Study on measuring device arrangement of array-type CdTe detector for BNCT-SPECT

Aim

To design the measuring device arrangement of array-type CdTe detector for BNCT-SPECT.

Background

In a boron neutron capture therapy, a very serious unsolved problem exists, namely that the treatment effect for BNCT cannot be known during irradiation in real time. Therefore, we have been developing a so-called BNCT-SPECT with a CdTe detector, which can obtain a three-dimensional image for the BNCT treatment effect by measuring 478 keV gamma-rays emitted from the excited state of ⁷Li nucleus created by the ¹⁰B(n,α) reaction. However, no practical uses were realized at present, because BNCT-SPECT requires very severe conditions for spatial resolution, measuring time, statistical accuracy and energy resolution.

Materials and methods

The design study was performed with numerical simulations carried out by a 3-dimenaional transport code, MCNP5 considering the detector assembly, irradiation room and even arrangement of arrayed CdTe crystals.

Results

The estimated count rate of 478 keV gamma-rays was sufficiently large being more than the target value of over 1000 counts/h. However, the S/N ratio did not meet the target of S/N > 1. We confirmed that deterioration of the S/N ratio was caused by the influence of Compton scattering especially due to capture gamma-rays of hydrogen. Theoretical calculations were thereafter carried out to find out whether anti-Compton measurement in an array-type CdTe detector could decrease the noise due to Compton scatterings.

Conclusions

The calculation result showed that the anti-coincidence would possibly increase the S/N ratio. In the next phase, an arrayed detector with two CdTe crystals will be produced to test removal possibility of the anti-coincident event.     

Classification of Structural MRI Images in Alzheimer's Disease from the Perspective of Ill-Posed Problems

Background

Machine learning neuroimaging researchers have often relied on regularization techniques when classifying MRI images. Although these were originally introduced to deal with “ill-posed” problems it is rare to find studies that evaluate the ill-posedness of MRI image classification problems. In addition, to avoid the effects of the “curse of dimensionality” very often dimension reduction is applied to the data.

Methodology

Baseline structural MRI data from cognitively normal and Alzheimer''s disease (AD) patients from the AD Neuroimaging Initiative database were used in this study. We evaluated here the ill-posedness of this classification problem across different dimensions and sample sizes and its relationship to the performance of regularized logistic regression (RLR), linear support vector machine (SVM) and linear regression classifier (LRC). In addition, these methods were compared with their principal components space counterparts.

Principal Findings

In voxel space the prediction performance of all methods increased as sample sizes increased. They were not only relatively robust to the increase of dimension, but they often showed improvements in accuracy. We linked this behavior to improvements in conditioning of the linear kernels matrices. In general the RLR and SVM performed similarly. Surprisingly, the LRC was often very competitive when the linear kernel matrices were best conditioned. Finally, when comparing these methods in voxel and principal component spaces, we did not find large differences in prediction performance.

Conclusions and Significance

We analyzed the problem of classifying AD MRI images from the perspective of linear ill-posed problems. We demonstrate empirically the impact of the linear kernel matrix conditioning on different classifiers'' performance. This dependence is characterized across sample sizes and dimensions. In this context we also show that increased dimensionality does not necessarily degrade performance of machine learning methods. In general, this depends on the nature of the problem and the type of machine learning method.     

Profiling dizziness in older primary care patients: an empirical study

Background

The diagnostic approach to dizzy, older patients is not straightforward as many organ systems can be involved and evidence for diagnostic strategies is lacking. A first differentiation in diagnostic subtypes or profiles may guide the diagnostic process of dizziness and can serve as a classification system in future research. In the literature this has been done, but based on pathophysiological reasoning only.

Objective

To establish a classification of diagnostic profiles of dizziness based on empirical data.

Design

Cross-sectional study.

Participants and Setting

417 consecutive patients of 65 years and older presenting with dizziness to 45 primary care physicians in the Netherlands from July 2006 to January 2008.

Methods

We performed tests, including patient history, and physical and additional examination, previously selected by an international expert panel and based on an earlier systematic review. We used the results of these tests in a principal component analysis for exploration, data-reduction and finally differentiation into diagnostic dizziness profiles.

Results

Demographic data and the results of the tests yielded 221 variables, of which 49 contributed to the classification of dizziness into six diagnostic profiles, that may be named as follows: “frailty”, “psychological”, “cardiovascular”, “presyncope”, “non-specific dizziness” and “ENT”. These explained 32% of the variance.

Conclusions

Empirically identified components classify dizziness into six profiles. This classification takes into account the heterogeneity and multicausality of dizziness and may serve as starting point for research on diagnostic strategies and can be a first step in an evidence based diagnostic approach of dizzy older patients.     

Hospital Door Handle Design and Their Contamination with Bacteria: A Real Life Observational Study. Are We Pulling against Closed Doors?

Objective

To determine whether microbial contamination of door handles in two busy intensive care units and one high dependency unit was related to their design, location, and usage.

Design

Observational study of the number of viable bacteria on existing door handles of different design at defined entry/exit points with simultaneous data collection of who used these doors and how often.

Setting

Two busy specialised intensive care units and one high dependency unit in a tertiary referral NHS neurological hospital.

Main outcome measures

Surface bacterial density on door handles with reference to design, location, and intensity of use.

Results

We found a significant correlation between the frequency of movements through a door and the degree to which it was contaminated (p = <0.01). We further found that the door''s location, design and mode of use all influenced contamination. When compared to push plate designs, pull handles revealed on average a five fold higher level of contamination; lever handles, however, displayed the highest levels of bacterial contamination when adjusted for frequency of use. We also observed differences in contamination levels at doors between clinical areas, particularly between the operating theatres and one of the ICUs.

Conclusions

Door handles in busy, “real life” high acuity clinical environments were variably contaminated with bacteria, and the number of bacteria found related to design, location, mode and frequency of operation. Largely ignored issues of handle and environmental design can support or undermine strategies designed to limit avoidable pathogen transmission, especially in locations designed to define “thresholds” and impose physical barriers to pathogen transmission between clinical areas. Developing a multidisciplinary approach beyond traditional boundaries for purposes of infection control may release hitherto unappreciated options and beneficial outcomes for the control of at least some hospital acquired infections.     

Experimental set up for the irradiation of biological samples and nuclear track detectors with UV C

Aim

In this work we present a methodology to produce an “imprint” of cells cultivated on a polycarbonate detector by exposure of the detector to UV C radiation.

Background

The distribution and concentration of ¹⁰B atoms in tissue samples coming from BNCT (Boron Neutron Capture Therapy) protocols can be determined through the quantification and analysis of the tracks forming its autoradiography image on a nuclear track detector. The location of boron atoms in the cell structure could be known more accurately by the simultaneous observation of the nuclear tracks and the sample image on the detector.

Materials and Methods

A UV C irradiator was constructed. The irradiance was measured along the lamp direction and at different distances. Melanoma cells were cultured on polycarbonate foils, incubated with borophenylalanine, irradiated with thermal neutrons and exposed to UV C radiation. The samples were chemically attacked with a KOH solution.

Results

A uniform irradiation field was established to expose the detector foils to UV C light. Cells could be seeded on the polycarbonate surface. Both imprints from cells and nuclear tracks were obtained after chemical etching.

Conclusions

It is possible to yield cellular imprints in polycarbonate. The nuclear tracks were mostly present inside the cells, indicating a preferential boron uptake.     

Quantifying the Potential Bias when Directly Comparing Standardised Mortality Ratios for In-Unit Neonatal Mortality

Introduction

The Standardised Mortality Ratio (SMR) is increasingly used to compare the performance of different healthcare providers. However, it has long been known that differences in the populations of the providers can cause biased results when directly comparing two SMRs. This is potentially a particular problem in neonatal medicine where units provide different levels of care.

Methods

Using data from The Neonatal Survey (TNS), babies born at 24 to 31 weeks gestational age from 2002 to 2011 and admitted to one of 11 UK neonatal units were identified. Risk-adjusted SMRs were calculated for each unit using a previously published model to estimate the expected number of deaths. The model parameters were then re-estimated based on data from each individual neonatal unit (“reference” unit) and these then applied to each of the other units to estimate the number of deaths each unit would have observed if they had the same underlying mortality rates as each of the “reference” hospitals. The ratios of the SMRs were then calculated under the assumption of identical risk-specific probabilities of death.

Results

7243 babies were included in all analyses. When comparing between Network Neonatal Units (Level 3) the ratio of SMRs ranged from 0.92 to 1.00 and for the comparisons within Local Neonatal Units (Level 2) ranged from 0.79 to 1.56. However when comparing between neonatal units providing different levels of care ratios up to 1.68 were observed.

Conclusions

If the populations of healthcare providers differ considerably then it is likely that bias will be an issue when directly comparing SMRs. In neonatal care, the comparison of Network Neonatal Units is likely to be useful but caution is required when comparing Local Neonatal Units or between units of different types. Tools to quantify the likely bias are required.     

Modeling the Building Blocks of Biodiversity

Background

Networks of single interaction types, such as plant-pollinator mutualisms, are biodiversity’s “building blocks”. Yet, the structure of mutualistic and antagonistic networks differs, leaving no unified modeling framework across biodiversity’s component pieces.

Methods/Principal Findings

We use a one-dimensional “niche model” to predict antagonistic and mutualistic species interactions, finding that accuracy decreases with the size of the network. We show that properties of the modeled network structure closely approximate empirical properties even where individual interactions are poorly predicted. Further, some aspects of the structure of the niche space were consistently different between network classes.

Conclusions/Significance

These novel results reveal fundamental differences between the ability to predict ecologically important features of the overall structure of a network and the ability to predict pair-wise species interactions.     

Structural imbalance promotes behavior analogous to aesthetic preference in domestic chicks

Background

Visual images may be judged ‘aesthetic’ when their positioning appears imbalanced. An apparent imbalance may signify an as yet incomplete action or event requiring more detailed processing. As such it may refer to phylogenetically ancient stimulus-response mechanisms such as those mediating attentional deployment.

Methodology/Principal Findings

We studied preferences for structural balance or imbalance in week-old domestic chicks (Gallus gallus), using a conditioning procedure to reinforce pecking at either “aligned” (balanced) or “misaligned” (imbalanced) training stimuli. A testing phase with novel balanced and imbalanced stimuli established whether chicks would retain their conditioned behavior or revert to chance responding. Whereas those trained on aligned stimuli were equally likely to choose aligned or misaligned stimuli, chicks trained on misaligned stimuli maintained the trained preference.

Conclusions/Significance

Our results are consistent with the idea that the coding of structural imbalance is primary and even overrides classical conditioning. Generalized to the humans, these results suggest aesthetic judgments based upon structural imbalance may be based on evolutionarily ancient mechanisms, which are shared by different vertebrate species.     

Know Thyself: Behavioral Evidence for a Structural Representation of the Human Body

Background

Representing one''s own body is often viewed as a basic form of self-awareness. However, little is known about structural representations of the body in the brain.

Methods and Findings

We developed an inter-manual version of the classical “in-between” finger gnosis task: participants judged whether the number of untouched fingers between two touched fingers was the same on both hands, or different. We thereby dissociated structural knowledge about fingers, specifying their order and relative position within a hand, from tactile sensory codes. Judgments following stimulation on homologous fingers were consistently more accurate than trials with no or partial homology. Further experiments showed that structural representations are more enduring than purely sensory codes, are used even when number of fingers is irrelevant to the task, and moreover involve an allocentric representation of finger order, independent of hand posture.

Conclusions

Our results suggest the existence of an allocentric representation of body structure at higher stages of the somatosensory processing pathway, in addition to primary sensory representation.     

Cost-Effectiveness of a Community Pharmacist-Led Sleep Apnea Screening Program – A Markov Model

Background

Despite the high prevalence and major public health ramifications, obstructive sleep apnea syndrome (OSAS) remains underdiagnosed. In many developed countries, because community pharmacists (CP) are easily accessible, they have been developing additional clinical services that integrate the services of and collaborate with other healthcare providers (general practitioners (GPs), nurses, etc.). Alternative strategies for primary care screening programs for OSAS involving the CP are discussed.

Objective

To estimate the quality of life, costs, and cost-effectiveness of three screening strategies among patients who are at risk of having moderate to severe OSAS in primary care.

Design

Markov decision model.

Data Sources

Published data.

Target Population

Hypothetical cohort of 50-year-old male patients with symptoms highly evocative of OSAS.

Time Horizon

The 5 years after initial evaluation for OSAS.

Perspective

Societal.

Interventions

Screening strategy with CP (CP-GP collaboration), screening strategy without CP (GP alone) and no screening.

Outcomes measures

Quality of life, survival and costs for each screening strategy.

Results of base-case analysis

Under almost all modeled conditions, the involvement of CPs in OSAS screening was cost effective. The maximal incremental cost for “screening strategy with CP” was about 455€ per QALY gained.

Results of sensitivity analysis

Our results were robust but primarily sensitive to the treatment costs by continuous positive airway pressure, and the costs of untreated OSAS. The probabilistic sensitivity analysis showed that the “screening strategy with CP” was dominant in 80% of cases. It was more effective and less costly in 47% of cases, and within the cost-effective range (maximum incremental cost effectiveness ratio at €6186.67/QALY) in 33% of cases.

Conclusions

CP involvement in OSAS screening is a cost-effective strategy. This proposal is consistent with the trend in Europe and the United States to extend the practices and responsibilities of the pharmacist in primary care.     

Testing for divergent transmission histories among cultural characters: a study using Bayesian phylogenetic methods and Iranian tribal textile data

Background

Archaeologists and anthropologists have long recognized that different cultural complexes may have distinct descent histories, but they have lacked analytical techniques capable of easily identifying such incongruence. Here, we show how Bayesian phylogenetic analysis can be used to identify incongruent cultural histories. We employ the approach to investigate Iranian tribal textile traditions.

Methods

We used Bayes factor comparisons in a phylogenetic framework to test two models of cultural evolution: the hierarchically integrated system hypothesis and the multiple coherent units hypothesis. In the hierarchically integrated system hypothesis, a core tradition of characters evolves through descent with modification and characters peripheral to the core are exchanged among contemporaneous populations. In the multiple coherent units hypothesis, a core tradition does not exist. Rather, there are several cultural units consisting of sets of characters that have different histories of descent.

Results

For the Iranian textiles, the Bayesian phylogenetic analyses supported the multiple coherent units hypothesis over the hierarchically integrated system hypothesis. Our analyses suggest that pile-weave designs represent a distinct cultural unit that has a different phylogenetic history compared to other textile characters.

Conclusions

The results from the Iranian textiles are consistent with the available ethnographic evidence, which suggests that the commercial rug market has influenced pile-rug designs but not the techniques or designs incorporated in the other textiles produced by the tribes. We anticipate that Bayesian phylogenetic tests for inferring cultural units will be of great value for researchers interested in studying the evolution of cultural traits including language, behavior, and material culture.     

Control of Cerebellar Long-Term Potentiation by P-Rex-Family Guanine-Nucleotide Exchange Factors and Phosphoinositide 3-Kinase

Background

Long-term potentiation (LTP) at the parallel fibre–Purkinje cell synapse in the cerebellum is a recently described and poorly characterized form of synaptic plasticity. The induction mechanism for LTP at this synapse is considered reciprocal to “classical” LTP at hippocampal CA1 pyramidal neurons: kinases promote increased trafficking of AMPA receptors into the postsynaptic density in the hippocampus, whereas phosphatases decrease internalization of AMPA receptors in the cerebellum. In the hippocampus, LTP occurs in overlapping phases, with the transition from early to late phases requiring the consolidation of initial induction processes by structural re-arrangements at the synapse. Many signalling pathways have been implicated in this process, including PI3 kinases and Rho GTPases.

Principal Findings

We hypothesized that analogous phases are present in cerebellar LTP, and took as the starting point for investigation our recent discovery that P-Rex – a Rac guanine nucleotide exchange factor which is activated by PtdIns(3,4,5)P₃ – is highly expressed in mouse cerebellar Purkinje neurons and plays a role in motor coordination. We found that LTP evoked at parallel fibre synapses by 1 Hz stimulation or by NO donors was not sustained beyond 30 min when P-Rex was eliminated or Rac inhibited, suggesting that cerebellar LTP exhibits a late phase analogous to hippocampal LTP. In contrast, inhibition of PI3 kinase activity eliminated LTP at the induction stage.

Conclusions

Our data suggest that a PI3K/P-Rex/Rac pathway is required for late phase LTP in the mouse cerebellum, and that other PI3K targets, which remain to be discovered, control LTP induction.     

Are Maternal Social Networks and Perceptions of Trust Associated with Suspected Autism Spectrum Disorder in Offspring? A Population-Based Study in Japan

Objective

To investigate the associations of maternal social networks and perceptions of trust with the prevalence of suspected autism spectrum disorders in 18-month-old offspring in Japan.

Methods

Questionnaires included measurements of maternal social networks (number of relatives or friends they could call upon for assistance), maternal perceptions of trust, mutual assistance (i.e. individual measures of “cognitive social capital”), and social participation (i.e. individual measures of “structural social capital”) as well as the Modified Checklist for Autism in Toddlers to detect suspected autism spectrum disorder (ASD). These tools were mailed to all families with 18-month-old toddlers in Chiba, a city near Tokyo (N = 6061; response rate: 64%). The association between social capital or social network indicators and suspected ASD were analyzed, adjusted for covariates by logistic regression analysis.

Results

Low maternal social trust was found to be significantly positively associated with suspected ASD in toddlers compared with high maternal social trust (adjusted odds ratio [OR]: 1.82, 95% confidence interval [CI]: 1.38 to 2.40); mutual aid was also significantly positively related (low vs. high: OR, 1.82, 95% CI: 1.38 to 2.40). However, maternal community participation showed U-shape association with suspected ASD of offspring. Maternal social network showed consistent inverse associations with suspected ASD of offspring, regardless of the type of social connection (e.g., relatives, neighbors, or friends living outside of their neighborhood).

Conclusions

Mothers'' cognitive social capital and social networks, but not structural social capital, might be associated with suspected ASD in offspring.     

Specific Features of Mandible Structure and Elemental Composition in the Polyphagous Amphipod Acanthogammarus grewingkii Endemic to Lake Baikal

Background

In crustaceans, several mechanisms provide for the mechanical strength of the cuticular “tools” (dactyli, claws, jaws), which serve to catch and crush food objects. Studies on the mandibles of the endemic Baikal amphipod Acanthogammarus grewingkii by means of electron microscopy and elemental analysis have revealed specific structural features of these mouthparts.

Methodology

The fine structure of the mandible has been studied by means of SEM, TEM, and AFM; methods used to analyze its elemental and phase composition include XEPMA, XPS, SEM-EDS analysis, and XRD.

Conclusion

Functional adaptations of the mandible in A. grewingkii provide for the optimum combination of mechanical hardness and fracture resistance, which is achieved due to a complex structure and composition of its cutting parts. Teeth of the mandible are covered by a thin layer of silica (10–20 µm). Their epicuticle is characterized by a high density, consists of three layers, and increases in thickness toward the tooth apex. The epicuticle is enriched with Br, while the concentrations of Ca and P reach the peak values in the softer internal tissues of the teeth. These data broaden the view of the diversity of adaptation mechanisms providing for the strengthening of cuticular “tools” in crustaceans.     

Predicted protein-protein interactions in the moss Physcomitrella patens: a new bioinformatic resource

Background

Physcomitrella patens, a haploid dominant plant, is fast becoming a useful molecular genetics and bioinformatics tool due to its key phylogenetic position as a bryophyte in the post-genomic era. Genome sequences from select reference species were compared bioinformatically to Physcomitrella patens using reciprocal blasts with the InParanoid software package. A reference protein interaction database assembled using MySQL by compiling BioGrid, BIND, DIP, and Intact databases was queried for moss orthologs existing for both interacting partners. This method has been used to successfully predict interactions for a number of angiosperm plants.

Results

The first predicted protein-protein interactome for a bryophyte based on the interolog method contains 67,740 unique interactions from 5,695 different Physcomitrella patens proteins. Most conserved interactions among proteins were those associated with metabolic processes. Over-represented Gene Ontology categories are reported here.

Conclusion

Addition of moss, a plant representative 200 million years diverged from angiosperms to interactomic research greatly expands the possibility of conducting comparative analyses giving tremendous insight into network evolution of land plants. This work helps demonstrate the utility of “guilt-by-association” models for predicting protein interactions, providing provisional roadmaps that can be explored using experimental approaches. Included with this dataset is a method for characterizing subnetworks and investigating specific processes, such as the Calvin-Benson-Bassham cycle.

Electronic supplementary material

The online version of this article (doi:10.1186/s12859-015-0524-1) contains supplementary material, which is available to authorized users.     

Structure-Based Phylogeny as a Diagnostic for Functional Characterization of Proteins with a Cupin Fold

Background

The members of cupin superfamily exhibit large variations in their sequences, functions, organization of domains, quaternary associations and the nature of bound metal ion, despite having a conserved β-barrel structural scaffold. Here, an attempt has been made to understand structure-function relationships among the members of this diverse superfamily and identify the principles governing functional diversity. The cupin superfamily also contains proteins for which the structures are available through world-wide structural genomics initiatives but characterized as “hypothetical”. We have explored the feasibility of obtaining clues to functions of such proteins by means of comparative analysis with cupins of known structure and function.

Methodology/Principal Findings

A 3-D structure-based phylogenetic approach was undertaken. Interestingly, a dendrogram generated solely on the basis of structural dissimilarity measure at the level of domain folds was found to cluster functionally similar members. This clustering also reflects an independent evolution of the two domains in bicupins. Close examination of structural superposition of members across various functional clusters reveals structural variations in regions that not only form the active site pocket but are also involved in interaction with another domain in the same polypeptide or in the oligomer.

Conclusions/Significance

Structure-based phylogeny of cupins can influence identification of functions of proteins of yet unknown function with cupin fold. This approach can be extended to other proteins with a common fold that show high evolutionary divergence. This approach is expected to have an influence on the function annotation in structural genomics initiatives.     

Detection of copy number variations and their effects in Chinese bulls

Background

Copy number variations (CNVs) are a main source of genomic structural variations underlying animal evolution and production traits. Here, with one pure-blooded Angus bull as reference, we describe a genome-wide analysis of CNVs based on comparative genomic hybridization arrays in 29 Chinese domesticated bulls and examined their effects on gene expression and cattle growth traits.

Results

We identified 486 copy number variable regions (CNVRs), covering 2.45% of the bovine genome, in 24 taurine (Bos taurus), together with 161 ones in 2 yaks (Bos grunniens) and 163 ones in 3 buffaloes (Bubalus bubalis). Totally, we discovered 605 integrated CNVRs, with more “loss” events than both “gain” and “both” ones, and clearly clustered them into three cattle groups. Interestingly, we confirmed their uneven distributions across chromosomes, and the differences of mitochondrion DNA copy number (gain: taurine, loss: yak & buffalo). Furthermore, we confirmed approximately 41.8% (253/605) and 70.6% (427/605) CNVRs span cattle genes and quantitative trait loci (QTLs), respectively. Finally, we confirmed 6 CNVRs in 9 chosen ones by using quantitative PCR, and further demonstrated that CNVR22 had significantly negative effects on expression of PLA2G2D gene, and both CNVR22 and CNVR310 were associated with body measurements in Chinese cattle, suggesting their key effects on gene expression and cattle traits.

Conclusions

The results advanced our understanding of CNV as an important genomic structural variation in taurine, yak and buffalo. This study provides a highly valuable resource for Chinese cattle’s evolution and breeding researches.

Electronic supplementary material

The online version of this article (doi:10.1186/1471-2164-15-480) contains supplementary material, which is available to authorized users.     

I-space: the effects of emotional valence and source of music on interpersonal distance

Background

The ubiquitous use of personal music players in over-crowded public transport alludes to the hypothesis that apart from making the journey more pleasant, listening to music through headphones may also affect representations of our personal space, that is, the emotionally-tinged zone around the human body that people feel is “their space”. We evaluated the effects of emotional valence (positive versus negative) and source (external, i.e. loudspeakers, versus embedded, i.e. headphones) of music on the participant''s interpersonal distance when interacting with others.

Methodology/Principal Findings

Personal space was evaluated as the comfort interpersonal distance between participant and experimenter during both active and passive approach tasks. Our results show that, during passive approach tasks, listening to positive versus negative emotion-inducing music reduces the representation of personal space, allowing others to come closer to us. With respect to a no-music condition, an embedded source of positive emotion-inducing music reduced personal space, while an external source of negative emotion-inducing music expanded personal space.

Conclusions/Significance

The results provide the first empirical evidence of the relation between induced emotional state, as a result of listening to positive music through headphones, and personal space when interacting with others. This research might help to understand the benefit that people find in using personal music players in crowded situations, such as when using the public transport in urban settings.     

Harmonization of the Practice of Independent Ethics Committees in Italy: Project E-Submission

Aim

The high variability of “centre-specific” documentation required by Independent Ethics Committee (IEC) plays a role in the time required for activation of participating centres of multicentre clinical trials. This study (a) provides a picture of the different activities, structural requirements and resources dedicated to the operation of the local IEC in Italy; (b) defines a detailed list of “centre-specific” documents considered as essential by the IEC for issuing its opinion and (c) suggests a “single document” to reduce the variability of the “centre-specific” documents required by the IEC.

Methodology

Two surveys were conducted through the portal of National Monitoring Centre of Clinical Trials (https://oss-sper-clin.agenziafarmaco.it/). The first survey focused on the local IEC resources and on the “centre-specific” documentation that local IEC required from the Sponsor and local Principal Investigator (PI). The second focused on “single document” required in the form of statements from the Sponsor and the PI. Answers were discussed and extended during regular scheduled teleconferences and plenary meeting.

Principal Findings

From 22/07/2009 to 15/12/2009, and from 19/04/2010 to 14/05/2010, 131 and 125 IECs responded to the first and the second surveys, respectively. 67% and 51% of IECs consider the structural requirements and the staff dedicated to the activity of the IECs as sufficient, respectively. Most of the IECs consider the “centre-specific” documentation as necessary for issuing the opinion, and a high percentage of IECs consider the proposed documentation as acceptable in substitution to any other “centre-specific” documentation already in use.

Conclusions

The harmonization of IECs practice in Italy is the first step to facilitate multicentre clinical trials. Similar efforts should be directed to reduce the total number of IECs and to standardize clinical trials approval procedures, focusing on administrative procedures as well.