Injury scoring is important to formulate prognoses for trauma patients. Although scores based on empirical estimation allow for better prediction, those based on expert consensus, e.g. the New Injury Severity Score (NISS) are widely used. We describe how the addition of a variable quantifying the number of injuries improves the ability of NISS to predict mortality.We analyzed 2488 injury cases included into the trauma registry of the Italian region Emilia-Romagna in 2006-2008 and assessed the ability of NISS alone, NISS plus number of injuries, and the maximum Abbreviated Injury Scale (AIS) to predict in-hospital mortality. Hierarchical logistic regression was used. We measured discrimination through the C statistics, and calibration through Hosmer-Lemeshow statistics, Akaike's information criterion (AIC) and calibration curves.The best discrimination and calibration resulted from the model with NISS plus number of injuries, followed by NISS alone and then by the maximum AIS . The predictive ability of all the models improved after inclusion of age, gender, mechanism of injury, and the motor component of Glasgow Coma Scale . The model with NISS plus number of injuries still showed the best performances, this time with borderline statistical significance.In NISS, the same weight is assigned to the three worst injuries, although the contribution of the second and third to the probability of death is smaller than that of the worst one. An improvement of the predictive ability of NISS can be obtained adjusting for the number of injuries. The importance of injury scoring is universally recognized and the literature on the subject is immense. Although the scores based on empirical estimation - e.g. Trauma Mortality Prediction Model  - are fiThe role of multiple injuries in outcome prediction and scoring is important because the majority of patients have more than one injury. For example, only 38.3% of patients of the American National Trauma Data Bank (NTDB) sustained a single injury . The wayIn this study we describe how, in accordance with the current knowledge, the addition of a simple variable that quantifies the number of injuries significantly improves the predictive ability of NISS for mortality.This study was conducted using data from the trauma registry of the region Emilia-Romagna (RRTG). Emilia-Romagna is an Italian region with about 4 million inhabitants where a trauma system was instituted in 2006. This system is based on three hubs with a defined area of competence that receive patients from scene and other hospitals according to agreed protocols via a pre-hospital Emergency Medical Service. The RRTG started in October 2006 and receives data from the three hubs and seven additional hospitals. The inclusion criteria are traumatic injuries with ISS>15 or admission to intensive care (ICU). ICU admission is decided by clinical judgment and there are no standard criteria. Patients dead on arrival or early in the Emergency Room are recorded in a separate database - not considered by the present study - because they often lack important information like injury severity. The RRTG collects information on demographics, injury, pre-hospital and hospital clinical course and outcome. Injury severity is coded according to the AIS version '98 by one trained coder per hospital. The training was self-managed by regional authorities, with no official certification by Association for the Advancement of Automotive Medicine.All 3754 cases of the years 2007-2009 were considered for inclusion. All of the cases of 2 hospitals (n = 1180) had to be excluded, because these hospitals recorded only the ISS and not the AIS codes of each lesion. Patients with burns, asphyxia or drowning and those with age <1 year (n = 86) were also excluded. These exclusions are habitual in studies on trauma mortality prediction modeling because severity indexes may perform differently with these injuries  and becaA variable (num_inj) expressing the number of AIS-coded injuries sustained by the patients was created, with three categories: one, two, and three or more injuries. The predictive abilities of NISS alone and NISS + num_inj were assessed and compared. The largest severity measure taken from a patient's set of AIS codes (max AIS) was also computed and its discrimination ability quantified and compared. Hierarchical logistic regression models were built, with in-hospital mortality as the outcome variable and single hospitals as the random effect (random intercept). The interaction between NISS and num_inj was also tested with both Wald statistics and the Likelihood Ratio test. The predictive ability was assessed according to discrimination and calibration. Discrimination was measured with the C statistics, also known as area under the ROC curve. The significance of the differences among ROC areas was also assessed . CalibraA second set of models also including age (continuous), gender , and mechanism of injury  were assessed and compared. Finally, a set of models further completed with physiological information - motor component of Glasgow Coma Scale  and systolic blood pressure  - were evaluated. The detailed description of these variables is shown in table A binary variable expressing whether the two worst injuries belong to the same AIS region or not was also tested in combination with NISS and num_inj.Missing data were treated with casewise exclusion . All the analyses were conducted using STATA 10.Because of the observational design of the study and the anonymity of the final database, neither patient consent nor approval of ethical committee was necessary.Table The models' performances are shown in table Figure Table The odds ratio of the variable measuring whether the two worst injuries belong to the same AIS region was 1.19  in the model with NISS and num_inj. Its inclusion virtually did not change the parameters of the other two variables. The interaction with num_inj was not significant either.Table We found that the predictive ability of models using NISS as injury-severity index is increased by the addition of a variable that summarizes the number of AIS-coded injuries sustained by the patients. The relationship between multiple injuries is fundamental in severity scoring because, as already said, the majority of patients are multiply injured. With hindsight, all the expert consensus and AIS-based scores devised so far oscillated between different ways to account for the following three factors: the contribution of multiple injuries, the weight assigned to injuries other than the worst, and the contribution of the anatomic regions. ISS postulated that the three most severe injuries determine the risk. At the same time it assigned a considerable discounting to additional injuries by disregarding altogether those of the same region. This rule factored in the importance of belonging to the same or different anatomic regions. NISS maintained the principle of considering the three worst injuries, but abolished any form of discounting and consideration for the regions. Essentially, it maximized the role of multiple injuries by giving to the second and third injury the same importance of the first one. The studies showing that max AIS predicts better than NISS and ISS ,19,20 brAnother line of research has revealed that patients with identical ISS/NISS scores resulting from different underlying AIS triplets carry quite different mortality risks -25. The The recent research on new empirical severity scores ,13 has sThe behavior of the variable num_inj in our study seems to confirm most of the previous findings. When adjusting for NISS, having two and more than two injuries instead of one lowers the risk of death to approximately one half and one fifth, respectively table . Table 4NISS tends to overestimate the risk of death in case of multiple injuries because it does not apply any discounting to the second and third worst lesions. On the other hand, considering only the most severe injury in absolute (max AIS) or by region (ISS) may cause an underestimation of the same risk, as shown by the lowest discrimination of max AIS in our study and by the studies reporting worse performances of max AIS or ISS compared to NISS -10,19,26An inevitable limitation of num_inj is that it does not discriminate between degrees of injuries. If the second injury is trivial - e.g. a patient with two lesions with AIS severity of 5 and 1 - the increase in prediction given by num_inj is likely to be negligible. A possible refinement, especially for severely injured populations, could be the adoption of a severity threshold (e.g. ≥2) for AIS codes to be included in num_inj.The fact that in models completed with physiological variables the gain in prediction brought by num_inj is not statistically significant should not be seen as a serious limitation. Physiological variables describe the actual clinical status of the patient that is an important predictor of final outcome. So it is reasonable that they may 'refine' more imperfect anatomic predictors. Yet physiological information is not always available. Moreover, it is possible that in a larger database the models with num_inj could perform significantly better also if completed with physiological variables and we encourage further research.In our case-mix max AIS performed worse than both NISS and NISS + num_inj. This leaves one question unanswered, i.e. how NISS with num_inj would perform in a population (presumably less-severely injured than ours) where max AIS works better than NISS. Since we tested the interaction of num_inj with NISS and found it non-significant, it would seem that the effect of num_inj be the same across the whole spectrum of injury severity, but, again, more research is needed to answer the question.Contrary to the findings of Osler et al. we could not show any effect of the two worst injuries belonging to the same AIS region or not. This contradicts a major tenet in the definitions of polytrauma, i.e. that the involvement of different regions increases mortality . UnfortuThis study has some limitations. The number of cases is small and further studies are awaited to confirm or dispute our findings. Moreover, the cases with ISS<16 are not representative of their entire population because RRTG enrolls them only if admitted to ICU. We chose to include in this study all eligible RRTG patients, subtracting to homogeneity, in order to maximize the number of cases. We recognize, however, that this limits the generalizability of our conclusions, calling for further studies in larger populations.A further limitation is that although we used NISS for selecting patients according to severity table , the RRTAnother possible criticism is that our outcome was hospital mortality instead of 30-day mortality, recommended by the Utstein template . UnfortuBecause the predictive performances of models were determined on the same sample of subjects that was used to construct the model, they were probably overestimated. However, such an overestimation would be common to all models and therefore should not affect the relative comparisons between them, the main goal of the study.In NISS, the same weight is assigned to the three worst injuries, although the contribution of the second and third to the likelihood of death is smaller than that of the worst one. An improvement of the predictive ability of NISS can be obtained adjusting for the number of injuries.The authors declare that they have no competing interests.SDB conceived the study, carried out the statistical analyses and drafted the manuscript. CV and MM participated in the statistical analyses. FV participated in the conception of the study, participated in the statistical analysis and revised the manuscript. ST helped to draft the manuscript. RDP revised it critically for important intellectual content. All authors read and approved the final manuscript.


Arabidopsis thaliana.Photosynthetic light acclimation is an important process that allows plants to optimize the efficiency of photosynthesis, which is the core technology for green energy. However, currently little is known about the molecular mechanisms behind the regulation of the photosynthetic light acclimation response. In this study, a systematic method is proposed to investigate this mechanism by constructing gene regulatory networks from microarray data of Arabidopsis thaliana via the maximum likelihood system identification method and Akaike's system order detection method to approach the real gene regulatory network of photosynthetic light acclimation.The potential TF-gene regulatory pairs of photosynthetic light acclimation have been obtained by data mining of literature and databases. Following the identification of these potential TF-gene pairs, they have been refined using Pearson's correlation, allowing the construction of a rough gene regulatory network. This rough gene regulatory network is then pruned using time series microarray data of By comparing the gene regulatory networks under the PSI-to-PSII light shift and the PSII-to-PSI light shift, it is possible to identify important transcription factors for the different light shift conditions. Furthermore, the robustness of the gene network, in particular the hubs and weak linkage points, are also discussed under the different light conditions to gain further insight into the mechanisms of photosynthesis.Arabidopsis thaliana from the physiological level. This has been achieved through the construction of gene regulatory networks from the limited data sources and literature via an efficient computation method. If more experimental data for whole-genome ChIP-chip data and microarray data with multiple sampling points becomes available in the future, the proposed method will be improved on by constructing the whole-genome gene regulatory network. These advances will greatly improve our understanding of the mechanisms of the photosynthetic system.This study investigates the molecular mechanisms of photosynthetic light acclimation for  Life on earth is dependent on energy derived from the sun, and photosynthesis is the only biological process able to harvest this energy. Plants must maintain high photosynthetic efficiency to ensure sufficient energy for survival and seed production for the next generation. As plants are sessile organisms and cannot escape environmental changes that directly affect photosynthetic light reactions, they have evolved regulatory mechanisms that optimize photosynthetic electron transport to acclimate the photosynthetic process to the prevailing environment ,2. ChangArabidopsis thaliana under an artificial light system. The artificial light system mimics light conditions by preferentially exciting PSI or PSII to induce more reduced or oxidized states of the PQ pool by shifting from PSI light to PSII light, or from PSII light to PSI light.Adjustment of photosystem stoichiometry is a long term response that occurs on a time scale of hours to days. It re-distributes excitation energy between PSII and PSI mainly by reconfiguring the relative amount of the two photosystems, enabling them to optimize light utilization -6. ImbalThe foremost purpose of the study of molecular biology is to decipher the mechanisms behind the biological processes of cells. Recently, the development of high-throughput genomic tools such as DNA microarray ,8 and chArabidopsis thaliana, the types of heterogeneous data are limited, making it difficult to apply a systematic approach to construct gene networks. In a previous study  = {1, 2,..., L}. For each potential regulator i ∈ S , i bexplains how the expression of target gene is affected by the regulatory ability of TF i. β is attributable to the degradation effect of the target gene itself and k denotes the basal molecular level. In addition, ε(t) represents a stochastic noise due to uncertainty within the model and measurement error of microarray data in the target gene. Here ε(t) is assumed to be a Gaussian noise with zero mean and unknown standard deviation. Because biological systems seem to exhibit nonlinear characteristics, we assume a sigmoidal regulatory binding relationship between the regulator and the target gene. Furthermore, i x(t) is the transcriptional regulatory function of TFs on their motif binding sites, as described by following the sigmoid function of mRNA expression profiles on their corresponding regulatory genes [i x(t) can be expressed as follows:where ry genes , where tr denotes the transition rate of sigmoid function and i mdenotes the mean of the TF gene expression profile.where Refinement of the rough gene regulatory network: The model describes how upstream transcriptional factors modulate their target genes' mRNA expression through a transcriptional gene regulatory network. With the help of dynamic gene regulation model, the problem of network construction, which is difficult to decipher in biology, is transferred into a pre-identified system in engineering. The rough regulatory network is a large system which contains several subsystems. Each subsystem consists of a target gene and its regulatory TFs. The state of each target gene at different time points depends on the time series microarray data. This produces a large network system in which each state of the subsystem is known and the parameters of the subsystem have been estimated. These difficult parameter estimations are conducted using system identification methods, working with one target gene at a time. This estimation method involves combining the maximum likelihood (ML) parameter estimation method with the most parsimonious model order detection, Akaike Information Criterion (AIC), to identify the unknown element of the network system. In short, the parameters of system can be estimated using the maximum likelihood method and AIC can then delete any interactions without significant influence on this network system. These deletions are based on the results of the ML method and the degree detection of interactions in the network system. By approaching the network one target gene at a time, it is possible to identify all of the parameters of the rough gene regulatory network. Finally, to produce the pruned gene regulatory network, the overall gene regulatory system is deciphered dynamically and insignificant regulations are eliminated. This pruned gene regulatory network is close to real gene regulatory network in the cell. The overall flowchart of the proposed method is shown in Figure Arabidopsis thaliana via maximum likelihood system identification and Akaike's system order detection through a dynamic gene regulatory model. We have combined several algorithms and tools to improve the performance of the gene network construction of the photosynthetic light acclimation. Details of the proposed gene regulatory networks construction algorithm are shown in the Supplementary Methods , which can be regarded as highly connected hubs of signal transduction in the two different light conditions. Inactivation of these highly connected hubs by mutation may lead to collapse of the photosynthetic LTR system. Interestingly, the two hubs appear to have high importance for different light shift conditions. For the reduced state of the PQ pool, the gene ATHB-1 is the top rank and the gene ARR10 is the second rank in Table The gene regulatory networks in Figures According to these results, the hubs ATHB-1 and ARR10 are identified with different significant status in opposite redox states of the PQ pool. As shown in , the iniIn Table Arabidopsis thaliana LTR-related TFs, which are predicted from our target gene pool via PlantPAN database. We seek evidence from the literature to validate their inferred function in regulation of the photosynthetic light acclimation response. ATHB-1 is involved in response to blue light [A total of 7 regulators are considered as potential ue light , while Aue light ,36 and iue light ,38. Thisue light  identifiAccording to the results, the transcription factors maintain homeostasis under two different qualities of light by altering regulation of two gene regulatory systems. Figure Arabidopsis [We explored The Arabidopsis Information Resource (TAIR) database to obtain annotations of seven TFs in the gene regulatory networks we constructed for this study. Interestingly, five of the seven TFs  are involved in the leaf senescence stage of bidopsis . ARR10 abidopsis ,41. HY5 bidopsis  and ATHBbidopsis . The divThrough analysis of these results, it is possible to predict the important TFs corresponding to opposite redox states of the PQ pool. More biological insight into the gene networks in two different photosystem light shift conditions is given in the discussion section below.The LTR is initiated whenever a photosynthetic organism is subjected to a stable light gradient for an extended period of time. Because this response can be easily investigated by growing plants in the laboratory under an artificial light source that preferentially excite PSII or PSI , the response has been well characterized at the biological level. However, the integration of gene regulation and metabolism during the acclimation process is currently poorly understood. Some studies have attempted to further our understanding of the LTR by identifying primary target genes under different light intensities and spectral qualities ,27,44-46E. coli with high accuracy [This study has employed a systems biology approach, combined with a prediction database to construct gene regulatory networks using microarray data. The proposed systematic approach can depict the transcriptional regulatory mechanism of a photosynthesis network as a dynamic system. Furthermore, the time profile of mRNA of each target gene can be described by the dynamic gene regulatory equation in (1). Some researchers have applied similar dynamic equations to construct regulatory networks in yeast and accuracy ,49. Howeaccuracy  via systSinapis alba L.) [The adjustment of photosystem stoichiometry is a long-term response to changed light quality by changing the relative number of the two photosystems -6. Figuralba L.)  which foalba L.) ,52. ConsRecent studies ,53 have Arabidopsis thaliana, the identification of transcriptional regulatory relationships relies on the prediction database. The candidate regulators are selected from the pool of potential regulators typically defined by computational prediction or sequence similarity analysis. If an important regulator is not included in the pool, it will inevitably escape identification by the proposed modeling approach.In this study, we use a multi-input/single-output regulatory model to dynamically describe our gene regulatory system. The model analyzes multiple regulators in respect to one target gene, combining time series microarray data to determine the regulatory relationship between this target gene and its upstream regulators. By using Pearson's correlation and the Akaike Information Criterion to prune the complex gene regulatory network, an accurate gene regulatory network of the LTR system in the nucleus can be formed. While our method combines many algorithms to construct a gene regulatory network for the photosynthetic acclimation system, the primary obstacle faced in development of this network is the construction of a rough gene regulatory network. Due to the lack of complete ChIP-chip data for Arabidopsis thaliana using an efficient computational framework. This type of systems biology approach has become increasingly common in recent years and can provide insight into the underlying mechanisms of the photosynthetic light acclimation response. Gene regulatory networks under PSI-to-PSII light shift and PSII-to-PSI light shift are compared to identify the important transcription factors involved in the regulation of photosynthetic long-term response. The hubs and "weak linkages" are also analyzed for the robust gene network under different light conditions. Although the gene regulatory networks are a small part of photosynthetic light acclimation response in plants, they may provide a foundation on which the overall molecular mechanism underlying the photosynthetic process in organisms may be deciphered. Moreover, it is hoped that the results of this study will attract more attention to the topic of photosynthetic light acclimation with large-scale experiments. As experimental data for whole-genome ChIP-chip data and microarray data with more multiple sampling points become available in the future, the performance of the proposed method will be improved and enable more efficient construction of genome-wide regulatory networks of photosynthetic system. Such genome-wide gene regulatory networks may provide a better understanding for the molecular interaction mechanisms between the chloroplastic, nucleic, and mitochondrial components of the cell under the long term photosynthetic acclimation response. For instance, the regulatory mechanisms for gene network of state transition, a short-term response, in the chloroplast. Furthermore, if more protein-protein interaction data becomes available, the protein interactions of the signal transduction pathway may be identified and integrated with the gene transcriptional regulatory network to provide more insight into the overall photosynthetic light acclimation response.The photosynthetic light acclimation response is a fundamental process in plants which can optimize the efficiency of photosynthesis in fluctuating light quality. However, little is known about the molecular mechanisms that regulate these acclimation responses. In this study, we investigate this molecular mechanism from the physiological level by constructing a gene regulatory network from the limited data sources for CWY developed the method, performed the simulation, evaluated the results and drafted the manuscript. BDH provided essential guidance and revised the manuscript. BSC conceived of the study and revised the manuscript. All authors have read and approved the final manuscript.Total 65 target genes. The Gene annotations for the 65 genes of interest are shown in this table.Click here for filePotential TF-gene pairs of each gene. The first column represents gene symbols and the second column lists their predictive regulators.Click here for fileSupplementary Methods. Details of system identification methods.Click here for fileConnection degree of each node. The degree of connection for each target gene under PSI-to-PSII and PSII-to-PSI light shifts.Click here for file


Two theories for the origin of animal life cycles with planktotrophic larvae are now discussed seriously: The terminal addition theory proposes a holopelagic, planktotrophic gastraea as the ancestor of the eumetazoans with addition of benthic adult stages and retention of the planktotrophic stages as larvae, i.e. the ancestral life cycles were indirect. The intercalation theory now proposes a benthic, deposit-feeding gastraea as the bilaterian ancestor with a direct development, and with planktotrophic larvae evolving independently in numerous lineages through specializations of juveniles.Information from the fossil record, from mapping of developmental types onto known phylogenies, from occurrence of apical organs, and from genetics gives no direct information about the ancestral eumetazoan life cycle; however, there are plenty of examples of evolution from an indirect development to direct development, and no unequivocal example of evolution in the opposite direction. Analyses of scenarios for the two types of evolution are highly informative. The evolution of the indirect spiralian life cycle with a trochophora larva from a planktotrophic gastraea is explained by the trochophora theory as a continuous series of ancestors, where each evolutionary step had an adaptational advantage. The loss of ciliated larvae in the ecdysozoans is associated with the loss of outer ciliated epithelia. A scenario for the intercalation theory shows the origin of the planktotrophic larvae of the spiralians through a series of specializations of the general ciliation of the juvenile. The early steps associated with the enhancement of swimming seem probable, but the following steps which should lead to the complicated downstream-collecting ciliary system are without any advantage, or even seem disadvantageous, until the whole structure is functional. None of the theories account for the origin of the ancestral deuterostome (ambulacrarian) life cycle.All the available information is strongly in favor of multiple evolution of non-planktotrophic development, and only the terminal addition theory is in accordance with the Darwinian theory by explaining the evolution through continuous series of adaptational changes. This implies that the ancestor of the eumetazoans was a holopelagic, planktotrophic gastraea, and that the adult stages of cnidarians (sessile) and bilaterians (creeping) were later additions to the life cycle. It further implies that the various larval types are of considerable phylogenetic value. The origin of the indirect  life cycle with a ciliated, planktotrophic larva and a benthic adult has been discussed for more than a century. Many authors have favored the idea that the planktotrophic larvae are ancestral in the (eu)metazoans, for example -4, whereHaeckel’s famous gastraea theory  proposedAn alternative theory interprets the various planktotrophic larval types as numerous independent deviations from an ancestral direct development of a planuloid ancestor; this has been called the intercalation or interpolation theory, for example ,10. A vaTrichoplax creeps on the digestive epithelium  is without foundation” [Out of many thousand small globular fossils with a diameter of up to 200 μm from the Doushantuo Formation, a few, called  tissues -36. Howendation” . Putativndation”  are of tOlivooides  from the slightly younger Dengying Formation through Lower Cambrian [Quadrapyrgites is tetraradial. The development from the about 500 μm-diameter egg to juvenile is clearly direct, and the new observations indicate that a strobilation process was present, indicating scyphozoan affinities, and putative ephyrae were also observed.Cambrian -41 have Dickinsonia has been interpreted as a placozoan [Kimberella as a mollusc [A considerable number of Ediacaran (Vendian) fossils have been interpreted as bilaterians , but thelacozoan , and Kim mollusc . None ofRepresentatives of the majority of Living metazoan phyla appear in the fossil record in the Cambrian, in the Early Cambrian (Atabdanian) Sirius Passet and Chengjiang faunas  and in t“Small shelly fossils” appear with increasing diversity through the Earliest Cambrian  and decline in the Middle Cambrian. They are mostly interpreted as molluscs, but a few as brachiopods and a number as extinct groups of uncertain affinities . Most ofPojetaia had an embryonic shell which is large for a planktotrophic species (about 100 × 150 μm), but the size of the putative larval shell (about 300 μm) indicates the presence of a planktotrophic larva [The Mollusca originated in the Late Precambrian , and theic larva .Athelata, Agaronia, and Latirus, whereas evolution in the opposite direction was not observed.Studies of evolution of later gastropod groups with analyses of larval types are scarce, but an analysis of protoconchs of six families of fossil “neogastropods” from Early Tertiary of the Gulf of Mexico area revealed a low proportion of species with large protoconchs in the Early Palaeocene with increasing numbers into the Eocene, indicating evolution of direct development . EvolutiBrachiopods can be traced back to the Early Cambrian, and the size of the larval shells of some of the earliest fossils indicate that the stem lineages of both Linguliformia and Rhynchonelliformia had planktotrophic larvae .Echinoderms have a very extensive fossil record, with non-pentameric stem groups in the Cambrian , but nonThe developmental type of fossil echinoids can in some cases be inferred from three types of structures  Figure : 1) PresThe Precambrian/Early Cambrian fossils contain no unambiguous information about the ancestral developmental type of the eumetazoans. The earliest gastropods and bivalves probably had planktotrophic larvae. Observations on fossils from later periods contain well-documented examples of evolution of groups with non-planktonic life cycles in lineages with planktotrophic development, but apparently no examples of evolution in the opposite direction.So, the fossil record indicates that the indirect development with planktotrophic larvae was ancestral.The idea behind this method is that the distribution of different developmental types should make it possible to deduce the developmental types of ancestors of increasing age, and it has been used in cladistic analyses for example of polychaetes ,63-65. HEcdysozoans lack ciliated outer epithelia completely , and this is unquestionably an apomorphy . CephaloEudendrium rameum[Anthopleura[Caryophyllia and Fungia[The cnidarian larva is usually called planula, a name originally given to the compact larva of the hydroid um rameum. The terthopleura and the nd Fungia,70, havend Fungia, so the Several spiralian phyla have representatives with indirect development with planktotrophic larvae. Hatschek  proposedPolygordius and Echiurus[Annelida, including Echiura, Sipuncula and Pogonophora, is now a well-documented clade , but unf Echiurus,85, and  Echiurus. The occ Echiurus,63,65 caSpirobranchus, Serpula, Hydroides, and Pomatoceros[Schizobranchia insignis[Many serpulids, such as matoceros,86 have  insignis is non-fThus, there is a considerable variation in polychaete development, but no pattern can be recognized indicating a de novo evolution of feeding larvae from ancestors with non-feeding larvae. The early radiation of the molluscan classes is still under discussion. Most recent studies of both the rich fossil record and the sequence data favor the monophyly of Aculifera and Conchifera . It seemConus[Lacuna within the Littorinidae show indication of evolution of planktotrophic species from direct developing ancestors. However, the term direct development is highly ambiguous when applied to gastropods. The development within the egg capsules may show embryos with fully differentiated veliger larvae, such as in Cassidaria  sp. [Only gastropods and bivalves have representatives with planktotrophic larvae. These larvae are called veligers because the locomotory and particle-collecting ciliary system of the trochophore is situated on a smaller or larger expansion called the velum. Of the major gastropod lineages Neritimorpha, Caenogastropoda and Heterobranchia have representatives with feeding veliger larvae, whereas the remaining two groups, Patellogastropoda and Vetigastropoda, only comprise species with non-feeding larvae with a prototroch . AnalyseConus  sp.  where thdea) sp. ,97. The dea) sp. ), this ddea) sp. .Dentalium  have the cell-lineage of a prototroch, so the very similar ciliary bands on the larval serosa of the protobranch Acila is very probably a prototroch too [The Bivalvia comprises the sister groups Protobranchia and Autobranchia , where troch too .The prototrochs of the molluscs with ciliated larvae or embryos all have the same cell-lineage and structure as those of all the other spiralians, so the homology of these ciliary bands can hardly be questioned. Further, it seems most likely that feeding veliger larvae are ancestral in Gastropoda and Autobranchia, but the ancestral larval type of the molluscs cannot be deduced directly.Entoprocts all have indirect development with more or less modified trochophora larva, which are feeding in most species ,103.Bryozoans all have indirect development. The planktotrophic cyphonautes larva is found in basal lineages of the Eurystomata ,105, andAlmost all phoronids and the linguliform brachiopods have indirect development with feeding “larvae”. The planktonic linguliform larvae are swimming juveniles, essentially having the anatomy of the benthic adults with ciliated tentacles having a ciliary sieving system on monociliate cells. Particles become captured by laterofrontal cilia which either make a flicking movement or elicit a tentacle flick, in both cases moving the particle closer to the water current towards the mouth ,113. TheSeveral studies have concluded that the feeding dipleurula is the ancestral larval type of echinoderms and enteropneusts (Ambulacraria) ,116 Fig. The plaMetacrinus has a lecithotrophic larva with a neotroch in the same shape as that of many of the early larval stages of the eleutherozoans; this ciliary band becomes reorganized into four circular bands through a process which is very similar to that observed in the initially planktotrophic larva of the holothurians Synapta and Stichopus[The radiation of the living echinoderm classes now seems well understood with Crinoidea as the sister group of the remaining classes (Eleutrerozoa) . FeedingStichopus,120. SevStichopus, for exaStichopus and in tStichopus,124. An The neotroch of feeding enteropneust tornaria larvae is of the simple shape of a dipleurula in the early larvae, but becomes highly complicated during development in some species, especially in the Ptychoderidae. It is the first ciliary band to develop at the young larvae, and is initially used both in particle collection and swimming. The large perianal ring of compound cilia, which is the only ciliary band of the direct developing larvae, develops a little later .Thus, there are many well-documented examples of evolution of non-planktotrophic development (lecithotrophic or direct) in all the phyla where ciliated planktotrophic larvae occur. The intercalation theory implies hundreds of examples of parallel evolution of planktotrophic trochophora larvae from non-feeding larvae, but no example of evolution from “direct development” to development with planktotrophic larvae. So, the tendencies are clearly in favor if the terminal addition theory.Almost all pelagic ciliated eumetazoan  larvae have a group of nerve cells with long cilia at the apical pole. This organ has traditionally been called the apical organ, and this is unambiguous in cnidarian and ambulacrarian larvae. Unfortunately, the homologous organ in spiralian larvae is in many species intimately connected with a pair of lateral ganglia to form a compound organ which has also been called an apical organ. To avoid confusion, I have in previously tried to introduce the name “apical ganglion” for the organ ,126,127,The homology of cnidarian and bilaterian apical organs have been questioned, especially because the apical-blastoporal axis and the animal-vegetal axis have the same orientation in the bilaterians, but opposite orientations in the cnidarians, i.e., the polar bodies are situated at the apical pole in bilaterians but at the blastoporal pole in cnidarians. However, it now appears that gene expression supports the homology both of the apical organs and of the gastrulation areas and that the position of the polar bodies (and thus of the an-veg axis) may have changed in the bilaterians .An apical organ is found in almost all cnidarian larvae. It comprises flask-shaped sensory cells and degenerates when the larva settles with the apical pole , in someCiliated spiralian larvae almost all have an apical organ, with the cerebral ganglia developing almost simultaneously, often in close apposition to the apical organ. A close connection between their cerebral commissure and neurites from the basal parts of the apical cells are usually found. The apical organ degenerates before or at metamorphosis in all species ,101,131,Among the ambulacrarians, the enteropneust tornaria larvae have a conspicuous apical organ, which degenerates after metamorphosis . EchinodIt appears that the apical organs are associated with the pelagic part of the life cycles and that they always disappear before or at metamorphosis. Thus, it fits well with the terminal addition theory, which proposes a planktonic gastraea with an apical organ as the ancestor of the eumetazoans  . There sInformation about the genes involved in the organization of larval ciliary feeding bands would be of great importance for the understanding of their evolution. Are the same genes responsible for example for the development of the neotroch of all dipleurula larvae, and could a silencing of one or more of these genes lead to the uniformly ciliated, lecithotrophic larvae seen in several species? Unfortunately, there are only very few studies of this type. Comparisons of gene expressions in trochophora and tornaria larvae are of questionable value because of the possibility of homoplasy/homocracy ,5,134.Heliocidaris tuberculata with a normal echinopluteus larva and the direct developing H. erythrogramma and Pseudoboleta maculata, which have ovoid, uniformly ciliated larvae without a functioning gut. Fertilizing of eggs of H. erythrogramma with sperm from the about 4-million years distant H. tuberculata resulted in short-armed, pluteus-type planktotrophic larvae which went through a normal metamorphosis [H. erythrogramma with sperm from the about 40-million years distant P. maculata resulted in very similar larvae, and it was concluded that their ancestral common species had indirect development with an echinopluteus larva [The only comparative studies of ciliated larvae of closely related species with different life cycles appears to be observations on the larval stages of the indirectly developing echinoid orphosis ,136. Expus larva . This coH. tuberculata and a stage of H. erythrogramma with developing primary tube feet [The later study of gene expression in gastrula and early pluteus stages of ube feet  comparesMolgula and Pelonaia[Manx expression results in the anuran development [Observations on development of ascidians have shown that tailless (anuran) larvae have evolved several times within  Pelonaia and thatelopment . This isStreblospio benedicti[Boccardia proboscidea[Pygospio elegans[More circumstantial evidence comes from studies of poecilogony, i.e. the presence of different developmental types in the same species, for example in Annelida and Mollusca. In the annelid family Spionidae, benedicti two morpoboscidea depositso elegans  gastrula. Cnidarians and (ctenophores) lack the long bilaterian Hox cluster. In the protostomes, Hox gene expression is documented in detail in the annelid istomium . A simil[Haliotis. In the [Haliotis. This coThe diagram showing “progressive evolutionary interpolation of larval development …”   larvae of ascidians demonstrate that the silencing of a single gene is responsible for the loss of the elongation of the tissues of the tail. However, the differentiation of the tissues characteristic of the chordates evolved in the chordate ancestors and has been retained in the anuran larvae.The modern version of the intercalation theory proposes a gastrula stage in the ancestral eumetazoan, so both this and the terminal-addition theory can accommodate the cnidarians which added a sessile stage to the planktonic stage. The ancestral bilaterian was probably a gastraea too, the difference between the two theories being whether the gastraea was pelagic and planktotrophic  or benthic and deposit-feeding .The terminal addition theory scenarios explain the life cycles of most protostome phyla, but provide no scenario for the deuterostomes. The trochaea theory for the origin of the spiralians is in full accordance with the Darwinian principle of evolution through gradualism and adaptation. It is in good accordance with the many examples of evolution of non-planktotrophic development within smaller clades which ancestrally have life cycles with planktotrophic larvae. The planktotrophic larvae have been modified in many fascinating ways in the various lineages, and lecithotrophic larvae or direct development has evolved in many other lineages. The speciation event which lead towards lecithotrophy or direct development in one of the two sister species may have happened quite recently, so that species pairs with one species with indirect and one (or a few) with direct development are now seen. More ancient speciation events produced ancestors of larger clades with direct development, from genera or families all the way to the largest clades of the animal kingdom, such as Ecdysozoa and Chordata Figure . It appeThe intercalation theory provides no adaptation-based scenario for the origin of the planktotrophic larvae.It can only be concluded that the ancestral eumetazoan/neuralian was a holopelagic, planktotrophic gastraea and that indirect (pelago-benthic) life cycles evolved in a few lineages through terminal addition of adult stages with the planktotrophic stages retained as larvae. In the cnidarians, the benthic stage was sessile, whereas the benthic stage in the bilaterians was vagile/creeping. It remains uncertain whether the vagile/creeing stage evolved in the last common ancestor of all bilaterians or separately in Protostomia and Deuterostomia. Non-feeding larvae and direct development developed in many clades Figure . This imThe author declare that he has no competing interests.


Action is often executed according to information provided by a visual signal. As this type of behavior integrates two distinct neural representations, perception and action, it has been thought that identification of the neural mechanisms underlying this process will yield deeper insights into the principles underpinning goal-directed behavior. Based on a framework derived from conditional visuomotor association, prior studies have identified neural mechanisms in the dorsal premotor cortex (PMd), dorsolateral prefrontal cortex (dlPFC), ventrolateral prefrontal cortex (vlPFC), and basal ganglia (BG). However, applications resting solely on this conceptualization encounter problems related to generalization and flexibility, essential processes in executive function, because the association mode involves a direct one-to-one mapping of each visual signal onto a particular action. To overcome this problem, we extend this conceptualization and postulate a more general framework, conditional visuo-goal association. According to this new framework, the visual signal identifies an abstract behavioral goal, and an action is subsequently selected and executed to meet this goal. Neuronal activity recorded from the four key areas of the brains of monkeys performing a task involving conditional visuo-goal association revealed three major mechanisms underlying this process. First, visual-object signals are represented primarily in the vlPFC and BG. Second, all four areas are involved in initially determining the goals based on the visual signals, with the PMd and dlPFC playing major roles in maintaining the salience of the goals. Third, the cortical areas play major roles in specifying action, whereas the role of the BG in this process is restrictive. These new lines of evidence reveal that the four areas involved in conditional visuomotor association contribute to goal-directed behavior mediated by conditional visuo-goal association in an area-dependent manner. When we drive a car and arrive at an intersection, we press the brake pedal if we see a red light, or we continue to press the gas pedal if we see a green light. More generally, we often act based on information provided by a visual signal. Because this type of goal-directed behavior integrates two forms of neural representations , it is thought that identification of the neural mechanisms underlying their integration will yield insights into the fundamental principles underpinning goal-directed behavior. Some studies in this domain have used the framework provided by arbitrary visuomotor mapping . In thisAccurate definitions of the goals and rules are therefore critical. Figure 1A). However, this assumption encounters a problem when generalization and flexibility are required. Because the perceptual and action signals are supposed to be linked on a one-to-one basis, it is necessary to account for every combination of perceptual and action signals. In reality, this requirement is untenable. For example, responding to a red light involves squeezing a brake lever if one is riding a bicycle, pressing a brake pedal if one is driving a car, and stopping one’s movement if one is walking. Moreover, many varieties of visual signals and gestures can be the source of the instruction to stop. Actually, coming to a halt in the context of a signal to do so requires that numerous combinations of perceptual and action signals have been the foci of preparation. This requirement involving one-to-one combinations leads to another problem when the information provided by sensory signals changes or when a new motor response is required to execute the action implied by the information. For example, if a red light were to become the signal for proceeding or if the positions of the brake and gas pedals were reversed, we would need to relearn every combination of perceptual and action signals. Thus, neuronal networks that rely solely on computations based on conditional visuomotor associations would face major difficulties when information processing requires generalization or flexibility.The conditional visuomotor association framework posits that neurons or networks directly link a visual signal to a bodily movement (action) in a rule-dependent manner . First, it assumes that the visual signals provide information about an abstract behavioral goal instead of a concrete action. Second, it assumes that individuals subsequently specify or select an action to achieve that goal. We will refer to this new processing mode as conditional visuo-goal association because the visual signal is linked to a goal rather than to an action. The conditional visuo-goal association framework posits that neurons or networks directly link a visual signal to a behavioral goal in a rule-dependent manner . This framework is considered to provide the goal-directed behavior with the generalization and flexibility. Once the goal is determined the subjects can specify or select an appropriate action to achieve the goal in various conditions, corresponding to the generalization. In addition, if the goal information provided by sensory signals changes, the subjects can address it by updating the association rules between the sensory signals and the goals, corresponding to the flexibility.These flaws seem to rule out conditional visuomotor association as the mechanism underlying higher cognitive functions, which are characterized by flexibility and the ability to generalize . Thus, wWe will first review the mechanisms underlying conditional visuomotor association and then attempt to extend them to conditional visuo-goal association to elucidate how this network can serve as a basis of the higher cognitive functions that subserve goal-directed behavior.Pioneering studies by A receptor agonist muscimol to temporarily inactivate the PMd or the ventral premotor cortex (PMv). They first identified clusters of task-related neurons in the PMd and PMv while monkeys performed a conditional visuomotor association task that required them to perform a wrist flexion (extension) movement when a red (green) signal was presented. They next injected muscimol into the cluster in either the PMd or the PMv to reversibly inactivate it. They found that inactivation of the PMd cluster led to directional errors , whereas inactivation of the PMv cluster led to reduced movement amplitudes and velocities . These findings provided compelling evidence that the PMd of monkeys is crucially involved in conditional visuomotor association .The lesions in these studies were fairly large and spanned multiple areas. In the studies conducted by Working with humans, Figure 2). The specific aspects of information processing in which the PMd participates were revealed by recording neurons while monkeys performed a variety of motor tasks. The PMd of human and non-human primates has been shown to play a crucial role in conditional visuomotor association . At the first level, information regarding which arm to use or for which target to reach is selected. At the second level, these two sets of information (the arm to be used and the location of the target) are collected and integrated to specify a reaching movement. This integration process must incorporate distinct types of information; although the arm is part of the participant’s body, the target exists outside of his or her body. After the reaching movement is planned, the neural processes at the third level prepare and execute it.The subjects in the studies discussed above could specify a forthcoming movement after the instruction cue was presented. However, prior studies also revealed that the PMd stores partial information about the direction or amplitude of movement when such information is provided in a stepwise manner . This phFigures B). One cue signals the location of the target (right or left), and the other cue signals which arm (right or left) to use. These instructions are given in the framework of what is known about conditional visuomotor association in that each compound visual signal is arbitrarily associated with each signal regarding arm use or target location. Therefore, after the first cue, it is necessary to collect and maintain information about the target location  or arm use . After the second cue, monkeys were able to combine the two successive instructions about target location and arm use. Thereafter, the monkeys prepared to reach for the designated target with the designated arm, and they executed the reaching movement once a GO signal appeared (the disappearance of the fixation point). Altogether, the task design allowed us to study the neural mechanisms of the three levels of hierarchical organization underlying the reaching movement. It further allowed us to examine whether PMd neurons retrieve a partial motor instruction given by an arbitrarily associated visual signal.A new behavioral task was developed to study the neuronal basis of these processes . This taFigure 5A discharged selectively after the appearance of the right-arm (RA) cue. The second group of neurons became active after the appearance of the cue regarding target location. The neuron shown in Figure 5B selectively discharged after the right-target (RT) cue was given, and, like those in the first group, its activity persisted until the second cue was presented. These findings revealed that PMd neurons retrieve and store a partial motor instruction, or a building block of action, when this information is embedded in a conditional visuomotor association. These processes correspond to the first level in the hierarchical organization of the reaching movement. When the second cue appeared, the third group of neurons became active. Neurons in this group seemed to represent the specific combination of the two instructions on arm use and target location given by the two cues. For example, the neuron shown in Figure 5C responded to the appearance of the second cue only when the combination of the two instructions on arm use and target location signaled the RA and the left target (LT). In other words, the third group of neurons was considered to contribute to the forthcoming reaching movement by integrating the two distinct sets of motor information, on arm use and target location. The existence of the three patterns of activity in the PMd suggests that this area contributes to planning reaching movements by collecting and integrating distinct sets of information on target location and arm use. These processes correspond to the second-level processing in the hierarchical organization and are the cardinal ones involved in action planning. We also found that during the preparation and execution periods of a reaching movement, PMd neurons selectively represented the specific combination of arm and target information . This design was also based on the notion that a visual signal often indicates an abstract aspect of behavior rather than an actual movement. For instance, a red traffic light instructs us to “stop”; subsequently, we execute an action to “stop” . Thus, it can be seen that we first make a decision about a behavioral goal (“stop”) based on a sensory signal (a red traffic light) and subsequently choose the appropriate action to achieve the goal. Figure 6 shows the time sequence of the behavioral task , although it was rarely selective for the visual objects themselves . Subsequently, when a pair of potential targets was presented as the choice cue, information about the spatial position of the choice cue was rapidly combined with information about the behavioral goal , resulting in the development of an action representation , which eventually replaced the behavioral goal representation. Our observations also revealed a subset of PMd neurons that first exhibited activity representing the behavioral goal, which changed into activity representing a mixture of the behavioral goal and the choice-cue location after the appearance of the choice cue, suggesting that these neurons directly contributed to the transition between the goal-related and the action-related use of the information. These results suggest that the PMd hosts a neural network involved in integrating the behavioral goals retrieved from visual-object signals with the locations of choice cues to specify forthcoming actions.While monkeys performed this task, we first recorded neurons from the PMd. The activity of PMd neurons initially reflected the behavioral goal, reaching toward the LT or the RT after the choice cue signaled by the visual objects . These results indicate that vlPFC outflow is directed toward the PMd in a multisynaptic fashion through these areas .Initially, the corticocortical pathways from the vlPFC to the PMd were analyzed. Fast Blue  was injected into the PMd to identify the cortical areas that send projection fibers directly to the PMd. Considerable retrograde labeling occurred in the dlPFC, area F7 (pre-PMd), pre-supplementary motor area (pre-SMA), and PMv , whereasSubsequently, the multisynaptic projections from the BG to the PMd were analyzed  after thFigure 2), raising the intriguing possibility that the circuits linking the PMd to the vlPFC and/or the BG may be involved in retrieving the abstract goals from the visual-object signals. To test this hypothesis, the response properties of neurons in the lateral PFC and the BG were compared with those of neurons in the PMd.These anatomical studies revealed that the PMd receives inputs across synapses from the vlPFC and the BG . For example, the neuron shown in Figure 10A strongly responded to the appearance of a yellow square. This object representation is consistent with anatomical reports that the vlPFC receives input from the inferotemporal cortex and with prior studies reporting ample object representations by vlPFC neurons . For example, the dlPFC neuron shown in Figure 10B selectively responded to the appearance of a red diamond and a blue cross signaling the LT. The limited representation of the visual-object signals in the dlPFC is in accord with the paucity of anatomical connectivity between the dlPFC and the inferotemporal cortex . These observations reveal that goal representation develops almost simultaneously in the PMd and vlPFC, which are indirectly interconnected, whereas goal development in the dlPFC, which is thought to mediate the pathway between these areas, tends to follow that in the PMd and vlPFC. These data did not support the view that the goal signals generated in the vlPFC travel cortico-cortically to the PMd via the dlPFC. To better understand the flow of information across the vlPFC, dlPFC, and PMd, the timing of the emergence of selectivity was compared with a measure of population selectivity . In the Figure 12A), and selectivity developed as early as it did in vlPFC neurons . This prompt representation of visual objects by BG neurons is consistent with previous reports , and the timing of selectivity development was no later than it was in the PMd, vlPFC, and dlPFC . These observations indicate that the GP is involved in the early determination of behavioral goals, suggesting that the GP may emit a signal to inform wide cortical areas that a certain object or goal has appeared, serving to trigger subsequent information processing in these areas. The representation of an abstract aspect of motor behavior is consistent with prior reports showing that neurons in the putamen and GP represent a target position or a movement direction as the intended movement direction . Furthermore, neurons that integrated representations of goals with choice-cue locations, which are considered to play a crucial role in the transformation from goal to action, were less numerous in the GP than in the PMd . Monkeys participating in the symbolic cue task could specify or select the forthcoming action (the absolute position of a target on the screen) after the appearance of the choice cue. We found that neuronal activity selective for actions developed in the GP as well as in the PMd, dlPFC, and vlPFC. In contrast to the timing of the development of goal selectivity, the timing of the development of action selectivity in the GP differed from that in cortical areas; action representation in the GP emerged 30 ms later than it did in the cortical areas . In contrast, the duration of goal selectivity of vlPFC neurons was comparable to that of GP neurons, supporting the hypothesis that vlPFC is not essential for maintaining working memory  revealed neural mechanisms underlying the specification and planning of actions based on sensory signals. However, applications resting solely on this conceptualization encounter problems related to generalization and flexibility, which are essential processes in executive function. To overcome this problem, we extended this conceptualization and postulated a more general framework, conditional visuo-goal association , in which the visual signal identifies an abstract behavioral goal, and an action is subsequently selected and executed to meet this goal. Neuronal activity recorded from the brain areas of monkeys performing a task involving conditional visuo-goal association revealed that they regulate the task in an area-dependent manner. By comparing the response properties of neurons in the GP, PMd, dlPFC, and vlPFC of monkeys engaging in goal-directed behavior mediated by conditional visuo-goal association, we revealed that these areas are commonly involved in the initial stages of goal determination based on visual signals. Neurons representing an abstract behavioral goal are considered to provide a foundation for executive function. In contrast, we found that GP activity follows the leading activity in the PMd, dlPFC, and vlPFC in specifying an action based on an abstract behavioral goal. Taken together with the finding that a shorter length of time represented goal and action by neurons in the GP compared with neurons in the PMd and dlPFC, these data suggest a unique involvement of the BG and the frontal cortical areas in goal-directed behavior. Increased understanding of the neural mechanisms underlying conditional visuo-goal association will yield deeper insights into the fundamental principles underpinning goal-directed behavior.Previous studies based on a framework derived from conditional visuomotor association (The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Facility maintenance management (FMM) has become an important topic for research on the operation phase of the construction life cycle. Managing FMM effectively is extremely difficult owing to various factors and environments. One of the difficulties is the performance of 2D graphics when depicting maintenance service. Building information modeling (BIM) uses precise geometry and relevant data to support the maintenance service of facilities depicted in 3D object-oriented CAD. This paper proposes a new and practical methodology with application to FMM using BIM technology. Using BIM technology, this study proposes a BIM-based facility maintenance management (BIMFMM) system for maintenance staff in the operation and maintenance phase. The BIMFMM system is then applied in selected case study of a commercial building project in Taiwan to verify the proposed methodology and demonstrate its effectiveness in FMM practice. Using the BIMFMM system, maintenance staff can access and review 3D BIM models for updating related maintenance records in a digital format. Moreover, this study presents a generic system architecture and its implementation. The combined results demonstrate that a BIMFMM-like system can be an effective visual FMM tool. Facility maintenance management (FMM) in the operation phase of facility's life cycle has become an important topic for research and academic study. Managing maintenance information about facilities contributes to successful facility management (FM). Managing FMM work effectively can be extremely difficult on the operation phase owing to various types of equipment and facilities. Furthermore, it is inconvenient for maintenance staff to maintain those facilities by relying on paper-based documents. The latest information technology solutions provide improved FMM. Unlike the manufacturing industry, information technology is limited in its use and application in construction , and mosRegarding FMM, maintenance staff usually refers to information such as specifications, checklists, maintenance reports, and maintenance records. Maintenance staff must record maintenance results on hard copies. Consequently, there can be significant gaps in data capture and entry. Such means of communicating information between the facility location and the management office are ineffective and inconvenient. According to the survey findings regarding maintenance work on a commercial building in Taiwan, the primary problems regarding data capture and sharing during the FMM process are as follows: (1) the efficiency and quality are low, especially through document-based media, (2) it is not easy to reference relevant detailed information on facilities, (3) there are data reentry problems, and (4) the use of desktops for operating BIM models cannot be extended to maintenance management service at facility location effectively. However, few suitable platforms exist to assist maintenance staff in using integrated FMM information system from BIM models and sharing maintenance information directly at the facility's location.The performance of FMM can be enhanced by using web technology for information sharing and communication. In this study, the FMM work includes inspection and maintenance works. Building Information Modeling (BIM) uses precise geometry and relevant data to support the maintenance service of facilities depicted in 3D object-oriented CAD. By integrating web and BIM technologies, the effectiveness of FMM work is enhanced and improved see . In ordeBIM digitally contains precise geometry and relevant data needed to support the design, procurement, fabrication, and construction activities to describe 3D object-oriented CAD . BIM is The BIM approach, which is used to retain facility information in a digital format, facilitates easy updates of FMM information in a 3D CAD environment. Although there were many practical applications for using BIM in the maintenance management stage, one of the challenges in broader application of BIM models to FMM is that currently the use of PC desktops limits on-site use of BIM models during the maintenance and inspection process. Another problem for most facilities is that vertical position can be difficult to illustrate clearly based on traditional 2D drawings. With the use of mobile devices executing the BIM models, these BIM models need to be processed in advance and reduced to a smaller file size to be used in mobile devices. This study will explore and make recommendations to solve these problems. In order to assist maintenance staff in obtaining the corresponding BIM model automatically for FMM, this study develops a proposed system to integrate web technology to automatically connect the BIM models. This study enhances FMM service using web technology integrated with the BIM approach. By using the web technology, users can quickly click the corresponding BIM model of a facility and access basic information and maintenance problems while managing FMM information during the operation phase. The application of BIM technology in the FMM both inside and outside of the buildings supports maintenance staff in handling FMM via the 3D BIM models. By accessing the mobile device, maintenance staff can obtain the corresponding BIM model of the facility and directly access FMM information about the facility such as instruction manuals, photos, video of operations, maintenance history, and manufacturer information. Furthermore, a 3D BIM model improves upon traditional 2D drawings that can make it difficult to illustrate the vertical location or position of facilities.The BIMFMM system consists of subsystems for BIM, mobile devices, and a hub center. The mobile devices subsystem is located on the client side, while the BIM models and hub center subsystem are on the server side. Each subsystem is briefly described below.In this study, BIM is used as an information model in the BIMFMM system. The BIM is applied to capture and store information about the facility, including basic descriptions, parameter-related information, maintenance records, and FMM reports. Autodesk Revit Architecture and Revit MEP were used to create and maintain the BIM model files. Autodesk Navisworks was used to integrate and read the BIM models of facilities. Information integration with the 3D BIM models was achieved using the Autodesk Navisworks API and Microsoft Visual Basic.NET (VB.NET) programming language. The BIMFMM system was developed by integrating the 3D BIM models of facilities and maintenance-related information using Navisworks API programming. Open Database Connectivity (ODBC) was utilized to integrate acquired data from different software programs and all maintenance information, such that BIM files can be exported to an ODBC database for connection with the BIMFMM system. There are two mobile devices used in the BIMFMM system. An Acer Iconia W700P tablet is used as the webcam-enabled tablet hardware. The Acer Iconia W700P tablet runs on Windows 8. An HP Pavilion notebook is used as the webcam-enabled notebook hardware. The HP Pavilion notebook runs the Windows 7 operating system. All data in the tablet and notebook are transmitted between the client and the server sides directly through the web via Wi-Fi or 3G. The hub center is an information center in the BIMFMM system that enables all participants to log onto a hub center and immediately obtain information required for FMM. Users can access different information and services via a single front-end access point on the Internet. For example, maintenance staff can log onto the hub center and securely access the latest FMM schedule information. FM managers can check maintenance status, results, and various other inspection-related data. All facilities-related pieces of information acquired within the hub center subsystem are recorded in a centralized system database. Maintenance staff can access required information via the hub center subsystem based on their access privileges.The amount of maintenance information stored will increase over time if all FMM pieces of information are recorded in the BIM model. Because BIM models cover a wealth of building information, central BIM models storage space should be reserved for crucial information, such as spatial information, facility ID and name of facility, facility location, and other critical information. In order to keep the system performance at an acceptable level, the information derived by other applications should be stored in an external location. Therefore, there is one database designed in the BIMFMM system, called the FMM database. The central BIM models stores only basic information . Related maintenance data and information are stored in the FMM database.The accuracy of the central BIM models will directly affect FMM operations in the BIMFMM system. In order to prevent too many users from simultaneously using central BIM models and in turn affecting the accuracy of the BIM models, the BIM engineer can update central BIM models and export into read-only BIM models (NWD file) directly in the server side. The latest read-only BIM models on the client side automatically re-syncs when read-only BIM models change on the server side. In this framework, all building facility pieces of information from BIM can be saved and updated in the read-only BIM models without accessing the central BIM models directly. Furthermore, central BIM models and read-only BIM model are saved on the server side. In the BIMFMM system, major three roles are involved in FMM including BIM engineer, FM manager, and maintenance staff. To ensure that the FMM operation does not affect the maintenance operation of the central BIM models, this study utilizes client-server system architecture. In the BIMFMM system, the read-only BIM model stores all facility basic information and location in the server side. Also, only BIM engineers are allowed to access and edit central BIM models by using BIM software and export into the read-only BIM models directly on the server side. On the client side, the FM manager and maintenance staff reference facility information through the read-only BIM models and edit FMM information through the FMM database in the BIMFMM system. The BIMFMM system server supports four distinct layers, each with its own responsibilities: management, data access, application, and presentation see . This foThe management layer provides BIM engineers with tools to edit and manage central BIM models by using BIM software. BIM engineers can create and integrate the read-only BIM models saved in the server through the Internet. Regarding the data access layer of the BIMFMM system, the FMM database stores all facilities maintenance records, while the read-only BIM models store complete facility information including facility number, name, and type in the BIM models. The FMM database records detailed maintenance information in accordance with the facility ID. The primary key establishes a relationship between facility ID and the main index. Therefore, information can be used for data association for data mapping to retrieve complete facilities maintenance information based on facility ID between read-only BIM models and FMM database.The application layer defines various applications for major system and API modules. These applications offer indexing, BIM model data updates and transfers, facility status visualization, and report generation functions. The application layer integrates and uses BIM software to open the BIM models by using developed API modules. Finally, the application layer can automatically acquire data and analyze BIM models based on a request and then send the results back to the client side.The presentation layer is the main implementation platform of the BIMFMM system. During the FMM process, the FM manager and maintenance staff can use a tablet (client side) and utilities in the BIMFMM system for the FMM operation. The presentation layer displays the location information of BIM model automatically, records maintenance information, illustrates different conditions and status of FMM, queries the history, and exports reports on FMM results. The BIMFMM system server is based on the Microsoft Windows Server 2008 operating system with an SQL Server 2008 R2 as the database. The BIMFMM system is developed using VB.NET programming, which is easily incorporated with ADO.NET to transact FMM and BIM information with an SQL Server database. The BIMFMM system consists of three different user areas, maintenance staff, FM manager, and BIM engineer areas. Access to the BIMFMM system is password-controlled.This section describes the implementation of each major functionality module in the BIMFMM system.The functional module provides maintenance staff with detailed FMM information on facilities by reviewing 3D BIM models. This module enables all maintenance staff to refer to related FMM information and historical maintenance records for the selected facility quickly and easily in the BIM-based environment. This module allows maintenance staff to refer to basic information and specifications associated with BIM models during the FMM process. This module also has a search function that enables the information to be found and retrieved easily. Maintenance staff can download up-to-date maintenance records through the BIM models and enter facility maintenance results directly into the BIM models. Additionally, the module can automatically produce the corresponding maintenance forms through the BIM models. Tablets display the checklist for every facility maintenance task. Maintenance staff can record maintenance information such dates, conditions, inspection results, descriptions of problems that have arisen during maintenance, and recommendations. Furthermore, maintenance staff can also check tasks that do not pass the inspection and select relevant tasks from lists in the BIM models. One of the benefits of the module is that maintenance results and records can be transferred between a tablet and the BIMFMM system by real-time synchronization, eliminating the need to enter the same data more than once.This functional module is designed to enable FM managers to monitor the FMM process. The process monitor module provides an easily accessed and portable environment where maintenance staff can trace and record all maintenance information and statuses through the visualized and colorized BIM model.Users can easily access the FMM reports functional module to identify needs and analyze FMM results information. Authorized records for interfaces can be extracted and summarized for the final FMM result-related reports. Furthermore, all FMM reports can be extracted using commercially available software such as Microsoft Excel.In order to integrate the system with the BIM models, the following API modules are developed in the BIMFMM system.This module allows users easily and quickly to access the related BIM models by entering ID code attached in surface of the facility. When the user enters ID code, this module will automatically identify the facility angle and facility location in the corresponding BIM models automatically for FMM.The module provides the visualization functionality for FMM status through a visualized BIM model. Through a systematic FMM analysis of test results, the module displays different colors to illustrate various conditions and FMM status . Users can access the overall different maintenance conditions and FMM statuses quickly through the visualized BIM model.There are two subsystems in the BIMFMM system. The first subsystem is the API monitoring subsystem for BIM engineers located on the server side. This subsystem deals with integration services of BIM models in the BIMFMM system. These services include updating facility maintenance information. Another subsystem is the maintenance subsystem located on the client side. This maintenance subsystem is developed for maintenance staff and FM managers to deal with FMM operations in the facility's location, such as clicking the BIM model of the facility, recording FMM, and reporting FMM results. There are three processes used in the BIMFMM system including the system initialization process, FMM information monitoring process, and maintenance implementation process.The purpose of the system initialization process is to provide adequate information on FMM operations. The system initialization process includes BIM models initialization and facility information initialization.BIM Models Initialization. The BIM model must provide all pieces of information and related models on a facility as an information requirement for facility maintenance operations. When the BIM models save complete facility information, the BIM engineer needs only to use BIM software (such as Revit) to create BIM models first. After the BIM models creation by Revit can export into many read-only BIM models (NWC file). All exported NWC files will be integrated a single read-only BIM model (NWD file) using Navisworks. Finally, the read-only BIM models (NWD files) can be downloaded on the client side of the BIMFMM system for FMM usage. When central BIM models change, BIM engineers only need to update central BIM models and export to read-only BIM models (NWD files); the BIMFMM system will automatically update read-only BIM model on the client side of the BIMFMM system.Facility Information Initialization. Facility information initialization is an important task in the FMM. After BIM models initialization, FMM staff adds new facility information and electronic documents directly in the system. The information will be saved in the FMM database. Furthermore, the facility information must be linked and associated with BIM models to create the relationship of facility information and BIM models in the MM database.After the facility information initialization process is completed, FM manager and maintenance staff may utilize BIMFMM system to handle the following FMM information monitoring and maintenance implementation tasks.When the system initialization process is completed, FM manager can view and access BIM models (NWD file) in the BIMFMM system and then open the BIMFMM system monitoring API module. When maintenance staff handles the FMM process, FM managers can monitor and refer the newest state of FMM with different color visualization of BIM models through the BIMFMM system.During the maintenance implementation process, the maintenance list varies according to the maintenance task categories. The design lets maintenance staff work on maintenance operations effectively according to the task categories and maintenance list. Maintenance staff can utilize the Web-enabled Tablet PC to access the BIMFMM system and show all the task categories and maintenance list based on different levels of access. After maintenance staff selects a particular task category, the system shows the history task form for that category. Maintenance staff can view the other task form, edit the unfinished task form, or add a new task form. When maintenance staff selects or adds a task form, the system retrieves facility information from the read-only BIM model based on the task types. Furthermore, a list of all related maintenance and results will be illustrated with the BIM model for FMM work preparation. Maintenance staff can access inspection information and the maintenance status effectively. During the maintenance implementation process, maintenance staff can use the system directly and select the corresponding BIM model of the facility. When the system receives the facility ID, the system automatically displays the facility's basic information and historical maintenance data in the BIM model. Furthermore, the facility's BIM model will be selected, focused, and highlighted using different color. User can obtain basic information on the facility by clicking the BIM model, or selecting from a maintenance list. After selecting the facility through one of the three methods, the maintenance staff can handle maintenance work and record the status and result of maintenance. Finally, all maintenance records and pieces of information are stored in the FMM database.During the process of maintenance operations, the maintenance status also can be enhanced by color visualization in the BIM model through the facility status visualization API module. Through the functionality that visually depicts the status of maintenance list items, the BIMFMM system will get related maintenance status from the maintenance list in the FMM database. Furthermore, the BIM model will visualize different colors based on the each maintenance status in the facilities, and other elements in BIM model will be displayed in translucent white to enhance the visualization effect see .Integrated with the above design concept, more complex operating procedures of FMM are simplified and developed in the BIMFMM system. One of the major characteristics of the BIMFMM system is to provide users an easy-to-use visualization for handling FMM work. By clicking the list, each task form will show the list of facilities requiring maintenance, historical maintenance information, and the status and condition of facilities maintenance. By clicking the corresponding BIM model of the facility, the BIM model are linked and illustrated quickly and effectively in facility location. All maintenance results are sent back and saved in the main BIM model. The proposed approach provides a means to update the facility information of the BIM model and FMM information synchronization. Finally, in order to let FMM engineers apply the system easily and effectively, the layout of the system is designed based on FMM engineers' suggestions. This study is applied to a building in Taiwan for the case study. This study utilizes a BIMFMM system in the FMM for the building. Existing approaches for tracking and managing FMM work rely on paper-based records. The bulk of FMM work was paper-based and documented by repeated manual entry, although an FMM system was developed for a standalone software application. Therefore, maintenance staff in the FM division utilized the BIMFMM system to enhance FMM work in the pilot case study. After the critical facilities were selected for FMM work, the unique ID for each facility was entered into the BIMFMM system database for quick search. Before the FMM work began, the maintenance staff could check the facility list from webcam-enabled tablets, refer to the relevant information, and begin preparation work without printing any paper documents. During the FMM process, the maintenance staff selected the relevant BIM model. The BIMFMM system showed the basic information and BIM model of the facility. Maintenance staff could then check further detailed information like maintenance instructions, notifications, and accessories list, all of which are supported by BIMFMM. After the FMM work, maintenance staff entered the results of maintenance, edited the description in the tablet, and provided the updated information to the system. When a facility required repairs, the system also provided the manufacturer's problem information for immediate reference. Finally, the facilities manager and the authorized maintenance staff accessed the updated information simultaneously from their offices.  Overall, the field test results indicate that the application of BIM is an effective tool for FMM in a building. All BIM models survived use in the pilot test over the two-month testing period. Approximately 18 users participated in field trials of the FMM process. The BIMFMM system was installed on the main server in the FM division of the building. During the field trials, verification and validation tests were performed to evaluate the system. Verification aims to evaluate whether the system operates correctly according to the design and specification; validation assesses the usefulness of the system. The verification test was carried out by checking whether the BIMFMM system could perform tasks as specified in the system analysis and design. The validation test was undertaken by asking selected case participants to use the system and provide feedback by answering a questionnaire. There were 25 participants involved in the evaluation test. To evaluate system function and the level of satisfaction with the system's capabilities, the users of the system were asked to grade the conditions of system testing, system function, and system capability separately, compared with the typical paper-based FMM approach. Some comments for future improvements to the BIMFMM system were also obtained from the case participants through the user satisfaction survey. Finally, The 92% of users obtained from user satisfaction survey indicates that the BIMFMM system is quite adaptable to current FMM practices in a building and is attractive to users. The overall result implies that the BIMFMM system is considered to be well designed and could enhance current time-consuming FMM processes. The over 98% satisfaction rate also indicates that the visual BIM model providing FMM support is very helpful. The 98% satisfaction rate for the BIMFMM system directly accessing the BIM model at facility location is also effective and necessary. Also, no additional work was required to complete documentation beyond the data collection process. The advantages and disadvantages of the BIMFMM system identified from the pilot study are identified. It was difficult for new users to operate BIM model in the BIMFMM system. Some maintenance staff was initially unfamiliar with BIM models. It usually takes time to learn how to use BIM models. In the case study, the use of the BIM system initially lengthened the FMM operation over the traditional approach, since users required time to find the corresponding BIM model and fill out the FMM information in the BIMFMM system. After the user is skilled and familiar with BIM model, the time required by the current approach and the proposed system is almost exactly the same in FMM operations.Based on the case study, BIM engineers needed to keep and update BIM models during the operation phase. When new equipment or facilities are purchased, BIM engineers must build a new BIM model for future maintenance use. Furthermore, the communications between maintenance staff and BIM engineers are necessary and important during the process. Maintenance staff should tell BIM engineers about any problem regarding the BIM models. The BIM engineers also must notify and discuss with maintenance staff after BIM engineer corrects the BIM models. BIM models require constant maintenance and updates. Another important issue is quality management of BIM models. Although the study proposed that the BIMFMM system help maintenance staff to handle visual facilities maintenance and management work, the advanced management procedures and mechanisms for quality management of BIM models for FMM must be identified and developed in the future. Particularly, the management mechanisms for updating the BIM models should be developed as the next step of BIMFMM system development.Although Navisworks provide user with the ability to access a huge integrated amount of BIM models, the integrated BIM models (NWD file) will become larger than original BIM models. Usually, it will take 2 to 5 minutes to download whole BIM models from the server side when applying BIM models in the tablet for FMM work. Therefore, it is necessary to develop appropriate mechanisms to improve the above problem. For example, the BIM models in the client side will be updated and downloaded only from the server side when BIM models changes in the server.The findings of this case study revealed several limitations of the BIMFMM system. The following are inherent problems recognized during the case study.The BIM approach, which is applied to retain facility information in a digital format, facilitates easy updating of FMM information in a BIM environment. Although there were many practical cases for using BIM during the maintenance management stage, the one of facing problem is that typically BIM models could only be used with PC desktops in an office, which limited their use onsite during facility maintenance. However, use of high-end desktops for operating BIM models could not be used effectively by maintenance staff onsite during the maintenance and inspection process. BIM models need to be processed and transferred via smaller files for use with mobile devices, which are more commonly used onsite. In order to assist maintenance staff with obtaining the corresponding BIM model automatically for FMM, this study develops the BIMFMM system to integrate web technology to automatically connect the BIM models. The BIMFMM system not only improves FMM efficiency but also provides a real-time service platform during the FMM process. In the case study, MM staff used webcam-enabled tablets to seamlessly enhance FMM work at facility locations, owing to the system's searching speed and ability to support related information collection and access during the FMM process. Meanwhile, on the server side, the BIMFMM system offers a hub center to provide the FM division with real time monitoring capacity during the FMM process. Integrated with characteristics of 3D BIM model illustration and BIM parametric design, the BIMFMM system quickly shows the necessary maintenance information using a facility's BIM model based on the selected task type and clearly presents the position and height of the selected facility.In a case study, the application of the BIMFMM system helped to improve the FMM work of a commercial building in Taiwan. Based on experimental results, this study demonstrated that BIM technology has significant potential to enhance FMM work. The integration of BIM technology with web technology helps FM managers and maintenance staff to effectively track and control the whole FMM process. Compared with current approaches, the combined results demonstrate that a BIMFMM system can be a useful mobile BIM-based FMM platform. Based on the case study finding, BIM models must be updated and corrected constantly. Another important issue is quality management of BIM models. The advanced management procedures and mechanisms for quality management of BIM models for FMM needs to be identified and developed in the future. Doing so will be the next step of BIMFMM system development. Finally, the limitations, facing problems, and suggestions are discussed based on the implementation of case studies in this study. Although there are some challenges indicated above, the proposed system has shown a great potential to be used for FMM in building with the promising results shown in this study.