Pruning the regulatory tree

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62897/1/457534a.pd

Machine learning algorithms for systematic review: reducing workload in a preclinical review of animal studies and reducing human screening error

BACKGROUND: Here, we outline a method of applying existing machine learning (ML) approaches to aid citation screening in an on-going broad and shallow systematic review of preclinical animal studies. The aim is to achieve a high-performing algorithm comparable to human screening that can reduce human resources required for carrying out this step of a systematic review. METHODS: We applied ML approaches to a broad systematic review of animal models of depression at the citation screening stage. We tested two independently developed ML approaches which used different classification models and feature sets. We recorded the performance of the ML approaches on an unseen validation set of papers using sensitivity, specificity and accuracy. We aimed to achieve 95% sensitivity and to maximise specificity. The classification model providing the most accurate predictions was applied to the remaining unseen records in the dataset and will be used in the next stage of the preclinical biomedical sciences systematic review. We used a cross-validation technique to assign ML inclusion likelihood scores to the human screened records, to identify potential errors made during the human screening process (error analysis). RESULTS: ML approaches reached 98.7% sensitivity based on learning from a training set of 5749 records, with an inclusion prevalence of 13.2%. The highest level of specificity reached was 86%. Performance was assessed on an independent validation dataset. Human errors in the training and validation sets were successfully identified using the assigned inclusion likelihood from the ML model to highlight discrepancies. Training the ML algorithm on the corrected dataset improved the specificity of the algorithm without compromising sensitivity. Error analysis correction leads to a 3% improvement in sensitivity and specificity, which increases precision and accuracy of the ML algorithm. CONCLUSIONS: This work has confirmed the performance and application of ML algorithms for screening in systematic reviews of preclinical animal studies. It has highlighted the novel use of ML algorithms to identify human error. This needs to be confirmed in other reviews with different inclusion prevalence levels, but represents a promising approach to integrating human decisions and automation in systematic review methodology

Biomedical Scientists' Perceptions of Ethical and Social Implications: Is There a Role for Research Ethics Consultation?

Research ethics consultation programs are being established with a goal of addressing the ethical, societal, and policy considerations associated with biomedical research. A number of these programs are modelled after clinical ethics consultation services that began to be institutionalized in the 1980s. Our objective was to determine biomedical science researchers' perceived need for and utility of research ethics consultation, through examination of their perceptions of whether they and their institutions faced ethical, social or policy issues (outside those mandated by regulation) and examination of willingness to seek advice in addressing these issues. We conducted telephone interviews and focus groups in 2006 with researchers from Stanford University and a mailed survey in December 2006 to 7 research universities in the U.S.A total of 16 researchers were interviewed (75% response rate), 29 participated in focus groups, and 856 responded to the survey (50% response rate). Approximately half of researchers surveyed (51%) reported that they would find a research ethics consultation service at their institution moderately, very or extremely useful, while over a third (36%) reported that such a service would be useful to them personally. Respondents conducting human subjects research were more likely to find such a service very to extremely useful to them personally than respondents not conducting human subjects research (20% vs 10%; chi(2) p<0.001).Our findings indicate that biomedical researchers do encounter and anticipate encountering ethical and societal questions and concerns and a substantial proportion, especially clinical researchers, would likely use a consultation service if they were aware of it. These findings provide data to inform the development of such consultation programs in general

Fungal enzyme sets for plant polysaccharide degradation

Enzymatic degradation of plant polysaccharides has many industrial applications, such as within the paper, food, and feed industry and for sustainable production of fuels and chemicals. Cellulose, hemicelluloses, and pectins are the main components of plant cell wall polysaccharides. These polysaccharides are often tightly packed, contain many different sugar residues, and are branched with a diversity of structures. To enable efficient degradation of these polysaccharides, fungi produce an extensive set of carbohydrate-active enzymes. The variety of the enzyme set differs between fungi and often corresponds to the requirements of its habitat. Carbohydrate-active enzymes can be organized in different families based on the amino acid sequence of the structurally related catalytic modules. Fungal enzymes involved in plant polysaccharide degradation are assigned to at least 35 glycoside hydrolase families, three carbohydrate esterase families and six polysaccharide lyase families. This mini-review will discuss the enzymes needed for complete degradation of plant polysaccharides and will give an overview of the latest developments concerning fungal carbohydrate-active enzymes and their corresponding families

Vitamin G: effects of green space on health, well-being, and social safety

BACKGROUND: Looking out on and being in the green elements of the landscape around us seem to affect health, well-being and feelings of social safety. This article discusses the design of a research program on the effects of green space in the living environment on health, well-being and social safety. METHODS/DESIGN: The program consists of three projects at three different scales: at a macro scale using data on the Netherlands as a whole, at an intermediate scale looking into the specific effect of green space in the urban environment, and at micro scale investigating the effects of allotment gardens. The projects are observational studies, combining existing data on land use and health interview survey data, and collecting new data through questionnaires and interviews. Multilevel analysis and GIS techniques will be used to analyze the data. DISCUSSION: Previous (experimental) research in environmental psychology has shown that a natural environment has a positive effect on well-being through restoration of stress and attentional fatigue. Descriptive epidemiological research has shown a positive relationship between the amount of green space in the living environment and physical and mental health and longevity. The program has three aims. First, to document the relationship between the amount and type of green space in people's living environment and their health, well-being, and feelings of safety. Second, to investigate the mechanisms behind this relationship. Mechanisms relate to exposure (leading to stress reduction and attention restoration), healthy behavior and social integration, and selection. Third, to translate the results into policy on the crossroads of spatial planning, public health, and safety. Strong points of our program are: we study several interrelated dependent variables, in different ordinary settings (as opposed to experimental or extreme settings), focusing on different target groups, using appropriate multilevel methods

Gipc3 mutations associated with audiogenic seizures and sensorineural hearing loss in mouse and human

Sensorineural hearing loss affects the quality of life and communication of millions of people, but the underlying molecular mechanisms remain elusive. Here, we identify mutations in Gipc3 underlying progressive sensorineural hearing loss (age-related hearing loss 5, ahl5) and audiogenic seizures (juvenile audiogenic monogenic seizure 1, jams1) in mice and autosomal recessive deafness DFNB15 and DFNB95 in humans. Gipc3 localizes to inner ear sensory hair cells and spiral ganglion. A missense mutation in the PDZ domain has an attenuating effect on mechanotransduction and the acquisition of mature inner hair cell potassium currents. Magnitude and temporal progression of wave I amplitude of afferent neurons correlate with susceptibility and resistance to audiogenic seizures. The Gipc3343A allele disrupts the structure of the stereocilia bundle and affects long-term function of auditory hair cells and spiral ganglion neurons. Our study suggests a pivotal role of Gipc3 in acoustic signal acquisition and propagation in cochlear hair cells

Leadership = Communication? The relations of leaders' communication styles with leadership styles, knowledge sharing and leadership outcomes

Purpose: The purpose of this study was to investigate the relations between leaders' communication styles and charismatic leadership, human-oriented leadership (leader's consideration), task-oriented leadership (leader's initiating structure), and leadership outcomes. Methodology: A survey was conducted among 279 employees of a governmental organization. The following six main communication styles were operationalized: verbal aggressiveness, expressiveness, preciseness, assuredness, supportiveness, and argumentativeness. Regression analyses were employed to test three main hypotheses. Findings: In line with expectations, the study showed that charismatic and human-oriented leadership are mainly communicative, while task-oriented leadership is significantly less communicative. The communication styles were strongly and differentially related to knowledge sharing behaviors, perceived leader performance, satisfaction with the leader, and subordinate's team commitment. Multiple regression analyses showed that the leadership styles mediated the relations between the communication styles and leadership outcomes. However, leader's preciseness explained variance in perceived leader performance and satisfaction with the leader above and beyond the leadership style variables. Implications: This study offers potentially invaluable input for leadership training programs by showing the importance of leader's supportiveness, assuredness, and preciseness when communicating with subordinates. Originality/value: Although one of the core elements of leadership is interpersonal communication, this study is one of the first to use a comprehensive communication styles instrument in the study of leadership. © 2009 The Author(s)

Phase 1b randomized, double-blind study of namilumab, an anti-granulocyte macrophage colony-stimulating factor monoclonal antibody, in mild-to-moderate rheumatoid arthritis

Change from baseline in swollen (a) and tender (b) joint counts. *Error bars show upper SE for placebo and lower SE for namilumab. SE standard error, SJC swollen joint count, TJC tender joint count. (PDF 1292 kb

American College of Medical Genetics guideline on the cytogenetic evaluation of the individual with developmental delay or mental retardation

The following are the recommendations of the American College of Medical Genetics (ACMG) Professional Practice and Guidelines Committee, which was convened to assist health care professionals in making decisions regarding cytogenetic diagnostic testing and counseling for mental retardation (MR) and developmental delay (DD). This document reviews available evidence concerning the value of conventional and molecular cytogenetic testing for the identification of chromosomal anomalies that play a role in the etiology of MR/DD, and, based on this evidence, specific recommendations for each method of testing are provided

Regulation of MYCN expression in human neuroblastoma cells

Contains fulltext : 81722.pdf (publisher's version ) (Open Access)BACKGROUND: Amplification of the MYCN gene in neuroblastoma (NB) is associated with a poor prognosis. However, MYCN-amplification does not automatically result in higher expression of MYCN in children with NB. We hypothesized that the discrepancy between MYCN gene expression and prognosis in these children might be explained by the expression of either MYCN-opposite strand (MYCNOS) or the shortened MYCN-isoform (DeltaMYCN) that was recently identified in fetal tissues. Both MYCNOS and DeltaMYCN are potential inhibitors of MYCN either at the mRNA or at the protein level. METHODS: Expression of MYCN, MYCNOS and DeltaMYCN was measured in human NB tissues of different stages. Transcript levels were quantified using a real-time reverse transcriptase polymerase chain reaction assay (QPCR). In addition, relative expression of these three transcripts was compared to the number of MYCN copies, which was determined by genomic real-time PCR (gQPCR). RESULTS: Both DeltaMYCN and MYCNOS are expressed in all NBs examined. In NBs with MYCN-amplification, these transcripts are significantly higher expressed. The ratio of MYCN:DeltaMYCN expression was identical in all tested NBs. This indicates that DeltaMYCN and MYCN are co-regulated, which suggests that DeltaMYCN is not a regulator of MYCN in NB. However, the ratio of MYCNOS:MYCN expression is directly correlated with NB disease stage (p = 0.007). In the more advanced NB stages and NBs with MYCN-amplification, relatively more MYCNOS is present as compared to MYCN. Expression of the antisense gene MYCNOS might be relevant to the progression of NB, potentially by directly inhibiting MYCN transcription by transcriptional interference at the DNA level. CONCLUSION: The MYCNOS:MYCN-ratio in NBs is significantly correlated with both MYCN-amplification and NB-stage. Our data indicate that in NB, MYCN expression levels might be influenced by MYCNOS but not by DeltaMYCN