected endogenous messages. Off-target edits could be eliminated by reducing the amount of guide RNA with a reduction in on-target editing. The catalytic rate of SDRE was compared with those for human ADARs on various substrates and found to be within an order of magnitude of most. These data underscore the promise of site-directed RNA editing as a therapeutic or experimental tool. PMID:27557710

A fast and automatic fusion algorithm for unregistered multi-exposure image sequence

NASA Astrophysics Data System (ADS)

Liu, Yan; Yu, Feihong

2014-09-01

Human visual system (HVS) can visualize all the brightness levels of the scene through visual adaptation. However, the dynamic range of most commercial digital cameras and display devices are smaller than the dynamic range of human eye. This implies low dynamic range (LDR) images captured by normal digital camera may lose image details. We propose an efficient approach to high dynamic (HDR) image fusion that copes with image displacement and image blur degradation in a computationally efficient manner, which is suitable for implementation on mobile devices. The various image registration algorithms proposed in the previous literatures are unable to meet the efficiency and performance requirements in the application of mobile devices. In this paper, we selected Oriented Brief (ORB) detector to extract local image structures. The descriptor selected in multi-exposure image fusion algorithm has to be fast and robust to illumination variations and geometric deformations. ORB descriptor is the best candidate in our algorithm. Further, we perform an improved RANdom Sample Consensus (RANSAC) algorithm to reject incorrect matches. For the fusion of images, a new approach based on Stationary Wavelet Transform (SWT) is used. The experimental results demonstrate that the proposed algorithm generates high quality images at low computational cost. Comparisons with a number of other feature matching methods show that our method gets better performance.

Improved Compressive Sensing of Natural Scenes Using Localized Random Sampling

PubMed Central

Barranca, Victor J.; Kovačič, Gregor; Zhou, Douglas; Cai, David

2016-01-01

Compressive sensing (CS) theory demonstrates that by using uniformly-random sampling, rather than uniformly-spaced sampling, higher quality image reconstructions are often achievable. Considering that the structure of sampling protocols has such a profound impact on the quality of image reconstructions, we formulate a new sampling scheme motivated by physiological receptive field structure, localized random sampling, which yields significantly improved CS image reconstructions. For each set of localized image measurements, our sampling method first randomly selects an image pixel and then measures its nearby pixels with probability depending on their distance from the initially selected pixel. We compare the uniformly-random and localized random sampling methods over a large space of sampling parameters, and show that, for the optimal parameter choices, higher quality image reconstructions can be consistently obtained by using localized random sampling. In addition, we argue that the localized random CS optimal parameter choice is stable with respect to diverse natural images, and scales with the number of samples used for reconstruction. We expect that the localized random sampling protocol helps to explain the evolutionarily advantageous nature of receptive field structure in visual systems and suggests several future research areas in CS theory and its application to brain imaging. PMID:27555464

Selection of stable scFv antibodies by phage display.

PubMed

Brockmann, Eeva-Christine

2012-01-01

ScFv fragments are popular recombinant antibody formats but often suffer from limited stability. Phage display is a powerful tool in antibody engineering and applicable also for stability selection. ScFv variants with improved stability can be selected from large randomly mutated phage displayed libraries with a specific antigen after the unstable variants have been inactivated by heat or GdmCl. Irreversible scFv denaturation, which is a prerequisite for efficient selection, is achieved by combining denaturation with reduction of the intradomain disulfide bonds. Repeated selection cycles of increasing stringency result in enrichment of stabilized scFv fragments. Procedures for constructing a randomly mutated scFv library by error-prone PCR and phage display selection for enrichment of stable scFv antibodies from the library are described here.

STUDY OF THE PREVALENCE OF Capillaria hepatica IN HUMANS AND RODENTS IN AN URBAN AREA OF THE CITY OF PORTO VELHO, RONDÔNIA, BRAZIL

PubMed Central

da Rocha, Elierson José Gomes; Basano, Sérgio de Almeida; de Souza, Márcia Maria; Honda, Eduardo Resende; de Castro, Márcio Botelho; Colodel, Edson Moleta; Silva, Jéssica Carolinne Damasceno e; Barros, Lauro Prado; Rodrigues, Elisa Sousa; Camargo, Luís Marcelo Aranha

2015-01-01

Introduction: Hepatic capillariosis, caused by Capillaria hepatica (Calodium hepaticum) (Bancroft, 1893), Travassos, 1915 (Nematoda, Trichinelloidea, Capillariidae), is a common zoonosis in rodents but is rare in humans. Seventy-two cases in humans have been reported worldwide since the first case was described by MACARTHUR in 192417,27. This study aimed to determine the prevalence of Capillaria hepatica in humans and rodents in an urban area of Porto Velho, the capital of Rondônia, in Brazil. Methods: After conducting a census of the area, 490 residents were randomly selected, and, after signing a term of consent, provided blood samples that were screened for anti-Capillaria hepatica antibodies. Simultaneously, rats were captured to assess the prevalence of this parasite in rodents by histopathological examination in liver sections. Results: A prevalence of 1.8% was found among residents who had specific antibodies at a dilution of 1:150, indicating exposure to parasite eggs; 0.8% of the subjects also had positive titers at a dilution of 1:400, indicating true infection. The prevalence in rats was 2%. Conclusions: The prevalence of infection with this parasite among humans and rats was low. While the prevalence encountered among humans was within the limits reported in the literature, the prevalence among rodents was much lower. PMID:25651325

Preferential cleavage sites for Sau3A restriction endonuclease in human ribosomal DNA.

PubMed

Kupriyanova, N S; Kirilenko, P M; Netchvolodov, K K; Ryskov, A P

2000-07-21

Previous studies of cloned ribosomal DNA (rDNA) variants isolated from the cosmid library of human chromosome 13 have revealed some disproportion in representativity of different rDNA regions (N. S. Kupriyanova, K. K. Netchvolodov, P. M. Kirilenko, B. I. Kapanadze, N. K. Yankovsky, and A. P. Ryskov, Mol. Biol. 30, 51-60, 1996). Here we show nonrandom cleavage of human rDNA with Sau3A or its isoshizomer MboI under mild hydrolysis conditions. The hypersensitive cleavage sites were found to be located in the ribosomal intergenic spacer (rIGS), especially in the regions of about 5-5.5 and 11 kb upstream of the rRNA transcription start point. This finding is based on sequencing mapping of the rDNA insert ends in randomly selected cosmid clones of human chromosome 13 and on the data of digestion kinetics of cloned and noncloned human genomic rDNA with Sau3A and MboI. The results show that a methylation status and superhelicity state of the rIGS have no effect on cleavage site sensitivity. It is interesting that all primary cleavage sites are adjacent to or entering into Alu or Psi cdc 27 retroposons of the rIGS suggesting a possible role of neighboring sequences in nuclease accessibility. The results explain nonequal representation of rDNA sequences in the human genomic DNA library used for this study. Copyright 2000 Academic Press.

From humans to hydra: patterns of cancer across the tree of life.

PubMed

Albuquerque, Thales A F; Drummond do Val, Luisa; Doherty, Aoife; de Magalhães, João Pedro

2018-04-16

Cancer is a disease of multicellularity; it originates when cells become dysregulated due to mutations and grow out of control, invading other tissues and provoking discomfort, disability, and eventually death. Human life expectancy has greatly increased in the last two centuries, and consequently so has the incidence of cancer. However, how cancer patterns in humans compare to those of other species remains largely unknown. In this review, we search for clues about cancer and its evolutionary underpinnings across the tree of life. We discuss data from a wide range of species, drawing comparisons with humans when adequate, and interpret our findings from an evolutionary perspective. We conclude that certain cancers are uniquely common in humans, such as lung, prostate, and testicular cancer; while others are common across many species. Lymphomas appear in almost every animal analysed, including in young animals, which may be related to pathogens imposing selection on the immune system. Cancers unique to humans may be due to our modern environment or may be evolutionary accidents: random events in the evolution of our species. Finally, we find that cancer-resistant animals such as whales and mole-rats have evolved cellular mechanisms that help them avoid neoplasia, and we argue that there are multiple natural routes to cancer resistance. © 2018 The Authors. Biological Reviews published by John Wiley & Sons Ltd on behalf of Cambridge Philosophical Society.

Alternative Modal Basis Selection Procedures for Nonlinear Random Response Simulation

NASA Technical Reports Server (NTRS)

Przekop, Adam; Guo, Xinyun; Rizzi, Stephen A.

2010-01-01

Three procedures to guide selection of an efficient modal basis in a nonlinear random response analysis are examined. One method is based only on proper orthogonal decomposition, while the other two additionally involve smooth orthogonal decomposition. Acoustic random response problems are employed to assess the performance of the three modal basis selection approaches. A thermally post-buckled beam exhibiting snap-through behavior, a shallowly curved arch in the auto-parametric response regime and a plate structure are used as numerical test articles. The results of the three reduced-order analyses are compared with the results of the computationally taxing simulation in the physical degrees of freedom. For the cases considered, all three methods are shown to produce modal bases resulting in accurate and computationally efficient reduced-order nonlinear simulations.

An investigation into the probabilistic combination of quasi-static and random accelerations

NASA Technical Reports Server (NTRS)

Schock, R. W.; Tuell, L. P.

1984-01-01

The development of design load factors for aerospace and aircraft components and experiment support structures, which are subject to a simultaneous vehicle dynamic vibration (quasi-static) and acoustically generated random vibration, require the selection of a combination methodology. Typically, the procedure is to define the quasi-static and the random generated response separately, and arithmetically add or root sum square to get combined accelerations. Since the combination of a probabilistic and a deterministic function yield a probabilistic function, a viable alternate approach would be to determine the characteristics of the combined acceleration probability density function and select an appropriate percentile level for the combined acceleration. The following paper develops this mechanism and provides graphical data to select combined accelerations for most popular percentile levels.

Interventions to reduce accidents in childhood: a systematic review.

PubMed

Barcelos, Raquel S; Del-Ponte, Bianca; Santos, Iná S

2017-12-30

To review the literature on interventions planned to prevent the incidence of injuries in childhood. The PubMed, Web of Science, and Bireme databases were searched by two independent reviewers, employing the single terms accidents, accident, injuries, injury, clinical trial, intervention, educational intervention, and multiple interventions, and their combinations, present in the article title or abstract, with no limits except period of publication (2006-2016) and studies in human subjects. Initially, 11,097 titles were located. Fifteen articles were selected for the review. Eleven were randomized trials (four carried out at the children's households, five in pediatric healthcare services, and two at schools), and four were non-randomized trials carried out at the children's households. Four of the randomized trials were analyzed by intention-to-treat and a protective effect of the intervention was observed: decrease in the number of risk factors, decrease in the number of medical consultations due to injuries, decrease in the prevalence of risk behaviors, and increase of the parents' knowledge regarding injury prevention in childhood. Traumatic injuries in childhood are amenable to primary prevention through strategies that consider the child's age and level of development, as well as structural aspects of the environment. Copyright © 2017 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Prediction of truly random future events using analysis of prestimulus electroencephalographic data

NASA Astrophysics Data System (ADS)

Baumgart, Stephen L.; Franklin, Michael S.; Jimbo, Hiroumi K.; Su, Sharon J.; Schooler, Jonathan

2017-05-01

Our hypothesis is that pre-stimulus physiological data can be used to predict truly random events tied to perceptual stimuli (e.g., lights and sounds). Our experiment presents light and sound stimuli to a passive human subject while recording electrocortical potentials using a 32-channel Electroencephalography (EEG) system. For every trial a quantum random number generator (qRNG) chooses from three possible selections with equal probability: a light stimulus, a sound stimulus, and no stimulus. Time epochs are defined preceding and post-ceding each stimulus for which mean average potentials were computed across all trials for the three possible stimulus types. Data from three regions of the brain are examined. In all three regions mean potential for light stimuli was generally enhanced relative to baseline during the period starting approximately 2 seconds before the stimulus. For sound stimuli, mean potential decreased relative to baseline during the period starting approximately 2 seconds before the stimulus. These changes from baseline may indicated the presence of evoked potentials arising from the stimulus. A P200 peak was observed in data recorded from frontal electrodes. The P200 is a well-known potential arising from the brain's processing of visual stimuli and its presence represents a replication of a known neurological phenomenon.

Selective decontamination of the digestive tract in gastrointestinal surgery: useful in infection prevention? A systematic review.

PubMed

Abis, Gabor S A; Stockmann, Hein B A C; van Egmond, Marjolein; Bonjer, Hendrik J; Vandenbroucke-Grauls, Christina M J E; Oosterling, Steven J

2013-12-01

Gastrointestinal surgery is associated with a high incidence of infectious complications. Selective decontamination of the digestive tract is an antimicrobial prophylaxis regimen that aims to eradicate gastrointestinal carriage of potentially pathogenic microorganisms and represents an adjunct to regular prophylaxis in surgery. Relevant studies were identified using bibliographic searches of MEDLINE, EMBASE, and the Cochrane database (period from 1970 to November 1, 2012). Only studies investigating selective decontamination of the digestive tract in gastrointestinal surgery were included. Two randomized clinical trials and one retrospective case-control trial showed significant benefit in terms of infectious complications and anastomotic leakage in colorectal surgery. Two randomized controlled trials in esophageal surgery and two randomized clinical trials in gastric surgery reported lower levels of infectious complications. Selective decontamination of the digestive tract reduces infections following esophageal, gastric, and colorectal surgeries and also appears to have beneficial effects on anastomotic leakage in colorectal surgery. We believe these results provide the basis for a large multicenter prospective study to investigate the role of selective decontamination of the digestive tract in colorectal surgery.

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

Bromberger, Seth A.; Klymko, Christine F.; Henderson, Keith A.

Betweenness centrality is a graph statistic used to nd vertices that are participants in a large number of shortest paths in a graph. This centrality measure is commonly used in path and network interdiction problems and its complete form requires the calculation of all-pairs shortest paths for each vertex. This leads to a time complexity of O(jV jjEj), which is impractical for large graphs. Estimation of betweenness centrality has focused on performing shortest-path calculations on a subset of randomly- selected vertices. This reduces the complexity of the centrality estimation to O(jSjjEj); jSj < jV j, which can be scaled appropriatelymore » based on the computing resources available. An estimation strategy that uses random selection of vertices for seed selection is fast and simple to implement, but may not provide optimal estimation of betweenness centrality when the number of samples is constrained. Our experimentation has identi ed a number of alternate seed-selection strategies that provide lower error than random selection in common scale-free graphs. These strategies are discussed and experimental results are presented.« less

Statistical auditing and randomness test of lotto k/N-type games

NASA Astrophysics Data System (ADS)

Coronel-Brizio, H. F.; Hernández-Montoya, A. R.; Rapallo, F.; Scalas, E.

2008-11-01

One of the most popular lottery games worldwide is the so-called “lotto k/N”. It considers N numbers 1,2,…,N from which k are drawn randomly, without replacement. A player selects k or more numbers and the first prize is shared amongst those players whose selected numbers match all of the k randomly drawn. Exact rules may vary in different countries. In this paper, mean values and covariances for the random variables representing the numbers drawn from this kind of game are presented, with the aim of using them to audit statistically the consistency of a given sample of historical results with theoretical values coming from a hypergeometric statistical model. The method can be adapted to test pseudorandom number generators.

Prevalence and magnitude of acidosis sequelae to rice-based feeding regimen followed in Tamil Nadu, India.

PubMed

Murugeswari, Rathinam; Valli, Chinnamani; Karunakaran, Raman; Leela, Venkatasubramanian; Pandian, Amaresan Serma Saravana

2018-04-01

In Tamil Nadu, a southern state of India, rice is readily available at a low cost, hence, is cooked (cooking akin to human consumption) and fed irrationally to cross-bred dairy cattle with poor productivity. Hence, a study was carried out with the objective to examine the prevalence of acidosis sequelae to rice-based feeding regimen and assess its magnitude. A survey was conducted in all the 32 districts of Tamil Nadu, by randomly selecting two blocks per districts and from each block five villages were randomly selected. From each of the selected village, 10 dairy farmers belonging to the unorganized sector, owning one or two cross-bred dairy cows in early and mid-lactation were randomly selected so that a sample size of 100 farmers per district was maintained. The feeding regimen, milk yield was recorded, and occurrence of acidosis and incidence of laminitis were ascertained by the veterinarian with the confirmative test to determine the impact of feeding cooked rice to cows. It is observed that 71.5% of farmers in unorganized sector feed cooked rice to their cattle. The incidence of acidosis progressively increased significantly (p<0.05) from 29.00% in cows fed with 0.5 kg of cooked rice to 69.23% in cows fed with more than 2.5 kg of cooked rice. However, the incidence of acidosis remained significantly (p<0.05) as low as 9.9% in cows fed feeding regimen without cooked rice which is suggestive of a correlation between excessive feeding cooked rice and onset of acidosis. Further, the noticeable difference in the incidence of acidosis observed between feeding cooked rice and those fed without rice and limited intake of oil cake indicates that there is a mismatch between energy and protein supply to these cattle. Among cooked rice-based diet, the incidence of laminitis increased progressively (p<0.05) from 9.2% to 37.9% with the increase in the quantum of cooked rice in the diet. The study points out the importance of protein supplementation in rice-based feeding regimen to set right the mismatched supply between nitrogen and fermentable organic matter in the rumen. This research has practical implications for animal health, welfare, nutrition, and management.

Prevalence and magnitude of acidosis sequelae to rice-based feeding regimen followed in Tamil Nadu, India

PubMed Central

Murugeswari, Rathinam; Valli, Chinnamani; Karunakaran, Raman; Leela, Venkatasubramanian; Pandian, Amaresan Serma Saravana

2018-01-01

Background and Aim In Tamil Nadu, a southern state of India, rice is readily available at a low cost, hence, is cooked (cooking akin to human consumption) and fed irrationally to cross-bred dairy cattle with poor productivity. Hence, a study was carried out with the objective to examine the prevalence of acidosis sequelae to rice-based feeding regimen and assess its magnitude. Materials and Methods A survey was conducted in all the 32 districts of Tamil Nadu, by randomly selecting two blocks per districts and from each block five villages were randomly selected. From each of the selected village, 10 dairy farmers belonging to the unorganized sector, owning one or two cross-bred dairy cows in early and mid-lactation were randomly selected so that a sample size of 100 farmers per district was maintained. The feeding regimen, milk yield was recorded, and occurrence of acidosis and incidence of laminitis were ascertained by the veterinarian with the confirmative test to determine the impact of feeding cooked rice to cows. Results It is observed that 71.5% of farmers in unorganized sector feed cooked rice to their cattle. The incidence of acidosis progressively increased significantly (p<0.05) from 29.00% in cows fed with 0.5 kg of cooked rice to 69.23% in cows fed with more than 2.5 kg of cooked rice. However, the incidence of acidosis remained significantly (p<0.05) as low as 9.9% in cows fed feeding regimen without cooked rice which is suggestive of a correlation between excessive feeding cooked rice and onset of acidosis. Further, the noticeable difference in the incidence of acidosis observed between feeding cooked rice and those fed without rice and limited intake of oil cake indicates that there is a mismatch between energy and protein supply to these cattle. Among cooked rice-based diet, the incidence of laminitis increased progressively (p<0.05) from 9.2% to 37.9% with the increase in the quantum of cooked rice in the diet. Conclusion The study points out the importance of protein supplementation in rice-based feeding regimen to set right the mismatched supply between nitrogen and fermentable organic matter in the rumen. This research has practical implications for animal health, welfare, nutrition, and management PMID:29805211

Human norovirus inactivation in oysters by high hydrostatic pressure processing: A randomized double-blinded study

USDA-ARS?s Scientific Manuscript database

This randomized, double-blinded, clinical trial assessed the effect of high hydrostatic pressure processing (HPP) on genogroup I.1 human norovirus (HuNoV) inactivation in virus-seeded oysters when ingested by subjects. The safety and efficacy of HPP treatments were assessed in three study phases wi...

Variation of mutational burden in healthy human tissues suggests non-random strand segregation and allows measuring somatic mutation rates.

PubMed

Werner, Benjamin; Sottoriva, Andrea

2018-06-01

The immortal strand hypothesis poses that stem cells could produce differentiated progeny while conserving the original template strand, thus avoiding accumulating somatic mutations. However, quantitating the extent of non-random DNA strand segregation in human stem cells remains difficult in vivo. Here we show that the change of the mean and variance of the mutational burden with age in healthy human tissues allows estimating strand segregation probabilities and somatic mutation rates. We analysed deep sequencing data from healthy human colon, small intestine, liver, skin and brain. We found highly effective non-random DNA strand segregation in all adult tissues (mean strand segregation probability: 0.98, standard error bounds (0.97,0.99)). In contrast, non-random strand segregation efficiency is reduced to 0.87 (0.78,0.88) in neural tissue during early development, suggesting stem cell pool expansions due to symmetric self-renewal. Healthy somatic mutation rates differed across tissue types, ranging from 3.5 × 10-9/bp/division in small intestine to 1.6 × 10-7/bp/division in skin.

Two independent apolipoprotein A5 haplotypes influence human plasma triglyceride levels.

PubMed

Pennacchio, Len A; Olivier, Michael; Hubacek, Jaroslav A; Krauss, Ronald M; Rubin, Edward M; Cohen, Jonathan C

2002-11-15

The recently identified apolipoprotein A5 gene (APOA5) has been shown to play an important role in determining plasma triglyceride concentrations in humans and mice. We previously identified an APOA5 haplotype (designated APOA5*2) that is present in approximately 16% of Caucasians and is associated with increased plasma triglyceride concentrations. In this report we describe another APOA5 haplotype (APOA5*3) containing the rare allele of the single nucleotide polymorphism c.56C>G that changes serine to tryptophan at codon 19 and is independently associated with high plasma triglyceride levels in three different populations. In a sample of 264 Caucasian men and women with plasma triglyceride concentrations above the 90th percentile or below the 10th percentile, the APOA5*3 haplotype was more than three-fold more common in the group with high plasma triglyceride levels. In a second independently ascertained sample of Caucasian men and women (n=419) who were studied while consuming their self-selected diets as well as after high-carbohydrate diets and high-fat diets, the APOA5*3 haplotype was associated with increased plasma triglyceride levels on all three dietary regimens. In a third population comprising 2660 randomly selected individuals, the APOA5*3 haplotype was found in 12% of Caucasians, 14% of African-Americans and 28% of Hispanics and was associated with increased plasma triglyceride levels in both men and women in each ethnic group. These findings establish that the APOA5 locus contributes significantly to inter-individual variation in plasma triglyceride levels in humans. Together, the APOA5*2 and APOA5*3 haplotypes are found in 25-50% of African-Americans, Hispanics and Caucasians and support the contribution of common human variation to quantitative phenotypes in the general population.

Potential of Using Mobile Phone Data to Assist in Mission Analysis and Area of Operations Planning

DTIC Science & Technology

2015-08-01

tremendously beneficial especially since a sizeable portion of the population are nomads , changing location based on season. A proper AO...provided: a. User_id: Selected User’s random ID b. Timestamp: 24 h format YYYY-MM-DD-HH:M0:00 (the second digits of the minutes and all the seconds...yearly were selected. This data provided: a. User_id: Selected User’s random ID b. Timestamp: 24 h format YYYY-MM-DD-HH:M0:00 (the second digits

Discriminative Projection Selection Based Face Image Hashing

NASA Astrophysics Data System (ADS)

Karabat, Cagatay; Erdogan, Hakan

Face image hashing is an emerging method used in biometric verification systems. In this paper, we propose a novel face image hashing method based on a new technique called discriminative projection selection. We apply the Fisher criterion for selecting the rows of a random projection matrix in a user-dependent fashion. Moreover, another contribution of this paper is to employ a bimodal Gaussian mixture model at the quantization step. Our simulation results on three different databases demonstrate that the proposed method has superior performance in comparison to previously proposed random projection based methods.

Topology-selective jamming of fully-connected, code-division random-access networks

NASA Technical Reports Server (NTRS)

Polydoros, Andreas; Cheng, Unjeng

1990-01-01

The purpose is to introduce certain models of topology selective stochastic jamming and examine its impact on a class of fully-connected, spread-spectrum, slotted ALOHA-type random access networks. The theory covers dedicated as well as half-duplex units. The dominant role of the spatial duty factor is established, and connections with the dual concept of time selective jamming are discussed. The optimal choices of coding rate and link access parameters (from the users' side) and the jamming spatial fraction are numerically established for DS and FH spreading.

Development of Solution Algorithm and Sensitivity Analysis for Random Fuzzy Portfolio Selection Model

NASA Astrophysics Data System (ADS)

Hasuike, Takashi; Katagiri, Hideki

2010-10-01

This paper focuses on the proposition of a portfolio selection problem considering an investor's subjectivity and the sensitivity analysis for the change of subjectivity. Since this proposed problem is formulated as a random fuzzy programming problem due to both randomness and subjectivity presented by fuzzy numbers, it is not well-defined. Therefore, introducing Sharpe ratio which is one of important performance measures of portfolio models, the main problem is transformed into the standard fuzzy programming problem. Furthermore, using the sensitivity analysis for fuzziness, the analytical optimal portfolio with the sensitivity factor is obtained.

Perceptual learning through optimization of attentional weighting: human versus optimal Bayesian learner

NASA Technical Reports Server (NTRS)

Eckstein, Miguel P.; Abbey, Craig K.; Pham, Binh T.; Shimozaki, Steven S.

2004-01-01

Human performance in visual detection, discrimination, identification, and search tasks typically improves with practice. Psychophysical studies suggest that perceptual learning is mediated by an enhancement in the coding of the signal, and physiological studies suggest that it might be related to the plasticity in the weighting or selection of sensory units coding task relevant information (learning through attention optimization). We propose an experimental paradigm (optimal perceptual learning paradigm) to systematically study the dynamics of perceptual learning in humans by allowing comparisons to that of an optimal Bayesian algorithm and a number of suboptimal learning models. We measured improvement in human localization (eight-alternative forced-choice with feedback) performance of a target randomly sampled from four elongated Gaussian targets with different orientations and polarities and kept as a target for a block of four trials. The results suggest that the human perceptual learning can occur within a lapse of four trials (<1 min) but that human learning is slower and incomplete with respect to the optimal algorithm (23.3% reduction in human efficiency from the 1st-to-4th learning trials). The greatest improvement in human performance, occurring from the 1st-to-2nd learning trial, was also present in the optimal observer, and, thus reflects a property inherent to the visual task and not a property particular to the human perceptual learning mechanism. One notable source of human inefficiency is that, unlike the ideal observer, human learning relies more heavily on previous decisions than on the provided feedback, resulting in no human learning on trials following a previous incorrect localization decision. Finally, the proposed theory and paradigm provide a flexible framework for future studies to evaluate the optimality of human learning of other visual cues and/or sensory modalities.

Subgroup Analysis of Trials Is Rarely Easy (SATIRE): a study protocol for a systematic review to characterize the analysis, reporting, and claim of subgroup effects in randomized trials.

PubMed

Sun, Xin; Briel, Matthias; Busse, Jason W; Akl, Elie A; You, John J; Mejza, Filip; Bala, Malgorzata; Diaz-Granados, Natalia; Bassler, Dirk; Mertz, Dominik; Srinathan, Sadeesh K; Vandvik, Per Olav; Malaga, German; Alshurafa, Mohamed; Dahm, Philipp; Alonso-Coello, Pablo; Heels-Ansdell, Diane M; Bhatnagar, Neera; Johnston, Bradley C; Wang, Li; Walter, Stephen D; Altman, Douglas G; Guyatt, Gordon H

2009-11-09

Subgroup analyses in randomized trials examine whether effects of interventions differ between subgroups of study populations according to characteristics of patients or interventions. However, findings from subgroup analyses may be misleading, potentially resulting in suboptimal clinical and health decision making. Few studies have investigated the reporting and conduct of subgroup analyses and a number of important questions remain unanswered. The objectives of this study are: 1) to describe the reporting of subgroup analyses and claims of subgroup effects in randomized controlled trials, 2) to assess study characteristics associated with reporting of subgroup analyses and with claims of subgroup effects, and 3) to examine the analysis, and interpretation of subgroup effects for each study's primary outcome. We will conduct a systematic review of 464 randomized controlled human trials published in 2007 in the 118 Core Clinical Journals defined by the National Library of Medicine. We will randomly select journal articles, stratified in a 1:1 ratio by higher impact versus lower impact journals. According to 2007 ISI total citations, we consider the New England Journal of Medicine, JAMA, Lancet, Annals of Internal Medicine, and BMJ as higher impact journals. Teams of two reviewers will independently screen full texts of reports for eligibility, and abstract data, using standardized, pilot-tested extraction forms. We will conduct univariable and multivariable logistic regression analyses to examine the association of pre-specified study characteristics with reporting of subgroup analyses and with claims of subgroup effects for the primary and any other outcomes. A clear understanding of subgroup analyses, as currently conducted and reported in published randomized controlled trials, will reveal both strengths and weaknesses of this practice. Our findings will contribute to a set of recommendations to optimize the conduct and reporting of subgroup analyses, and claim and interpretation of subgroup effects in randomized trials.

Subgroup Analysis of Trials Is Rarely Easy (SATIRE): a study protocol for a systematic review to characterize the analysis, reporting, and claim of subgroup effects in randomized trials

PubMed Central

Sun, Xin; Briel, Matthias; Busse, Jason W; Akl, Elie A; You, John J; Mejza, Filip; Bala, Malgorzata; Diaz-Granados, Natalia; Bassler, Dirk; Mertz, Dominik; Srinathan, Sadeesh K; Vandvik, Per Olav; Malaga, German; Alshurafa, Mohamed; Dahm, Philipp; Alonso-Coello, Pablo; Heels-Ansdell, Diane M; Bhatnagar, Neera; Johnston, Bradley C; Wang, Li; Walter, Stephen D; Altman, Douglas G; Guyatt, Gordon H

2009-01-01

Background Subgroup analyses in randomized trials examine whether effects of interventions differ between subgroups of study populations according to characteristics of patients or interventions. However, findings from subgroup analyses may be misleading, potentially resulting in suboptimal clinical and health decision making. Few studies have investigated the reporting and conduct of subgroup analyses and a number of important questions remain unanswered. The objectives of this study are: 1) to describe the reporting of subgroup analyses and claims of subgroup effects in randomized controlled trials, 2) to assess study characteristics associated with reporting of subgroup analyses and with claims of subgroup effects, and 3) to examine the analysis, and interpretation of subgroup effects for each study's primary outcome. Methods We will conduct a systematic review of 464 randomized controlled human trials published in 2007 in the 118 Core Clinical Journals defined by the National Library of Medicine. We will randomly select journal articles, stratified in a 1:1 ratio by higher impact versus lower impact journals. According to 2007 ISI total citations, we consider the New England Journal of Medicine, JAMA, Lancet, Annals of Internal Medicine, and BMJ as higher impact journals. Teams of two reviewers will independently screen full texts of reports for eligibility, and abstract data, using standardized, pilot-tested extraction forms. We will conduct univariable and multivariable logistic regression analyses to examine the association of pre-specified study characteristics with reporting of subgroup analyses and with claims of subgroup effects for the primary and any other outcomes. Discussion A clear understanding of subgroup analyses, as currently conducted and reported in published randomized controlled trials, will reveal both strengths and weaknesses of this practice. Our findings will contribute to a set of recommendations to optimize the conduct and reporting of subgroup analyses, and claim and interpretation of subgroup effects in randomized trials. PMID:19900273

Limited Effects of a 2-Year School-Based Physical Activity Intervention on Body Composition and Cardiorespiratory Fitness in 7-Year-Old Children

ERIC Educational Resources Information Center

Magnusson, Kristjan Thor; Hrafnkelsson, Hannes; Sigurgeirsson, Ingvar; Johannsson, Erlingur; Sveinsson, Thorarinn

2012-01-01

The aim of this study was to assess the effects of a 2-year cluster-randomized physical activity and dietary intervention program among 7-year-old (at baseline) elementary school participants on body composition and objectively measured cardiorespiratory fitness. Three pairs of schools were selected and matched, then randomly selected as either an…

The Long-Term Effectiveness of a Selective, Personality-Targeted Prevention Program in Reducing Alcohol Use and Related Harms: A Cluster Randomized Controlled Trial

ERIC Educational Resources Information Center

Newton, Nicola C.; Conrod, Patricia J.; Slade, Tim; Carragher, Natacha; Champion, Katrina E.; Barrett, Emma L.; Kelly, Erin V.; Nair, Natasha K.; Stapinski, Lexine; Teesson, Maree

2016-01-01

Background: This study investigated the long-term effectiveness of Preventure, a selective personality-targeted prevention program, in reducing the uptake of alcohol, harmful use of alcohol, and alcohol-related harms over a 3-year period. Methods: A cluster randomized controlled trial was conducted to assess the effectiveness of Preventure.…

Modified Bat Algorithm for Feature Selection with the Wisconsin Diagnosis Breast Cancer (WDBC) Dataset

PubMed

Jeyasingh, Suganthi; Veluchamy, Malathi

2017-05-01

Early diagnosis of breast cancer is essential to save lives of patients. Usually, medical datasets include a large variety of data that can lead to confusion during diagnosis. The Knowledge Discovery on Database (KDD) process helps to improve efficiency. It requires elimination of inappropriate and repeated data from the dataset before final diagnosis. This can be done using any of the feature selection algorithms available in data mining. Feature selection is considered as a vital step to increase the classification accuracy. This paper proposes a Modified Bat Algorithm (MBA) for feature selection to eliminate irrelevant features from an original dataset. The Bat algorithm was modified using simple random sampling to select the random instances from the dataset. Ranking was with the global best features to recognize the predominant features available in the dataset. The selected features are used to train a Random Forest (RF) classification algorithm. The MBA feature selection algorithm enhanced the classification accuracy of RF in identifying the occurrence of breast cancer. The Wisconsin Diagnosis Breast Cancer Dataset (WDBC) was used for estimating the performance analysis of the proposed MBA feature selection algorithm. The proposed algorithm achieved better performance in terms of Kappa statistic, Mathew’s Correlation Coefficient, Precision, F-measure, Recall, Mean Absolute Error (MAE), Root Mean Square Error (RMSE), Relative Absolute Error (RAE) and Root Relative Squared Error (RRSE). Creative Commons Attribution License

Color- and motion-specific units in the tectum opticum of goldfish.

PubMed

Gruber, Morna; Behrend, Konstantin; Neumeyer, Christa

2016-01-05

Extracellular recordings were performed from 69 units at different depths between 50 and [Formula: see text]m below the surface of tectum opticum in goldfish. Using large field stimuli (86[Formula: see text] visual angle) of 21 colored HKS-papers we were able to record from 54 color-sensitive units. The colored papers were presented for 5[Formula: see text]s each. They were arranged in the sequence of the color circle in humans separated by gray of medium brightness. We found 22 units with best responses between orange, red and pink. About 12 of these red-sensitive units were of the opponent "red-ON/blue-green-OFF" type as found in retinal bipolar- and ganglion cells as well. Most of them were also activated or inhibited by black and/or white. Some units responded specifically to red either with activation or inhibition. 18 units were sensitive to blue and/or green, 10 of them to both colors and most of them to black as well. They were inhibited by red, and belonged to the opponent "blue-green-ON/red-OFF" type. Other units responded more selectively either to blue, to green or to purple. Two units were selectively sensitive to yellow. A total of 15 units were sensitive to motion, stimulated by an excentrically rotating black and white random dot pattern. Activity of these units was also large when a red-green random dot pattern of high L-cone contrast was used. Activity dropped to zero when the red-green pattern did not modulate the L-cones. Neither of these motion selective units responded to any color. The results directly show color-blindness of motion vision, and confirm the hypothesis of separate and parallel processing of "color" and "motion".

What to expect from an evolutionary hypothesis for a human disease: The case of type 2 diabetes.

PubMed

Watve, Milind; Diwekar-Joshi, Manawa

2016-10-01

Evolutionary medicine has a promise to bring in a conceptual revolution in medicine. However, as yet the field does not have the same theoretical rigour as that of many other fields in evolutionary studies. We discuss here with reference to type 2 diabetes mellitus (T2DM) what role an evolutionary hypothesis should play in the development of thinking in medicine. Starting with the thrifty gene hypothesis, evolutionary thinking in T2DM has undergone several transitions, modifications and refinements of the thrift family of hypotheses. In addition alternative hypotheses independent of thrift are also suggested. However, most hypotheses look at partial pictures; make selective use of supportive data ignoring inconvenient truths. Most hypotheses look at a superficial picture and avoid getting into the intricacies of underlying molecular, neuronal and physiological processes. Very few hypotheses have suggested clinical implications and none of them have been tested with randomized clinical trials. In the meanwhile the concepts in the pathophysiology of T2DM are undergoing radical changes and evolutionary hypotheses need to take them into account. We suggest an approach and a set of criteria to evaluate the relative merits of the alternative hypotheses. A number of hypotheses are likely to fail when critically evaluated against these criteria. It is possible that more than one selective process are at work in the evolution of propensity to T2DM, but the intercompatibility of the alternative selective forces and their relative contribution needs to be examined. The approach we describe could potentially lead to a sound evolutionary theory that is clinically useful and testable by randomized controlled clinical trials. Copyright © 2016 Elsevier GmbH. All rights reserved.

Prevalence and Characterization of Motile Salmonella in Commercial Layer Poultry Farms in Bangladesh

PubMed Central

Barua, Himel; Biswas, Paritosh K.; Olsen, Katharina E. P.; Christensen, Jens P.

2012-01-01

Salmonella is a globally widespread food-borne pathogen having major impact on public health. All motile serovars of Salmonella enterica of poultry origin are zoonotic, and contaminated meat and raw eggs are an important source to human infections. Information on the prevalence of Salmonella at farm/holding level, and the zoonotic serovars circulating in layer poultry in the South and South-East Asian countries including Bangladesh, where small-scale commercial farms are predominant, is limited. To investigate the prevalence of Salmonella at layer farm level, and to identify the prevalent serovars we conducted a cross-sectional survey by randomly selecting 500 commercial layer poultry farms in Bangladesh. Faecal samples from the selected farms were collected following standard procedure, and examined for the presence of Salmonella using conventional bacteriological procedures. Thirty isolates were randomly selected, from the ninety obtained from the survey, for serotyping and characterized further by plasmid profiling and pulsed-field gel electrophoresis (PFGE). Results of the survey showed that the prevalence of motile Salmonella at layer farm level was 18% (95% confidence interval 15–21%), and Salmonella Kentucky was identified to be the only serovar circulating in the study population. Plasmid analysis of the S. Kentucky and non-serotyped isolates revealed two distinct profiles with a variation of two different sizes (2.7 and 4.8 kb). PFGE of the 30 S. Kentucky and 30 non-serotyped isolates showed that all of them were clonally related because only one genotype and three subtypes were determined based on the variation in two or three bands. This is also the first report on the presence of any specific serovar of Salmonella enterica in poultry in Bangladesh. PMID:22558269

Prevalence and characterization of motile Salmonella in commercial layer poultry farms in Bangladesh.

PubMed

Barua, Himel; Biswas, Paritosh K; Olsen, Katharina E P; Christensen, Jens P

2012-01-01

Salmonella is a globally widespread food-borne pathogen having major impact on public health. All motile serovars of Salmonella enterica of poultry origin are zoonotic, and contaminated meat and raw eggs are an important source to human infections. Information on the prevalence of Salmonella at farm/holding level, and the zoonotic serovars circulating in layer poultry in the South and South-East Asian countries including Bangladesh, where small-scale commercial farms are predominant, is limited. To investigate the prevalence of Salmonella at layer farm level, and to identify the prevalent serovars we conducted a cross-sectional survey by randomly selecting 500 commercial layer poultry farms in Bangladesh. Faecal samples from the selected farms were collected following standard procedure, and examined for the presence of Salmonella using conventional bacteriological procedures. Thirty isolates were randomly selected, from the ninety obtained from the survey, for serotyping and characterized further by plasmid profiling and pulsed-field gel electrophoresis (PFGE). Results of the survey showed that the prevalence of motile Salmonella at layer farm level was 18% (95% confidence interval 15-21%), and Salmonella Kentucky was identified to be the only serovar circulating in the study population. Plasmid analysis of the S. Kentucky and non-serotyped isolates revealed two distinct profiles with a variation of two different sizes (2.7 and 4.8 kb). PFGE of the 30 S. Kentucky and 30 non-serotyped isolates showed that all of them were clonally related because only one genotype and three subtypes were determined based on the variation in two or three bands. This is also the first report on the presence of any specific serovar of Salmonella enterica in poultry in Bangladesh.

Cluster randomization and political philosophy.

PubMed

Chwang, Eric

2012-11-01

In this paper, I will argue that, while the ethical issues raised by cluster randomization can be challenging, they are not new. My thesis divides neatly into two parts. In the first, easier part I argue that many of the ethical challenges posed by cluster randomized human subjects research are clearly present in other types of human subjects research, and so are not novel. In the second, more difficult part I discuss the thorniest ethical challenge for cluster randomized research--cases where consent is genuinely impractical to obtain. I argue that once again these cases require no new analytic insight; instead, we should look to political philosophy for guidance. In other words, the most serious ethical problem that arises in cluster randomized research also arises in political philosophy. © 2011 Blackwell Publishing Ltd.

Feature selection for the classification of traced neurons.

PubMed

López-Cabrera, José D; Lorenzo-Ginori, Juan V

2018-06-01

The great availability of computational tools to calculate the properties of traced neurons leads to the existence of many descriptors which allow the automated classification of neurons from these reconstructions. This situation determines the necessity to eliminate irrelevant features as well as making a selection of the most appropriate among them, in order to improve the quality of the classification obtained. The dataset used contains a total of 318 traced neurons, classified by human experts in 192 GABAergic interneurons and 126 pyramidal cells. The features were extracted by means of the L-measure software, which is one of the most used computational tools in neuroinformatics to quantify traced neurons. We review some current feature selection techniques as filter, wrapper, embedded and ensemble methods. The stability of the feature selection methods was measured. For the ensemble methods, several aggregation methods based on different metrics were applied to combine the subsets obtained during the feature selection process. The subsets obtained applying feature selection methods were evaluated using supervised classifiers, among which Random Forest, C4.5, SVM, Naïve Bayes, Knn, Decision Table and the Logistic classifier were used as classification algorithms. Feature selection methods of types filter, embedded, wrappers and ensembles were compared and the subsets returned were tested in classification tasks for different classification algorithms. L-measure features EucDistanceSD, PathDistanceSD, Branch_pathlengthAve, Branch_pathlengthSD and EucDistanceAve were present in more than 60% of the selected subsets which provides evidence about their importance in the classification of this neurons. Copyright © 2018 Elsevier B.V. All rights reserved.

Effects of zinc supplementation on subscales of anorexia in children: A randomized controlled trial.

PubMed

Khademian, Majid; Farhangpajouh, Neda; Shahsanaee, Armindokht; Bahreynian, Maryam; Mirshamsi, Mehran; Kelishadi, Roya

2014-01-01

This study aims to assess the effects of zinc supplementation on improving the appetite and its subscales in children. This study was conducted in 2013 in Isfahan, Iran. It had two phases. At the first step, after validation of the Child Eating Behaviour Questionaire (CEBQ), it was completed for 300 preschool children, who were randomly selected. The second phase was conducted as a randomized controlled trial. Eighty of these children were randomly selected, and were randomly assigned to two groups of equal number receiving zinc (10 mg/day) or placebo for 12 weeks. Overall 77 children completed the trial (39 in the case and 3 in the control group).The results showed that zinc supplement can improve calorie intake in children by affecting some CEBQ subscales like Emotional over Eating and Food Responsible. Zinc supplementation had positive impact in promoting the calorie intake and some subscales of anorexia.

Efficient production of artificially designed gelatins with a Bacillus brevis system.

PubMed

Kajino, T; Takahashi, H; Hirai, M; Yamada, Y

2000-01-01

Artificially designed gelatins comprising tandemly repeated 30-amino-acid peptide units derived from human alphaI collagen were successfully produced with a Bacillus brevis system. The DNA encoding the peptide unit was synthesized by taking into consideration the codon usage of the host cells, but no clones having a tandemly repeated gene were obtained through the above-mentioned strategy. Minirepeat genes could be selected in vivo from a mixture of every possible sequence encoding an artificial gelatin by randomly ligating the mixed sequence unit and transforming it into Escherichia coli. Larger repeat genes constructed by connecting minirepeat genes obtained by in vivo selection were also stable in the expression host cells. Gelatins derived from the eight-unit and six-unit repeat genes were extracellularly produced at the level of 0.5 g/liter and easily purified by ammonium sulfate fractionation and anion-exchange chromatography. The purified artificial gelatins had the predicted N-terminal sequences and amino acid compositions and a solgel property similar to that of the native gelatin. These results suggest that the selection of a repeat unit sequence stable in an expression host is a shortcut for the efficient production of repetitive proteins and that it can conveniently be achieved by the in vivo selection method. This study revealed the possible industrial application of artificially designed repetitive proteins.

Molecular mechanisms of retroviral integration site selection

PubMed Central

Kvaratskhelia, Mamuka; Sharma, Amit; Larue, Ross C.; Serrao, Erik; Engelman, Alan

2014-01-01

Retroviral replication proceeds through an obligate integrated DNA provirus, making retroviral vectors attractive vehicles for human gene-therapy. Though most of the host cell genome is available for integration, the process of integration site selection is not random. Retroviruses differ in their choice of chromatin-associated features and also prefer particular nucleotide sequences at the point of insertion. Lentiviruses including HIV-1 preferentially integrate within the bodies of active genes, whereas the prototypical gammaretrovirus Moloney murine leukemia virus (MoMLV) favors strong enhancers and active gene promoter regions. Integration is catalyzed by the viral integrase protein, and recent research has demonstrated that HIV-1 and MoMLV targeting preferences are in large part guided by integrase-interacting host factors (LEDGF/p75 for HIV-1 and BET proteins for MoMLV) that tether viral intasomes to chromatin. In each case, the selectivity of epigenetic marks on histones recognized by the protein tether helps to determine the integration distribution. In contrast, nucleotide preferences at integration sites seem to be governed by the ability for the integrase protein to locally bend the DNA duplex for pairwise insertion of the viral DNA ends. We discuss approaches to alter integration site selection that could potentially improve the safety of retroviral vectors in the clinic. PMID:25147212

The role of selective estrogen receptor modulators in the treatment of schizophrenia.

PubMed

Bratek, Agnieszka; Krysta, Krzysztof; Drzyzga, Karolina; Barańska, Justyna; Kucia, Krzysztof

2016-09-01

Gender differences in schizophrenia have been recognized for a long time and it has been widely accepted that sex steroid hormones, especially estradiol, are strongly attributed to this fact. Two hypotheses regarding estradiol action in psychoses gained special research attention - the estrogen protection hypothesis and hypoestrogenism hypothesis. A growing number of studies have shown benefits in augmenting antipsychotic treatment with estrogens or selective estrogen receptor modulators (SERM). This review is focused on the role of selective estrogen receptor modulators in the treatment of schizophrenic patients. In order to achieve this result PubMed was searched using the following terms: schizophrenia, raloxifene, humans. We reviewed only randomized, placebo-controlled studies. Raloxifene, a selective estrogen receptor modulator was identified as useful to improve negative, positive, and general psychopathological symptoms, and also cognitive functions. All reviewed studies indicated improvement in at least one studied domain. Augmentation with raloxifene was found to be a beneficial treatment strategy for chronic schizophrenia both in female and male patients, however potential side effects (a small increase in the risk of venous thromboembolism and endometrial cancer) should be carefully considered. SERMs could be an effective augmentation strategy in the treatment of both men women with schizophrenia, although further research efforts are needed to study potential long-term side effects.

Using environmental heterogeneity to plan for sea-level rise.

PubMed

Hunter, Elizabeth A; Nibbelink, Nathan P

2017-12-01

Environmental heterogeneity is increasingly being used to select conservation areas that will provide for future biodiversity under a variety of climate scenarios. This approach, termed conserving nature's stage (CNS), assumes environmental features respond to climate change more slowly than biological communities, but will CNS be effective if the stage were to change as rapidly as the climate? We tested the effectiveness of using CNS to select sites in salt marshes for conservation in coastal Georgia (U.S.A.), where environmental features will change rapidly as sea level rises. We calculated species diversity based on distributions of 7 bird species with a variety of niches in Georgia salt marshes. Environmental heterogeneity was assessed across six landscape gradients (e.g., elevation, salinity, and patch area). We used 2 approaches to select sites with high environmental heterogeneity: site complementarity (environmental diversity [ED]) and local environmental heterogeneity (environmental richness [ER]). Sites selected based on ER predicted present-day species diversity better than randomly selected sites (up to an 8.1% improvement), were resilient to areal loss from SLR (1.0% average areal loss by 2050 compared with 0.9% loss of randomly selected sites), and provided habitat to a threatened species (0.63 average occupancy compared with 0.6 average occupancy of randomly selected sites). Sites selected based on ED predicted species diversity no better or worse than random and were not resilient to SLR (2.9% average areal loss by 2050). Despite the discrepancy between the 2 approaches, CNS is a viable strategy for conservation site selection in salt marshes because the ER approach was successful. It has potential for application in other coastal areas where SLR will affect environmental features, but its performance may depend on the magnitude of geological changes caused by SLR. Our results indicate that conservation planners that had heretofore excluded low-lying coasts from CNS planning could include coastal ecosystems in regional conservation strategies. © 2017 Society for Conservation Biology.

A pilot study for the analysis of dream reports using Maslow's need categories: an extension to the emotional selection hypothesis.

PubMed

Coutts, Richard

2010-10-01

The emotional selection hypothesis describes a cyclical process that uses dreams to modify and test select mental schemas. An extension is proposed that further characterizes these schemas as facilitators of human need satisfaction. A pilot study was conducted in which this hypothesis was tested by assigning 100 dream reports (10 randomly selected from 10 dream logs at an online web site) to one or more categories within Maslow's hierarchy of needs. A "match" was declared when at least two of three judges agreed both for category and for whether the identified need was satisfied or thwarted in the dream narrative. The interjudge reliability of the judged needs was good (92% of the reports contained at least one match). The number of needs judged as thwarted did not differ significantly from the number judged as satisfied (48 vs. 52%, respectively). The six "higher" needs (belongingness, esteem, cognitive, aesthetic, self-actualization, and transcendence) were scored significantly more frequently (81%) than were the two lowest or "basic" needs (physiological and safety, 19%). Basic needs were also more likely to be judged as thwarted, while higher needs were more likely to be judged as satisfied. These findings are discussed in the context of Maslow's hierarchy of needs as a framework for investigating theories of dream function, including the emotional selection hypothesis and other contemporary dream theories.

Toward an evolutionary-predictive foundation for creativity : Commentary on "Human creativity, evolutionary algorithms, and predictive representations: The mechanics of thought trials" by Arne Dietrich and Hilde Haider, 2014 (Accepted pending minor revisions for publication in Psychonomic Bulletin & Review).

PubMed

Gabora, Liane; Kauffman, Stuart

2016-04-01

Dietrich and Haider (Psychonomic Bulletin & Review, 21 (5), 897-915, 2014) justify their integrative framework for creativity founded on evolutionary theory and prediction research on the grounds that "theories and approaches guiding empirical research on creativity have not been supported by the neuroimaging evidence." Although this justification is controversial, the general direction holds promise. This commentary clarifies points of disagreement and unresolved issues, and addresses mis-applications of evolutionary theory that lead the authors to adopt a Darwinian (versus Lamarckian) approach. To say that creativity is Darwinian is not to say that it consists of variation plus selection - in the everyday sense of the term - as the authors imply; it is to say that evolution is occurring because selection is affecting the distribution of randomly generated heritable variation across generations. In creative thought the distribution of variants is not key, i.e., one is not inclined toward idea A because 60 % of one's candidate ideas are variants of A while only 40 % are variants of B; one is inclined toward whichever seems best. The authors concede that creative variation is partly directed; however, the greater the extent to which variants are generated non-randomly, the greater the extent to which the distribution of variants can reflect not selection but the initial generation bias. Since each thought in a creative process can alter the selective criteria against which the next is evaluated, there is no demarcation into generations as assumed in a Darwinian model. We address the authors' claim that reduced variability and individuality are more characteristic of Lamarckism than Darwinian evolution, and note that a Lamarckian approach to creativity has addressed the challenge of modeling the emergent features associated with insight.

Prediction of the developmental toxicity hazard potential of halogenated drinking water disinfection by-products tested by the in vitro hydra assay

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

Fu, L.J.; Johnson, E.M.; Newman, L.M.

A series of seven randomly selected potential halogenated water disinfection by-products were evaluated in vitro by the hydra assay to determine their developmental toxicity hazard potential. For six of the chemicals tested by this assay (dibromoacetonitrile; trichloroacetonitrile; 2-chlorophenol; 2,4,6-trichlorophenol; trichloroacetic acid; dichloroacetone) it was predicted that they would be generally equally toxic to both adult and embryonic mammals when studied by means of standard developmental toxicity teratology tests. However, the potential water disinfection by-product chloroacetic acid (CA) was determined to be over eight times more toxic to the embryonic developmental portion of the assay than it was to the adults.more » Because of this potential selectivity, CA is a high-priority item for developmental toxicity tests in pregnant mammals to confirm or refute its apparent unique developmental hazard potential and/or to establish a NOAEL by the route of most likely human exposure.« less

Gut bacteria selectively promoted by dietary fibers alleviate type 2 diabetes.

PubMed

Zhao, Liping; Zhang, Feng; Ding, Xiaoying; Wu, Guojun; Lam, Yan Y; Wang, Xuejiao; Fu, Huaqing; Xue, Xinhe; Lu, Chunhua; Ma, Jilin; Yu, Lihua; Xu, Chengmei; Ren, Zhongying; Xu, Ying; Xu, Songmei; Shen, Hongli; Zhu, Xiuli; Shi, Yu; Shen, Qingyun; Dong, Weiping; Liu, Rui; Ling, Yunxia; Zeng, Yue; Wang, Xingpeng; Zhang, Qianpeng; Wang, Jing; Wang, Linghua; Wu, Yanqiu; Zeng, Benhua; Wei, Hong; Zhang, Menghui; Peng, Yongde; Zhang, Chenhong

2018-03-09

The gut microbiota benefits humans via short-chain fatty acid (SCFA) production from carbohydrate fermentation, and deficiency in SCFA production is associated with type 2 diabetes mellitus (T2DM). We conducted a randomized clinical study of specifically designed isoenergetic diets, together with fecal shotgun metagenomics, to show that a select group of SCFA-producing strains was promoted by dietary fibers and that most other potential producers were either diminished or unchanged in patients with T2DM. When the fiber-promoted SCFA producers were present in greater diversity and abundance, participants had better improvement in hemoglobin A1c levels, partly via increased glucagon-like peptide-1 production. Promotion of these positive responders diminished producers of metabolically detrimental compounds such as indole and hydrogen sulfide. Targeted restoration of these SCFA producers may present a novel ecological approach for managing T2DM. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Single-round selection yields a unique retroviral envelope utilizing GPR172A as its host receptor.

PubMed

Mazari, Peter M; Linder-Basso, Daniela; Sarangi, Anindita; Chang, Yehchung; Roth, Monica J

2009-04-07

The recognition by a viral envelope of its cognate host-cell receptor is the initial critical step in defining the viral host-range and tissue specificity. This study combines a single-round of selection of a random envelope library with a parallel cDNA screen for receptor function to identify a distinct retroviral envelope/receptor pair. The 11-aa targeting domain of the modified feline leukemia virus envelope consists of a constrained peptide. Critical to the binding of the constrained peptide envelope to its cellular receptor are a pair of internal cysteines and an essential Trp required for maintenance of titers >10(5) lacZ staining units per milliliter. The receptor used for viral entry is the human GPR172A protein, a G-protein-coupled receptor isolated from osteosarcoma cells. The ability to generate unique envelopes capable of using tissue- or disease-specific receptors marks an advance in the development of efficient gene-therapy vectors.

Hemispheric and facial asymmetry: faces of academe.

PubMed

Smith, W M

1998-11-01

Facial asymmetry (facedness) of selected academic faculty members was studied in relation to brain asymmetry and cognitive specialization. Comparisons of facedness were made among humanities faculty (H), faculty members of mathematics and physics (M-P), psychologists (P), and a group of randomly selected individuals (R). Facedness was defined in terms of the relative sizes (in square centimeters) of the two hemifaces. It was predicted that the four groups would show differences in facedness, namely, H, right face bias; M-P, left face bias; P, no bias; and R, no bias. The predictions were confirmed, and the results interpreted in terms of known differences in hemispheric specialization of cognitive functions as they relate to the dominant cognitive activity of each of the different groups. In view of the contralateral control of the two hemifaces (below the eyes) by the two hemispheres of the brain, the two sides of the face undergo differential muscular development, thus creating facial asymmetry. Other factors, such as gender, also may affect facial asymmetry. Suggestions for further research on facedness are discussed.

[Screening specific recognition motif of RNA-binding proteins by SELEX in combination with next-generation sequencing technique].

PubMed

Zhang, Lu; Xu, Jinhao; Ma, Jinbiao

2016-07-25

RNA-binding protein exerts important biological function by specifically recognizing RNA motif. SELEX (Systematic evolution of ligands by exponential enrichment), an in vitro selection method, can obtain consensus motif with high-affinity and specificity for many target molecules from DNA or RNA libraries. Here, we combined SELEX with next-generation sequencing to study the protein-RNA interaction in vitro. A pool of RNAs with 20 bp random sequences were transcribed by T7 promoter, and target protein was inserted into plasmid containing SBP-tag, which can be captured by streptavidin beads. Through only one cycle, the specific RNA motif can be obtained, which dramatically improved the selection efficiency. Using this method, we found that human hnRNP A1 RRMs domain (UP1 domain) bound RNA motifs containing AGG and AG sequences. The EMSA experiment indicated that hnRNP A1 RRMs could bind the obtained RNA motif. Taken together, this method provides a rapid and effective method to study the RNA binding specificity of proteins.

Analysis of world terror networks from the reduced Google matrix of Wikipedia

NASA Astrophysics Data System (ADS)

El Zant, Samer; Frahm, Klaus M.; Jaffrès-Runser, Katia; Shepelyansky, Dima L.

2018-01-01

We apply the reduced Google matrix method to analyze interactions between 95 terrorist groups and determine their relationships and influence on 64 world countries. This is done on the basis of the Google matrix of the English Wikipedia (2017) composed of 5 416 537 articles which accumulate a great part of global human knowledge. The reduced Google matrix takes into account the direct and hidden links between a selection of 159 nodes (articles) appearing due to all paths of a random surfer moving over the whole network. As a result we obtain the network structure of terrorist groups and their relations with selected countries including hidden indirect links. Using the sensitivity of PageRank to a weight variation of specific links we determine the geopolitical sensitivity and influence of specific terrorist groups on world countries. The world maps of the sensitivity of various countries to influence of specific terrorist groups are obtained. We argue that this approach can find useful application for more extensive and detailed data bases analysis.

GABAergic neurons in ferret visual cortex participate in functionally specific networks

PubMed Central

Wilson, Daniel E.; Smith, Gordon B.; Jacob, Amanda; Walker, Theo; Dimidschstein, Jordane; Fishell, Gord J.; Fitzpatrick, David

2017-01-01

Summary Functional circuits in the visual cortex require the coordinated activity of excitatory and inhibitory neurons. Molecular genetic approaches in the mouse have led to the ‘local nonspecific pooling principle’ of inhibitory connectivity, in which inhibitory neurons are untuned for stimulus features due to the random pooling of local inputs. However, it remains unclear whether this principle generalizes to species with a columnar organization of feature selectivity such as carnivores, primates, and humans. Here we use virally-mediated GABAergic-specific GCaMP6f expression to demonstrate that inhibitory neurons in ferret visual cortex respond robustly and selectively to oriented stimuli. We find that the tuning of inhibitory neurons is inconsistent with the local non-specific pooling of excitatory inputs, and that inhibitory neurons exhibit orientation-specific noise correlations with local and distant excitatory neurons. These findings challenge the generality of the non-specific pooling principle for inhibitory neurons, suggesting different rules for functional excitatory-inhibitory interactions in non-murine species. PMID:28279352

Health-risk behaviors in agriculture and related factors, southeastern Anatolian region of Turkey.

PubMed

Yavuz, Hasret; Simsek, Zeynep; Akbaba, Muhsin

2014-01-01

Human behavior plays a central role in the maintenance of health and the prevention of diseases. This study aimed to determine the risky behaviors of farm operators selected from a province of Turkey's southeastern Anatolian region, as well as the factors related to risky behaviors. In this cross-sectional analysis, 380 farm operators were enrolled through simple random selection method, and the response rate was 85%. Health-risk behavior was measured using the Control List of Occupational Risks in Agriculture. Of 323 farm operators, 85.4% were male. The prevalence of risky behaviors related to measures of environmental risks were higher in animal husbandry, transportation, transportation and maintenance of machinery, pesticide application, child protection, thermal stress, and psychosocial factors in the work place. Education, age, duration of work, and size of agricultural area were associated with risky behaviors in a multiple linear regression (P < .05). Findings showed that a certified training program and a behavior surveillance system for agriculture should be developed.

Leveraging ongoing research to evaluate the health impacts of South Africa's salt reduction strategy: a prospective nested cohort within the WHO-SAGE multicountry, longitudinal study

PubMed Central

Charlton, Karen; Menyanu, Elias; Biritwum, Richard Berko; Naidoo, Nirmala; Pieterse, Chiné; Madurai, Savathree (Lorna); Baumgartner, Jeannine; Asare, George A; Thiele, Elizabeth; Schutte, Aletta E; Kowal, Paul

2016-01-01

Introduction Attempting to curb the rising epidemic of hypertension, South Africa implemented legislation in June 2016 mandating maximum sodium levels in a range of manufactured foods that contribute significantly to population salt intake. This natural experiment, comparing two African countries with and without salt legislation, will provide timely information on the impact of legislative approaches addressing the food supply to improve blood pressure in African populations. This article outlines the design of this ongoing prospective nested cohort study. Methods and analysis Baseline sodium intake was assessed in a nested cohort of the WHO Study on global AGEing and adult health (WHO-SAGE) wave 2 (2014–2015), a multinational longitudinal study on the health and well-being of adults and the ageing process. The South African cohort consisted of randomly selected households (n=4030) across the country. Spot and 24-hour urine samples are collected in a random subsample (n=1200) and sodium, potassium, creatinine and iodine analysed. Salt behaviour and sociodemographic data are captured using face-to-face interviews, alongside blood pressure and anthropometric measures. Ghana, the selected control country with no formal salt policy, provided a nested subsample (n=1200) contributing spot and 24-hour urine samples from the SAGE Ghana cohort (n=5000). Follow-up interviews and urine collection (wave 3) in both countries will take place in 2017 (postlegislation) to assess change in population-level sodium intake and blood pressure. Ethics and dissemination SAGE was approved by the WHO Ethics Review Committee (reference number RPC149) with local approval from the North-West University Human Research Ethics Committee and University of the Witwatersrand Human Research Ethics Committee (South Africa), and University of Ghana Medical School Ethics and Protocol Review Committee (Ghana). The results of the study will be published in peer-reviewed international journals, presented at national and international conferences, and summarised as research and policy briefs. PMID:27903563

Omentectomy added to Roux-en-Y gastric bypass surgery: a randomized, controlled trial.

PubMed

Dillard, Troy H; Purnell, Jonathan Q; Smith, Mark D; Raum, William; Hong, Dennis; Laut, Jamie; Patterson, Emma J

2013-01-01

Excess visceral adipose tissue predicts for incipient diabetes mellitus and cardiovascular disease. Human data are mixed regarding the benefits of selective visceral adipose tissue reduction. We investigated the effects of omentectomy added to laparoscopic Roux-en-Y gastric bypass on glucose homeostasis and lipids, inflammatory markers, and adipokines 90 days postoperatively in nondiabetic patients at the Legacy Good Samaritan Hospital and Oregon Health and Science University (Portland, OR). A single-blind, randomized study of laparoscopic Roux-en-Y gastric bypass plus omentectomy versus laparoscopic Roux-en-Y gastric bypass alone in 28 subjects (7 men and 21 women). The groups were matched at baseline for gender, age, and body mass index (BMI). The eligibility criteria included age ≥18 years, BMI ≥40 and <50 kg/m(2) without co-morbid conditions or BMI ≥35 and <50 kg/m(2) with co-morbid conditions. The primary outcome measures were changes in the fasting plasma glucose, insulin, and homostatic model assessment of insulin resistance. The secondary measures were BMI and the high-sensitivity C-reactive protein, tumor necrosis factor-α, interleukin, total and high-molecular-weight adiponectin, fibrinogen, and plasminogen activator inhibitor-1 levels. After surgery, the BMI decreased significantly in both groups and was not different at the follow-up point. Although many outcome parameters improved with weight loss in both groups postoperatively, only the omentectomy group experienced statistically significant decreases in fasting glucose (P < .05), total (P = .004) and very-low-density lipoprotein (P = .001) cholesterol, and an increase in the high-molecular-weight/total adiponectin ratio (P = .013). Omentectomy added to laparoscopic Roux-en-Y gastric bypass results in favorable changes in glucose homeostasis, lipid levels, and adipokine profile at 90 days postoperatively. These data support the hypothesis that selective ablation of visceral adipose tissue conveys metabolic benefits in nondiabetic humans. Copyright © 2013 American Society for Metabolic and Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

The genealogy of samples in models with selection.

PubMed

Neuhauser, C; Krone, S M

1997-02-01

We introduce the genealogy of a random sample of genes taken from a large haploid population that evolves according to random reproduction with selection and mutation. Without selection, the genealogy is described by Kingman's well-known coalescent process. In the selective case, the genealogy of the sample is embedded in a graph with a coalescing and branching structure. We describe this graph, called the ancestral selection graph, and point out differences and similarities with Kingman's coalescent. We present simulations for a two-allele model with symmetric mutation in which one of the alleles has a selective advantage over the other. We find that when the allele frequencies in the population are already in equilibrium, then the genealogy does not differ much from the neutral case. This is supported by rigorous results. Furthermore, we describe the ancestral selection graph for other selective models with finitely many selection classes, such as the K-allele models, infinitely-many-alleles models. DNA sequence models, and infinitely-many-sites models, and briefly discuss the diploid case.

The Genealogy of Samples in Models with Selection

PubMed Central

Neuhauser, C.; Krone, S. M.

1997-01-01

We introduce the genealogy of a random sample of genes taken from a large haploid population that evolves according to random reproduction with selection and mutation. Without selection, the genealogy is described by Kingman's well-known coalescent process. In the selective case, the genealogy of the sample is embedded in a graph with a coalescing and branching structure. We describe this graph, called the ancestral selection graph, and point out differences and similarities with Kingman's coalescent. We present simulations for a two-allele model with symmetric mutation in which one of the alleles has a selective advantage over the other. We find that when the allele frequencies in the population are already in equilibrium, then the genealogy does not differ much from the neutral case. This is supported by rigorous results. Furthermore, we describe the ancestral selection graph for other selective models with finitely many selection classes, such as the K-allele models, infinitely-many-alleles models, DNA sequence models, and infinitely-many-sites models, and briefly discuss the diploid case. PMID:9071604

Csa-19, a radiation-responsive human gene, identified by an unbiased two-gel cDNA library screening method in human cancer cells

NASA Technical Reports Server (NTRS)

Balcer-Kubiczek, E. K.; Meltzer, S. J.; Han, L. H.; Zhang, X. F.; Shi, Z. M.; Harrison, G. H.; Abraham, J. M.

1997-01-01

A novel polymerase chain reaction (PCR)-based method was used to identify candidate genes whose expression is altered in cancer cells by ionizing radiation. Transcriptional induction of randomly selected genes in control versus irradiated human HL60 cells was compared. Among several complementary DNA (cDNA) clones recovered by this approach, one cDNA clone (CL68-5) was downregulated in X-irradiated HL60 cells but unaffected by 12-O-tetradecanoyl phorbol-13-acetate, forskolin, or cyclosporin-A. DNA sequencing of the CL68-5 cDNA revealed 100% nucleotide sequence homology to the reported human Csa-19 gene. Northern blot analysis of RNA from control and irradiated cells revealed the expression of a single 0.7-kilobase (kb) messenger RNA (mRNA) transcript. This 0.7-kb Csa-19 mRNA transcript was also expressed in a variety of human adult and corresponding fetal normal tissues. Moreover, when the effect of X- or fission neutron-irradiation on Csa-19 mRNA was compared in cultured human cells differing in p53 gene status (p53-/- versus p53+/+), downregulation of Csa-19 by X-rays or fission neutrons was similar in p53-wild type and p53-null cell lines. Our results provide the first known example of a radiation-responsive gene in human cancer cells whose expression is not associated with p53, adenylate cyclase or protein kinase C.

Changing Friend Selection in Middle School: A Social Network Analysis of a Randomized Intervention Study Designed to Prevent Adolescent Problem Behavior.

PubMed

DeLay, Dawn; Ha, Thao; Van Ryzin, Mark; Winter, Charlotte; Dishion, Thomas J

2016-04-01

Adolescent friendships that promote problem behavior are often chosen in middle school. The current study examines the unintended impact of a randomized school-based intervention on the selection of friends in middle school, as well as on observations of deviant talk with friends 5 years later. Participants included 998 middle school students (526 boys and 472 girls) recruited at the onset of middle school (age 11-12 years) from three public middle schools participating in the Family Check-up model intervention. The current study focuses only on the effects of the SHAPe curriculum-one level of the Family Check-up model-on friendship choices. Participants nominated friends and completed measures of deviant peer affiliation. Approximately half of the sample (n = 500) was randomly assigned to the intervention, and the other half (n = 498) comprised the control group within each school. The results indicate that the SHAPe curriculum affected friend selection within school 1 but not within schools 2 or 3. The effects of friend selection in school 1 translated into reductions in observed deviancy training 5 years later (age 16-17 years). By coupling longitudinal social network analysis with a randomized intervention study, the current findings provide initial evidence that a randomized public middle school intervention can disrupt the formation of deviant peer groups and diminish levels of adolescent deviance 5 years later.

Randomness and diversity matter in the maintenance of the public resources

NASA Astrophysics Data System (ADS)

Liu, Aizhi; Zhang, Yanling; Chen, Xiaojie; Sun, Changyin

2017-03-01

Most previous models about the public goods game usually assume two possible strategies, i.e., investing all or nothing. The real-life situation is rarely all or nothing. In this paper, we consider that multiple strategies are adopted in a well-mixed population, and each strategy represents an investment to produce the public goods. Past efforts have found that randomness matters in the evolution of fairness in the ultimatum game. In the framework involving no other mechanisms, we study how diversity and randomness influence the average investment of the population defined by the mean value of all individuals' strategies. The level of diversity is increased by increasing the strategy number, and the level of randomness is increased by increasing the mutation probability, or decreasing the population size or the selection intensity. We find that a higher level of diversity and a higher level of randomness lead to larger average investment and favor more the evolution of cooperation. Under weak selection, the average investment changes very little with the strategy number, the population size, and the mutation probability. Under strong selection, the average investment changes very little with the strategy number and the population size, but changes a lot with the mutation probability. Under intermediate selection, the average investment increases significantly with the strategy number and the mutation probability, and decreases significantly with the population size. These findings are meaningful to study how to maintain the public resource.

Gender-related differences in the human rights needs of patients with mental illness.

PubMed

Vijayalakshmi, Poreddi; Reddemma, Konduru; Math, Suresh Bada

2012-06-01

Individuals with mental illness commonly experience human rights violations while seeking to meet their basic needs. There is lack of research in developing countries on gender-related differences in human rights needs. This study investigated gender differences in perceived human rights needs at the family and community levels in individuals with mental illness in India. This descriptive study surveyed 100 asymptomatic individuals with mental illness at a tertiary care center. Subject selection employed a random sampling method. Data were collected using face-to-face interviews based on a structured needs assessment questionnaire. Data were analyzed and interpreted using descriptive and inferential statistics. Subjects enjoyed a satisfactory level of fulfillment in the physical dimension of human rights needs, which included food, housing, and clothing. Men expressed lower satisfaction than women with perceived human rights needs fulfillment in the emotional dimension. This included fear of family members (χ = 9.419, p < .024) and being called derogatory names (χ = 8.661, p < .034). Women expressed lower satisfaction than men with perceived human rights needs fulfillment in social and ethical dimensions. The former included freedom to leave the home (χ = 11.277, p < .010), and the latter included sexual abuse by family members (χ = 9.491, p < .019). Men felt more discriminated than women due to perceptions of mental illness in the community domain (χ = 10.197, p < .037). This study suggests that family members and communities need to be educated regarding the human rights needs of people with mental illness and that legislation must be strengthened to meet the human rights needs of this disadvantaged population.

Positive human contact on the first day of life alters the piglet's behavioural response to humans and husbandry practices.

PubMed

Muns, Ramon; Rault, Jean-Loup; Hemsworth, Paul

2015-11-01

This experiment examined the effects of positive human contact at suckling on the first day of life on the behavioural and physiological responses of piglets to both humans and routine husbandry procedures. Forty litters from multiparous sows were randomly allocated to one of two treatments: Control (CC, minimal human interaction with day-old piglets) or Positive Contact (PC, human talking and caressing piglets during 6 suckling bouts on their first day of life, day 1). In each litter, 2 males and 2 females were randomly selected and their behavioural responses to tail docking (day 2), and to an experimenter (day 35) were studied. Escape behaviour at tail docking was assessed according to intensity (on a scale from 0 to 4 representing no movement to high intensity movement) and duration (on a scale from 0 to 3 representing no movement to continuous movement). At day 15 of age, a human approach and avoidance test was performed on focal piglets and at day 15, escape behaviour to capture before and after testing was recorded again. Blood samples for cortisol analysis were obtained from the focal piglets 30 min after tail docking and 1 h after weaning. Escape behaviour to tail docking of the PC piglets was of shorter duration than that of the CC piglets (P = 0.05). There was a tendency for the escape behaviour both before and after testing at day 15 to be of a lower intensity (P = 0.11 and P = 0.06, respectively) and a shorter duration (P = 0.06 and P = 0.08, respectively) in the PC piglets. There was a tendency for PC piglets to have higher cortisol concentrations after tail docking than the CC piglets (P = 0.07). Male piglets had higher cortisol concentrations after tail docking and after weaning than female piglets (P = 0.02 and P = 0.03). The results indicate that Positive Contact treatment reduced the duration of escape behaviour of piglets to tail docking. The role of classical conditioning, habituation and developmental changes in the observed effects of the Positive Contact treatment is unclear. Nonetheless, this experiment demonstrated that brief positive human contacts early in life can alter the behavioural responses of piglets to subsequent stressful events.

Does Mother Know Best? Treatment Adherence as a Function of Anticipated Treatment Benefit

PubMed Central

Glymour, M. Maria; Nguyen, Quynh; Matsouaka, Roland; Tchetgen Tchetgen, Eric J.; Schmidt, Nicole M.; Osypuk, Theresa L.

2016-01-01

Background We describe bias resulting from individualized treatment selection, which occurs when treatment has heterogeneous effects and individuals selectively choose treatments of greatest benefit to themselves. This pernicious bias may confound estimates from observational studies and lead to important misinterpretation of intent-to-treat analyses of randomized trials. Despite the potentially serious threat to inferences, individualized treatment selection has rarely been formally described or assessed. Methods The Moving to Opportunity (MTO) trial randomly assigned subsidized rental vouchers to low-income families in high-poverty public housing. We assessed the Kessler-6 psychological distress and Behavior Problems Index outcomes for 2,829 adolescents 4–7 years after randomization. Among families randomly assigned to receive vouchers, we estimated probability of moving (treatment), predicted by pre-randomization characteristics (c-statistic=0.63). We categorized families into tertiles of this estimated probability of moving, and compared instrumental variable effect estimates for moving on Behavior Problems Index and Kessler-6 across tertiles. Results Instrumental variable estimated effects of moving on behavioral problems index were most adverse for boys least likely to move (b=0.93; 95% CI: 0.33, 1.53) compared to boys most likely to move (b=0.14; 95% CI: −0.15, 0.44; p=.02 for treatment*tertile interaction). Effects on Kessler-6 were more beneficial for girls least likely to move compared to girls most likely to move (−0.62 vs. 0.02; interaction p=.03). Conclusions Evidence of Individualized treatment selection differed by child gender and outcome and should be evaluated in randomized trial reports, especially when heterogeneous treatment effects are likely and non-adherence is common. PMID:26628424

Alternative Modal Basis Selection Procedures For Reduced-Order Nonlinear Random Response Simulation

NASA Technical Reports Server (NTRS)

Przekop, Adam; Guo, Xinyun; Rizi, Stephen A.

2012-01-01

Three procedures to guide selection of an efficient modal basis in a nonlinear random response analysis are examined. One method is based only on proper orthogonal decomposition, while the other two additionally involve smooth orthogonal decomposition. Acoustic random response problems are employed to assess the performance of the three modal basis selection approaches. A thermally post-buckled beam exhibiting snap-through behavior, a shallowly curved arch in the auto-parametric response regime and a plate structure are used as numerical test articles. The results of a computationally taxing full-order analysis in physical degrees of freedom are taken as the benchmark for comparison with the results from the three reduced-order analyses. For the cases considered, all three methods are shown to produce modal bases resulting in accurate and computationally efficient reduced-order nonlinear simulations.

Ray tracing method for simulation of laser beam interaction with random packings of powders

NASA Astrophysics Data System (ADS)

Kovalev, O. B.; Kovaleva, I. O.; Belyaev, V. V.

2018-03-01

Selective laser sintering is a technology of rapid manufacturing of a free form that is created as a solid object by selectively fusing successive layers of powder using a laser. The motivation of this study is due to the currently insufficient understanding of the processes and phenomena of selective laser melting of powders whose time scales differ by orders of magnitude. To construct random packings from mono- and polydispersed solid spheres, the algorithm of their generation based on the discrete element method is used. A numerical method of ray tracing is proposed that is used to simulate the interaction of laser radiation with a random bulk packing of spherical particles and to predict the optical properties of the granular layer, the extinction and absorption coefficients, depending on the optical properties of a powder material.

SELECTING SITES FOR COMPARISON WITH CREATED WETLANDS

EPA Science Inventory

The paper describes the method used for selecting natural wetlands to compare with created wetlands. The results of the selection process and the advantages and disadvantages of the method are discussed. The random site selection method required extensive field work and may have ...

A Novel Feature Optimization for Wearable Human-Computer Interfaces Using Surface Electromyography Sensors

PubMed Central

Zhang, Xiong; Zhao, Yacong; Zhang, Yu; Zhong, Xuefei; Fan, Zhaowen

2018-01-01

The novel human-computer interface (HCI) using bioelectrical signals as input is a valuable tool to improve the lives of people with disabilities. In this paper, surface electromyography (sEMG) signals induced by four classes of wrist movements were acquired from four sites on the lower arm with our designed system. Forty-two features were extracted from the time, frequency and time-frequency domains. Optimal channels were determined from single-channel classification performance rank. The optimal-feature selection was according to a modified entropy criteria (EC) and Fisher discrimination (FD) criteria. The feature selection results were evaluated by four different classifiers, and compared with other conventional feature subsets. In online tests, the wearable system acquired real-time sEMG signals. The selected features and trained classifier model were used to control a telecar through four different paradigms in a designed environment with simple obstacles. Performance was evaluated based on travel time (TT) and recognition rate (RR). The results of hardware evaluation verified the feasibility of our acquisition systems, and ensured signal quality. Single-channel analysis results indicated that the channel located on the extensor carpi ulnaris (ECU) performed best with mean classification accuracy of 97.45% for all movement’s pairs. Channels placed on ECU and the extensor carpi radialis (ECR) were selected according to the accuracy rank. Experimental results showed that the proposed FD method was better than other feature selection methods and single-type features. The combination of FD and random forest (RF) performed best in offline analysis, with 96.77% multi-class RR. Online results illustrated that the state-machine paradigm with a 125 ms window had the highest maneuverability and was closest to real-life control. Subjects could accomplish online sessions by three sEMG-based paradigms, with average times of 46.02, 49.06 and 48.08 s, respectively. These experiments validate the feasibility of proposed real-time wearable HCI system and algorithms, providing a potential assistive device interface for persons with disabilities. PMID:29543737

What does the fox say? Monitoring antimicrobial resistance in the environment using wild red foxes as an indicator.

PubMed

Mo, Solveig Sølverød; Urdahl, Anne Margrete; Madslien, Knut; Sunde, Marianne; Nesse, Live L; Slettemeås, Jannice Schau; Norström, Madelaine

2018-01-01

The objective of this study was to estimate and compare the occurrence of AMR in wild red foxes in relation to human population densities. Samples from wild red foxes (n = 528) included in the Norwegian monitoring programme on antimicrobial resistance in bacteria from food, feed and animals were included. All samples were divided into three different groups based on population density in the municipality where the foxes were hunted. Of the 528 samples included, 108 (20.5%), 328 (62.1%) and 92 (17.4%) originated from areas with low, medium and high population density, respectively. A single faecal swab was collected from each fox. All samples were plated out on a selective medium for Enterobacteriaceae for culturing followed by inclusion and susceptibility testing of one randomly selected Escherichia coli to assess the overall occurrence of AMR in the Gram-negative bacterial population. Furthermore, the samples were subjected to selective screening for detection of E. coli displaying resistance towards extended-spectrum cephalosporins and fluoroquinolones. In addition, a subset of samples (n = 387) were subjected to selective culturing to detect E. coli resistant to carbapenems and colistin, and enterococci resistant to vancomycin. Of these, 98 (25.3%), 200 (51.7%) and 89 (23.0%) originated from areas with low, medium and high population density, respectively. Overall, the occurrence of AMR in indicator E. coli from wild red foxes originating from areas with different human population densities in Norway was low to moderate (8.8%). The total occurrence of AMR was significantly higher; χ2 (1,N = 336) = 6.53, p = 0.01 in areas with high population density compared to areas with medium population density. Similarly, the occurrence of fluoroquinolone resistant E. coli isolated using selective detection methods was low in areas with low population density and more common in areas with medium or high population density. In conclusion, we found indications that occurrence of AMR in wild red foxes in Norway is associated with human population density. Foxes living in urban areas are more likely to be exposed to AMR bacteria and resistance drivers from food waste, garbage, sewage, waste water and consumption of contaminated prey compared to foxes living in remote areas. The homerange of red fox has been shown to be limited thereby the red fox constitutes a good sentinel for monitoring antimicrobial resistance in the environment. Continuous monitoring on the occurrence of AMR in different wild species, ecological niches and geographical areas can facilitate an increased understanding of the environmental burden of AMR in the environment. Such information is needed to further assess the impact for humans, and enables implementation of possible control measures for AMR in humans, animals and the environment in a true "One Health" approach.

Issues Relating to Selective Reporting When Including Non-Randomized Studies in Systematic Reviews on the Effects of Healthcare Interventions

ERIC Educational Resources Information Center

Norris, Susan L.; Moher, David; Reeves, Barnaby C.; Shea, Beverley; Loke, Yoon; Garner, Sarah; Anderson, Laurie; Tugwell, Peter; Wells, George

2013-01-01

Background: Selective outcome and analysis reporting (SOR and SAR) occur when only a subset of outcomes measured and analyzed in a study is fully reported, and are an important source of potential bias. Key methodological issues: We describe what is known about the prevalence and effects of SOR and SAR in both randomized controlled trials (RCTs)…

High-oleic canola oil consumption enriches LDL particle cholesteryl oleate content and reduces LDL proteoglycan binding in humans

PubMed Central

Jones, Peter J. H.; MacKay, Dylan. S.; Senanayake, Vijitha K.; Pu, Shuaihua; Jenkins, David J. A.; Connelly, Philip W.; Lamarche, Benoît; Couture, Patrick; Kris-Etherton, Penny M.; West, Sheila G.; Liu, Xiaoran; Fleming, Jennifer A.; Hantgan, Roy R.; Rudel, Lawrence L.

2015-01-01

Oleic acid consumption is considered cardio-protective according to studies conducted examining effects of the Mediterranean diet. However, animal models have shown that oleic acid consumption increases LDL particle cholesteryl oleate content which is associated with increased LDL-proteoglycan binding and atherosclerosis. The objective was to examine effects of varying oleic, linoleic and docosahexaenoic acid consumption on human LDL-proteoglycan binding in a non-random subset of the Canola Oil Multi-center Intervention Trial (COMIT) participants. COMIT employed a randomized, double-blind, five-period, cross-over trial design. Three of the treatment oil diets; 1) a blend of corn/safflower oil (25:75); 2) high oleic canola oil; and 3) DHA-enriched high oleic canola oil were selected for analysis of LDL-proteoglycan binding in 50 participants exhibiting good compliance. LDL particles were isolated from frozen plasma by gel filtration chromatography and LDL cholesteryl esters quantified by mass-spectrometry. LDL-proteoglycan binding was assessed using surface plasmon resonance. LDL particle cholesterol ester fatty acid composition was sensitive to the treatment fatty acid compositions, with the main fatty acids in the treatments increasing in the LDL cholesterol esters. The corn/safflower oil and high-oleic canola oil diets lowered LDL-proteoglycan binding relative to their baseline values (p=0.0005 and p=0.0012, respectively). At endpoint, high-oleic canola oil feeding resulted in lower LDL-proteoglycan binding than corn/safflower oil (p=0.0243) and DHA-enriched high oleic canola oil (p=0.0249), although high-oleic canola oil had the lowest binding at baseline (p=0.0344). Our findings suggest that high-oleic canola oil consumption in humans increases cholesteryl oleate percentage in LDL, but in a manner not associated with a rise in LDL-proteoglycan binding. PMID:25528432

Crowdsourcing reproducible seizure forecasting in human and canine epilepsy

PubMed Central

Wagenaar, Joost; Abbot, Drew; Adkins, Phillip; Bosshard, Simone C.; Chen, Min; Tieng, Quang M.; He, Jialune; Muñoz-Almaraz, F. J.; Botella-Rocamora, Paloma; Pardo, Juan; Zamora-Martinez, Francisco; Hills, Michael; Wu, Wei; Korshunova, Iryna; Cukierski, Will; Vite, Charles; Patterson, Edward E.; Litt, Brian; Worrell, Gregory A.

2016-01-01

See Mormann and Andrzejak (doi:10.1093/brain/aww091) for a scientific commentary on this article.   Accurate forecasting of epileptic seizures has the potential to transform clinical epilepsy care. However, progress toward reliable seizure forecasting has been hampered by lack of open access to long duration recordings with an adequate number of seizures for investigators to rigorously compare algorithms and results. A seizure forecasting competition was conducted on kaggle.com using open access chronic ambulatory intracranial electroencephalography from five canines with naturally occurring epilepsy and two humans undergoing prolonged wide bandwidth intracranial electroencephalographic monitoring. Data were provided to participants as 10-min interictal and preictal clips, with approximately half of the 60 GB data bundle labelled (interictal/preictal) for algorithm training and half unlabelled for evaluation. The contestants developed custom algorithms and uploaded their classifications (interictal/preictal) for the unknown testing data, and a randomly selected 40% of data segments were scored and results broadcasted on a public leader board. The contest ran from August to November 2014, and 654 participants submitted 17 856 classifications of the unlabelled test data. The top performing entry scored 0.84 area under the classification curve. Following the contest, additional held-out unlabelled data clips were provided to the top 10 participants and they submitted classifications for the new unseen data. The resulting area under the classification curves were well above chance forecasting, but did show a mean 6.54 ± 2.45% (min, max: 0.30, 20.2) decline in performance. The kaggle.com model using open access data and algorithms generated reproducible research that advanced seizure forecasting. The overall performance from multiple contestants on unseen data was better than a random predictor, and demonstrates the feasibility of seizure forecasting in canine and human epilepsy. PMID:27034258

Holes influence the mutation spectrum of human mitochondrial DNA

NASA Astrophysics Data System (ADS)

Villagran, Martha; Miller, John

Mutations drive evolution and disease, showing highly non-random patterns of variant frequency vs. nucleotide position. We use computational DNA hole spectroscopy [M.Y. Suarez-Villagran & J.H. Miller, Sci. Rep. 5, 13571 (2015)] to reveal sites of enhanced hole probability in selected regions of human mitochondrial DNA. A hole is a mobile site of positive charge created when an electron is removed, for example by radiation or contact with a mutagenic agent. The hole spectra are quantum mechanically computed using a two-stranded tight binding model of DNA. We observe significant correlation between spectra of hole probabilities and of genetic variation frequencies from the MITOMAP database. These results suggest that hole-enhanced mutation mechanisms exert a substantial, perhaps dominant, influence on mutation patterns in DNA. One example is where a trapped hole induces a hydrogen bond shift, known as tautomerization, which then triggers a base-pair mismatch during replication. Our results deepen overall understanding of sequence specific mutation rates, encompassing both hotspots and cold spots, which drive molecular evolution.

A remote sensing and geographic information system approach to sampling malaria vector habitats in Chiapas, Mexico

NASA Astrophysics Data System (ADS)

Beck, L.; Wood, B.; Whitney, S.; Rossi, R.; Spanner, M.; Rodriguez, M.; Rodriguez-Ramirez, A.; Salute, J.; Legters, L.; Roberts, D.; Rejmankova, E.; Washino, R.

1993-08-01

This paper describes a procedure whereby remote sensing and geographic information system (GIS) technologies are used in a sample design to study the habitat of Anopheles albimanus, one of the principle vectors of malaria in Central America. This procedure incorporates Landsat-derived land cover maps with digital elevation and road network data to identify a random selection of larval habitats accessible for field sampling. At the conclusion of the sampling season, the larval counts will be used to determine habitat productivity, and then integrated with information on human settlement to assess where people are at high risk of malaria. This aproach would be appropriate in areas where land cover information is lacking and problems of access constrain field sampling. The use of a GIS also permits other data (such as insecticide spraying data) to the incorporated in the sample design as they arise. This approach would also be pertinent for other tropical vector-borne diseases, particularly where human activities impact disease vector habitat.

Graph Learning in Knowledge Bases

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

Goldberg, Sean; Wang, Daisy Zhe

The amount of text data has been growing exponentially in recent years, giving rise to automatic information extraction methods that store text annotations in a database. The current state-of-theart structured prediction methods, however, are likely to contain errors and it’s important to be able to manage the overall uncertainty of the database. On the other hand, the advent of crowdsourcing has enabled humans to aid machine algorithms at scale. As part of this project we introduced pi-CASTLE , a system that optimizes and integrates human and machine computing as applied to a complex structured prediction problem involving conditional random fieldsmore » (CRFs). We proposed strategies grounded in information theory to select a token subset, formulate questions for the crowd to label, and integrate these labelings back into the database using a method of constrained inference. On both a text segmentation task over academic citations and a named entity recognition task over tweets we showed an order of magnitude improvement in accuracy gain over baseline methods.« less

Modeling On-Body DTN Packet Routing Delay in the Presence of Postural Disconnections.

PubMed

Quwaider, Muhannad; Taghizadeh, Mahmoud; Biswas, Subir

2011-01-01

This paper presents a stochastic modeling framework for store-and-forward packet routing in Wireless Body Area Networks ( WBAN ) with postural partitioning. A prototype WBANs has been constructed for experimentally characterizing and capturing on-body topology disconnections in the presence of ultrashort range radio links, unpredictable RF attenuation, and human postural mobility. Delay modeling techniques for evaluating single-copy on-body DTN routing protocols are then developed. End-to-end routing delay for a series of protocols including opportunistic, randomized, and two other mechanisms that capture multiscale topological localities in human postural movements have been evaluated. Performance of the analyzed protocols are then evaluated experimentally and via simulation to compare with the results obtained from the developed model. Finally, a mechanism for evaluating the topological importance of individual on-body sensor nodes is developed. It is shown that such information can be used for selectively reducing the on-body sensor-count without substantially sacrificing the packet delivery delay.

Modeling On-Body DTN Packet Routing Delay in the Presence of Postural Disconnections

PubMed Central

Quwaider, Muhannad; Taghizadeh, Mahmoud; Biswas, Subir

2014-01-01

This paper presents a stochastic modeling framework for store-and-forward packet routing in Wireless Body Area Networks (WBAN) with postural partitioning. A prototype WBANs has been constructed for experimentally characterizing and capturing on-body topology disconnections in the presence of ultrashort range radio links, unpredictable RF attenuation, and human postural mobility. Delay modeling techniques for evaluating single-copy on-body DTN routing protocols are then developed. End-to-end routing delay for a series of protocols including opportunistic, randomized, and two other mechanisms that capture multiscale topological localities in human postural movements have been evaluated. Performance of the analyzed protocols are then evaluated experimentally and via simulation to compare with the results obtained from the developed model. Finally, a mechanism for evaluating the topological importance of individual on-body sensor nodes is developed. It is shown that such information can be used for selectively reducing the on-body sensor-count without substantially sacrificing the packet delivery delay. PMID:25530749

Dairy consumption and body mass index among adults: Mendelian randomization analysis of 184802 individuals from 25 studies

USDA-ARS?s Scientific Manuscript database

Background: Associations between dairy intake and body mass index (BMI) have been inconsistently observed in epidemiological studies; and the causal relationship remains ill defined. Using the Mendelian randomization (MR) approach and meta-analysis of selected randomized controlled trials (RCTs), we...

Balancing Participation across Students in Large College Classes via Randomized Participation Credit

ERIC Educational Resources Information Center

McCleary, Daniel F.; Aspiranti, Kathleen B.; Foster, Lisa N.; Blondin, Carolyn A.; Gaylon, Charles E.; Yaw, Jared S.; Forbes, Bethany N.; Williams, Robert L.

2011-01-01

The study examines the effects of randomized credit on the percentage of students participating at four predefined levels. Students recorded their comments on specially designed record cards, and days were randomly selected for participation credit. This arrangement balanced participation across students while cutting instructor time for recording…

Determinants of selective reporting: A taxonomy based on content analysis of a random selection of the literature

PubMed Central

van den Bogert, Cornelis A.; van Soest-Poortvliet, Mirjam C.; Fazeli Farsani, Soulmaz; Otten, René H. J.; ter Riet, Gerben; Bouter, Lex M.

2018-01-01

Background Selective reporting is wasteful, leads to bias in the published record and harms the credibility of science. Studies on potential determinants of selective reporting currently lack a shared taxonomy and a causal framework. Objective To develop a taxonomy of determinants of selective reporting in science. Design Inductive qualitative content analysis of a random selection of the pertinent literature including empirical research and theoretical reflections. Methods Using search terms for bias and selection combined with terms for reporting and publication, we systematically searched the PubMed, Embase, PsycINFO and Web of Science databases up to January 8, 2015. Of the 918 articles identified, we screened a 25 percent random selection. From eligible articles, we extracted phrases that mentioned putative or possible determinants of selective reporting, which we used to create meaningful categories. We stopped when no new categories emerged in the most recently analyzed articles (saturation). Results Saturation was reached after analyzing 64 articles. We identified 497 putative determinants, of which 145 (29%) were supported by empirical findings. The determinants represented 12 categories (leaving 3% unspecified): focus on preferred findings (36%), poor or overly flexible research design (22%), high-risk area and its development (8%), dependence upon sponsors (8%), prejudice (7%), lack of resources including time (3%), doubts about reporting being worth the effort (3%), limitations in reporting and editorial practices (3%), academic publication system hurdles (3%), unfavorable geographical and regulatory environment (2%), relationship and collaboration issues (2%), and potential harm (0.4%). Conclusions We designed a taxonomy of putative determinants of selective reporting consisting of 12 categories. The taxonomy may help develop theory about causes of selection bias and guide policies to prevent selective reporting. PMID:29401492

Structural Alteration of Gut Microbiota during the Amelioration of Human Type 2 Diabetes with Hyperlipidemia by Metformin and a Traditional Chinese Herbal Formula: a Multicenter, Randomized, Open Label Clinical Trial

PubMed Central

2018-01-01

ABSTRACT Accumulating evidence implicates gut microbiota as promising targets for the treatment of type 2 diabetes mellitus (T2DM). With a randomized clinical trial, we tested the hypothesis that alteration of gut microbiota may be involved in the alleviation of T2DM with hyperlipidemia by metformin and a specifically designed herbal formula (AMC). Four hundred fifty patients with T2DM and hyperlipidemia were randomly assigned to either the metformin- or AMC-treated group. After 12 weeks of treatment, 100 patients were randomly selected from each group and assessed for clinical improvement. The effects of the two drugs on the intestinal microbiota were evaluated by analyzing the V3 and V4 regions of the 16S rRNA gene by Illumina sequencing and multivariate statistical methods. Both metformin and AMC significantly alleviated hyperglycemia and hyperlipidemia and shifted gut microbiota structure in diabetic patients. They significantly increased a coabundant group represented by Blautia spp., which significantly correlated with the improvements in glucose and lipid homeostasis. However, AMC showed better efficacies in improving homeostasis model assessment of insulin resistance (HOMA-IR) and plasma triglyceride and also exerted a larger effect on gut microbiota. Furthermore, only AMC increased the coabundant group represented by Faecalibacterium spp., which was previously reported to be associated with the alleviation of T2DM in a randomized clinical trial. Metformin and the Chinese herbal formula may ameliorate type 2 diabetes with hyperlipidemia via enriching beneficial bacteria, such as Blautia and Faecalibacterium spp. PMID:29789365

Correlated randomness and switching phenomena

NASA Astrophysics Data System (ADS)

Stanley, H. E.; Buldyrev, S. V.; Franzese, G.; Havlin, S.; Mallamace, F.; Kumar, P.; Plerou, V.; Preis, T.

2010-08-01

One challenge of biology, medicine, and economics is that the systems treated by these serious scientific disciplines have no perfect metronome in time and no perfect spatial architecture-crystalline or otherwise. Nonetheless, as if by magic, out of nothing but randomness one finds remarkably fine-tuned processes in time and remarkably fine-tuned structures in space. Further, many of these processes and structures have the remarkable feature of “switching” from one behavior to another as if by magic. The past century has, philosophically, been concerned with placing aside the human tendency to see the universe as a fine-tuned machine. Here we will address the challenge of uncovering how, through randomness (albeit, as we shall see, strongly correlated randomness), one can arrive at some of the many spatial and temporal patterns in biology, medicine, and economics and even begin to characterize the switching phenomena that enables a system to pass from one state to another. Inspired by principles developed by A. Nihat Berker and scores of other statistical physicists in recent years, we discuss some applications of correlated randomness to understand switching phenomena in various fields. Specifically, we present evidence from experiments and from computer simulations supporting the hypothesis that water’s anomalies are related to a switching point (which is not unlike the “tipping point” immortalized by Malcolm Gladwell), and that the bubbles in economic phenomena that occur on all scales are not “outliers” (another Gladwell immortalization). Though more speculative, we support the idea of disease as arising from some kind of yet-to-be-understood complex switching phenomenon, by discussing data on selected examples, including heart disease and Alzheimer disease.

Clinical evaluations of mineralized collagen in the extraction sites preservation

PubMed Central

Feng, Lu; Zhang, Liang; Cui, Yun; Song, Tian-Xi; Qiu, Zhi-Ye; Wang, Xiu-Mei; Tan, Bao-Sheng

2016-01-01

The purpose of this study was to explore the different effects between biomimetic mineralized collagen (MC) and ordinary physically blended hydroxyapatite/collagen (HA/Col) composite in evaluating new bone formation and regenerated bone height in human extraction sockets. Thirty-four patients who cannot retain teeth caused by trauma or decay were randomly selected from Department of Stomatology of Dongzhimen Hospital from December 2013 to December 2014. The patients were randomly divided into two groups. After the operation of tooth extraction, 17 patients were implanted with biomimetic MC (MC group), and other 17 patients were implanted with ordinary physically blended nHA/Col composite (nHA/Col group). X-ray positioning projection by auto-photographing was taken to test the distance between the lowest position and the neighboring CEJm-CEJd immediately, 1 month and 3 months after the operation. The height of new bone formation of the MC group was significantly higher than the nHA/Col group. Biomimetic MC showed better clinical outcomes in the bone formation for extraction site preservation and would have broad application prospect in the field of oral and maxillofacial surgeries. PMID:26815224

Reverse Nearest Neighbor Search on a Protein-Protein Interaction Network to Infer Protein-Disease Associations.

PubMed

Suratanee, Apichat; Plaimas, Kitiporn

2017-01-01

The associations between proteins and diseases are crucial information for investigating pathological mechanisms. However, the number of known and reliable protein-disease associations is quite small. In this study, an analysis framework to infer associations between proteins and diseases was developed based on a large data set of a human protein-protein interaction network integrating an effective network search, namely, the reverse k -nearest neighbor (R k NN) search. The R k NN search was used to identify an impact of a protein on other proteins. Then, associations between proteins and diseases were inferred statistically. The method using the R k NN search yielded a much higher precision than a random selection, standard nearest neighbor search, or when applying the method to a random protein-protein interaction network. All protein-disease pair candidates were verified by a literature search. Supporting evidence for 596 pairs was identified. In addition, cluster analysis of these candidates revealed 10 promising groups of diseases to be further investigated experimentally. This method can be used to identify novel associations to better understand complex relationships between proteins and diseases.

The current status of REH theory. [Random Evolutionary Hits in biological molecular evolution

NASA Technical Reports Server (NTRS)

Holmquist, R.; Jukes, T. H.

1981-01-01

A response is made to the evaluation of Fitch (1980) of REH (random evolutionary hits) theory for the evolutionary divergence of proteins and nucleic acids. Correct calculations for the beta hemoglobin mRNAs of the human, mouse and rabbit in the absence and presence of selective constraints are summarized, and it is shown that the alternative evolutionary analysis of Fitch underestimates the total fixed mutations. It is further shown that the model used by Fitch to test for the completeness of the count of total base substitutions is in fact a variant of REH theory. Considerations of the variance inherent in evolutionary estimations are also presented which show the REH model to produce no more variance than other evolutionary models. In the reply, it is argued that, despite the objections raised, REH theory applied to proteins gives inaccurate estimates of total gene substitutions. It is further contended that REH theory developed for nucleic sequences suffers from problems relating to the frequency of nucleotide substitutions, the identity of the codons accepting silent and amino acid-changing substitutions, and estimate uncertainties.

Randomized in vitro and in vivo evaluation of different biopsy needles and devices for breast biopsy.

PubMed

Helbich, T H; Rudas, M; Böhm, G; Huber, S; Wagner, T; Taucher, S; Wolf, G; Mostbeck, G H

1999-01-01

In an experimental study (in vitro and in vivo) we evaluated the efficacy of various biopsy needles/devices for breast biopsy. In vitro, biopsies of five human cadaveric breast specimens were performed using 33 different needles/devices ranging from 14 to 20-gauge. Of these 33 needles/devices, 22 optimally performing needles were selected for the in vivo study. In the clinical part of the study, 44 breast lesions were randomly biopsied with each of the 22 needles/devices under stereotactic guidance. Tissue specimens were analysed quantitatively and qualitatively. Several automatic long-throw guns (Acecut, Asap, Biopty, Magnum) obtained greater tissue areas and had a better histopathologic score than the conventional type of a side-notch needle like Trucut, an aspiration needle like Surecut, or an end-cut needle like Autovac. The automatic long-throw guns performed better than the short-throw Monopty gun. Regardless of needle size (14-20-gauge), breast biopsies should be routinely performed with automated long-throw side-notch guns (Acecut, Asap, Biopty, Magnum).

Comparison of in vivo 3D cone-beam computed tomography tooth volume measurement protocols.

PubMed

Forst, Darren; Nijjar, Simrit; Flores-Mir, Carlos; Carey, Jason; Secanell, Marc; Lagravere, Manuel

2014-12-23

The objective of this study is to analyze a set of previously developed and proposed image segmentation protocols for precision in both intra- and inter-rater reliability for in vivo tooth volume measurements using cone-beam computed tomography (CBCT) images. Six 3D volume segmentation procedures were proposed and tested for intra- and inter-rater reliability to quantify maxillary first molar volumes. Ten randomly selected maxillary first molars were measured in vivo in random order three times with 10 days separation between measurements. Intra- and inter-rater agreement for all segmentation procedures was attained using intra-class correlation coefficient (ICC). The highest precision was for automated thresholding with manual refinements. A tooth volume measurement protocol for CBCT images employing automated segmentation with manual human refinement on a 2D slice-by-slice basis in all three planes of space possessed excellent intra- and inter-rater reliability. Three-dimensional volume measurements of the entire tooth structure are more precise than 3D volume measurements of only the dental roots apical to the cemento-enamel junction (CEJ).

jmzIdentML API: A Java interface to the mzIdentML standard for peptide and protein identification data.

PubMed

Reisinger, Florian; Krishna, Ritesh; Ghali, Fawaz; Ríos, Daniel; Hermjakob, Henning; Vizcaíno, Juan Antonio; Jones, Andrew R

2012-03-01

We present a Java application programming interface (API), jmzIdentML, for the Human Proteome Organisation (HUPO) Proteomics Standards Initiative (PSI) mzIdentML standard for peptide and protein identification data. The API combines the power of Java Architecture of XML Binding (JAXB) and an XPath-based random-access indexer to allow a fast and efficient mapping of extensible markup language (XML) elements to Java objects. The internal references in the mzIdentML files are resolved in an on-demand manner, where the whole file is accessed as a random-access swap file, and only the relevant piece of XMLis selected for mapping to its corresponding Java object. The APIis highly efficient in its memory usage and can handle files of arbitrary sizes. The APIfollows the official release of the mzIdentML (version 1.1) specifications and is available in the public domain under a permissive licence at http://www.code.google.com/p/jmzidentml/. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Efficacy of Stent-Retriever Thrombectomy in Magnetic Resonance Imaging Versus Computed Tomographic Perfusion-Selected Patients in SWIFT PRIME Trial (Solitaire FR With the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke).

PubMed

Menjot de Champfleur, Nicolas; Saver, Jeffrey L; Goyal, Mayank; Jahan, Reza; Diener, Hans-Christoph; Bonafe, Alain; Levy, Elad I; Pereira, Vitor M; Cognard, Christophe; Yavagal, Dileep R; Albers, Gregory W

2017-06-01

The majority of patients enrolled in SWIFT PRIME trial (Solitaire FR With the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke) had computed tomographic perfusion (CTP) imaging before randomization; 34 patients were randomized after magnetic resonance imaging (MRI). Patients with middle cerebral artery and distal carotid occlusions were randomized to treatment with tPA (tissue-type plasminogen activator) alone or tPA+stentriever thrombectomy. The primary outcome was the distribution of the modified Rankin Scale score at 90 days. Patients with the target mismatch profile for enrollment were identified on MRI and CTP. MRI selection was performed in 34 patients; CTP in 139 patients. Baseline National Institutes of Health Stroke Scale score was 17 in both groups. Target mismatch profile was present in 95% (MRI) versus 83% (CTP). A higher percentage of the MRI group was transferred from an outside hospital ( P =0.02), and therefore, the time from stroke onset to randomization was longer in the MRI group ( P =0.003). Time from emergency room arrival to randomization did not differ in CTP versus MRI-selected patients. Baseline ischemic core volumes were similar in both groups. Reperfusion rates (>90%/TICI [Thrombolysis in Cerebral Infarction] score 3) did not differ in the stentriever-treated patients in the MRI versus CTP groups. The primary efficacy analysis (90-day mRS score) demonstrated a statistically significant benefit in both subgroups (MRI, P =0.02; CTP, P =0.01). Infarct growth was reduced in the stentriever-treated group in both MRI and CTP groups. Time to randomization was significantly longer in MRI-selected patients; however, site arrival to randomization times were not prolonged, and the benefits of endovascular therapy were similar. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01657461. © 2017 American Heart Association, Inc.

The effect of atomoxetine on random and directed exploration in humans.

PubMed

Warren, Christopher M; Wilson, Robert C; van der Wee, Nic J; Giltay, Eric J; van Noorden, Martijn S; Cohen, Jonathan D; Nieuwenhuis, Sander

2017-01-01

The adaptive regulation of the trade-off between pursuing a known reward (exploitation) and sampling lesser-known options in search of something better (exploration) is critical for optimal performance. Theory and recent empirical work suggest that humans use at least two strategies for solving this dilemma: a directed strategy in which choices are explicitly biased toward information seeking, and a random strategy in which decision noise leads to exploration by chance. Here we examined the hypothesis that random exploration is governed by the neuromodulatory locus coeruleus-norepinephrine system. We administered atomoxetine, a norepinephrine transporter blocker that increases extracellular levels of norepinephrine throughout the cortex, to 22 healthy human participants in a double-blind crossover design. We examined the effect of treatment on performance in a gambling task designed to produce distinct measures of directed exploration and random exploration. In line with our hypothesis we found an effect of atomoxetine on random, but not directed exploration. However, contrary to expectation, atomoxetine reduced rather than increased random exploration. We offer three potential explanations of our findings, involving the non-linear relationship between tonic NE and cognitive performance, the interaction of atomoxetine with other neuromodulators, and the possibility that atomoxetine affected phasic norepinephrine activity more so than tonic norepinephrine activity.

Searching for Survivors through Random Human-Body Movement Outdoors by Continuous-Wave Radar Array

PubMed Central

Liu, Miao; Li, Zhao; Liang, Fulai; Jing, Xijing; Lu, Guohua; Wang, Jianqi

2016-01-01

It is a major challenge to search for survivors after chemical or nuclear leakage or explosions. At present, biological radar can be used to achieve this goal by detecting the survivor’s respiration signal. However, owing to the random posture of an injured person at a rescue site, the radar wave may directly irradiate the person’s head or feet, in which it is difficult to detect the respiration signal. This paper describes a multichannel-based antenna array technology, which forms an omnidirectional detection system via 24-GHz Doppler biological radar, to address the random positioning relative to the antenna of an object to be detected. Furthermore, since the survivors often have random body movement such as struggling and twitching, the slight movements of the body caused by breathing are obscured by these movements. Therefore, a method is proposed to identify random human-body movement by utilizing multichannel information to calculate the background variance of the environment in combination with a constant-false-alarm-rate detector. The conducted outdoor experiments indicate that the system can realize the omnidirectional detection of random human-body movement and distinguish body movement from environmental interference such as movement of leaves and grass. The methods proposed in this paper will be a promising way to search for survivors outdoors. PMID:27073860