Universidad de Cádiz

Context. We present the second Gaia data release, Gaia DR2, consisting of astrometry, photometry, radial velocities, and information on astrophysical parameters and variability, for sources brighter than magnitude 21. In addition epoch astrometry and photometry are provided for a modest sample of minor planets in the solar system. Aims. A summary of the contents of Gaia DR2 is presented, accompanied by a discussion on the differences with respect to Gaia DR1 and an overview of the main limitations which are still present in the survey. Recommendations are made on the responsible use of Gaia DR2 results. Methods. The raw data collected with the Gaia instruments during the first 22 months of the mission have been processed by the Gaia Data Processing and Analysis Consortium (DPAC) and turned into this second data release, which represents a major advance with respect to Gaia DR1 in terms of completeness, performance, and richness of the data products. Results. Gaia DR2 contains celestial positions and the apparent brightness in G for approximately 1.7 billion sources. For 1.3 billion of those sources, parallaxes and proper motions are in addition available. The sample of sources for which variability information is provided is expanded to 0.5 million stars. This data release contains four new elements: broad-band colour information in the form of the apparent brightness in the G BP (330–680 nm) and G RP (630–1050 nm) bands is available for 1.4 billion sources; median radial velocities for some 7 million sources are presented; for between 77 and 161 million sources estimates are provided of the stellar effective temperature, extinction, reddening, and radius and luminosity; and for a pre-selected list of 14 000 minor planets in the solar system epoch astrometry and photometry are presented. Finally, Gaia DR2 also represents a new materialisation of the celestial reference frame in the optical, the Gaia -CRF2, which is the first optical reference frame based solely on extragalactic sources. There are notable changes in the photometric system and the catalogue source list with respect to Gaia DR1, and we stress the need to consider the two data releases as independent. Conclusions. Gaia DR2 represents a major achievement for the Gaia mission, delivering on the long standing promise to provide parallaxes and proper motions for over 1 billion stars, and representing a first step in the availability of complementary radial velocity and source astrophysical information for a sample of stars in the Gaia survey which covers a very substantial fraction of the volume of our galaxy.

Gaia is a cornerstone mission in the science programme of the EuropeanSpace Agency (ESA). The spacecraft construction was approved in 2006, following a study in which the original interferometric concept was changed to a direct-imaging approach. Both the spacecraft and the payload were built by European industry. The involvement of the scientific community focusses on data processing for which the international Gaia Data Processing and Analysis Consortium (DPAC) was selected in 2007. Gaia was launched on 19 December 2013 and arrived at its operating point, the second Lagrange point of the Sun-Earth-Moon system, a few weeks later. The commissioning of the spacecraft and payload was completed on 19 July 2014. The nominal five-year mission started with four weeks of special, ecliptic-pole scanning and subsequently transferred into full-sky scanning mode. We recall the scientific goals of Gaia and give a description of the as-built spacecraft that is currently (mid-2016) being operated to achieve these goals. We pay special attention to the payload module, the performance of which is closely related to the scientific performance of the mission. We provide a summary of the commissioning activities and findings, followed by a description of the routine operational mode. We summarise scientific performance estimates on the basis of in-orbit operations. Several intermediate Gaia data releases are planned and the data can be retrieved from the Gaia Archive, which is available through the Gaia home page.

Natural products and their structural analogues have historically made a major contribution to pharmacotherapy, especially for cancer and infectious diseases. Nevertheless, natural products also present challenges for drug discovery, such as technical barriers to screening, isolation, characterization and optimization, which contributed to a decline in their pursuit by the pharmaceutical industry from the 1990s onwards. In recent years, several technological and scientific developments - including improved analytical tools, genome mining and engineering strategies, and microbial culturing advances - are addressing such challenges and opening up new opportunities. Consequently, interest in natural products as drug leads is being revitalized, particularly for tackling antimicrobial resistance. Here, we summarize recent technological developments that are enabling natural product-based drug discovery, highlight selected applications and discuss key opportunities.

There is a rising concern regarding the accumulation of floating plastic debris in the open ocean. However, the magnitude and the fate of this pollution are still open questions. Using data from the Malaspina 2010 circumnavigation, regional surveys, and previously published reports, we show a worldwide distribution of plastic on the surface of the open ocean, mostly accumulating in the convergence zones of each of the five subtropical gyres with comparable density. However, the global load of plastic on the open ocean surface was estimated to be on the order of tens of thousands of tons, far less than expected. Our observations of the size distribution of floating plastic debris point at important size-selective sinks removing millimeter-sized fragments of floating plastic on a large scale. This sink may involve a combination of fast nano-fragmentation of the microplastic into particles of microns or smaller, their transference to the ocean interior by food webs and ballasting processes, and processes yet to be discovered. Resolving the fate of the missing plastic debris is of fundamental importance to determine the nature and significance of the impacts of plastic pollution in the ocean.

Context. At about 1000 days after the launch of Gaia we present the first Gaia data release, Gaia DR1, consisting of astrometry and photometry for over 1 billion sources brighter than magnitude 20.7.
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\nAims. A summary of Gaia DR1 is presented along with illustrations of the scientific quality of the data, followed by a discussion of the limitations due to the preliminary nature of this release.
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\nMethods. The raw data collected by Gaia during the first 14 months of the mission have been processed by the Gaia Data Processing and Analysis Consortium (DPAC) and turned into an astrometric and photometric catalogue.
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\nResults. Gaia DR1 consists of three components: a primary astrometric data set which contains the positions, parallaxes, and mean proper motions for about 2 million of the brightest stars in common with the Hipparcos and Tycho-2 catalogues – a realisation of the Tycho-Gaia Astrometric Solution (TGAS) – and a secondary astrometric data set containing the positions for an additional 1.1 billion sources. The second component is the photometric data set, consisting of mean G-band magnitudes for all sources. The G-band light curves and the characteristics of ~3000 Cepheid and RR Lyrae stars, observed at high cadence around the south ecliptic pole, form the third component. For the primary astrometric data set the typical uncertainty is about 0.3 mas for the positions and parallaxes, and about 1 mas yr-1 for the proper motions. A systematic component of ~0.3 mas should be added to the parallax uncertainties. For the subset of ~94 000 Hipparcos stars in the primary data set, the proper motions are much more precise at about 0.06 mas yr-1. For the secondary astrometric data set, the typical uncertainty of the positions is ~10 mas. The median uncertainties on the mean G-band magnitudes range from the mmag level to ~0.03 mag over the magnitude range 5 to 20.7.
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\nConclusions. Gaia DR1 is an important milestone ahead of the next Gaia data release, which will feature five-parameter astrometry for all sources. Extensive validation shows that Gaia DR1 represents a major advance in the mapping of the heavens and the availability of basic stellar data that underpin observational astrophysics. Nevertheless, the very preliminary nature of this first Gaia data release does lead to a number of important limitations to the data quality which should be carefully considered before drawing conclusions from the data.

Abstract The aim of this paper is to identify the works that have had the greatest impact on strategic management research and to analyze the changes that have taken place in the intellectual structure of this discipline. The methodology is based on the bibliometric techniques of citation and co‐citation analysis which are applied to all the articles published in the Strategic Management Journal from its first issue in 1980 through 2000. Copyright © 2004 John Wiley & Sons, Ltd.

Bibliometrics has become an essential tool for assessing and analyzing the output of scientists, cooperation between universities, the effect of state-owned science funding on national research and development performance and educational efficiency, among other applications. Therefore, professionals and scientists need a range of theoretical and practical tools to measure experimental data. This review aims to provide an up-to-date review of the various tools available for conducting bibliometric and scientometric analyses, including the sources of data acquisition, performance analysis and visualization tools. The included tools were divided into three categories: general bibliometric and performance analysis, science mapping analysis, and libraries; a description of all of them is provided. A comparative analysis of the database sources support, pre-processing capabilities, analysis and visualization options were also provided in order to facilitate its understanding. Although there are numerous bibliometric databases to obtain data for bibliometric and scientometric analysis, they have been developed for a different purpose. The number of exportable records is between 500 and 50,000 and the coverage of the different science fields is unequal in each database. Concerning the analyzed tools, Bibliometrix contains the more extensive set of techniques and suitable for practitioners through Biblioshiny. VOSviewer has a fantastic visualization and is capable of loading and exporting information from many sources. SciMAT is the tool with a powerful pre-processing and export capability. In views of the variability of features, the users need to decide the desired analysis output and chose the option that better fits into their aims.

BACKGROUND: Although at present there is broad agreement among researchers, health professionals, and policy makers on the need to control and combat health misinformation, the magnitude of this problem is still unknown. Consequently, it is fundamental to discover both the most prevalent health topics and the social media platforms from which these topics are initially framed and subsequently disseminated. OBJECTIVE: This systematic review aimed to identify the main health misinformation topics and their prevalence on different social media platforms, focusing on methodological quality and the diverse solutions that are being implemented to address this public health concern. METHODS: We searched PubMed, MEDLINE, Scopus, and Web of Science for articles published in English before March 2019, with a focus on the study of health misinformation in social media. We defined health misinformation as a health-related claim that is based on anecdotal evidence, false, or misleading owing to the lack of existing scientific knowledge. We included (1) articles that focused on health misinformation in social media, including those in which the authors discussed the consequences or purposes of health misinformation and (2) studies that described empirical findings regarding the measurement of health misinformation on these platforms. RESULTS: A total of 69 studies were identified as eligible, and they covered a wide range of health topics and social media platforms. The topics were articulated around the following six principal categories: vaccines (32%), drugs or smoking (22%), noncommunicable diseases (19%), pandemics (10%), eating disorders (9%), and medical treatments (7%). Studies were mainly based on the following five methodological approaches: social network analysis (28%), evaluating content (26%), evaluating quality (24%), content/text analysis (16%), and sentiment analysis (6%). Health misinformation was most prevalent in studies related to smoking products and drugs such as opioids and marijuana. Posts with misinformation reached 87% in some studies. Health misinformation about vaccines was also very common (43%), with the human papilloma virus vaccine being the most affected. Health misinformation related to diets or pro-eating disorder arguments were moderate in comparison to the aforementioned topics (36%). Studies focused on diseases (ie, noncommunicable diseases and pandemics) also reported moderate misinformation rates (40%), especially in the case of cancer. Finally, the lowest levels of health misinformation were related to medical treatments (30%). CONCLUSIONS: The prevalence of health misinformation was the highest on Twitter and on issues related to smoking products and drugs. However, misinformation on major public health issues, such as vaccines and diseases, was also high. Our study offers a comprehensive characterization of the dominant health misinformation topics and a comprehensive description of their prevalence on different social media platforms, which can guide future studies and help in the development of evidence-based digital policy action plans.

The major challenge of photocatalytic water splitting, the prototypical reaction for the direct production of hydrogen by using solar energy, is to develop low-cost yet highly efficient and stable semiconductor photocatalysts. Herein, an effective strategy for synthesizing extremely active graphitic carbon nitride (g-C3N4) from a low-cost precursor, urea, is reported. The g-C3N4 exhibits an extraordinary hydrogen-evolution rate (ca. 20,000 μmol h(-1) g(-1) under full arc), which leads to a high turnover number (TON) of over 641 after 6 h. The reaction proceeds for more than 30 h without activity loss and results in an internal quantum yield of 26.5% under visible light, which is nearly an order of magnitude higher than that observed for any other existing g-C3N4 photocatalysts. Furthermore, it was found by experimental analysis and DFT calculations that as the degree of polymerization increases and the proton concentration decreases, the hydrogen-evolution rate is significantly enhanced.

There is a critical need for improved methane-oxidation catalysts to both reduce emissions of methane, a greenhouse gas, and improve the performance of gas turbines. However, materials that are currently available either have low activity below 400°C or are unstable at higher temperatures. Here, we describe a supramolecular approach in which single units composed of a palladium (Pd) core and a ceria (CeO(2)) shell are preorganized in solution and then homogeneously deposited onto a modified hydrophobic alumina. Electron microscopy and other structural methods revealed that the Pd cores remained isolated even after heating the catalyst to 850°C. Enhanced metal-support interactions led to exceptionally high methane oxidation, with complete conversion below 400°C and outstanding thermal stability under demanding conditions.

Chronic pain (CP) seriously affects the patient's daily activities and quality of life, but few studies on CP have considered its effects on the patient's social and family environment. In this work, through a review of the literature, we assessed several aspects of how CP influences the patient's daily activities and quality of life, as well as its repercussions in the workplace, and on the family and social environment. Finally, the consequences of pain on the health care system are discussed. On the basis of the results, we concluded that in addition to the serious consequences on the patient's life, CP has a severe detrimental effect on their social and family environment, as well as on health care services. Thus, we want to emphasize on the need to adopt a multidisciplinary approach to treatment so as to obtain more comprehensive improvements for patients in familial and social contexts. Accordingly, it would be beneficial to promote more social- and family-oriented research initiatives.

The objective of the present systematic review was to investigate whether physical fitness in childhood and adolescence is a predictor of cardiovascular disease (CVD) risk factors, events and syndromes, quality of life and low back pain later in life. Physical fitness-related components were: cardiorespiratory fitness, musculoskeletal fitness, motor fitness and body composition. Adiposity was considered as both exposure and outcome. The results of 42 studies reporting the predictive validity of health-related physical fitness for CVD risk factors, events and syndromes as well as the results of five studies reporting the predictive validity of physical fitness for low back pain in children and adolescents were summarised. Strong evidence was found indicating that higher levels of cardiorespiratory fitness in childhood and adolescence are associated with a healthier cardiovascular profile later in life. Muscular strength improvements from childhood to adolescence are negatively associated with changes in overall adiposity. A healthier body composition in childhood and adolescence is associated with a healthier cardiovascular profile later in life and with a lower risk of death. The evidence was moderate for the association between changes in cardiorespiratory fitness and CVD risk factors, and between cardiorespiratory fitness and the risk of developing the metabolic syndrome and arterial stiffness. Moderate evidence on the lack of a relationship between body composition and low back pain was found. Due to a limited number of studies, inconclusive evidence emerged for a relationship between muscular strength or motor fitness and CVD risk factors, and between flexibility and low back pain.

Summary Resprouting as a response to disturbance is now widely recognized as a key functional trait among woody plants and as the basis for the persistence niche. However, the underlying mechanisms that define resprouting responses to disturbance are poorly conceptualized. Resprouting ability is constrained by the interaction of the disturbance regime that depletes the buds and resources needed to fund resprouting, and the environment that drives growth and resource allocation. We develop a b uds‐ p rotection‐ r esources ( BPR ) framework for understanding resprouting in fire‐prone ecosystems, based on bud bank location, bud protection, and how buds are resourced. Using this framework we go beyond earlier emphases on basal resprouting and highlight the importance of apical, epicormic and below‐ground resprouting to the persistence niche. The BPR framework provides insights into: resprouting typologies that include both fire resisters (i.e. survive fire but do not resprout) and fire resprouters; the methods by which buds escape fire effects, such as thick bark; and the predictability of community assembly of resprouting types in relation to site productivity, disturbance regime and competition. Furthermore, predicting the consequences of global change is enhanced by the BPR framework because it potentially forecasts the retention or loss of above‐ground biomass. Contents Summary 19 I. Introduction 20 II. Resprouters rather than ‘sprouters’ 21 III. How do plants resprout? 21 IV. Life‐history consequences of resprouting 27 V. Environmental constraints on resprouting 28 VI. Resprouting, community patterns and assembly 29 VII. Global change, carbon storage and resprouting 30 VIII. Conclusions 31 Acknowledgements 31 References 32

Abstract Marine plastic debris floating on the ocean surface is a major environmental problem. However, its distribution in the ocean is poorly mapped, and most of the plastic waste estimated to have entered the ocean from land is unaccounted for. Better understanding of how plastic debris is transported from coastal and marine sources is crucial to quantify and close the global inventory of marine plastics, which in turn represents critical information for mitigation or policy strategies. At the same time, plastic is a unique tracer that provides an opportunity to learn more about the physics and dynamics of our ocean across multiple scales, from the Ekman convergence in basin-scale gyres to individual waves in the surfzone. In this review, we comprehensively discuss what is known about the different processes that govern the transport of floating marine plastic debris in both the open ocean and the coastal zones, based on the published literature and referring to insights from neighbouring fields such as oil spill dispersion, marine safety recovery, plankton connectivity, and others. We discuss how measurements of marine plastics (both in situ and in the laboratory), remote sensing, and numerical simulations can elucidate these processes and their interactions across spatio-temporal scales.

Buildings are a major contributor to climate change, accounting for one third of global energy consumption and one quarter of CO2 emissions. However, comprehensive information is lacking for the development, evaluation and monitoring of mitigation policies. This paper discusses the remaining challenges in terms of reliability and consistency of the available data. A review of energy use in buildings is presented to analyse its evolution by building types, energy services and fuel sources. Residential buildings are the most consuming, although tertiary expansion requires further analysis to develop sound specific indicators. Heating Ventilation and Air Conditioning (HVAC) systems concentrate 38% of buildings consumption, calling for strengthened standards and incentives for retrofitting. Electrification is rapidly increasing, representing a potential tool for climate change mitigation, if renewable power was promoted. However, energy use in buildings will only curb if global cooperation enables developing nations to break the link between economic growth, urbanisation and consumption. To this aim, efficiency gains both in construction and equipment, decarbonisation of the energy mix and a global awareness on energy conservation are all needed.

Context. Gaia Data Release 2 provides high-precision astrometry and three-band photometry for about 1.3 billion sources over the full sky. The precision, accuracy, and homogeneity of both astrometry and photometry are unprecedented. Aims. We highlight the power of the Gaia DR2 in studying many fine structures of the Hertzsprung-Russell diagram (HRD). Gaia allows us to present many different HRDs, depending in particular on stellar population selections. We do not aim here for completeness in terms of types of stars or stellar evolutionary aspects. Instead, we have chosen several illustrative examples. Methods. We describe some of the selections that can be made in Gaia DR2 to highlight the main structures of the Gaia HRDs. We select both field and cluster (open and globular) stars, compare the observations with previous classifications and with stellar evolutionary tracks, and we present variations of the Gaia HRD with age, metallicity, and kinematics. Late stages of stellar evolution such as hot subdwarfs, post-AGB stars, planetary nebulae, and white dwarfs are also analysed, as well as low-mass brown dwarf objects. Results. The Gaia HRDs are unprecedented in both precision and coverage of the various Milky Way stellar populations and stellar evolutionary phases. Many fine structures of the HRDs are presented. The clear split of the white dwarf sequence into hydrogen and helium white dwarfs is presented for the first time in an HRD. The relation between kinematics and the HRD is nicely illustrated. Two different populations in a classical kinematic selection of the halo are unambiguously identified in the HRD. Membership and mean parameters for a selected list of open clusters are provided. They allow drawing very detailed cluster sequences, highlighting fine structures, and providing extremely precise empirical isochrones that will lead to more insight in stellar physics. Conclusions. Gaia DR2 demonstrates the potential of combining precise astrometry and photometry for large samples for studies in stellar evolution and stellar population and opens an entire new area for HRD-based studies.

In this paper, we present a statistical criterion for accepting/rejecting the pairwise reciprocal comparison matrices in the analytic hierarchy process. We have studied the consistency in random matrices of different sizes. We do not agree with the traditional criterion of accepting matrices due to their inflexibility and because it is too restrictive when the size of the matrix increases. Our system is capable of adapting the acceptance requirements to different scopes and consistency necessities. The advantages of our consistency system are the introduction of adaptability in the acceptance criterion and the simplicity of the index we have used, the eigenvalue (λ max ) and the simplicity of the criterion.

OBJECTIVES: To assess the association between gender and suicide attempt/death and identify gender-specific risk/protective factors in adolescents/young adults. METHODS: Systematic review (5 databases until January 2017). Population-based longitudinal studies considering non-clinical populations, aged 12-26 years, assessing associations between gender and suicide attempts/death, or evaluating their gender risk/protective factors, were included. Random effect meta-analyses were performed. RESULTS: Sixty-seven studies were included. Females presented higher risk of suicide attempt (OR 1.96, 95% CI 1.54-2.50), and males for suicide death (HR 2.50, 95% CI 1.8-3.6). Common risk factors of suicidal behaviors for both genders are previous mental or substance abuse disorder and exposure to interpersonal violence. Female-specific risk factors for suicide attempts are eating disorder, posttraumatic stress disorder, bipolar disorder, being victim of dating violence, depressive symptoms, interpersonal problems and previous abortion. Male-specific risk factors for suicide attempt are disruptive behavior/conduct problems, hopelessness, parental separation/divorce, friend's suicidal behavior, and access to means. Male-specific risk factors for suicide death are drug abuse, externalizing disorders, and access to means. For females, no risk factors for suicide death were studied. CONCLUSIONS: More evidence about female-specific risk/protective factors of suicide death, for adolescent/young adults, is needed.

1. Introduction The redefinition of neuropathic pain,23 which specifically excludes the concept of “dysfunction,” has left a large group of patients without a valid pathophysiological descriptor for their experience of pain. This group comprises people who have neither obvious activation of nociceptors nor neuropathy (defined as disease or damage of the somatosensory system) but in whom clinical and psychophysical findings suggest altered nociceptive function. Typical such patient groups include those labelled as having fibromyalgia, complex regional pain syndrome (CRPS) type 1, other instances of “musculoskeletal” pain (such as “nonspecific” chronic low-back pain), and “functional” visceral pain disorders (such as irritable bowel syndrome, bladder pain syndrome). The aim of this topical review was to propose, for debate, a third mechanistic descriptor intended for chronic pain characterized by altered nociceptive function. 1.1. Historical review Before developing any argument for a third descriptor to accommodate these patients, it is worthwhile reviewing the history of pain terminology. Traditionally, pain mechanisms have been divided into “nociceptive” and “neuropathic” categories. See Table 1 for the historical overview of these definitions.Table 1.: Historical overview of mechanistic pain terminology.1.2. Implications of the changed definition of “neuropathic pain” In the 2005 iteration, “nociceptive” pain was the norm, the “default” or common sense experience of injury = damage ≤pain, familiar to humans. But it evolved that any pain that was not “nociceptive” might be termed “neuropathic” because the latter descriptor included “dysfunction,” which was taken to include any inferred change in nociceptive function. Although it has always been possible to invoke another category, such as “unknown” or “idiopathic,” that strategy runs a poor third to the other 2, as there is no implication of a putative mechanism. The 2011 redefinition of neuropathic pain makes biological and etymological sense. The note that accompanies this definition is stringent: Neuropathic pain is a clinical description (and not a diagnosis), which requires a demonstrable lesion or a disease that satisfies established neurological diagnostic criteria. This robust definition is not being challenged. However, the note that accompanies the 2011 redefinition of nociceptive pain—pain that arises from actual or threatened damage to nonneural tissue and is due to activation of nociceptors—states: This termis designed to contrast with neuropathic pain. The term is used to describe pain occurring with a normally functioning somatosensory nervous system to contrast with the abnormal function seen in neuropathic pain (emphasis added). This perpetuates the “nociceptive–neuropathic” dichotomy as above, except that now the “default” position is neuropathic pain, so that any pain condition that is not characterized by damage to neuronal tissue may attract the term “nociceptive.” This is not only counterintuitive, as surely “a normally functioning somatosensory nervous system” should be taken as the basis for any contrast, but also it fails to accommodate a large group of patients in whom “activation of nociceptors” cannot be confidently established. 2. Proposals This situation requires clarification. The proposals put forward here, as presented in Table 2, include: (1) Assertion of nociceptive pain (2) Confirmation of definition of neuropathic pain, but not as default (3) Need for a third descriptor. Table 2.: Proposed taxonomy for the classification of pain compared with the existing IASP taxonomy from 2011 (http://www.iasp-pain.org/Taxonomy), changes highlighted.2.1. Assertion of nociceptive pain “Nociceptive pain” is the most common human experience of pain. Therefore, we propose that the current IASP 2011 definition of nociceptive pain be used, but that the note be shortened to: “The term is used to describe pain occurring with a normally functioning somatosensory nervous system.” Nociceptive pain should not be defined as the alternative to neuropathic pain. This common-sense biological position presumes that the tissue was “normal” before the noxious stimulus and that the somatosensory apparatus is also “normal.” 2.2. Confirmation of definition of neuropathic pain, but not as default The new definition of neuropathic pain does not require amendment. However, because it is not as common as nociceptive pain and it does not reflect the usual experience of pain, it should not be the default descriptor. 2.3. Need for a third descriptor Even with these points of clarification, the situation of only 2 descriptors will remain unsatisfactory for those patients in whom “activation of nociceptors” cannot be confidently demonstrated or assumed and who also do not meet the definition of “definite” or “probable” neuropathic pain. Appending “possible” neuropathic pain leaves them in taxonomic limbo. In the current state of knowledge, there are reasons to infer that altered nociceptive function does occur in patients experiencing pain in a regional (or more widespread) distribution, unassociated with frank signs of neuropathy but characterized by hypersensitivity in apparently normal tissues. The similarity of such findings to those in frank neural injury or disease suggests that common mechanism(s) may be relevant. A reasonable inference from the presence of these findings is that there has occurred a change in nociceptive processing, probably in the central nervous system. The latter is supported by the findings of demonstrated changes in cerebral activation,16,19,38,39,45 connectivity,4,14,20,25,33,37,41,50 and even in specific cerebral structures1,5,18,22,24,31,36,44 in certain clinical pain states, when also adjusted for depression or anxiety.5,18,21,22,36 However, in these pain conditions, there is no consistent evidence of a lesion or disease of the somatosensory system as a primary cause of the pain, thus disqualifying the pain from attracting the neuropathic descriptor. 2.4. Proposal for a third descriptor It is proposed that a new term be introduced to describe pain states characterized by clinical and psychophysical findings that suggest altered nociception, despite there being no clear evidence of actual or threatened tissue damage causing the activation of nociceptors or evidence for disease or lesion of the somatosensory system causing the chronic pain. The candidate adjectives for this third descriptor include: (1) “Nociplastic,” from “nociceptive plasticity,” to reflect change in function of nociceptive pathways. (2) “Algopathic,” from “algos” (Greek for pain) plus “pathic” (from Greek “patheia” for suffering), paraphrased as “a pathological perception/sensation of pain not generated by injury.” (3) “Nocipathic,” from “nociceptive pathology,” to denote a pathological (ie, not “normal”) state of nociception. The term is intended for clinical usage and is neither a diagnosis nor a synonym for “central sensitization of nociception,” which is a neurophysiological concept. It may well be that the phenomenon of hypersensitivity occurring in ostensibly normal, uninjured tissue without evidence of neuropathy leads to a clinical inference that sensitization may be the underlying mechanism, so that the term is used as a descriptor for that situation. Such reasoning is no different from the phenomenon of observable tissue damage leading to the inference of activation of nociceptors and applying the term “nociceptive pain,” or from the phenomenon of signs of neuropathy leading to the inference of disease or damage of neural structures and applying the term “neuropathic pain.” 3. Discussion 3.1. Do we need a third mechanistic descriptor? The present IASP terminology does not reflect the current understanding that chronic pain is not necessarily a symptom but can result from altered nociceptive function and thus constitute a condition in itself. Consequently, the pain of some large patient groups suffering from altered nociceptive function is currently classified as “pain of unknown origin.” An argument in favour of continuing to use the current nondescriptors “unknown” or “idiopathic” relies on confusion that might arise out of challenges in defining a new descriptor. However, the inability of the current IASP pain terminology to harmonize with current concepts has resulted in the use of other nondefined descriptors such as “dysfunctional”40 or “pathological”35 pain, which not only give no insight into possible mechanisms but also carry implications that may stigmatize patients.9,10 The use of a third mechanistic descriptor in clinical practice has the potential to confer validity on the patient's experience of pain and to facilitate communication between patients, clinicians, and other stakeholders. Clinicians would be encouraged to screen for signs of altered nociceptive function, thus improving diagnosis and treatment, as patients suffering from altered nociceptive function typically respond better to centrally than peripherally targeted therapies. The term would also facilitate research efforts, by identifying altered nociceptive function as an important area for mechanistic studies, establishment of treatment guidelines and development of new treatment strategies. 3.2. When should the descriptor be used and when not? The descriptor is primarily intended for patients suffering from chronic pain conditions characterized by evidence of altered nociceptive processing, such as those currently labelled as fibromyalgia,22 CRPS,47 nonspecific chronic low-back pain,16 irritable bowel syndrome,39 and other “functional” visceral pain disorders.8,48 In addition, patients suffering initially from nociceptive pain, such as osteoarthritis, may develop alterations in nociceptive processing manifested as altered descending pain inhibition3,28 accompanied by spread of hypersensitivity.2,17,29 These patients would then be considered to have a combination of nociceptive and “nociplastic/algopathic/nocipathic” contributors to their pain. The new descriptor is intended to distinguish patients suffering from conditions where altered nociception has been documented from those where the pain mechanisms are still truly unknown. Therefore, the new descriptor does not apply to patients reporting pain without hypersensitivity. As such, it is neither a synonym for idiopathic pain or pain of unknown origin nor a label awarded by exclusion. 3.3. Problems regarding validity and use of the new descriptor Opponents of a new descriptor may argue that mechanisms implicit in the terms “nociceptive” and “neuropathic” are proven, in contrast to the inference of functional changes in the nervous system, which as yet cannot be confirmed. A nociceptive focus may be visualized by radiology or reflected in some laboratory findings. It is argued that neuropathy can be identified by quantitative sensory testing, nerve conduction studies, intra-epidermal nerve fiber density assessments, or by imaging of the central nervous system. However, despite the fact that pathology can be documented for nociceptive and neuropathic pain, the relationship between that pathology and pain mechanisms remains elusive. The latter is illustrated by the low concordance between the degree of tissue damage/inflammation and pain11 or by the low proportion of people with peripheral nerve injury who develop chronic neuropathic pain.32 Although it is true that no specific structural pathology underlying “nociplastic/algopathic/nocipathic” pain has been found, altered nociceptive processing has been documented by quantitative sensory testing,7,15,27,42,47,48 sensory evoked potentials,12,13,34 and functional magnetic resonance imaging.16,19,38,48 Importantly, these functional changes have in many instances been related to pain severity.1,31,41,43 Therefore, while acknowledging these limitations in the current and the proposed pain terminology, there remains a rationale for using the new descriptor to distinguish patients with altered nociception from patients with pain of unknown origin. One unresolved situation is when a patient with nociceptive pain could be classified as also having “nociplastic/algopathic/nocipathic” pain. Clinicians are faced with a continuum of signs of hypersensitivity in patients with chronic pain. Individual differences in sensitivity to stimuli are marked even in healthy subjects26,30 and no clinically useful method to quantify nociceptor activation exists. Although tests of descending pain inhibition could be used clinically,6 the validity and reliability of these tests in a clinical setting remain to be established.49 Therefore, nociceptive and “nociplastic/algopathic/nocipathic” pain should not be regarded as exclusive categorical labels but rather, pragmatically, as concurrent possible mechanistic contributors to the patient's pain. This would be similar to the concurrence of nociceptive and neuropathic contributors in other situations. 3.4. Is future progress in pain research likely to affect the use of the descriptors? These mechanistic terms are descriptors of putative contributors to the experience of pain, not diagnoses; they are placeholders for current concepts and not “set in concrete.” As our knowledge of pain mechanisms advances, so should pain terminology change. 3.5. Concluding remarks This topical review suggests introducing a third mechanistic pain descriptor to be used in patients with clinically determined altered nociception. If the suggestion is well received, the next step will be to define a set of clinically useful positive classification criteria. The term is mechanistic and thus complementary to, but not synonymous with, the proposed ICD-11 diagnostic term “primary pain.”46 By writing this article, the authors hope to open up a fruitful debate regarding modernization of mechanistic pain terminology. Conflict of interest statement E. Kosek has received consultancy and speaker fees in the past 36 months from Eli Lilly and Company and Orion and has ongoing research collaborations with Eli Lilly and Company and AbbVie. M. Cohen has received consultancy fees from Mundipharma and Pfizer for preparation and presentation of educational material. R. Baron has received grants/research support from Pfizer, Genzyme, Grünenthal, and Mundipharma. He is a member of the EU Project No 633491: DOLOR-isk. A member of the IMI “Europain” collaboration and industry members of this are: AstraZeneca, Pfizer, Esteve, UCB-Pharma, Sanofi Aventis, Grünenthal, Eli Lilly, and Boehringer Ingelheim. German Federal Ministry of Education and Research (BMBF): Member of the ERA_NET NEU-RON/IM-PAIN Project. German Research Network on Neuropathic Pain, NoPain system biology. German Research Foundation (DFG). He has received speaking fees from Pfizer, Genzyme, Grünenthal, Mundipharma, Sanofi Pasteur, Medtronic, Eisai, Lilly, Boehringer Ingelheim, Astellas, Desitin, Teva Pharmaceuticals, Bayer Schering, MSD, and bioCSL. He has been a consultant for Pfizer, Genzyme, Grünenthal, Mundipharma, Allergan, Sanofi Pasteur, Medtronic, Eisai, Lilly, Boehringer Ingelheim, Astellas, Novartis, Bristol-Myers Squibb, Biogenidec, AstraZeneca, Merck, AbbVie, Daiichi Sankyo, Glenmark Pharmaceuticals, and bioCSL. G. F. Gebhart, J. -A. Mico, and A. S.C. Rice have nothing to declare. W. Rief has received consultancy fees from Heel and speaker's fees from Bayer. K. Sluka has been Consultant for DJO, Inc, and Bayer, Inc, received research funding from Medtronic, Inc and royalties from IASP Press.

The present study summarises the work developed by the ALPHA (Assessing Levels of Physical Activity) study and describes the procedures followed to select the tests included in the ALPHA health-related fitness test battery for children and adolescents. The authors reviewed physical fitness and health in youth findings from cross-sectional studies. The authors also performed three systematic reviews dealing with (1) the predictive validity of health-related fitness, (2) the criterion validity of field-based fitness tests and (3) the reliability of field-based fitness tests in youth. The authors also carried out 11-methodological studies to determine the criterion validity and the reliability of several field-based fitness tests for youth. Finally, the authors performed a study in the school setting to examine the reliability, feasibility and safety of the selected tests. The selected fitness tests were (1) the 20 m shuttle run test to assess cardiorespiratory fitness; (2) the handgrip strength and (3) standing broad jump to assess musculoskeletal fitness, and (4) body mass index, (5) skinfold thickness and (5) waist circumference to assess body composition. When there are time limits, the authors propose the high-priority ALPHA health-related fitness test battery, which comprises all the evidence-based fitness tests except the measurement of the skinfold thickness. The time required to administer this battery to a group of 20 youth by one physical education teacher is less than 2 h. In conclusion, the ALPHA fitness tests battery is valid, reliable, feasible and safe for the assessment of health-related physical fitness in children and adolescents to be used for health monitoring purposes at population level.