Validation Of New Tools Research Articles

Enhancing Protocols for Concussion Management in Professional Soccer Events.

Every year, there are an estimated 1.7 to 3.8 million sports-related traumatic brain injuries. A sports concussion results from an external force or a blow to the head or body, causing cranial encephalic trauma that can affect motor skills and brain function, producing varying symptoms related to an alteration in neurological functioning. Soccer poses a risk of concussions due to heading, where the player's head directly hits the ball to redirect or accelerate it. However, most concussions are caused by contact between players, such as head-to-head or head-to-elbow contact. This study analyzed the incidence of concussions or mild traumatic brain injuries in professional soccer during the "Copa America 2019"to understand the feasibility of soccer concussion protocols and propose evidence-based enhancements. The data were previously collectedby our first two authors, O. Pangrazioand F. Forriol, during the 46th edition of the "Copa America 2019," where the South American Football Confederation implementedthe Concussion Fast Recognition Protocolto detect traumatic brain injuries. The descriptive basic data will help to raise awareness and motivate further research in this field. We have analyzed and correlated it with global data to provide a comprehensive review and tangible evidence of the population size where soccer protocols are typically applied, thus calculating incidence rates to measure it mathematically. Our study reveals that the incidence rate of concussions during the "Copa America 2019"was 5.3 per 1,000 athlete exposures, with a total of three concussions occurring among 567 players. Despite the effectiveness of current protocols in detecting concussions rapidly and accurately, the relatively low incidence rate at this level of professional competition poses a challenge to validating these protocols. These results indicate that while the protocols in place are efficient, the testing and validation of new tools and approaches would be more beneficial at different levels of play where the incidence rates of concussions are higher. In environments with a greater frequency of concussions, the robustness and reliability of these protocols can be more thoroughly evaluated, ensuring they provide optimal protection and care for athletes. The incidence of concussions is low in professional soccer tournaments. Protocols are necessary to protect players and educate sports professionals. However, their validation is difficult given the low incidence of concussions at this level of competition. Our proposed protocol helps unify a basic approach in the field and an advanced approach in any emergency department, providing better detection of concussions and improved outcomes for players. This protocol should be validated in populations with higher incidence rates to demonstrate its effectiveness.

Protocol for the establishment of a serine integrase-based platform for functional validation of genetic switch controllers in eukaryotic cells.

Serine integrases (Ints) are a family of site-specific recombinases (SSRs) encoded by some bacteriophages to integrate their genetic material into the genome of a host. Their ability to rearrange DNA sequences in different ways including inversion, excision, or insertion with no help from endogenous molecular machinery, confers important biotechnological value as genetic editing tools with high host plasticity. Despite advances in their use in prokaryotic cells, only a few Ints are currently used as gene editors in eukaryotes, partly due to the functional loss and cytotoxicity presented by some candidates in more complex organisms. To help expand the number of Ints available for the assembly of more complex multifunctional circuits in eukaryotic cells, this protocol describes a platform for the assembly and functional screening of serine-integrase-based genetic switches designed to control gene expression by directional inversions of DNA sequence orientation. The system consists of two sets of plasmids, an effector module and a reporter module, both sets assembled with regulatory components (as promoter and terminator regions) appropriate for expression in mammals, including humans, and plants. The complete method involves plasmid design, DNA delivery, testing and both molecular and phenotypical assessment of results. This platform presents a suitable workflow for the identification and functional validation of new tools for the genetic regulation and reprogramming of organisms with importance in different fields, from medical applications to crop enhancement, as shown by the initial results obtained. This protocol can be completed in 4 weeks for mammalian cells or up to 8 weeks for plant cells, considering cell culture or plant growth time.

Unbiased Comparison between Theoretical and Experimental Molecular Structures and Properties: Toward an Accurate Reduced-Cost Evaluation of Vibrational Contributions.

The tremendous development of hardware and software is constantly increasing the role of quantum chemical (QC) computations in the assignment and interpretation of experimental results. However, an unbiased comparison between theory and experiment requires the proper account of vibrational averaging effects. In particular, high-resolution spectra in the gas phase are now available for molecules containing up to about 50 atoms, which are too large for a brute-force approach with the available QC methods of sufficient accuracy. In the present paper, we introduce hybrid approaches, which allow the accurate evaluation of vibrational averaging effects for molecules of this size beyond the harmonic approximation, with special attention being devoted to rotational constants. After the validation of new tools for relatively small molecules, the β-estradiol hormone and a prototypical molecular motor have been considered to witness the feasibility of accurate computations for large molecules.

A Systematic Review of Inflammatory Bowel Disease Epidemiology and Health Outcomes in Sexual and Gender Minority Individuals

A Systematic Review of Inflammatory Bowel Disease Epidemiology and Health Outcomes in Sexual and Gender Minority Individuals

Epidemiology and factors predicting survival of amyotrophic lateral sclerosis in a large Chinese cohort.

Background:Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder associated with loss of motor neurons. Our objective was to explore the epidemiology, clinical features, and survival factors of 1809 patients with ALS.Methods:We analyzed 1809 ALS patients, who were recruited from the Peking University Third Hospital from January 2005 to December 2015. Demographic data and disease-related parameters were collected. Kaplan-Meier curves were used to compare survival time. Cox proportional hazards function and the hazard ratio were used to identify adjusted prognostic predictors.Results:The results showed that the average annual incidence in Beijing alone was 0.38 cases/100,000 person-years and the mean age of onset was 48.88 ± 11.35 (95% confidence interval [CI]: 48.17–49.85) years. The median survival time from onset to death/tracheostomy was 58.89 ± 33.03 (95% CI: 51.46–63.84) months. In the adjusted Cox proportional hazard model, age of onset, diagnosis delay, rate of disease progression (Amyotrophic Lateral Sclerosis Functional Rating Scale Revised decline [points/month]), and body mass index all had an independent effect on survival in ALS.Conclusions:Our study provides information on epidemiology, clinical features, and survival factors of patients with ALS in China. These results can be helpful in clinical practice, clinical trial design, and validation of new tools to predict disease progression.

Assessing quality of life in older adults: psychometric properties of the OPQoL-brief questionnaire in a nursing home population

BackgroundWell-adapted and validated quality-of-life measurement models for the nursing home population are scarce. Therefore, the aim of this study was to test the psychometrical properties of the OPQoL-brief questionnaire among cognitively intact nursing home residents. The research question addressed evidence related to the dimensionality, reliability and construct validity, all of which considered interrelated measurement properties.MethodsCross-sectional data were collected during 2017–2018, in 27 nursing homes representing four different Norwegian municipalities, located in Western and Mid-Norway. The total sample comprised 188 of 204 (92% response rate) long-term nursing home residents who met the inclusion criteria: (1) municipality authority’s decision of long-term nursing home care; (2) residential time 3 months or longer; (3) informed consent competency recognized by responsible doctor and nurse; and (4) capable of being interviewed.ResultsPrincipal component analysis and confirmative factor analyses indicated a unidimensional solution. Five of the original 13 items showed low reliability and validity; excluding these items revealed a good model fit for the one-dimensional 8-items measurement model, showing good internal consistency and validity for these 8 items.ConclusionFive out of the 13 original items were not high-quality indicators of quality-of-life showing low reliability and validity in this nursing home population. Significant factor loadings, goodness-of-fit indices and significant correlations in the expected directions with the selected constructs (anxiety, depression, self-transcendence, meaning-in-life, nurse-patient interaction, and joy-of-life) supported the psychometric properties of the OPQoL-brief questionnaire. Exploring the essence of quality-of-life when residing in a nursing home is highly warranted, followed by development and validation of new tools assessing quality-of-life in this population. Such knowledge and well-adapted scales for the nursing home population are beneficial and important for the further development of care quality in nursing homes, and consequently for quality-of-life and wellbeing in this population.

European Court of Justice decision for genome editing: Consequences on food/feed risk assessment and detection

On 25 July 2018 the European Court of Justice (ECJ) clarified that organisms obtained by mutagenesis are genetically modified organisms (GMOs) as defined in the European Directive 18/2001/EC. However, the GMO directive shouldn't apply to organisms obtained by mutagenesis using techniques developed and applied before the respective Directive came into force (i.e. the application of chemical or physical mutageneous agents) and that have a long ‘history of safe’ use. Accordingly a safety assessment and labelling of products containing or consisting of GMOs obtained by mutagenesis developed after the Directive came into force will be needed. From a scientific point of view a similar basis for the risk assessment can be assumed when comparing ‘classical’ GMOs and GMOs obtained by mutagenesis using new plant breeding techniques (NPBTs). In both cases a conventional organism has been modified. Therefore the classical approach of comparing the GMO with the non-GM variety is the straight way to conduct the safety assessment. In contrast, for the identification of GMOs obtained by mutagenesis using NPBTs the development and validation of new tools are needed. However, scientifically it will not be possible to distinguish between GMOs bearing a single mutation, if it is either the result of the intended use of NPBTs, the application of chemical or physical mutageneous agents or the natural process of spontaneously occurring mutations.

Numerical Modelling of the Fire Extinguishing Gas Retention in Small Compartments

Active fire protection systems are critical elements of good process safety. Among them, gaseous extinguishing systems provide quick, clean suppression and prolonged protection due to long retention process of the gas. Standard design methods do not provide sufficient tools for optimisation of the retention process, thus the necessity for development and validation of new tools and methods—such as Computational Fluid Dynamics (CFD) simulations. This paper presents a simplified approach to CFD modelling, by the omission of the discharge phase of the gas system. As the flow field after discharge is stable and driven mainly by the hydrostatic pressure difference, buoyancy and diffusion, this simplified approach appears as an efficient and cost-effective approach. This hypothesis was tested through performing CFD simulations, and their comparison against experimental measurements in a bench scale in a small compartment (0.72 m3), for six mixtures that differ in their density. Modelling the retention of the standard IG55 mixture was very close to the experiment. Modelling of mixtures with a density close to the density of ambient air has proven to be a challenge. However, the obtained results had sufficient accuracy (in most cases relative error <10%). This study shows the viability of the simplified approach in modelling the retention process, and indicates additional benefits of the numerical analyses in the determination of the fire safety of protected premises.

Clinical trials on the way to secure the translational and clinical efficacy

Position of the problem: To date only 10% of NSCLC patients are detected in stage I, at a stage when the disease is curable by surgery alone (90% of patients are alive at 5 years). Most of the patients, over 60%, are unfortunately detected in late metastatic stage IV and remain incurable, with a median survival of 12 months, and less than 5% of patients alive at 5 years. The lecture will present WIN Consortium efforts to significantly improve the clinical outcome of lung cancer patients: A major portion is international collaboration to improve molecular profiling and data management and design of innovative trials, driven by new biomarker based platforms, tools and strategies.Combination of targeted therapies: The key feature of future therapies in metastatic NSCLC, is switching from current monotherapies to combinatorial modes, as only way to fight against secondary resistance that occurs in all patients. This switch will need the identification and validation of new tools to match individually the patient's tumor biology profile to the most appropriate combination of therapies.The main limitations of current biomarker and mainly companion diagnostics (Cdx) are:a)multiplicity of drugs that require a large number of tests (and different technologies) to be performed on limited amount of biological samples.b)inability to prioritize the best therapeutic options for each individual patient.The lecture will present the Simplified Interventional Mapping System (SIMS), a Systems Biology based novel generation of multiplex combinatorial Cdx which provides biological support to prioritize and to select the classes of drugs that are predicted to be most effective at the individual patient level. The example used is metastatic Non-Small Cell Lung Carcinoma (NSCLC), but the method applies to any solid tumor. SIMS is based on the use of dual biopsies in order to compare tumor with its histologically matched normal tissue from the same patients. SIMS algorithm integrates data of DNA sequencing, CNV, and the differential expression of mRNA and miRNA between tumor and matched normal tissue from 121 NSCLC patients. SIMS converts thousands of genomic and transcriptomic measurements into a simple and actionable result (a 1 to 10 score) that may be usable by physicians to select the optimal drug or drugs' combinations therapy. One of the most interesting hypothesis being the tri-therapy approaches, following the historical success in AIDS. Comparing tumor and normal tissue biopsies has proven feasible in the ongoing WINTHER trial (NCT01856296) SIMS outlines novel therapeutic possibilities by focusing on pertinent classes of targeted biotherapeutics to be used in appropriate combinations, and is a novel generation of combinatorial multiplex companion test enabling to match patients to drugs.

Unequivocal determination of caulamidines A and B: application and validation of new tools in the structure elucidation tool box.

Ambiguities and errors in the structural assignment of organic molecules hinder both drug discovery and total synthesis efforts. Newly described NMR experimental approaches can provide valuable structural details and a complementary means of structure verification. The caulamidines are trihalogenated alkaloids from a marine bryozoan with an unprecedented structural scaffold. Their unique carbon and nitrogen framework was deduced by conventional NMR methods supplemented by new experiments that define 2-bond heteronuclear connectivities, reveal very long-range connectivity data, or visualize the 35,37Cl isotopic effect on chlorinated carbons. Computer-assisted structural elucidation (CASE) analysis of the spectroscopic data for caulamidine A provided only one viable structural alternative. Anisotropic NMR parameters, specifically residual dipolar coupling and residual chemical shift anisotropy data, were measured for caulamidine A and compared to DFT-calculated values for the proposed structure, the CASE-derived alternative structure, and two energetically feasible stereoisomers. Anisotropy-based NMR experiments provide a global, orthogonal means to verify complex structures free from investigator bias. The anisotropic NMR data were fully consistent with the assigned structure and configuration of caulamidine A. Caulamidine B has the same heterocyclic scaffold as A but a different composition and pattern of halogen substitution. Caulamidines A and B inhibited both wild-type and drug-resistant strains of the malaria parasite Plasmodium falciparum at low micromolar concentrations, yet were nontoxic to human cells.

A longitudinal four-dimensional computed tomography and cone beam computed tomography dataset for image-guided radiation therapy research in lung cancer.

To describe in detail a dataset consisting of serial four-dimensional computed tomography (4DCT) and 4D cone beam CT (4DCBCT) images acquired during chemoradiotherapy of 20 locally advanced, nonsmall cell lung cancer patients we have collected at our institution and shared publicly with the research community. As part of an NCI-sponsored research study 82 4DCT and 507 4DCBCT images were acquired in a population of 20 locally advanced nonsmall cell lung cancer patients undergoing radiation therapy. All subjects underwent concurrent radiochemotherapy to a total dose of 59.4-70.2 Gy using daily 1.8 or 2 Gy fractions. Audio-visual biofeedback was used to minimize breathing irregularity during all fractions, including acquisition of all 4DCT and 4DCBCT acquisitions in all subjects. Target, organs at risk, and implanted fiducial markers were delineated by a physician in the 4DCT images. Image coordinate system origins between 4DCT and 4DCBCT were manipulated in such a way that the images can be used to simulate initial patient setup in the treatment position. 4DCT images were acquired on a 16-slice helical CT simulator with 10 breathing phases and 3 mm slice thickness during simulation. In 13 of the 20 subjects, 4DCTs were also acquired on the same scanner weekly during therapy. Every day, 4DCBCT images were acquired on a commercial onboard CBCT scanner. An optically tracked external surrogate was synchronized with CBCT acquisition so that each CBCT projection was time stamped with the surrogate respiratory signal through in-house software and hardware tools. Approximately 2500 projections were acquired over a period of 8-10 minutes in half-fan mode with the half bow-tie filter. Using the external surrogate, the CBCT projections were sorted into 10 breathing phases and reconstructed with an in-house FDK reconstruction algorithm. Errors in respiration sorting, reconstruction, and acquisition were carefully identified and corrected. 4DCT and 4DCBCT images are available in DICOM format and structures through DICOM-RT RTSTRUCT format. All data are stored in the Cancer Imaging Archive (TCIA, http://www.cancerimagingarchive.net/) as collection 4D-Lung and are publicly available. Due to high temporal frequency sampling, redundant (4DCT and 4DCBCT) data at similar timepoints, oversampled 4DCBCT, and fiducial markers, this dataset can support studies in image-guided and image-guided adaptive radiotherapy, assessment of 4D voxel trajectory variability, and development and validation of new tools for image registration and motion management.

ANÁLISE FATORIAL E ANÁLISE DE CLUSTER NO MAPEAMENTO DE CONCEPÇÕES EPISTEMOLÓGICAS DE PROFESSORES SOBRE A CIÊNCIA E A ECOLOGIA

A construção e a validação de novas ferramentas para pesquisas epistemológicas no contexto educacional mostram-se extremamente importantes, e são poucos os trabalhos na área que realizam um processo de validação utilizando técnicas da estatística multivariada. Como a literatura aponta, existem inúmeros instrumentos disponíveis para o mapeamento de visões sobre a ciência como um todo, mas poucos voltados para a caracterização de concepções campo-dependentes, ou seja, concepções sobre áreas específicas da ciência, como a ecologia, que configura entre aquelas que têm recebido menor atenção dos pesquisadores. Desse modo, o presente artigo teve como objetivos: i) validar novos questionários para o mapeamento de concepções epistemológicas sobre a ciência e a ecologia profissionais e sobre o ensino de ecologia (ecologia escolar), e ii) caracterizar os perfis de concepções epistemológicas de uma amostra inicial de professores respondentes, em função do desempenho obtido nesses questionários. Elaboramos três questionários do tipo Likert com escala de cinco pontos, e realizamos um survey online, de corte transversal, com amostragem não probabilística por conveniência. O número amostral analisado correspondeu a um total de 80 sujeitos. Foi possível avaliar, por meio da análise fatorial exploratória e da análise de consistência interna (alfa de Cronbach), a capacidade dos nossos instrumentos de medir os construtos-alvo, o que em outras pesquisas normalmente é feito apenas de maneira qualitativa e subjetiva (análise pautada exclusivamente no conteúdo e não na estrutura interna). Já a análise de agrupamento permitiu definir quais grupos de professores mostraram perfis de concepções epistemológicas mais atualizadas/sofisticadas, e quais apresentaram concepções mais limitadas/ingênuas, contribuindo também com critérios mais objetivos para a interpretação dos resultados.

Pharmacogenomic Testing and Personalized Treatment of Depression

There is wide variation in antidepressant efficacy and tolerability during the treatment of major depressive disorder, a brain disease associated with significant morbidity and mortality risk. The ability to rapidly identify optimal treatment, thereby shortening the time to symptomatic remission, could reduce these risks and associated costs. Up to 42% of variance in antidepressant response is associated with common genetic variation, and there are over 10 psychotropic medications for which the US Food and Drug Administration-approved labeling reflects a genetic test. Most published studies have examined functional variations in genes of the cytochrome p450 system, relevant to metabolism of many antidepressants. However, there are few data supporting the clinical usefulness of specific pharmacogenetic tests. Randomized trials and cost-effectiveness studies are emerging, but larger-scale studies are needed. Specific challenges in translating genetic association results to clinical practice include need for replication to address risk of type I error, overestimation of effect sizes, absence of data from generalizable cohorts, and absence of comparative data that would suggest one specific intervention over another. Several opportunities to accelerate development and validation of new tools for stratification remain, including integration of these tests with clinical data or other biomarkers and application of electronic health records for test development and investigation. Although common genetic variation, particularly in genes of the cytochrome p450 system, has been associated with antidepressant response, evidence that this variation may be successfully applied to guide treatment selection is just emerging. Larger-scale studies facilitated by informatics tools will clarify the usefulness of such tests.

Characterization and validation of new tools for measuring site-specific cardiac troponin I phosphorylation

Phosphorylation of cardiac troponin I is a well established mechanism by which cardiac contractility is modulated. However, there are a number of phosphorylation sites on TnI which contribute singly or in combination to influence cardiac function. Accordingly, methods for accurately measuring site-specific TnI phosphorylation are needed. Currently, two strategies are employed: mass spectrometry, which is costly, difficult and has a low throughput; and Western blotting using phospho-specific antibodies, which is limited by the availability of reagents. In this report, we describe a cohort of new site-specific TnI phosphoantibodies, generated against physiologically relevant phosphorylation sites, that are superior to the current commercially available antibodies: to phospho-serine 22/23 which shows a >5-fold phospho-specificity for phosphorylated TnI; to phospho-serine 43, which has >3-fold phospho-specificity for phosphorylated TnI; and phospho-serine150 which has >2-fold phospho-specificity for phosphorylated TnI. These new antibodies demonstrated greater sensitivity and specificity for the phosphorylated TnI than the most widely used commercially available reagents. For example, at a protein load of 20μg of total cardiac extract, a commercially available antibody recognized both phosphorylated and dephosphorylated TnI to the same degree. At the same protein load our phospho-serine 22/23 antibody exhibited no cross-reactivity with dephosphorylated TnI. These new tools should allow a more accurate assessment and a better understanding of the role of TnI phosphorylation in the response of the heart to pathologic stress.

Signalling with retinoids in the human lung: validation of new tools for the expression study of retinoid receptors

BackgroundRetinoid Receptors are involved in development and cell homeostasis. Alterations of their expressions have been observed in lung cancer. However, retinoid chemoprevention trials in populations at risk to develop such tumors have failed. Therefore, the pertinence of new clinical trials using second generation retinoid requires prior better understanding of retinoid signalling. This is our aim when validating extensively research tools, focused on Retinoic Acid Receptor beta, whose major role in lung cancer is documented.MethodsBiocomputing was used to assess the genomic organization of RAR beta. Its putative RAR-beta1' promoter features were investigated experimentally. Specific measures realized, with qRT-PCR Syber Green assays and a triplex of Taqman probes, were extensively validated to establish Retinoid Receptors mRNAs reference values for in vivo normal human bronchial cells, lung tumors and cell lines. Finally, a pan-RAR-beta antibody was generated and extensively validated by western-blot and immunoprecipitation.ResultsNo promoter-like activity was found for RAR-beta1'. RAR-beta2 mRNAs increase signs the normal differentiation of the human bronchial epithelium while a decrease is observed in most lung cancer cell lines. Accordingly, it is also, along with RXR beta, down-regulated in lung tumors. When using nuclear extracts of BEAS-2B and normal lung cells, only the RAR-beta2 long protein isoform was recognized by our antibody.ConclusionRigorous samples processing and extensive biocomputing, were the key factors for this study. mRNA reference values and validated tools can now be used to advance researches on retinoid signalling in the lung.

Antiadrenergic therapy of chronic heart failure: surprises and new opportunities.

The great British-American scientist-philosopher Alfred North Whitehead divided progress into three stages, the second of which was termed precision, in which the “right ways and wrong ways” of an original idea are elucidated.1 During this period, reinterpretation of the basic idea occurs and is essential to progress. Whitehead’s message is that important ideas are dynamic instruments that are constantly changing as new and usually unexpected information becomes available. This is why tests of particular hypotheses, including those tested in Phase III clinical trials, are often unsupportive, and why therapeutic paradigms constantly change. Within such an ephemeral milieu, the key to ultimate success is to view each unexpected or negative result as an opportunity for constructing and testing even more novel and valuable hypotheses within the framework of the general idea, to ascend to the final stage where progress can be “generalized.”1 Whitehead’s philosophical legacy is impressively in play in the area of antiadrenergic therapy of chronic heart failure (CHF). The unarguable basic idea is that the biologically powerful adrenergic compensatory mechanism plays a critical role in the natural history of CHF. It is the details or nuances within the general paradigm that continue to change, and lately, surprisingly so. As recently reviewed,2 the importance of dysfunctional adrenergic activation in CHF was first elucidated by work performed by Braunwald’s group at the National Institutes of Health in the 1960s. Among other things, this early work provided the first evidence of marked adrenergic activation in CHF. However, on the basis of reduction in myocardial tissue norepinephrine, and the short-term effects of large doses of antiadrenergic agents,3 the overall interpretation was that adrenergic support was deficient in CHF. This view prevailed for 10 to 15 years, and it contributed to the original logic behind developing Type III phosphodiesterase inhibitors …

Multi-parametric survey for archaeology: how and why, or how and why not?

Many papers or conference presentations, particularly over the last ten years, have referred to multi-parametric geophysical surveys and integrated interpretations in archaeological prospection. Several experiments of this kind have been undertaken by our laboratory, with mostly fascinating results, but our experience leads us to be rather suspicious of the over-systematic choice of extreme solutions and we would recommend an appropriate and balanced choice, within the limits of the budget available for an operation, between the two following procedures: 1) Routine survey with an extremely large variety of instruments: this allows a better understanding of the underground situation than survey with a single instrument but reduces the area that can be surveyed. A limited number of specific circumstances should lead one to adopt this option. They include: previous knowledge or equally previous ignorance of the targets under investigation, preliminary selection of the most efficient method on a scientific and economic basis, comparative experiments for the validation of new tools, specific detection of targets of different nature into the ground as well as uncertainty about the efficiency of each available method for the actual nature of the investigated site. 2) Survey of a much larger area with only one method, chosen because it is particularly fast and efficient: there is an obvious value in extensive exploration in order to evaluate the size, distribution and limits of a large number of archaeological features. The strict selection of appropriate methods, chosen to meet the aims of a project should consider not only geophysics but all kinds of conventional or non-conventional archaeological methods as well, brought together to permit an integrated interpretation. This highly specialized job does not fall within the normal experience of exploration geophysicists who usually deal with geological features or most field archaeologists who are mainly involved in excavations. It must be undertaken by particularly trained operators, whether they belong to private companies (under appropriate official control) or to public organizations.