Since this technique is based on sequencing a single gene, or even only parts of a single gene rather than the entire genome, the number of reads needed per sample to assess the microbial community structure is lower than that required for metagenome sequencing. This makes marker gene sequencing affordable to nearly any laboratory. Despite the relative ease and cost-efficiency of data generation, analyzing the resulting sequence data requires computational skills that may go beyond the standard repertoire of a current molecular biologist/ecologist. We have developed Cascabel, a scalable, flexible, and easy-to-use amplicon sequence data analysis pipeline, which uses Snakemake and a combination of existing and newly developed solutions for its computational steps. Cascabel takes the raw data as input and delivers a table of operational taxonomic units (OTUs) or Amplicon Sequence Variants (ASVs) in BIOM and text format and representative sequences. Cascabel is a highly versatile software that allows users to customize several steps of the pipeline, such as selecting from a set of OTU clustering methods or performing ASV analysis. In addition, we designed Cascabel to run in any linux/unix computing environment from desktop computers to computing servers making use of parallel processing if possible. The analyses and results are fully reproducible and documented in an HTML and optional pdf report. Cascabel is freely available at Github: https://github.com/AlejandroAb/CASCABEL.Marker gene sequencing of the rRNA operon  or cytochrome c oxidase I (CO1) is a popular means to assess microbial communities of the environment, microbiomes associated with plants and animals, as well as communities of multicellular organisms  On current sequencing platforms, up to hundreds of samples can be combined (multiplexed) in a single sequencing run, decreasing the sequencing costs per sample tremendously, and generating massive amounts of data. Not surprisingly, community compositions based on DNA analyses have been generated from most of the habitats on earth, including the human body  , the current bottleneck is the computational analysis of the  sequence data. For scientists with little background in bioinformatics, the amount of data and complexity of data analysis can be overwhelming. Popular software solutions for the individual steps from raw sequence data to an OTU or ASV table, e.g., QIIME . Although most often amplicons are designed and sequenced such that forward and reverse reads overlap and can be merged into one continuous sequence, for example the primer pair 515F (GTGCCAGCMGCCGCGGTAA), 926R (CCGYCAATTYMTTTRAGTTT) amplifies bacterial and archaeal 16S as well as eukaryotic 18S regions  performed are completely documented and reproducible. All scripts of Cascabel are located within the project folder, and together with the Snakemake and configuration file, every run of the pipeline is completely reproducible at any time. All software versions used are documented in the run reports (in HTML and pdf format). The code of all Cascabel scripts is open source, although we use some third-party modules which are not open source, e.g., UCLUST, USEARCH , and the output. The user defines via a configuration file  in yaml format, how these “rules” are chained to perform amplicon sequence data analysis from the raw data to the final OTU or ASV table. Cascabel saves the OTU or ASV table in BIOM and text format to allow further analysis and interpretation with statistical or visualization tools. For most of the rules, Cascabel provides several alternative algorithms or tools and allows passing arguments via the config file to the algorithm being used. In addition, rules can be skipped, and the pipeline can be entered and exited at every step. This makes Cascabel very flexible and highly customizable. Moreover, the pipeline is easily extendable and amendable to personal needs, allowing for example the analysis of any marker gene sequence data.Our pipeline makes use of the workflow management engine Snakemake  which are not readily available or straightforward for a non-bioinformatician to implement with existing amplicon sequence data analysis tools. The first one is a custom dereplication rule for very large data sets based on VSEARCH , and the config file specifying the tools and parameters used for running the pipeline. When working with one sequencing library, users can pass file paths to the raw data and metadata directly in the config file. When working with multiple libraries, users can choose between listing the input file names in a text file and referring to this file in the config file, or using the helper script initSample.sh. This script is run for each library to initialize the folder structure expected by Cascabel. With all three options, the folder structure will look like the one illustrated in Running Cascabel (https://github.com/AlejandroAb/CASCABEL). However, we strongly advise to make informed choices about parameter settings matching the individual needs of the experiment and data set. With the files in place, Cascabel is started with a one-line command on the terminal. Snakemake takes care of executing the rules in a computationally efficient manner, making optimal use of available resources, e.g., distributing jobs over several nodes. Cascabel. In Cascabel.We provide example config files with default parameters for double- and single barcoded paired-end reads for OTU and ASV analysis on the github page of Cascabel has an interactive and a non-interactive mode. In interactive mode, several modules have a check-point which needs to be passed to continue with the analysis. If the check fails   analysis with DADA2 .Cascabel offers pynast  generates HTML and optional pdf reports with documentation, figures and tables summarizing the results of individual rules, as well as all software versions and parameter settings used. If more than one library was analyzed, there will be a report for each library as well as a report summarizing all libraries (otu_report or asv_report). Among other graphics, the otu_report shows the percentages and the total number of reads after filtering (“combined reads”), dereplicated reads, OTUs, OTUs assigned to a taxonomic level, OTUs excluding singletons (“no singletons”), and assigned OTUs excluding singletons  and the results saved in a different “Run” folder. Each run has its own reports and is therefore fully documented and reproducible. Confusion about parameter settings for a specific analysis cannot happen.A unique feature of The “Run” parameter is also useful to analyse data from primers which generate multiple fragments with different lengths. The data can then be analyzed with individual runs for each expected fragment length. For example, when using primers which amplify both bacterial/archaeal 16S and eukaryotic 18S sequences, albeit with different length, one run can target the shorter fragment and a second run the longer fragment. If the longer fragment generates non-overlapping read pairs, these can be analyzed with the “unpaired” workflow as indicated in the config file.To facilitate comparing different taxonomy assignment approaches, the user can perform taxonomic assignments for the same run using different methods and the results will be saved in individual “taxonomy” folders. When starting a new taxonomic assignment, the existing OTU representative sequences are used so no processing time is wasted by performing the same upstream rules several times.Cascabel remove temporary files at the end of the analyses. For many rules, the user can pass additional parameters to the command or tool at hand using the “extra_params” parameter in the config file.The user can make use of all intermediate files generated by individual rules, and most importantly the OTU or ASV table and representative sequences for follow-up analyses. To save disk space, the user can also opt to have Cascabel, we applied it to 16S rRNA gene amplicon data generated from water column samples taken from Lake Chala. Cascabel offers two routes of analysis: OTU and ASV analysis. Some rules apply to both routes, others only to one of them. This is indicated in the header of the rule in the config file by either “BOTH_WF,” “OTU_WF,” or “ASV_WF.” If choosing “OTU_WF,” for example, the “ASV_WF” rules and their parameter settings are ignored. We chose ‘ANALYSIS_TYPE: “OTU”’ here. After validating the input files, Cascabel proceeded with analyzing sequence data quality with FastQC . If the amplicon is so long that the forward and reverse read do not overlap, Cascabel can be run using the rule “UNPAIRED DATA WORK FLOW” and setting “UNPAIRED_DATA_PIPELINE” to true. After forward and reverse read assembly or merging, the quality of the assembled reads was again assessed with FastQC. Then, the sequencing library was demultiplexed based on the barcode sequences provided in the barcode mapping file (rules “write_dmx_files” and “extract_barcodes”). This step is optional to allow processing already demultiplexed data. We demultiplexed the Lake Chala data based on a sample barcode of 12 nucleotides at the beginning of the forward and the reverse read, using the “barcode_paired_stitched” configuration which merges the barcode sequence of the forward read with the barcode sequence of the reverse read. Barcode sequences were provided in a barcode mapping file, such as exemplified in To demonstrate the functionality of Andrews, . In intede novo based on sequence abundance, but we set this rule (“search_chimera”) to false. The next step is to filter out sequences with unexpected length. To facilitate setting length thresholds, Cascabel generates a smoothed histogram of observed sequence lengths, which is shown in the library report . This step is optional, but recommended to decrease the runtime of OTU clustering and avoid memory issues with very large datasets.After demultiplexing, sequence chimeras can be removed based on a reference database, e.g., the gold database, and/or y report . In inteCascabel creates an OTU abundance table in BIOM and plain text format (rule “make_otu_table”). The OTUs were also summarized at different taxonomic levels making use of the rule “summarize_taxa.” Subsequently, we removed singletons (rule “filter_otu”), aligned representative sequences , filtered the alignment , and made a phylogenetic tree (“make_tree”). Removing singletons reduced the number of OTUs in the analyzed dataset to roughly 500, 000. To align representative sequences, we used pynast and fasttree to generate a phylogenetic tree. Finally, Cascabel generated a Krona chart, and HTML and pdf reports of the analysis, documenting all software and parameters used. For OTU clustering, we chose UCLUST with a similarity threshold of 0.97, resulting in roughly 2.5 million OTUs (rule “cluster_OTUs”). We selected the longest sequence of an OTU as representative sequence to be used for taxonomic assignment of the OTU (rule “pick_representatives”). Then we used VSEARCH to assign taxonomy to the representative sequences based on the SILVA database . From the abundances of the OTU sequences within each of the samples, Cascabel using the OTU workflow on the Lake Chala dataset was 14.5 h. Currently, we experience a bottleneck in the runtime of the barcode error correction, which took 10.25 h on this large dataset and will be improved in future versions of Cascabel. We also ran the ASV workflow on the same data . The highest precision was achieved by UCLUST (1.0), however, with a very low F1 statistic (0.19). The performance of DADA2 was lower than the one of Swarm, with an F1 statistic of 0.8. Thus, we observed substantial differences between different methods and parameter settings, and there was no one setting that would perform best on all three datasets. On the contrary, the best results were obtained with different methods and parameter settings for different marker genes. These results confirm that it is important to have a flexible pipeline to adapt it to the needs of the dataset at hand, but also that it is important to include a mock community ideally in every sequencing run that is performed to allow making informed choices about method and parameter selection. We also compared the different clustering algorithms in terms of runtime. The 16S mock community consisted of 207,197 paired-end reads of 300 nucleotides each, considerably smaller than the Lake Chala dataset, and therefore the analyses were much faster. The analysis with UCLUST (config_4.yaml) took 43 min and 18 s, of which 38 min and 42 s were spent on searching chimeras de novo. Swarm needed 5 min and 16 s for a run including chimera search against a reference database (config_12.yaml), searching chimeras took 1 min and 24 s of the total time. A DADA2 run (config_14.yaml) needed 8 min and 52 s including DADA2's own chimera search method.We evaluated the results of the individual runs in terms of the number of genera identified correctly (true positives), the number of genera missed  and the number of genera identified which were not part of the mock community . We evaluated all runs with respect to true and false positives, and show the individual true and false positive genera for a selection of the runs which we performed on the mock datasets. The selection included at least one run using UCLUST, one using Swarm and one ASV run with DADA2. We also varied Swarm parameters, reference databases, clustering thresholds, and chimera detection, but evaluating all possible combinations of parameters would not be feasible. An overview of the runs performed and the evaluation in terms of true and false positives, false negatives, precision, recall and F1 statistic , is shown in Cascabel has been developed at the Royal Netherlands Institute for Sea Research (NIOZ) to facilitate, unify and easily track data provenance of amplicon sequence data analyses. Apparent advantages of using this pipeline compared to custom scripts are that the individual steps of the pipeline have been tested by many members of the community at the NIOZ who are experienced in amplicon sequencing data analyses . With some minor modifications, Cascabel can even be used to analyze long read amplicon sequence data.Cascabel which offers interfaces to VSEARCH and mothur executables. Having a medium-sized user group at the institute, we did not want to overload a public server and setting up and maintaining our own server would also need resources that we preferred to allocate to the development of a workflow for which we have full control and flexibility. With Cascabel being invoked from the command line, the user can make use of the full potential that Snakemake has to offer, e.g., ––prioritize to force the execution of specific rules prior to others when distributing tasks across computing resources, ––until to run the pipeline up to a specific rule, ––summary, which shows the rules executed so far and ––dag which shows the rules executed and the ones yet to be done in a directed acyclic graph. Moreover, we consider Cascabel's report an essential element to move forward in terms of user-friendly data provenance and reproducibility.Galaxy  was collected from the water column of Lake Chala, a lake situated on the border of Kenya and Tanzania, east of Mount Kilimanjaro in Africa, from September 2013 to May 2014 from a total of 111 samples as described in van Bree et al. . DNA wasThe V4 region of the 16S rRNA gene was amplified with the primers forward:515F: GTGYCAGCMGCCGCGGTAA , we supplied the file paths to the raw sequence data (fastq files) in the “GENERAL PARAMETERS SECTION” (subsection “INPUT FILES”). Note that fastq files can also be provided as gzipped files, then in the “INPUT TYPE” section of the general parameter section, the parameter gzip_input needs to be set to “T” (True). The barcode mapping file was passed to Cascabel via the “metadata” parameter in the subsection “INPUT FILES” of the config file. In the “GENERAL PARAMETERS SECTION,” we chose a project name (“CascabelTest”) and set the “RUN” parameter to “report_test,” Cascabel then used these names to generate a project folder and a run folder. All settings and parameters chosen to analyze the example data set are documented in the config files . Fastq files were downloaded from the European Nucleotide Archive (ENA) using an in-house download tool (https://github.com/AlejandroAb/ENA-downloader-tool).To show the flexibility and assess the performance of running The datasets generated for this study can be found in the SRA of NCBI, BioProject PRJNA526242.AA implemented the pipeline, with contributions from JE. MB, LV, SB, and HW tested the pipeline. AA, JB, and JE designed the pipeline, with contributions from LV. JE wrote the manuscript. All authors contributed to and approved the final version of the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Despite the cost and health consequences, a large number of people continue to smoke cigarettes worldwide every day. Notwithstanding, there have been a number of interventions to help people stop smoking but, in general, these have produced only limited success, and better interventions are needed. Accruing evidence affirmed that rumination and executive function play a pivotal role in cigarette smoking behavior, and in this editorial, we describe and discuss the key findings between these constructs and smoking, and argue that an impairment in executive functions does not act alone, but interacts with rumination by directing attention to depressive thoughts, thereby reducing the ability of smokers to engage in constructive behaviors, such as quitting smoking. Finally, we offer a new theory-driven model based on a deep understanding of the interactions between executive functions and rumination and potential moderator effects. Tobacco cigarette smoking is a grave epidemic that will cause more than 6-8 million deaths before 2030 . NotwithAccruing evidence has supported the role of rumination  and EF  as potenWhy have I smoked?” - “ It was the worst decision of my life” - “If I could come back and change my actions” etc.) increases depressive symptomatology  and attentive-oriented (ii): (i) negative emotions increase more quickly during a quit attempt in smokers, and in particular those with a higher level of non-planning impulsivity  hiulsivity . In thisulsivity . It is lulsivity . Strong ulsivity . Evidenculsivity , 2008 anulsivity  in that ulsivity .umbrella term” used to refer to a set of psychological processes supporting goal-directed behaviors but there is a lack of an accepted definition within the literature. temporal window”, in which the deficit progressively arises , and with “greater knowledge” we would be better placed to train health professionals who work within smoking cessation.


The “magic” word complexity evokes a multitude of meanings that obscure its real sense. Here we try and generate a bottom-up reconstruction of the deep sense of complexity by looking at the convergence of different features shared by complex systems. We specifically focus on complexity in biology but stressing the similarities with analogous features encountered in inanimate and artefactual systems in order to track an integrative path toward a new “mainstream” of science overcoming the actual fragmentation of scientific culture. What we do mean by “biological complexity”? A number of attempts have been made to catch the meaning and the implications that such a word actually has to lay out the fundamentals of a theory of biological organization. It is bewildering that, in most cases, we must resign ourselves to self-evident statements like the following: “In a general sense, the adjective “complex” describes a system or component that by design or function or both is difficult to understand and verify . Yet, weWe think that a fair way to face with this challenge implies to begin by “deconstructing” the word and exploring its etymological meaning. Complex means “composed of interconnected parts, formed by a combination of simple things or elements.” The lemma “complex” comes from Latin complexus “surrounding, encompassing,” past participle of complecti, “to encircle, embrace,” from -com “with, together” + plectere, “to weave, braid, twine, entwine” . First aIn his seminal paper, Warren Weaver stressed that we are usually facing three order of situations about complexity: (1) organized simplicity, where the relationships among particles do not change across time and laws of classical physics holds up; (2) disorganized complexity, where the behavior of a huge number of entities—each of one has an individually erratic or unknowable behavior—can be caught by looking at macroscopic parameters governed by laws of statistical mechanics (thermodynamics), altogether with the support of probability theory; (3) organized complexity, a specific feature of systems (like the living ones) where several entities  establish relationships that can change over time, enabling the overall system in acquiring a form, according to organizing principles. This latter kind of complexity occupies a pivotal place at the mesoscopic scale—an intermediate position between atomic and macroscopic dimensions—where entities interact so allowing coherent “organization” to emerge. This kind of complexity allows collective organizing principle to “arise” from microscopic rules, while being—strictly speaking—independent of them . Both bisynistanai “to place together, organize, form in order,” from syn- “together.” Overall, system means a “set of correlated principles, facts, and ideas.” Again, as for the word “complex,” “system” appears at the beginning of the 17th century and was then applied to identify, animal body as an “organized whole” since 1680 [In the above definitions, another word comes into play: system. The lemma comes from Greek through Latin—i.e., “organized whole,” a whole compounded of parts—from the stem of the verb nce 1680 . Here, wlocal processes and the global structure of the living beings, connecting different organization layers. The existence of between layers correlations stems from the fact that molecules, molecular aggregates, organelles, cells, tissues, and organs are constrained to cooperate to keep the functionality of the whole. These constraints lie in the boundary and initial conditions, so that “the organization becomes cause in the matter” [To do so, we have first to choose a proper level of observation, specifically the one where the mesoscopic properties arise. Understanding the logic of organisms implies the possibility to recognize correlations between the  matter” . In the Second, how the system can be described, i.e., what are the variables (the “observables” in the language of physics) to look at? In order to give some hints on the choice of variables to consider, it is worth noting that any system is delineated by spatial and temporal boundaries, through which the system dynamically interact with the environment.This makes interface variables as the most promising field of investigation. It is worth stressing that some sort of organized interfaces emerge anytime when a complex system must face the (largely unpredictable) solicitations coming from its environment. The structure and function of such an interface is then a privileged observatory on the system itself.form, tightly committed in performing well-defined tasks and functions. This prompts to look at size invariant relations among descriptors that encompass the concept of shape.Interfaces provide a system with a recognizable structure, as such epitomized by a specific Lastly, a complex, living systems evolves over time through successive critical transitions, reaching different stable-states, which are usually depicted altogether by a Waddington-like landscape . This sumergere “to dip, sink”) evokes the rising from a liquid by virtue of buoyancy, thus suggesting how the interaction among upward forces at the lower levels can produce recognizable effects at a level higher than that in which interactions among components take place. Therefore, understanding those properties require that the description of complex processes ought to be performed by looking at the level at which these properties “emerge.” An emergent property need not be more complicated than the underlying non-emergent properties that generate it. For instance, the laws of thermodynamics are remarkably simple, even if the laws that govern the interactions between component particles are usually more “complicated” and frequently mathematically intractable.Emergence, a concept first introduced by Aristotle , was reiEmergence has been reported in purely physical settings as well as in living organisms. An example from physics of such emergence is water, which behavior appears unpredictable even after an exhaustive study of the properties of its constituent atoms . Anotheremergence is not an epistemic construct. Instead, it reflects a true ontological reality shared by complex systems of very different nature [This statement introduces some very relevant questions given that emergent phenomena share some common—universal traits that are largely insensitive to changes in their microphysical base, as pointed out by studies of the Renormalization Group . “Univert nature .Transitions between different levels of organization, associated with appearance of emergent properties, call into question a pivotal aspect of complex systems: symmetry breaking.By symmetry, we mean the existence of different viewpoints from which the system appears the same (superimposition). It is worth noting that the symmetry present in the microscopic equations is not present in the macroscopic system, due to phase transitions. According to Laughlin, while for many particle systems, nothing can be calculated exactly from the microscopic equations, mesoscopic and macroscopic levels can be effectively described in their own terminology and have properties that do not depend on many microscopic details. This does not mean that the microscopic interactions are irrelevant, but simply that you do not see them anymore—you only see a renormalized effect of them .Let us to consider water across its phase transition as an example. When water is in a liquid state there is no privileged direction , whereas when water is solidified as ice, it assumes a crystalline structure with spatially periodic patterns. This implies that the system is no longer symmetric by continuous rotations: it has a few privileged directions determined by its crystalline structure, which means that it has a smaller symmetry group . These conditions are mirrored by parallel changes in the system’s energy balance: in the liquid state, entropy dominates, associated with a more disordered phase, while in the crystalline, more ordered phase, energy dominates. In a broad sense, a system that travel across different symmetry breakings to reach configuration characterized by low symmetry moves from a disordered to a more ordered condition. Living objects, given that they are placed in between the full disordered systems (gas) and the full ordered solids , show an intermediate value of order, subject to a regimen of extended critical transitions, i.e., a succession of symmetry breaking events .As a consequence, symmetry-based explanations using symmetry breaking (SB) as the key explanatory tool have complemented and replaced traditional causal explanations in various domains of physics . The devDownstream a symmetry breaking, the way the entities are connected among themselves dictates the shape—the form—the system will assume. In other words, the form epitomizes the entirety of relationships the components establish among them. In turn, the form influences the dynamical relationships among components as well as with the external milieu . AccordiOverall, these investigations provided further support to the issue raised by Folkman and Moscona in 1970s . RelevanMaking a long story short, any system is governed by both constitutive and network laws. Constitutive laws refer to the physics governing single elements , whereas network laws stem from the specific wiring architecture irrespective of the physical nature of its elements, i.e., a social network has emergent properties identical to an electrical circuit if they share the same wiring architecture. Thus, we can sketch a raw definition of mesoscopic realm as the place where network laws prevail. This opens the way to a new quest for universal principles based on the assumption that any system is made of interacting parts. Therefore, it is not by accident that shape displays a relevant functional and heuristic (diagnostic) role in several biological and medical settings , especiaThe same topology, which gives rise to the same network properties, can result from infinite collections of different elements. Therefore, there is a level of causality and explanation that is purely relational in nature and that does not refer to the objects involved in it . This meThe literal meaning of scale is the unit by which we can quantify an observed quantity. We can infer the scale (in terms of measurement unit) from the limitation of the proportionality relation. We reach the scale that determines “smallness” when proportionality relations are destroyed. In other words, the scale problem emphasizes that “levels of organization can be thought of as local maxima of regularity and predictability in the phase space of alternative modes of organization of matter” . TherefoIt is worth noting that the reductionist approach—as well as linear theory—keeps silent about the scale—it is “unaware” of the scale, and in this way misses the complexity of living objects . AddressRelationships in complex systems are mostly nonlinear. A linear system is governed by linear differential equations, and it obeys the law of superposition, thereby ensuring that outputs will be proportional to inputs. On the contrary, nonlinear systems are governed by a set of simultaneous (nonlinear) equations in which the unknowns  appear as variables of a polynomial of degree higher than one or in the argument of a function which is not a polynomial of degree one. In these conditions, changes in variables over time may appear chaotic, unpredictable, or counterintuitive, contrasting with much simpler linear systems. In other words, nonlinear dynamics is at the root of emergent phenomena as this kind of output is precisely the consequence of nonlinearity. In addition, nonlinear systems display the astonishing property of extreme sensitivity to the initial conditions, which further add unpredictability and lay out the way for the appearance of true novelty. Despite physical sciences have been “revolutionized” by the (re)discovery of nonlinearity since 1970s, biologists have been reluctant in accepting it. Many biologists still turn to reductive explanations based on well-defined causal chains, thereby missing the implications of emergence for understanding their phenomena. Sad to say, first attempts to introduce nonlinear thought into chemistry and biology have been disappointing, leading to a substantial rejection by the mainstream, the seminal contributions made by Herbert Fröhlich notwithstanding . VicissiTaking seriously, nonlinearity implies a critical appraisal of ergodicity. Ergodic systems are defined as those for which the time spent by the systems in a region of the phase space of microstates is proportional to the size of that region. In other words, in the long term, all accessible microstates are equiprobable and are all eventually visited. In contrast, non-ergodic systems do not visit all microstates and possess memory of the initial state. They are characterized by historical memory whereby the present state of the system depends on the previous history, and accordingly, the future states are not precisely predictable. This non-ergodic behavior is caused by competing short- and long-range interactions, which result in frustration and can produce complex patterns, including bistability and hysteresis .Processes of this type can be described by a space-phase diagram, first introduced by Poincaré and then applied by Prigogine to the study of irreversible phenomena . AccordiClassically, a number of differential ordinary equations (ODE) can be used to describe a dynamical system, which is recognizable in the phase space by a vector, obtained from system’s physical quantities (variables or observables). Linear equations of the  thermodynamics of reversible processes (belonging to closed systems in opposition to open systems like those occurring in living organisms) are usually analyzed in terms of fixed-point attractors. The system is “attracted” to the steady state of minimal energy and tends to “forget” its initial conditions. On the other hand, nonlinear systems have more than one solution: new, unexpected “solutions” emerge when the system passes through a bifurcation point, eventually going towards a catastrophe . The sysTo sum up, complex systems, governed by nonlinear dynamics undergo a sequence of modifications across space and time, through subsequent symmetry breakings downstream to bifurcation points. This behavior allows systems to reach different attractors  by travelling across a number of critical transitions.This approach highlights how relevant are symmetry breaking and critical transitions in allowing a system to assume new configurations, ultimately producing true novelty in biological systems. This model has been applied especially in understanding biological morphogenetic models. Living cells, starting from a complete symmetric configuration in which the genome express totipotency, are committed towards cell fate specification by which cells differentiate, acquiring different (quasi) stable phenotypes . Along this process, cells reorganize their genome pattern of expression by rewiring the gene regulatory network as well as their shape, involving in such a complex activity of thousands of genes, proteins, cytoskeletal components, and many other intracellular structures. The coordinated control of a huge number of entities must overcome several hurdles (intrinsic instability in gene expression due to stochastic fluctuations and thermodynamics barriers) and integrate a disparate set of external and structural constraints that fold disorganized cell processes into a specific (deterministic) outcome. It is amazing that such a “Brownian-like” turbulence—reflecting the disordered behavior of the microscopic level might be harnessed through only a small number of control parameters that underpin highly complex morphogenetic processes . This apIndeed, the genotype-to-phenotype mapping is not one-to-one but one-to-many , given tConstraints belong to two classes: (a) holonomic  and, (b) non-holonomic  .This latter kind of “constraints,” in which dynamics works on the constraint to recreate them, have emerged as critical determinants of self-organizing systems, by manifesting a “closure of constraints” . OverallA comprehensive model, based on specific organizing, biological principles, has highlighted how, according to such premises, self-organizing processes, constrained by both physical and auto-generated constraints are instrumental in driving morphogenetic processes, given that “evolution” cannot be explained only in terms of natural selection .Biological processes involve assembled molecular components (open complexes) responsible for mesoscopic properties, spatial-temporal multiscale organization, according to the epigenetic (thermodynamic) landscape in which system’s transitions occur . ThermodThese distortion modes have three basic forms we can define as “breathers” “solitary waves or solitons,” and “blow-up” modes. The first form is responsible for the oscillation of the system around its equilibrium position; the name “breather” derives from the continuous local opening/closing of DNA double helix making transcription possible caused by localized and transient interruptions (nicks) of the helix. This is “business-as-usual” and corresponds to the continuous “small-avalanches” happening in a sandpile that do not alter its slope . The solitons  are soliThis result is of utmost importance in biological complexity given that it establishes a deep structure/function link we can directly observe by experimental methods .In the search for a definition of the word “complex,” we encountered a number of relevant issues that can help in providing a compelling set of identification rules. Physics always tries to find a precise and rigorous definition of its concepts, so the question: What is meant by complexity? Physicist Seth Lloyd  collecteNoteworthy, the fundamental mechanism that describes the emergent properties and complexity of a system is based on the occurrence of bifurcations that enact the occurrence of symmetry breakings . BifurcaAlthough there may be many nominal degrees of freedom available, the system may organize its motion through the Waddington’s like landscape into only a few effective degrees of freedom than those nominally accessible. The system is attracted toward a lower dimensional phase-space, favoring the development of specific, recognizable structures (the “forms”) provided by self-organizing processes. The interplay among internal/external cues, coupled with the presence of constraints, which act through a sequence of extended criticalities, reduces progressively the degrees of freedom of the system, until an outcome is reached . A simildetails—including the scale, the correlation in between structure changes, transitions over time of the pattern organization, and fluctuations in system’s robustness—in shaping the overall system’s function. However, the experimental approach needs to translate from the continuous multivariate description of the system into discrete configurations: such discrete configurations are the hidden treasure we must look for in our scientific enterprises. A schematic picture regarding how levels are intertwined across different scales is described in The most important lesson we can derive from the above-sketched “Complexity Portrait” outlines the relevance of too often neglected Within this landscape, complexity degrees, occurrence of constraints, and entropy fluctuations proceed in opposite way, ultimately giving rise to an ordered structure while starting from a chaotic/stochastic microscopic condition.We want to spend a few words about the methodological tools by which we can put the advocated complexity definition at work. It is normal for a physicist to associate the study of dynamics to a set of differential equations but this approach is practically unfeasible in biological systems that are nonstationary and lack of a sufficient number of experimental points to avoid chance correlation and model indeterminacy. The same kind of information (even if at a different detail) can be obtained by computational unsupervised approaches like principal component analysis ,92 or ReOn the same heading, a correlation matrix has the same mathematical structure of a graph adjacency matrix that in turn has a one-to-one correspondence with the wiring of a complex network. That is to say that the mathematics of complexity has “no clothes” and that the methodological choices only stem from the contingent features of the studied phenomena. This methodological freedom stems from the shared organized complexity character  of systems coming from all the science fields. This shared character is exactly what we tried to describe in this essay.


This paper critically examines epistemological, ontological, and axiological tensions of activism in three related contexts. These are, first,  volunteer tourism ideologies and practices in Central America, including U.S.-American teenagers volunteering in medical centers where, entirely untrained, they do sutures and injections, deliver babies, and help with amputations. Second, the paper considers and critiques local norms  and materials  that may be discursively constructed as resistance to western imperialism. Finally, the critique turns back on the researcher gaze itself, problematizing the notion of academic activism in spaces, like these, where criticality itself is an imported—arguably luxurious—folly. Local people, it is apparent, do not want convoluted theorizing or Western hand-wringing; they want proper medical care. The paper therefore considers the extent to which academic work in such spaces can call itself activism at all. Three years of ethnographic research inform the paper , including hundreds of hours of interviews and participant observational fieldwork, in Spanish and English, with local stakeholders  and Western volunteer tourists. The paper is theorized with reference to postcolonial theory, critical medical ethics, and liberation theology. Jacobellis vs. Ohio case. Nico Jacobellis, a cinema manager, had been fined for showing the Louis Malle film Les Amants; the State of Ohio had deemed the film obscene. But was it? And, if so, how was “obscenity” to be defined? Previously, the Supreme Court had upheld a deductive ruling , defining obscenity as material where the “dominant theme, taken as a whole, appeals to the prurient interest” of the “average person, applying contemporary community standards.”  But the 1964 case was different—and intellectually of great interest—as it relied on inductive , contested values , and the short-handled agricultural hoe (section titled “El Cortito”). These are contested spaces offering rich conceptual pickings. Against a potent, recent, and very bloody history of U.S. cultural imperialism in Guatemala, western sojourners and their local hosts array themselves along a continuum of positions, from wishing to invite/impose U.S. norms and practices (under rubrics of “helping” and “expertise”) to subscribing to (agri)cultural relativism and not wishing to exacerbate axiological violence through the adoption/imposition of foreign ways. Finally, I briefly consider academic activism (section titled “Academia”), and the capacity—or otherwise—of academic work to effect change.This paper teases out these theoretical issues through the following examples. First, I examine foreign volunteer workers in Central America. Second, I consider local people’s voluntourism—both as a phenomenon and as a discourse community (section titled “Volunteers”). It is also worth noting that this conceptual paper is not intended as an ethnography in its own right. Instead, it draws upon interpretive data already presented and analyzed in a book-length study  among Western sojourners engaging in volunteer projects, learning Spanish, and/or staying in host families in Guatemala and Nicaragua. One hundred and twenty people participated directly in the study—in interviews and focus groups—including NGO directors, teachers, homestay hosts, Spanish-language students, and volunteer workers. The nationality breakdown of the interviewees was as follows: 63 U.S.-Americans, 27 Guatemalans, 14 Europeans , eight Nicaraguans, five Canadians, and three Australians. In total, the study was based on 104 hr of interview recordings and 407 pages of field notes. Its data were coded and analyzed inductively, following the principles of constructivist grounded theory  and volunteer tourism—sometimes referred to in its portmanteau form, th study  for the d theory .Everything in Latin America starts with history and politics. And ancient and modern, these are histories covered in blood:Latin America is the region of open veins. Everything, from discovery until our times, has always been transmuted into European—or later United States—capital, and as such has accumulated in distant centers of power. Everything: the soil, its fruits and its mineral-rich depths, the people and their capacity to work and to consume, natural resources and human resources. Production methods and class structure have been successively determined from outside…always for the benefit of the foreign metropolis of the moment. Five hundred years after the sinking of European teeth into Indigenous throats, Latin America still lives the open veins of colonization. So much blood. So much death.First, there was the Spanish conquest, and then, for hundreds of years, there was exploitation. Independence came, but by the 1920s, all that had changed was the master . By 1930conquista [conquest] and foreign exploitation. But then, in the 1930s and again in 1979, the people’s protests worked, to some extent. Again, they rose up against a U.S.-funded puppet and even though the Sandinistas—the Nicaraguan revolutionaries—celebrated victory in 1979, the civil war dragged on through the 1980s, killing about 30,000 people. More blood. More death  Bolivia. So, there’s a history, here, of international helpers . This codependency is thus still one in which power is tilted heavily in favor of those from outside, and as Galeano argues (above), Latin America is (still) a region of open veins, its resources transmuted into, determined from, and accumulated in distant centers of power for the benefit of the foreign metropolis of the moment.gringo press in Central America, you see ads in English for volunteer jobs. Here’s one: “Weekend staff at Black Cat Hostel. Free food, cheap drinks. 3 months minimum commitment. … Evening and weekend bar staff needed at the Old School Bar. Guaranteed fun. Give José a call” . Here is another: “Put your education to use by teaching at the Community Center! … support education [for] over 200 kids in need in the community”  volunteer tourism, it will thrive. So, when their quotes are read from outside the volunteer-tourism discourse community (as I and presumably some readers are doing), the participants sound naïve (at best) and actively harmful and neoimperialist (at worst). But then does critiquing their discourses fall into precisely the trap of “academic activism” described in the “Academia” section? Is there a risk, here, of axiological and epistemological imperialism of our own, in which our morally superior, more “woke” discourses trump those of naïve volunteer tourists who are gamely trying to “help”? Herein is part of the paradox that even this paper itself may problematically be part of academic activism. This discussion continues in the “Academia” section.But is this participant uniquely blind to her own positioning? Should we blame her? I don’t think so. Along with so many others, this participant is part of a wider discourse in which “helping” irreducibly constructs the “helped” as rather helpless. This is well documented in critiques of “development” e.g.,  and is aty world . And as But some voluntourism is even more harmful and here—I’m sorry—we come back to blood:I was talking to someone who was in the process of applying to medical school, and he was like, ‘You’re going on an international volunteer trip for medicine?’ I said, ‘Yeah, I’m really excited’. He was like, ‘Yeah, I helped deliver a baby my first day [in Guatemala]. I literally landed and I went to the clinic and I did that. Then I performed a pap smear, too’. A man, an American male, doing that to …a Guatemalan woman. There’s just so many different …lines that are crossed and a lack of understanding between those two parties.  when I attended the Pride parade? And was a cop-out (or was I decolonizing tourism?) when I chose not to engage with my host’s homophobia? It is easy to frame either course of action as activism, or not. I might ask: who am I to tell Guatemalans what to think? But I might equally ask: where was my calling out of social injustices? Neither question can be adequately resolved within the vague rubric of “activism.”Some interviewees grappled with the same issue: did a sexual education class a couple of weeks ago.…For the [high-school] kids to be in our program, the Nica[raguan] parents have to be accepting of what we’re teaching them.…When we’re teaching tolerance for homosexuality…because there is a deeply, deeply embedded homophobic culture [in Nicaragua].…I think [ours] is just a very progressive approach to education. In a lot of our home universities, our schools, it wouldn’t be seen that way, but compared to the culture here, it is. —was banned in California in 1975, after a series of Industrial Safety Board hearings. In these, evidence was sought from employers, union leaders, farm workers  and the physicians treating the back injuries caused by their bending double to use the short-handled hoe. Evidence against el cortito included medical:The short-handled hoeWhen I used the short-handled hoe my head would ache, and my eyes hurt because of the pressure of bending down so long. My back would hurt whenever I stood up or bent over. I moved down the row [of crops] as fast as I could so I could get to the end and rest my back for a moment.  postcolonial resistance. Decolonization, on the one hand, and calling out social injustice, on the other, may thus be contradictory. Either may be the purpose of activism, which is why, as a construct, activism is rather empty.There is no easy answer. Pitted against one another are, on the one hand, an ethical universalism and its potential for the reinscribing of neocolonial power relations, versus, on the other hand, cultural relativism and the risk that phenomena like homophobia and Related, how are we to define activism in an academic setting? “There have been few attempts to ground medical ethics in political economy, history, anthropology, sociology, and the other contextualizing disciplines.” (p. 204)…“The quandary ethics of the individual constitute most of the discussion of medical ethics.…The countless people whose life course is shortened by unequal access to health care are not topics of discussion.” (p. 174)There is a need, therefore, to go beyond the individualist ethics of medical practice, which tend to be the focus of academic medical ethics. Instead, we must consider structural violence, including questions of who does, or does not, get to become a patient in the first place. This is a critical medical ethics that concerns itself less with whatever Candace or George are doing to their Central American patients and more with larger-scale social justice.Farmer’s reframing of medical ethics is an example of theorizing as activism. His thinking goes beyond the immediate “case” and into underlying constructs to understand what is happening at a generalizable level . Similarly, I critique as structurally violent the existence of “volunteer tourism” within a postcolonial power relationship; this is another example of theorizing as activism.not jump to critiquing, but instead to listen to and to hear where others are coming from. Perhaps this text, itself, is paradoxically part of the problem it is critiquing: by roundly critiquing George and Candace, am I perpetuating my own kind of axiological violence? This is another way in which we need to problematize “activism” much more than we already do. But as posited above, is there a risk that those of us engaged with academic activism are guilty of precisely the same imperialisms of which we are so roundly critical elsewhere, trammeling young volunteers’ attempts at “helping” within our own critical discourses of systemic change? Perhaps it is necessary for everyone to start somewhere. Perhaps it is even necessary, sometimes, for us to Then, in academic activism, there is also the question of reach. Are all my academic words—and yours—subsumed into the white noise of neoliberal productivity in which we churn out more and more to appease the small administrative gods who value less and less e.g., ? Does anGive a man a fish and he can eat for a day. Give him a fishing rod and he can feed himself. Alternatively, don’t poison the fishing waters, abduct his great-grandparents into slavery, then turn up 400 years later on your gap year talking a lot of shite about fish.Reading this, I crumble. Even as I write academic publications and tell myself I am “doing activism,” a popular entertainer makes a comment that, in four short lines, conveys precisely the point that I am trying, in hundreds of thousands of words, to make. And people hear him. In contrast, conscientização, a “consciousness raising” and, I hope, a seed of conscientização for others, too. I teach in higher education and it may be that some of my hard-won conscientização will leak out into my classes. Perhaps, instead of medical volunteering in Central America , my students might choose, instead, to learn Spanish, or weaving, or art, or Mayan cosmology—anything, really—in Central America . This is my hope.Here is what I cling to. After But I do despair that comedians, such as Frankie Boyle, are the center of cultural gravity in a way that even the most successful academics are not. If my activism is not about improving Nicaraguan clinics and I must rely on those I can influence, would I not be better placed as an influencer outside of academia? I wonder.“Activism,” explored here, is difficult to define and thus to measure, and the actions of all the “activists” in this article would be easy to reframe in other ways. Putting untrained U.S.-American teenagers in positions of power, in which they pretend to be doctors for those who cannot afford proper medical care—this could equally well be called human experimentation. Similarly, is Barbara’s resistance false consciousness? And is my own academic activism wishful thinking? Or even axiological violence? This paper has asked at least as many questions as it has answered. I wish it were otherwise, but as I hope to have conveyed, there is a need for complexity here, and the rush toward facile answers is part of the problem.internacionalistas: those who went to help the green shoots of the people’s revolutions in Central America in the 1980s, before “helping” was subsumed, a generation later, into the neoliberal voluntourism industry.Decolonization, on the one hand, and addressing social injustice, on the other, are sometimes contradictory, and “activism” needs to address this. This paper has explored some of the issues inherent in who gets to claim they are doing activism and why. It has suggested a framework of structural violence, much bigger than activism itself, that acknowledges intersectional power relations. This draws, perhaps improbably, from the idealism and liberation theology of the original


Shared decision-making (SDM) is a process in which the doctor provides clear and complete medical information to patients about their treatment, and patients provide information on his/her preferences. Patients and clinicians bring different, but equally important, knowledge to the decision-making process. Through the adoption of SDM, it should be possible to overcome the barriers that hinder the acceptance of long-acting injectable antipsychotics (LAIs) by patients, and often also by psychiatrists. The present paper is a critical appraisal of recent literature on the impact of SDM in improving adherence to pharmacological treatments and in implementing the use of LAIs in the treatment of patients with schizophrenia. SDM is recognized as a promising strategy to improve collaboration between clinicians and patients in achieving recovery. When considering drug treatments, clinicians must evaluate the patient’s preferences, expectations and concerns towards the development of a personalized treatment strategy. Moreover, an active involvement in the decision process could reduce the patient’s perception of being coerced into the use of LAIs. Involving patients in the choice of therapy is not sufficient to increase pharmacological adherence if, at the same time, there is no constant work of comparison and communication with the reference psychiatric team. SDM can be particularly effective for LAI prescription, since patient can have prejudices and unjustified fears related to the LAI formulation, which the doctor must resolve. In accordance with its most common acceptation, clinical decision-making has been traditionally practiced as a one-way evidence-based process on behalf of the clinicians alone: a “contextual, continuous, and evolving process where data are gathered, interpreted, and evaluated by the clinician in order to select an evidence-based choice of action” . In recIn the general medical setting, the type of decision-making is influenced by the balance achieved in the clinician–patients relationship and positions itself along a continuum, ranging from the paternalistic (clinician-led or passive style), through shared decision-making (SDM), up to the patient-led active style  . The unfWith specific reference to the SDM style, studies have demonstrated that it has a positive impact on the patient’s levels of satisfaction and adherence to treatments, as well as on his/her quality of life and empowerment . This haThese latter aspects related to adherence are especially relevant in the setting of schizophrenia and psychotic disorders, where adherence to pharmacological treatments is frequently far from optimal and represents the main cause of relapse –18 and hIn such scenario, SDM is certainly an interesting approach to achieve greater knowledge of LAIs and acceptance on behalf of patients and families , 36. The present clinical review aims to provide an update on the available interventions for improving SDM in routine care and to discuss the positive role of SDM style in improving adherence to pharmacological treatments and in the definition of a personalized treatment plan for patients with schizophrenia, particularly in switching pharmacological regimen from oral to LAI formulations.The present review was based on search of key words “shared decision making”, “intervention”, “schizophrenia”, “psychosis”, “schizophrenia spectrum disorder” matched with “adherence”, “intervention”, “training”, “long-acting injectable antipsychotic”, “LAI” in the main databases MEDLINE, ISI Web of Knowledge—Web of Science Index, Cochrane Reviews Library and PsychoINFO. The search considered recent papers published between 2009 and 2019, as publications from previous years had already been covered by Duncan et al. . The seaThe main features of the included studies , 38–44 aIshii et al.  developFinnerty et al.  proposedIn Germany, Hamann et al.  tested tAnother randomized-controlled study carried out in Germany  includeIn US, Kane et al. promoted the PRELAPSE study, which is a randomized-controlled trial including first episode and first-phase patients with schizophrenia allocated to receiving either LAI or treatment as usual . In theIn recent years, much effort has been dedicated to find ways of making SDM more effective. The main differences among these experiences are related to the target group , the type of decision-supporting tool , and the duration of the follow-up period.Regarding the target groups, all experimental interventions specifically addressed to patients , 45 resuInterestingly, projects specifically addressed to mental health professionals have shown promising results in improving the quality of therapeutic alliance and patient acceptance of pharmacological treatments. In the case of the TEMPO training , long-tAlbeit encouraging, however, none of the approaches above could provide key data regarding the stability and the maintenance of the positive effects over time, due to their short-term follow-up. Another issue is the feasibility of these interventions in the clinical routine care, their cost-effectiveness and their usefulness in managing crisis situations.As regards the web-based tools, engagement through the MyCHOIS–CommonGround website was associated with a higher level of ongoing engagement in out-patient mental health service compared to that of the control group, although no significant differences were found in the adherence rate with antipsychotic medication. Another noticeable advantage was the cost-effectiveness of the intervention which makes it particularly suitable for attaining long-term outcomes in patients with severe mental disorders –50. MorSDM is recognized as a promising strategy for enhancing collaboration between clinicians and patients, given the complementary knowledge and expertise of both parties . PatientIt is clear that in many cases patients being prescribed antipsychotics would need to understand the advantages and long-term positive impacts on their functional outcome, especially in the case of LAIs where this should be discussed as early as possible . Many mFrom the patients’ viewpoint, patients admit preferring a more directive/paternalistic practitioner style during crisis, but they report also to feel pressured or being persuaded or coerced into accepting pharmacological treatments like LAIs if they fail to take their oral prescribed medication. Clinical decision-making should change on the basis of contextual variables and the style should be tailored to fit patients’ needs and preferences, according to the stage of the illness .However, the adoption of SDM appears useful in the long-term treatment of patients with schizophrenia where medication non-adherence plays an important role in relapse rates, poor outcome, and high costs . As sugIn recent years, considerable resources have been invested to make the SDM a routine way of working: computerized programs, role-play techniques, training groups for mental health staff . The maiSDM can be promoted in several ways: either by having the patient complete questionnaires during hospitalization to express their opinion regarding the satisfaction with the treatment received or through online platforms in which patients can express their treatment preferences, even before seeing their doctor—in a positive perspective of an active involvement of patients in the treatment of their mental illness.The introduction of specific smartphone apps has led to the dissemination of a SDM protocol, but it must be considered that the use of apps requires specific skills. Therefore, it is likely that only patients with high level of personal functioning and less severe symptomatology can use these support tools, gaining a positive reinforcement , 60.Based on the results of the eight studies included in this literature review, interventions focused on enhancement of the adoption in SDM in the clinical routine care seem promising, although these results are preliminary and only the short-term efficacy of these approaches has been confirmed. The interventions proposed appear feasible and well-accepted by both patients and clinicians, confirming the findings from the ROAMER study which showed that all stakeholders of mental health want to be actively involved in the planning and management of care , 62. BefHowever, as pointed out by Das et al. , patienOther factors hampering the underutilization of LAIs in clinical routine care include the overestimation of patient’s adherence; the time-consuming process of using SDM style for proposing the LAIs treatment; the heterogeneity of international guidelines and the prejudice that therapeutic relationship would be weakened by the adoption of LAIs, particularly in the early stages of the disease .Therefore, international and national scientific associations should clearly state the potential beneficial role of using LAIs in the early stage of the disorder, supporting the use of LAIs and SDM style in proposing the switch from oral to LAI formulation to patients with schizophrenia.It is essential that psychiatrists introduce the use of SDM into their clinical practice, not limiting themselves to accepting the patient’s preferences, but providing clear and comprehensive information . The SDMInvolving patients in the choice of therapy is not sufficient to increase pharmacological adherence if, at the same time, there is no constant work of comparison and communication with the reference psychiatric team. Therefore, in our opinion, resources should be allocated for health personnel dedicated training and to support patients, for example with ad hoc courses . The results will then be monitored over time in order to evaluate the impact of these interventions on the recovery rates in patients with schizophrenia.


In the era of the rapid development of today's Internet, people often feel overwhelmed by vast official news streams or unofficial self-media tweets. To help people obtain the news topics they care about, there is a growing need for systems that can extract important events from this amount of data and construct the evolution procedure of events logically into a story. Most existing methods treat event detection and evolution as two independent subtasks under an integrated pipeline setting. However, the interdependence between these two subtasks is often ignored, which leads to a biased propagation. Besides, due to the limitations of news documents' semantic representation, the performance of event detection and evolution is still limited. To tackle these problems, we propose a Joint Event Detection and Evolution (JEDE) model, to detect events and discover the event evolution relationships from news streams in this paper. Specifically, the proposed JEDE model is built upon the Siamese network, which first introduces the bidirectional GRU attention network to learn the vector-based semantic representation for news documents shared across two subtask networks. Then, two continuous similarity metrics are learned using stacked neural networks to judge whether two news documents are related to the same event or two events are related to the same story. Furthermore, due to the limited available dataset with ground truths, we make efforts to construct a new dataset, named EDENS, which contains valid labels of events and stories. The experimental results on this newly created dataset demonstrate that, thanks to the shared representation and joint training, the proposed model consistently achieves significant improvements over the baseline methods. Besides, some popular social media, such as Twitter, Sina Weibo, and Facebook, also has become an attractive platform for people for expressing opinions, broadcasting news, and discussing topics. Compared with the former traditional news media, the tweet stream produced by the emerging social media or self-media often contains many informal expressions or irrelevant information. Despite massive information about a number of ongoing hot events is spread at every moment, people still feel unable to acquire useful information about the events of concern. In solving the problem of information overload, event detection and evolution on news streams have drawn extensive research attention over the past few years  represents the concatenation operation.Based on the general GRU representation and following the , bidirecH= into a fix-length vector as the shared semantic representation for d; that is, H∗=Att. Specifically, we first map each hidden vector representation hi into a normalized vector representation ui in a hidden space; that is, ui=tanh(Whhi+bh), where Wh and bh are trainable parameters and the value range of ui is between −1 and 1. Then, an attention weight αi is computed from the inner product between ui and a trainable vector us, followed by a softmax operation; that is, Finally, the attention mechanism  is appliH= and the learned attention weights α=; that is, H∗=∑iαihi. It can be seen that, by assigning different attention weights to each vector representation, important features are emphasized and noisy or irrelevant information is suppressed, so that we can achieve a more discriminative semantic representation of news report documents for subsequent tasks.The final output vector is the product between the input hidden vector representation sequence k events E={E1, E2,…, Ek}, where each event includes several news reports; that is, Ei={Ri1, Ri2,…, Rin}, i=1,2,…, k. For an incoming news report R, we first calculate the similarity score sij between it and each new report Rij in the existing event cluster Ei and take the maximum similarity score si=maxj{sij} to measure the similarity between it and the event cluster Ei. Then, we consider a threshold μ − 3δ to decide whether the news report R belongs to an existing cluster, where μ is the mean of all previous similarity scores and δ is the standard deviation. If all similarity scores {si}, i=1,2,…, k are below the threshold, we empirically think a new event cluster is detected by including the news report R. Otherwise, the news report is added to the most similar existing event cluster, that is, Em, m=argmaxi{si}.For the event detection task, our goal is to aggregate news reports related to the same event together . To thisRi and Rj. For this, we consider the Siamese network [Ri and Rj, we first extract their own semantic representation vector Hi∗ and Hj∗, as described in Pdec, as formulated inAccording to the above description, it can be seen that the core of the incremental clustering is to calculate the similarity between two news reports  network . Specifiσ represents the sigmoid function, and Wdech, bdech, Wdec, and Bdec are trainable model parameters.Here, ⊕ denotes the concatenation operation, Ht∗ of Ri and Rj from the news publish time to the Siamese network, resulting inIn addition, for the event detection task, the temporal information is also crucial. Hence, we additionally feed the temporal vector Hti∗ and Htj∗ denote the news publish time vector of Ri and Rj, respectively. It is noted that the temporal vector Ht∗ of time t is mapped from the Unix timestamp of t using the same pretrained word2vec tool as Here, E={E1, E2,…, EE||}, where |E| is the number of events in the whole dataset, and Ei={Ri1, Ri2,…, Rin}, where in is the number of news report documents in the event Ei.The result of event detection network is the detected events set; that is, l stories S={S1, S2,…, Sl}, where each story includes several detected events, that is, Si={Ei1, Ei2,…, Ein}, i=1,2,…, l. For an incoming event E, our online algorithm to grow the story first identifies the story to which the event belongs. If it does not belong to any existing stories, we create a new story by including it. Afterwards, for all events in each story, we simply connect them by their timestamp order. More specifically, we first calculate the similarity score δij between E and each event Eij in the existing story cluster Si and further take the maximum similarity score δi=maxj{δij} to measure the similarity between it and the story cluster Si. Then, we still apply a similar threshold strategy to event detection to decide whether the new event E belongs to an existing story Si. If the similarity δi is below the threshold, a new story is established. Otherwise, the event is added to the most similar existing story group, that is, Sm, m=argmaxi{δi}.After detecting a series of events, we further organize these events into multiple stories in an online manner. Each story covers several interrelated events, which are connected based on their temporal order to characterize the evolving process of that story. Suppose that we have discovered Ei and Ej, we first take the average of semantic representation vectors of news reports which are subordinate to them, as their own semantic representation vectors εi and εj. Then, two vectors and corresponding timestamp vectors are concatenated together and fed into the former event detection network to generate the hidden feature vector Hdec, as formulated in . The original dataset does not contain available labels for all the two subtasks that we investigate. Hence, we have taken efforts to manually annotate 1,931 news report documents with their corresponding event id and story id, which we from now on refer to as EDENS (Event Detection and Evolution from News Streams) dataset, where the number of stories is 12, the number of events is 694, and each story contains 58 events on average, covering different topics in the open domain, as presented in The proposed JEDE model is evaluated on a real-world Chinese News Report Documents dataset collected by the crawler tool , Recall (R), and F1 score are used to evaluate the clustering performance of the event detection and evolution tasks. Formally, they are defined as follows:T={E1, E2,…, EE||} or {S1, S2,…, SS||} is the set of artificially detected real-world events or stories (ground truth), and T′={E1′, E2′,…, EE′||′} or {S1′, S2′,…, SS′||′} is the set of events or stories detected from our model in this paper.The Precision  from the standard TDT evaluation procedure [Cmiss and Cfa are the costs of a missed detection and a false alarm, respectively, and set to Cmiss=0.5, Cfa=0.5 in the experiments. In addition, Nmiss and Nfa are the number of missed detections and false alarms, respectively, and len(cluster) is the size of the event cluster.For the event detection task, we also take the same evaluation method as in  that therocedure  is used Cmin is a linear combination of missed detection and false alarm error probabilities, which allows a fair comparison between different methods based on such a single metric value. Lower Cmin shows better performance.From the above formulation, it can be seen that Besides, we use ACC  to evaluate the accuracy of event detection and evolution, which is the ratio of the correctly detected results of our model in all annotated results.JEDS  is a joiLSH   are pure; that is, most events only contain documents that talk about the same real-world breaking news.According to Given the set of events extracted by our JEDE model, we further evaluate the performance of the event evolution task on the large twelve stories mentioned above. As described in , the eveFlat structure : this stTimeline structure : this stGraph structure : this stTree structure : this stSpecifically, for task (b), following , events To make fair comparisons, we use the same preprocessing and event cluster procedures proposed in our JEDE model to develop different story structures. Specifically, the JEDE models with flat, timeline, graph, and tree structures are termed as JEDE-Flat, JEDE-Timeline, JEDE-Graph, and JEDE-Tree, respectively. In addition, the Story Forest model, which introduces the tree structure (d) in We enlisted 50 volunteers to blindly evaluate the results given by different approaches, and, in line with , the outJEDE w/o shared uses a separate bidirectional GRU attention network in event detection and evolution to learn a semantic representation of news reports or events. In this pipeline setting, there is no parameter sharing. The temporal information is not used in learning the similarity metrics of event detection and evolution.H∗ for event detection and evolution without neural stacking and backpropagation between tasks. The temporal information is not used in learning the similarity metrics of event detection and evolution.JEDE w/o stack employs a bidirectional GRU attention network to learn a shared semantic representation JEDE w/o time uses a shared semantic representation and stacked event detection and evolution. The temporal information is not used in learning the similarity metrics of event detection and evolution.JEDE is the proposed Joint Event Detection and Evolution model, which learns a shared semantic representation from a bidirectional GRU attention network for both subtasks and stacks both subtasks with backpropagation training. The temporal information is also used in learning the similarity metrics of event detection and evolution.In order to investigate whether the joint model improves the accuracy of both tasks in our pipeline setting, we compare our model with several variants, including the following:In this subsection, we provide a qualitative analysis to present the evolution process of events from our model JEDE, taking the story of “The ZTE incident” for example. According to In this paper, we propose an effective neural network model JEDE for Joint Event Detection and Evolution, which benefits both tasks through information sharing between the two tasks. Our model takes the vast streams of trending and breaking news as input and clusters related news reports into several events as well as organizing events in various sensible story structures such as either a tree or a timeline or a flat structure in an online manner. Different from previous popular pipeline settings, our model first uses the bidirectional GRU network and attention mechanism to learn the vectorial semantic representation of news reports as well as events, without the bag-of-words assumption, which is globally shared on both event detection and evolution tasks. Then, two similarity metrics about a pair of news documents or events are learned continuously by neural stacking, so that information is better shared between the predecessor event detection and successor event evolution networks. Empirical experiments on a newly annotated real-world dataset EDENS demonstrate the superior performance of our model over several baseline models on both subtasks. In summary, our model is able to effectively deal with event detection and evolution online for massive amounts of breaking news data.Despite the remarkable improvements, the proposed model still faces some challenges. For example, as we all know, event description is crucial in event mining task. However, our model just simply uses the title of the earliest news report to summary an event, but without considering the richer contextual information contained in the clustered news reports. Hence, a well designed summarization module is necessary in the future joint model. Besides, this paper primarily talks about events about formal news media, and it is implicitly assumed that detected events are all realistic, due to the authority of formal news reports. However, for emerging social media, lack of supervision and free Twitter expressions may produce some rumor events, which may hinder people's understanding of the truth about topics of interest , 50. Thi


According to many conceptual frameworks, the first step in the monitoring cycle of health inequalities is the selection of relevant topics and indicators. However, some difficulties may arise during this selection process due to a high variety of contextual factors that may influence this step. In order to help accomplish this task successfully, a comprehensive review of the most common topics and indicators for measuring and monitoring health inequalities in countries/regions with similar socioeconomic and political status as Catalonia was performed.We describe the processes and criteria used for selecting health indicators from reports, studies, and databases focusing on health inequalities. We also describe how they were grouped into well-known health topics. The topics were filtered and ranked by the number of indicators they accounted for.We found 691 indicators used in the study of health inequalities. The indicators were grouped into 120 topics, 34 of which were selected for having five indicators or more. Most commonly found topics in the list include “Life expectancy”, “Infant mortality”, “Obesity and overweight (BMI)”, “Mortality rate”, “Regular smokers/tobacco consumption”, “Self-perceived health”, “Unemployment”, “Mental well-being”, “Cardiovascular disease/hypertension”, “Socioeconomic status (SES)/material deprivation”.A wide variety of indicators and topics for the study of health inequalities exist across different countries and organisations, although there are some clear commonalities. Reviewing the use of health indicators is a key step to know the current state of the study of health inequalities and may show how to lead the way in understanding how to overcome them. Dirección General de Salud Pública) and the Foreign Health of Health Ministry and Social Policy  requested the constitution of the Commission for the Reduction of Social and Health Inequalities  [Strong efforts to tackle health inequalities can be seen at international and national level since the 1980s. In early 2008, the World Health Organization’s (WHO) Global Commission on Social Determinants of Health called for action on the social determinants of health, the conditions in which persons are born, grow, work, live, and age, to “close the gap in a generation” [CRDSS-E) , and anoCRDSS-E) . In 2011CRDSS-E) . The decCRDSS-E) .At a regional level in Catalonia, tackling health inequalities is one of the main goals of both the Catalan Health Plan 2016–2020   and the Overall, much effort has been devoted to monitoring and tackling health inequalities at regional, national, and international levels. Even so, OECD countries continue to present large disparities in health, including, for example, significant differences in life expectancy between people with the highest and lowest levels of education . The selIn order to help accomplish this task successfully, the objective of this study is to perform a systematic review of the most common topics and indicators used for measuring and monitoring health inequalities in the reports, projects, and databases of international, national, and regional governmental organizations.The main purpose of this study is to provide a broad overview of health inequalities topics considered relevant by different public health organizations. Nevertheless, the focus of this review is on countries/regions with similar socioeconomic and political status to Catalonia. It may also be useful for other organizations who decide to study or monitor health inequalities to accomplish its very first step: topic selection. In addition, gaining some insights about which health issues are being prioritized, as well as which indicators were used, are considered secondary goals.health inequalities”, “health observatories” and “health inequalities indicators”. Occasionally, names of concrete regions, countries, or organisations were added to these terms . The search was performed from March to June of 2019. Once finished, a set of inclusion criteria was applied; studies included in the review had to:Include health inequalities indicators: All the reports that contained no health indicators were automatically discarded .Have been carried out by a governmental organisation or a related entity, whether at an international, national, or regional level: the reports not published by governmental (or government-related) organisations were discarded.Have a socioeconomic and political status similar (or highly related) to Catalonia: some reports were discarded due to significant differences in the socioeconomic profile of the countries they were studying in comparison to Catalonia or Spain.First, a bibliographic search was performed using PubMed, Google Scholar, and Google search engine with the terms “Once the reports were selected, the authors performed a quality control check of the indicators shown in the reports and databases. The indicators had to match the basic anatomy of an indicator as a minimum requirement to be considered an indicator. This basic anatomy consists of containing data, i.e. the numerical data input; and containing good metadata, like a title and an explanation of how an indicator is defined and calculated . In addiAfter this selection process, the indicators were grouped into topics by semantic matching of their definition as well as by the area of knowledge there are intended to measure. Most of the topics were supported by references of relevant organisations like the WHO or the United Nations (UN)  used for their calculation. For example, in the first topic “Life expectancy”, indicators have different variations: “Life expectancy at birth” , 40–42, Furthermore, in the case of a health outcomes or diagnostics  the concrete disease or cause may also play an important role in the heterogeneity found among the health indicators. Indicators are focused on different aspects, such as prevalence and incidence, mortality, preventive measures, or treatments. For example, for the topic “HIV”: “HIV incidence” , 33, 40,Mortality/life expectancy: “Life expectancy” , 45, “InIncidence/mortality rates of specific diseases: “Cardiovascular disease/hypertension”, “Cancer ” , “Diabet◦ “Living and working conditions” where this could be studied at an individual level, was highly ranked: “Unemployment”  and “Pri◦ This was similar for “Individual lifestyle factors and social and community networks” topics, which can also be studied at an individual level: “Obesity and overweight (BMI)” , 55, “Re◦ Socioeconomic level: “Socioeconomic status (SES)/material deprivation” , 60.◦ Healthcare system: “Healthcare resources” and “Policy and Legislation”.Social determinants of health :◦ “LiviThe results of the study show that the most common topics are related to:The results of the study showed that the most common topics were related to mortality/life expectancy, incidence/mortality rates of specific diseases , and social determinants of health, such as living and working conditions, and individual lifestyle factors and social and community networks, according to Dahlgren and Whitehead’s model of the social determinants of health . The indTo include health inequalities indicators was a fundamental requirement for any report in order to be included in the review. Hence, although some reports provided in-depth insights about tackling health inequalities  the theTo into be carried out by a governmental or a government-related organisation was also an important requirement, as many academic and/or private institutions carry out studies and reviews of health inequalities, but their policy-making influence is limited. Their reports tend to be focused on concrete knowledge fields, such as gender influence [In addition, nfluence , the effnfluence , or accenfluence ; which ato have a socioeconomic and politic status similar or highly related to Catalonia criteria was intended to exclude reports whose health indicators were adapted to least developed/developing countries where, for example, access to treatments of diarrhea for infants may still be an issue [Lastly, an issue . Hence, These criteria were applied to all the reports and studies found after an extensive search. The addition of country/region names in the search responded to the need of knowing how particular regions of interest were dealing with health inequalities. Interest in regions was mainly based on previous knowledge of concrete public health organizations studying those regions, as well as interest in looking for other organizations in charge of tackling health inequalities in regions similar to Catalonia. Nevertheless, as in any review, it is not possible to ensure that absolutely all the reports suitable for this study were found during the search, nor that they were selected after applying the selection criteria.Percentage of 15-year-olds who were overweight in 2009–10, EU Member States by sex” [Obesity rate by body mass index (BMI) (sdg_02_10)” [As stated above, the most frequent health indicators were grouped into topics according to the health domain they were measuring (with each indicator related to only one topic). For example, although “ by sex”  and “Obe_02_10)” , 66 are .Most of the selected health indicators were taken from the official statistics of different countries or international organisations, whose development and methodology has been closely consolidated over many years and respond to international standards. In addition, most of these indicators are related to relevant knowledge areas for the study of health inequalities, such as lifestyle habits, deprivation, and mortalityTo prioritise the most relevant topics, all the groups with less than five health indicators were deleted. This meant that, unfortunately, interesting topics such as the “Years of potential life lost” , 36, 42,All the topics aim to measure and study the relation between determinants of health and health outcomes. Interestingly, three of the top five topics in the list ”, which may help to understand possible sexual health inequalities . In the As may be expected, the health indicators used in other reports produced by the Catalan Health System Observatory, such as the “Community Health Indicators”, match the implicit measurement concept behind many of the topics: obesity and overweight, mortality by age (including infant), self-perceived health, and population with primary studies are some of them .As can be seen in Table The health indicators within each topic often cover a different aspect relevant to health inequalities. For example, in the topic “Tuberculosis” , 42, 43 Common stratifiers are sex, age, and studied region, something that is coherent with the determinants of health perspective and the focus on inequalities. However, the stratifiers found are highly heterogeneous and may also include socioeconomic status, educational level, or nationality/country of origin, among many others.This comprehensive review was carried out to help accomplish the first step in the process for tackling and monitoring health inequalities: selecting high-impact issues and health indicators , 20. TheReviewing the most common health indicators and topics used in the study of health inequalities may help research teams in different ways. First, having an overview of what is being done by their neighbouring countries or regions may highlight issues that should not be missed when selecting relevant health topics to study. Second, even if some topics might not ultimately be chosen as a priority of action, having a complete list of key issues will provide an overview of what is relevant in the study of health inequalities, as well as some interesting insights. Lastly, knowing what other research institutions are working on will promote potential collaborations between organizations, creating synergies and bonds that may lead to better understanding and monitoring of health inequalities.At a regional level, these results are highly valuable for the first stages of health inequalities monitoring cycles in Catalonia. This study provided the basis for choosing health topics to study as well as helped gain insights about which indicators should be used. In addition, regions with similar socioeconomic status and goals in tackling health inequalities may benefit from this research. Similarly, at a national and international level these results may help organizations shift the focus towards undermined health inequalities topics or explore new areas of knowledge (yet unstudied or with a different perspective).