Geary  suggested that heritable and environmentally caused differences in mitochondrial functioning affect the integrity and efficiency of neurons and supporting glia cells and may thus contribute to individual differences in higher-order cognitive functioning and physical health. In our comment, we want to pose three questions aimed at different aspects of Geary’s theory that critically evaluate his theory in the light of evidence from neurocognitive, cognitive enhancement, and behavioral genetics research. We question (1) if Geary’s theory explains why certain cognitive processes show a stronger age-related decline than others; (2) if intervention studies in healthy younger adults support the claim that variation in mitochondrial functioning underlies variation in human intelligence; and (3) if predictions arising from the matrilineal heredity of mitochondrial DNA are supported by behavioral genetics research. We come to the conclusion that there are likely many more biological and social factors contributing to variation in human intelligence than mitochondrial functioning. In the summary of his theory on intelligence differences, In our comment, we want to pose three questions aimed at different aspects of Geary’s theory that critically evaluate his theory in the light of evidence from neurocognitive, cognitive enhancement, and behavioral genetics research. This argument relies on the assumption that working memory processes require intermodular neural connections that are supported by intact axonal connections between modules, whereas other cognitive processes rely to a larger degree on intramodular connections. Hence, both higher energy use and the dependence on a larger number of intermodular axonal connections are supposed to account for the greater age-related decline in WM than in STM. We believe that this conclusion is neither supported by cognitive theories on memory systems nor by neuroscientific evidence. Cognitive psychologists have been abandoning a strict distinction between WM and STM towards a broader definition of working memory that includes short-term memory processes . If therIn addition, language-related abilities such as verbal understanding and verbal production, which are reflected in measures of crystallized intelligence, stay relatively stable across the lifespan and show a much more decelerated age-related decline than both WM and STM . HoweverOne very elegant test of Geary’s hypothesis would be to increase mitochondrial functioning through pharmaceutical or training-based interventions and to assess whether these interventions show effects on general cognitive performance. A recent review on the beneficial effects of creatine supplementation summarized three studies assessing the effects on intelligence test performance in younger adults . CreatinSimilarly, effects of resveratrol administration seem to protect against neurodegenerative effects on cognitive function . ResveraTaken together, these results suggest that these nutritional supplementations only affect cognitive functioning in older adults, in individuals with certain neurodegenerative diseases, and in individuals with dietary restrictions. In a similar vein, animal studies have shown that experimental interventions modulating mitochondrial fusion/fission dynamics can facilitate neural regeneration , underliThere is evidence that variations in mitochondrial DNA (mtDNA) have an effect on mitochondrial functioning and several body systems, including the brain . When, iA tentative explanation of this null finding may be that there are no main effects of mtDNA variations on mitochondrial functioning, but that the latter is affected by mito-nuclear interactions only. However, this argument is at odds with the evidence that differences in mtDNA do have sizable effects on mitochondrial and body system functioning, as noted above. Another tentative explanation of this null finding may be that differences in mitochondrial functioning translate only with a very small effect size into differences in intelligence—too small to be detected in the study of Taken together, Geary’s theory is very compelling because it provides an elegant account of many important empirical phenomena of intelligence research. Moreover, it integrates biological and cognitive approaches to studying intelligence by acknowledging that elementary cognitive processes underlying human intelligence are bound to the integrity of the brain, which is one of many bodily organs and is, therefore, affected by basic physiology. We discussed different findings from neurocognitive, cognitive enhancement, and behavioral genetics research that challenged various aspects of his theory. First, we discussed recent research from cognitive psychology and cognitive neuroscience that questioned Geary’s prediction that networks relying on long-distance intermodular information transmission show a greater age-related decline due to more extensive myelin degradation. As both WM and STM processes require long-distance intermodular information transmission, it is implausible to assume that individual differences in axonal integrity and neural plasticity or age-related myelin degradation account for the phenomenon of greater age-related decline in WM than in STM. Second, we looked into the nutritional interventions discussed by Geary and concluded that these nutritional supplementations only affect cognitive functioning in older adults, in individuals with certain neurodegenerative diseases, and in individuals with dietary restrictions, whereas they do not show any cognitive benefits in healthy young adults. Third, we reviewed evidence from behavioral genetics research that challenged the prediction arising from the matrilineal heredity of mitochondrial DNA that the mother–offspring correlation of intelligence should be larger than father–offspring correlation. Data from a large-scale national cohort study showed that mother– and father–offspring correlations were virtually identical.While our reservations based on neurocognitive and cognitive enhancement research only concerned certain parts of Geary’s theory, the discussed evidence from behavioral genetics research questioned a core assumption of the theory, namely that variations in mitochondrial DNA have an effect on mitochondrial functioning, which, in turn, has an effect on human intelligence. While we cannot and do not want to rule out that some amount of variation in human intelligence can be attributed to individual differences in mitochondrial functioning, the findings discussed above let us conclude that there are likely many more factors contributing to individual differences in intelligence, ranging from genes  to stru


Currently available test methods are not well-suited for the identification of chemicals that disturb hormonal processes involved in female reproductive development and function. This renders women’s reproductive health at increasing risk globally, which, coupled with increasing incidence rates of reproductive disorders, is of great concern. A woman’s reproductive health is largely established during embryonic and fetal development and subsequently matures during puberty. The endocrine system influences development, maturation, and function of the female reproductive system, thereby making appropriate hormone levels imperative for correct functioning of reproductive processes. It is concerning that the effects of human-made chemicals on the endocrine system and female reproductive health are poorly addressed in regulatory chemical safety assessment, partly because adequate test methods are lacking. Our EU-funded project FREIA aims to address this need by increasing understanding of how endocrine disrupting chemicals (EDCs) can impact female reproductive health. We will use this information to provide better test methods that enable fit-for-purpose chemical regulation and then share our knowledge, promote a sustainable society, and improve the reproductive health of women globally. Together with seven other projects, FREIA is part of the cluster EURION: European Cluster to Improve Identification of Endocrine Disruptors (http://www.eurion-cluster.eu).The number of women with reproductive health problems is increasing globally and scientific knowledge clearly points towards exposure to human-made chemicals being a contributing factor. It is clear that many chemicals in our food and the environment can disrupt endocrine processes and thereby threaten the reproductive health of humans, livestock, and wildlife globally . These cThe core objective of FREIA is to provide improved testing capabilities for the identification of EDCs that are harmful for female reproduction, as is expressed in the full project title “Female Reproductive toxicity of EDCs: a human evidence-based screening and Identification Approach”. European law requires chemicals to go through a safety evaluation before being allowed on the market. Regulators assess the endocrine disrupting properties of a chemical mostly based on data from standard test protocols that are agreed upon by the Organisation for Economic Co-operation and Development (OECD) and described in the Guidance Document on Standardised Test Guidelines for Evaluating Chemicals for Endocrine Disruption OECD GD150) [0 [5]. UnThe FREIA project focuses in particular on effects related to ovarian function, including the role of various steroid hormones and gonadotropins. The project also comprises the development of the mammary gland from the fetal stage to adulthood, because mammary gland development is known to be a sensitive endpoint for EDC identification. We acknowledge that this is only part of what constitutes ‘female reproductive health’.Good reproductive health is important for the health and well-being of women and, if they wish to conceive, for the health of their children and future generations. Estimations show that up to one in six couples in Western countries experience problems conceiving or carrying pregnancy to term; however, the prevalence of subfertility varies widely between studies due to differences in study design and classifications . A womanA woman’s reproductive health is largely established during embryonic and fetal development and later, during puberty. Female reproductive disorders in adulthood can originate from interference with hormone levels and function during development, as was clearly demonstrated by the “DES disaster”, where overt reproductive effects have been described in children born from women taking the synthetic oestrogen diethylstilbestrol (DES) as a drug during pregnancy. The adverse health effects include a rare form of vaginal cancer in girls, increased incidence of uterine fibroids, endometriosis, impaired fecundity and earlier age at menopause . StartliIn the transition from (unborn) child to an adult woman, many hormonal processes are activated or reactivated. This means that basic biology of the female reproductive system is very different in the embryo, fetus, newborn, young girl, adolescent, and adult women. Consequently, the effect of EDC exposure on the female reproductive system depends on the age or life stage when exposure occurs . In addiAt birth, a baby girl has per ovary approximately 300,000 primordial follicles containing immature eggs or oocytes, which constitutes the ovarian reserve . The humIn girls, puberty typically starts between the age of 10–14 years, and is activated by hormonal signalling. Puberty is characterised by ovarian and adrenal maturation. The transition into puberty is driven by the reactivation of the pulsatory release of gonadotropin-releasing hormone (GnRH) by the hypothalamus leading to gonadarche—i.e., ovarian maturation—increased sex steroid production and initiation of adult pattern folliculogenesis. In humans, ovarian development in puberty is preceded by adrenarche, the maturation of the adrenal cortex, and associated increased secretion of the adrenal androgens dehydroepiandrosterone (DHEA) and its sulfate (DHEAS). This adrenarche component of puberty is unique to humans and some other higher primates. Both hormonal signalling and pubertal onset are susceptible to disturbances resulting from EDC exposure. Several studies have shown that early-life exposure to DES interferes with the programming of pulsatile GnRH secretion and feedback regulation at a time when endogenous oestradiol levels are low . LikewisDuring a woman’s reproductive years , approximately 400 follicles will mature to the ovulatory stage until menopause marks the end of the ability to conceive a child. Each month, several primordial follicles will start to mature, but typically only a single oocyte completes the maturation process (folliculogenesis) every month. The follicles that do not complete folliculogenesis will die by atresia. During folliculogenesis, a follicle expands in size via oocyte growth, granulosa cell proliferation, theca cell recruitment from the stroma, and their subsequent proliferation. The granulosa cells synthesise oestrogens from the androgens supplied by the theca cells. Similar to the human testis, an alternative steroid producing pathway (“backdoor pathway”) is suggested based on gene and protein expression profiles . HoweverTo maintain the periodical maturation and ovulation of oocytes and have a regular menstrual cycle, correct signalling of the hypothalamic-pituitary-gonadal (HPG) axis is an essential prerequisite. This ensures that the ovaries produce appropriate levels of hormones at the correct time. In mammals, including humans, the HPG axis is under negative- and positive feedback control of the sex steroids. An enigmatic feature in women is the switch from negative- to positive-feedback actions of oestradiol in the preovulatory phase, leading to a luteinizing hormone (LH) surge that triggers ovulation . It is cIn order to achieve the main goal of FREIA and improve test methods for identification of EDCs that cause female reproductive toxicity, we need human-relevant biomarkers for ovarian toxicity spanning fetal development to childhood, puberty, and adulthood. The FREIA project has a keen focus on molecular characterisation of human ovarian and adrenal tissues and how they are affected by EDC exposure. In uniquely powered human fetal studies, ovaries and adrenals from elective terminations of normally-progressing pregnancies are being used, along with ovarian tissue donated by adult patients. In FREIA, we culture these human tissues in vitro and expose these to selected chemicals, i.e., DES (to target oestrogen receptor) and ketoconazole (to target steroidogenesis). Next, we analyse effects on morphological, protein, endocrine, and transcriptional level using a range of test methods. The focus on both human ovary and adrenal is important here, considering that the human fetal zone is not replicated in routine test animals. Moreover, steroidogenic pathways appear to be tissue-specific, as depicted above, and sex-specific. For example, in the second trimester, circulating levels of the major adrenal hormone DHEA in the female human fetus are not significantly different from serum and testicular levels the male at the same age, while intra-ovarian levels are much lower . The outhttps://aopwiki.org/aops/7), which is mainly based on rodent data. It pertains to reduced aromatase levels leading to reduced oestrogen synthesis, altered cyclicity, and ultimately impaired fertility. Clearly, this is severely inadequate in covering the different susceptible windows and molecular pathways that most likely will underpin EDC-related female reproductive toxicity in humans.There is a global trend to move away from standardised animal-based testing for endocrine disrupting properties of chemicals to more human-relevant methods that are based on our understanding of mechanisms of toxicity. To date, studies reporting associations between exposure to EDCs and altered development or function of the ovaries with female reproductive toxicity are, perhaps inevitably, mostly descriptive. Thus, they provide limited information on the mechanisms driving the effects caused by EDCs. This is problematic since we need mechanistic understanding to adhere to the recently adopted criteria for identification of pesticides and biocides with endocrine disrupting properties. These criteria require information on the endocrine mode of action of a chemical, the adverse effect and a ‘biologically plausible link’ between the endocrine mode of action and the adverse effect . A solutTo address this obvious shortcoming, we will start by compiling putative AOPs (pAOPs) for female reproductive toxicity with a focus on ovarian development and function . These pAOPs will guide our efforts towards pinpointing test methods that can best capture key events targeted by chemicals and leading up to female reproductive disorders. They will also highlight important knowledge gaps that we need to focus on in the years to come to elaborate a more robust testing strategy aimed at safeguarding women’s reproductive health. Specifically, we intend to use the newly constructed pAOPs to develop an integrated approach to testing and assessment (IATA) or ‘FREIA test strategy’ for female reproductive toxicity. Ultimately, this will enable us to prepare a guidance document that describes how to use and interpret the FREIA test strategy on female reproductive toxicity .(1)Ovarian follicle counts performed in adult animals is included in selected OECD test guidelines, including the Extended One-Generation Reproductive Toxicity Study (TG 443). FREIA aims to improve follicle counting as currently recommended methods are highly affected by the size of the ovary and does not necessarily reflect the total follicle number.(2)Comparison of gene expression changes in key cell types in rat ovaries and in granulosa cells from human follicular fluids will help us to find biomarkers for oocyte quality, which are currently lacking in OECD test guidelines.(3)Morphological changes in early mammary development by image analysis of mammary gland whole mounts are considered sensitive markers of endocrine disruption in female rodents, yet is currently not part of any OECD test guideline. We will improve whole mount examination in the rat mammary gland. An unbiased and sensitive software tool will be applied for examination of mammary gland whole mounts collected at young age .(4)Puberty is a time with great hormonal changes, including a dramatic increase in DHEA over the adrenarche, yet this is largely overlooked in current test strategies dealing with EDCs. In FREIA we will evaluate the need for implementation of elements of the female pubertal assay, an established protocol (US EPA OPPTS 890.145), into current or future OECD test guidelines.(5)Changes in GnRH secretion preceding pubertal onset is considered a key event in ovarian dysfunction after EDC exposure. The effects of DES and ketoconazole on pulsatile GnRH release and hypothalamic transcriptional markers will be studied in primary rodent hypothalamic explants and compared with effects on GnRH release of in vivo exposed hypothalamus. This will allow the study of effects of prenatal exposure on the programming of maturation of GnRH secretion.A better mechanistic understanding of the processes that direct normal ovarian development and function will help us identify the best test methods that are needed to capture key steps leading to female reproductive disorders, which is the ultimate goal of FREIA. Considering that chemical safety assessment is still largely dependent on in vivo rodent studies, it is important to characterise relevant endpoints and maximise predictivity for female reproductive toxicity in these studies. Some in vivo endpoints that FREIA addresses are listed below (this is not intended to be an exhaustive list). In addition, we will explore the potential to include these (optimised) endpoints in existing OECD test guidelines, when deemed feasible.(1)http://qsar.food.dtu.dk/) to open the possibility of integrating dedicated QSARs into toxicological risk assessment strategies.Quantitative structure-activity relationships (QSARs) allow us to predict molecular targets based on physico-chemical properties of a chemical. We will improve existing QSARs for aromatase and PPAR-gamma, two of the key events in a proposed adverse outcome pathway for female reproductive toxicity. These QSAR models and predictions will be made publicly available via the freely available DTU Danish (Q)SAR database ((2)Oestrogen receptor ER-beta (ESR2) plays a central role in ovarian development and function , yet con(3)G-coupled protein oestrogen receptor (GPER) is suggested to act as selector during folliculogenesis  and may (4)It is not known whether the standardised steroidogenic assay OECD TG 456, which uses the adrenal corticocarcinoma cell line H295R and focuses only on progesterone, testosterone, and oestradiol synthesis, is sufficiently applicable to describe (interactions with) ovarian-specific steroidogenesis. This issue will be clarified by comparing steroidomic profiles obtained from human fetal ovarian and adrenal gland cultures, adult primary human ovarian tissue cultures, and human-derived granulosa cell lines.(5)For obvious ethical reasons, in vitro studies to assess human oocyte maturation and competency after fertilisation cannot be used for routine screening of EDCs in a regulatory context. In contrast, bovine ovarian tissues and follicles can easily be obtained from slaughterhouses. From these collected follicles, oocytes can be isolated and matured and used for in vitro fertilisation experiments, where embryonic development can be followed routinely until blastocyst hatching and elongation. Several studies have demonstrated the value of such bovine oocytes as experimental model for human reproductive parameters . This teIn FREIA, we use carefully designed, fit-for-purpose in silico and in vitro models with relevant cell types to experimentally assess and quantify putative molecular and cellular events underlying EDC-induced female reproductive toxicity. These models will be optimised, and standardised protocols will be provided at the end of the FREIA project. These include, but are not limited to:In the European Union, chemicals have to go through a safety evaluation before being allowed on the market. The type of information that needs to be provided by industry to the regulators, however, depends as much on the production volume and intended application for the chemical as on its inherent properties. In other words, the required toxicity tests depend on whether a chemical is a pesticide, biocide, food additive, cosmetics additive, or an industrial chemical. Specific criteria and guidance for identification of EDCs only exist for pesticides and biocides . In the Clearly, the outcomes of the FREIA project will significantly improve our understanding of female reproductive toxicity and, more specifically, how EDCs contribute. Together with outcomes of the European Human Biomonitoring Initiative (HBM4EU) and the Scottish Advanced Fetal Research (SAFeR) Study, we can make important contributions to our understanding of how lifestyle factors can influence EDC-related disease risk, specifically regarding female reproductive health. While EDC exposures during early development might prime a woman’s predisposition to compromised reproductive health, these effects can be amplified through additional exposures or lifestyle factors after birth. After all, the ovarian reserve should last for decades, yet, it is continuously exposed to EDCs. The scientific knowledge generated in the FREIA project will provide openings to map out options to improve female reproductive health, for example through lifestyle choices that may reduce exposure to EDCs. These options will be discussed with relevant stakeholders and gathered in a health promotion strategy that builds on existing expertise  and (grass root) initiatives, such as “toxin-free Stockholm” . We have established partnerships with major actors in policy and advocacy on (women’s) health protection. These include the Health and Environment Alliance (HEAL), the International Federation of Gynecologists and Obstetrics (FIGO), and the International Federation of Fertility Societies (IFFS). These partnerships allow us to communicate our scientific findings in light of the importance of a healthy lifestyle and a sustainable environment, and to inform society how to avoid the potential health risks associated with EDCs.The main objective of the FREIA project is to provide dedicated, human-relevant, test methods to identify EDCs that cause female reproductive toxicity, before the end of 2023. The FREIA consortium consists of 11 partners with outstanding scientific and regulatory expertise on endocrine disruption in relation to women’s reproductive health, early life development, epidemiology, endocrinology, and toxicology. Our combined expertise, the availability of human female tissues, together with advances in international AOP frameworks, provide an unparalleled opportunity to improve existing test methods and develop dedicated novel in vitro and in silico methods to identify EDCs that affect female reproductive health. The FREIA project has a strong focus on developing test methods and strategies that have the widest reach and at the same time are harmonised enough to allow inclusion in internationally validated and accepted guidelines, such as the OECD TG conceptual framework for testing and assessment of endocrine disruptors . Moreove


Pulmonary manifestations of systemic lupus erythematosus (SLE) are wide-ranging and debilitating in nature. Previous studies suggest that anywhere between 20 and 90% of patients with SLE will be troubled by some form of respiratory involvement throughout the course of their disease. This can include disorders of the lung parenchyma , pleura , and pulmonary vasculature , whilst shrinking lung syndrome is a rare complication of the disease. Furthermore, the risks of respiratory infection (which often mimic acute pulmonary manifestations of SLE) are increased by the immunosuppressive treatment that is routinely used in the management of lupus. Although these conditions commonly present with a combination of dyspnea, cough and chest pain, it is important to consider that some patients may be asymptomatic with the only suggestion of the respiratory disorder being found incidentally on thoracic imaging or pulmonary function tests. Treatment decisions are often based upon evidence from case reports or small cases series given the paucity of clinical trial data specifically focused on pulmonary manifestations of SLE. Many therapeutic options are often initiated based on studies in severe manifestations of SLE affecting other organ systems or from experience drawn from the use of these therapeutics in the pulmonary manifestations of other systemic autoimmune rheumatic diseases. In this review, we describe the key features of the pulmonary manifestations of SLE and approaches to investigation and management in clinical practice. Systemic lupus erythematosus (SLE) is a chronic, autoimmune disorder that can present with a wide array of clinical and immunological abnormalities . PulmonaClinical assessment of patients with SLE should routinely consider careful evaluation for respiratory involvement. Symptoms including dyspnea, pleuritic chest pain, reduced exercise tolerance, cough, and hemoptysis should prompt investigation for potential underlying lung disease , 4. HoweThe exact prevalence of SLE-related lung disease is unknown and previous studies have varied widely in their estimates. Most report that between 20 and 90% of SLE patients will experience some form of lung involvement during the course of their disease , 7. HoweIn this review, we discuss the latest understanding on the ways in which lupus can affect the respiratory system, highlight how these patients may present clinically, and outline current approaches for investigation and management.The estimated prevalence of SLE-associated interstitial lung diseases (ILD) is suggested to be between 3 and 9% , 13. AltPatients present similarly in most types of ILD with symptoms such as cough and dyspnea although it is important to consider that some may be asymptomatic . DiagnosThere are a lack of clinical trials assessing the treatment of SLE-related ILD and in particular there are no head-to-head studies. Therefore, recommendations are predominantly based on case reports, small case series, physician expertise, and by applying findings from studies of ILD in other autoimmune rheumatic diseases. Intravenous cyclophosphamide was reported to show significant improvement vital capacity in two SLE patients with ILD in which both patients presented with pleuritic chest pain in the context of active SLE . AnotherCurrent treatment often includes the use of high dose corticosteroids along with agents such as cyclophosphamide and rituximab in severe cases , 29 to iIn some cases, chronic ILD may be the long-term sequelae of an acute process, for example acute lupus pneumonitis. This is a rare manifestation of SLE that has been reported to occur in 1–4% of patients . ClinicaAcute lupus pneumonitis may also be the initial presenting symptom of SLE. A case series of five patients in which acute lupus pneumonitis was the first feature of SLE reported that all five were female, aged 14–26 years old. They were all ANA positive, whilst three were also positive for anti-dsDNA antibodies. Fever was present in all cases with cough as a presenting symptom in four of the five patients, with hypoxia noted in three. All patients received corticosteroids and four patients were treated with cyclophosphamide either as monotherapy or in combination with intravenous immunoglobulins (IVIg). The one patient who did not receive cyclophosphamide was treated with azathioprine. Three patients survived but two died as a result of infection . Others Pleural involvement is the most common SLE-related lung disease . ClinicaDiagnosis of pleural involvement in SLE is usually clinical with typical features in the patient history. It is however important to exclude other causes of pleural inflammation that can occur in SLE including infection, pulmonary embolism, malignancy, congestive cardiac failure , or periAlthough not necessary for diagnosis, if there is clinical uncertainty as to the cause of a pleural effusion, aspiration can be performed. Pleural fluid in patients with SLE classically show elevated levels of protein, lactate dehydrogenase (LDH), leukocytes, and in some cases ANA positivity , 39.The mainstay treatment of pleurisy in SLE has traditionally been non-steroidal anti-inflammatory drugs (NSAIDs) with some patients requiring corticosteroids . Rarely,Pulmonary arterial hypertension (PAH) is a progressive disorder characterized by a resting mean pulmonary artery pressure above 25 mmHg and a pulmonary wedge pressure below 15 mmHg . There aClinical symptoms of PAH in SLE are often non-specific and range from generalized fatigue and weakness to chest pain and dyspnea at rest . InitialManagement of PAH in SLE is similar to that of idiopathic PAH. However, most randomized controlled trials that have specifically analyzed the management of PAH associated with connective tissue diseases often have not included a subgroup analysis of SLE patients . Drugs sNumerous observational cohort studies have also noted benefit with corticosteroids and immunosuppressive therapy including cyclophosphamide, cyclosporine and MMF –70. One Pulmonary embolism (PE) also needs to be considered in the acute setting in any patient with SLE who presents with pleuritic chest pain . In the more chronic setting, chronic pulmonary embolic disease can also lead to pulmonary hypertension (chronic thromboembolic pulmonary hypertension). It is particularly important to consider embolic disease in those patients who have secondary anti-phospholipid syndrome (APS), given the obvious increased risk of thrombosis associated with the disease. Previous studies have reported that one-third of patients with SLE will have positive anti-phospholipid antibodies and those with a positive lupus anticoagulant have previously been shown to have a six-fold increased risk of venous thrombosis. In comparison, a positive anti-cardiolipin antibody carried twice the risk when compared with SLE patients without positive anti-cardiolipin antibodies . PreviouThe “gold standard” investigation for PE is computed topography pulmonary angiogram (CTPA), which can identify the presence of thrombosis within the pulmonary vasculature. However, it is important to consider that SLE patients presenting with pleuritic chest pain and hypoxia may instead be suffering from pleurisy (as described above). Results from the Michigan Lupus Cohort assessed the outcomes of 182 patients with SLE who had previously undergone a total of 357 CTPA scans. The authors found a significant decrease in the likelihood of confirming PE in patients who had previously had three or more scans, thus suggesting that repeated scanning of patients without a previously proven PE is unlikely to confirm a new diagnosis .In the context of PE associated with APS, lifelong anticoagulation is likely to be recommended. Recent studies investigating direct oral anticoagulants have recommended against their use in arterial thrombosis, such as PE .de novo in patients with SLE who are have anti-phospholipid antibodies without previous thrombotic events. This suggests that this is not entirely the result of anticoagulant therapy and may represent an as yet unclassified mechanism for pulmonary vasculitis , is a rare but severe manifestation of SLE that is associated with a high mortality rate of up to 90% . This hasculitis . As withFindings from small cases series and cohort studies have highlighted that dyspnea and pulmonary infiltrates on thoracic imaging are almost universally in seen. Fever is reported in the majority of cases although occult hemoptysis is only seen in just over half of patients at presentation . Many paGiven a lack of clinical trial data from DAH in SLE, treatment recommendations are usually based upon other autoimmune conditions associated with pulmonary hemorrhage (such as ANCA-associated vasculitis) and often include pulsed intravenous steroids in combination with cyclophosphamide , rituximShrinking lung syndrome (SLS) is an uncommon manifestation of SLE with an estimated prevalence of ~1–2% , 83, 84.Patients with SLS often present with symptoms of pleuritic chest pain and progressive dyspnea . Due to Evidence for the optimal management of SLS is limited. Corticosteroids and immunosuppressive agents including azathioprine, MMF and rituximab have been used to varying degrees of efficacy , 89–92. Pulmonary manifestations of SLE can present with a wide array of symptoms and can often be difficult to differentiate from other conditions, most notably infection. The key differences between these disorders are summarized in It is important to consider that SLE-related lung disorders are likely to be under-represented due to the fact that respiratory involvement may be asymptomatic. Furthermore, serositis  is the only respiratory symptom included in the revised 1997 American College of Rheumatology (ACR) criteria for SLE  and no aRA conducted a literature review of relevant respiratory disorders. SAY, EKD, and CW expanded upon this. All authors agreed to the finalized version of this manuscript prior to submission.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.


Cultural and ethnic differences stemming from migration are a source of social exclusion in old age. This topic is of concern in part because an increased migration flow coupled with growing anti-immigrants sentiments in much of the Western world can ignite social exclusion mechanisms even when unintended. Given these trends, we ask whether racism figures in research on ethno-cultural and racial older minorities. Thus, based on a scoping review of peer-reviewed articles published between 1998-2017 (n=336), this presentation asks if, and how, racialization and racism inform this research. In answering these questions, this presentation will argue that the role that racism plays as a social exclusion mechanism that affects older ethnic and racial minorities needs to be studied in a systematic fashion. Part of a symposium sponsored by the International Aging and Migration Interest Group.


However, despite the past decades of research within the ecological dynamics framework developing an evidence-based, theoretical conceptualisation of skill acquisition, expertise and talent development, an ongoing challenge resides within its practical integration into sporting environments. This article provides two case examples in which high-level sports organisations have utilised an ecological dynamics framework for performance preparation in Australian football and Association Football. A unique perspective is offered on experiences of professional sport organisations attempting to challenge traditional ideologies for athlete performance preparation by progressing the theoretical application of ecological dynamics. These case examples intend to promote the sharing of methodological ideas to improve athlete development, affording opportunities for practitioners and applied scientists to accept, reject or adapt the approaches presented here to suit their specific ecosystems.A fundamental challenge for practitioners in high-level sporting environments concerns how to support athletes in adapting behaviours to solve emergent problems during competitive performance. Guided by an ecological dynamics framework, the design and integration of competitive performance preparation models that place athlete-environment interactions at the heart of the learning process may address this challenge. This ecological conceptualisation of performance preparation signifies a shift in a coach’s role; evolving from a consistent solution provider to a learning environment  Ecological dynamics offers a theoretical framework to guide performance preparation in sport from high-performance to developmental environments.designers that promote athlete-environment interactions.The use of ecological dynamics as a framework for performance preparation requires practitioners to view themselves as learning The continued sharing of case exemplars within sport science could drive the methodological advancement of contemporary performance preparation models that offer practical use for sports practitioners.“There is nothing so practical as a good theory”—Kurt Lewin (1951)micro-structure of practice  and at the macro-structure of talent development (over extended periods of many years) [In high-level sport, practitioners are required to prepare athletes for the demands of present competitive performance environments, whilst concurrently developing athletes of the future. These tasks signify the implementation of practical support activity operating at two integrated, but different, timescales in the y years) , 2. The complex adaptive systems composed of many interacting parts or degrees of freedom, which need to be coordinated and continuously regulated in achieving task goals [Athlete-environment interactions have been modelled as sk goals , 3. Two sk goals . Externask goals .An important direction of constraint on athlete self-regulation in performance concerns the exploitation of inherent self-organising tendencies for individuals to locally adapt and adjust to emerging competition demands, from an internally driven source. From an ecological ontology, ‘self-regulation’ refers to the development and exploitation of deeply intertwined, functional relationships between a performer’s actions, perceptions, intentions, emotions and the environment . This indesigners: professionals who harness the continuous, non-linear and deeply integrated interactions emerging between the performer, task and environmental subsystems [athlete-environment interaction at the core of the learning process, and views the coach as an integral member of a multidisciplinary team of support practitioners who co-design representative and information-rich practice environments [Over the years, applied scientists working in the theoretical framework of ecological dynamics, have re-conceptualised the role of practitioners in athlete development and performance preparation –10. Thisbsystems , 12. Sucronments , 14. ThiDuring the last two decades, research has provided theory and data for the establishment of ecological dynamics as an important theoretical framework for performance preparation in sport –21. HereThe application of an ecological dynamics framework in sport is growing, yet challenging, with Renshaw and Chow  citing tThe first design feature of this framework is the interaction between the knowledge sources, blending and exploiting existing experiential and empirical knowledge on ecological dynamics and application of its key principles. As highlighted elsewhere , sport sdesigner, who facilitates athlete-environment interactions. In this role, re-conceptualisation, the coach is responsible for identifying and manipulating key constraints of the practice environment in an attempt to guide the attention of performers to regulatory information sources available in the surrounding landscape [with the athlete, placing their needs at the centre of the performance preparation model. Further, the re-conceptualisation of the coaches’ role in performance preparation requires an understanding that they are integral members of a multidisciplinary team of sporting practitioners that work together to design individualised learning environments [The next design feature was the re-positioning of the coaches’ role in performance preparation. As discussed by Woods et al. , when coandscape , 12. An ronments . This apronments : individronments . This apIn the remaining sections of this paper, we unpack other important design features of this framework. Accompanying the empirical conceptualisation of each design feature is a hypothetical example applied to Australian football , allowing the reader insight into how such a concept could be brought to life in practice.represent or faithfully simulate competition demands. Founded on initial insights of Brunswik [representative learning design. Representative training activities are high in specificity of information sampled from a competitive performance environment, which is to be designed into practice task settings. As shown by Pinder and colleagues [ecological niche [By identifying critical sources of information that support utilisation of relevant affordances , a coacBrunswik , and latBrunswik , 33, 34,lleagues , 36, repal niche . This atal niche . With thsampled from competition to allow them to be designed into a practice activity which simulates the competitive performance environment.An important feature of successful performance within Australian football is effective ball disposal between teammates, which can occur via a handball or kick. To design representative learning environments, a practice task needs to be guided by information sources that shape actions and behaviours within competition. Thus, informational constraints could be One strategy to facilitate the sampling of constraints could be to ask a coach to heuristically select key constraints they perceived to shape kicking actions. Through performance analysis, these constraints  could then be sampled from competition and practice landscapes, allowing a coach to base his/her experiential knowledge on performance data from a database of relevant kicks performed in competition. For example, when the same notational analysis is applied to a practice task intended to augment kicking skill, a coach could contrast the sampled constraints from competition and the practice task (such as ‘time in possession’) to ensure that a specific training activity was more ‘game like’ or not. To visualise such an approach, a performance scientist could plot the percentage of total kicks performed within different temporal epochs  from both competition and practice landscapes, enabling a concise identification of potential points of difference. These performance data could offer more detailed insights into determining where (if any) mismatches between training and competition environmental demands may exist, providing a basis for training activity re-design to more closely align the constraints observed during game play. By engaging performers to discuss their performance needs, this co-design approach can create more ‘game like’ training activities. Clearly, greater depth of, and diversity in key constraints and their interaction sampled from both competition and practice landscapes, would enable deeper insight into the representativeness of training tasks. One way to achieve this could be through the use of more advanced machine learning techniques, such as rule induction .the ability to find a motor solution for any external situation, that is, to adequately solve any emerging motor problem correctly (i.e. adequately and accurately), quickly (with respect to both decision-making and achieving a correct result), rationally  and resourcefully (i.e. quick-wittedly and initiatively)”  (p. 134). In contrast to early connotations of specificity of practice, Bernstein’s [A fundamental implication of ecological dynamics is the rationale that the concept of skill acquisition could integrate the notion of ‘skill adaptation’ (for detailed arguments see ), being nstein’s  insightsThe implications of this ecological conceptualisation of ‘skill’ are important to consider for sporting practitioners, as it suggests that practice tasks should promote an environment in which athletes are faced with continual problems, which they are required to solve. To enable this design approach, and aid ensuing exploration, a team of practitioners could consider the manipulation of a range of key constraints to educate an athlete’s attention towards features of their environment critical to the solving of emergent problems specific to his/her action capabilities. A guiding framework to assist with the manipulation of constraints is that proposed by Newell . The keydo athletes rehearse problems or repeat stable solutions?, could capture the fundamentality of a constraints-led approach , whilst affording a digestible platform for practitioners responsible for bringing it to life via their experiential knowledge. In this following example, a practice task consisting of a constraint manipulation is discussed with reference to the promotion of perceptual attunement and adaptable performance solutions to an emergent tactical problem.Questions such as: Match simulations are a common training task within performance preparation frameworks in elite Australian football environments. To guide the perceptual attunement of players within these simulations towards the solving of dynamic, emergent tactical problems, a coach could consider artificially manipulating practice game scorelines. Specifically, by strategically placing one team marginally in front  towards the end of the match simulation, a coach could encourage self-organised player-environment interactions, as both teams search their performance landscapes for affordances that allow them to either preserve or (re)gain the lead.To quantify emergent ball passing interactions between the players, following the constraint manipulation , performance analysis could be used in conjunction with principles of the constraints-led framework discussed earlier. Specifically, constraints shaping kicking between teammates could be sampled “pre- tactical problem” (i.e. before a score-imposed change) and “post-tactical problem” (i.e. after a score-imposed change). The distribution of kicks within a certain constraint category could then be compared between conditions to facilitate insight into possible ball passing interactions in response to the tactical problem. This would ultimately furnish the coach insights into how the players self-regulate performance in an adaptive response to constraint manipulation. This process assists the coach in identifying the informational constraints that players detect when attempting to solve emergent problems within competition, thus enabling them to manipulate these features to educate a player’s attention in future practice designs. As per the first example, understanding passing interactions could be further enhanced through the utilisation of more advanced analytical techniques, such as network analysis . Such ancomplex adaptive system, in which the non-linearity and dynamics of performer-environment interactions continually invite actions and behaviours towards the achievement of the same, or similar, task goals [system degeneracy, a concept that describes how the same system output can emerge through the use of structurally different elements or configurations [A central tenet of ecological dynamics is the appreciation of an athlete or team as a sk goals . Accordiurations .Given the re-positioning of skill acquisition as ‘skill adaptation’ within ecological dynamics, it is the progressive attunement to relevant continuously emerging and decaying affordances that a coach should consider within their practice designs, not the rehearsal of the same (static) solution to the task goal. It is through this attunement process that an athlete can learn to functionally adapt movements to exploit key constraints to achieve the same task goal . Thus, pdo athletes have the freedom to explore solutions to problems designed?, draws the attention of sport practitioners to inherent degeneracy tendencies described in the following example. In this practice design, two teams are tasked to deceive opponents to either maintain or obtain ball possession by any means they felt necessary to achieve this task goal. To promote these functional behaviours, a coach could first anchor points or a score to successful deceptive actions, immediately channelling the player’s attention towards the utilisation of deceptive affordances offered within the performance landscape. Second, to promote self-regulated exploration of a variety of deceptive behaviours, a coach could use team convolution, exemplified through the environmental constraint manipulation of placing competing teams in the same coloured bibs during practice games. Such a constraint manipulation would increase practice task difficulty by challenging players to self-regulate by using scanning behaviours to search for, discover and explore affordances for passing the ball offered in the revised performance landscape.In recognition of the empirical knowledge on system degeneracy, and in a similar vein to the design features previously unpacked, questions such as: To observe emergent deceptive behaviours, a coach could then quantify the type of deception strategy actualised by the players within the practice task. Designing a practice landscape that facilitates manipulation of constraints for task goal achievement will challenge players to search for multiple opportunities for action, and not rehearse one (static) performance solution. Task goals could be achieved by exploiting the use of structurally different system elements .knowledge of [Conceptualised through ecological dynamics, self-regulation broadly emphasises emergent interactions between a performer and the environment. From this perspective, performers learn to self-regulate through the acquisition and exploitation of functional relationships between their actions, perceptions, intentions, emotions and environment . Exposurledge of  their pedo athlete’s problem solve autonomously?, could be commonly raised amongst a team of practitioners. To facilitate this process within practice designs and assist players in their capability to self-regulate their perception-action couplings without global intervention from a coach, questioning could be an effective strategy [knowledge about the environment, [knowledge of the performance environment [Questioning that draws player attention towards number inequalities (overloads or underloads) in certain field locations.Knowledge of these number inequalities could subsequently lead to the self-organised exploitation of functional movement strategies, facilitated by scanning with and without the ball, when outnumbering or being outnumbered by opposition.Questioning that draws player attention towards environmental features likely to influence ball disposal .Knowledge of these extrinsic environmental features could lead to self-organised ball disposal interactions between teammates, such as resting with the ball in extreme heat to preserve anaerobic capacity.Questioning that draws player attention towards tactical strategies imposed by an opposing team .To capture the fundamentality of self-regulation conceptualised through ecological dynamics, questions such as strategy . Questioronment, ). Ratherironment , exempliironment . Some exThe last feature of Heads Up Footy is the appreciation of a learner-centred environment, allowing individual needs to be prioritised within practice designs . As discare athletes given opportunities to lead the programme?, to support player engagement and autonomy. Such an approach can bring to life the often-misunderstood concept of athlete-environment-centred, widening understanding of what constitutes ‘experiential knowledge’ in high-performance sport. It affords athletes’ input on integral parts of their learning environment, focusing their attention on the relative value of their experiential knowledge from years of competitive performance. To facilitate this process, and afford opportunities for players to lead their performance development programme, a few strategies are described below:Embrace the notion of co-design within practice tasksExample: Including players (where possible/appropriate) in discussions orienting the specific design of practice tasks. This approach enables deeper insights into what affordances players perceive and actualise within their landscapes (which coaches can only understand from a second-hand perspective), allowing the design of tasks that better represent competition demands, in addition to informed constraint manipulation to educate attention.Management of time within weekly schedulesExample: Players being free to manage aspects of their preparation perceived to need additional support. This could include (but is not delimited to) additional education, recovery strategising and/or additional work on specific skill, mental and physical condition and tactical development.Facilitate player-led training sessionsExample: Allowing players opportunities to autonomously (without continuous coach interaction/input) design, implement and review training activities. By doing so, it is likely they will develop richer knowledge of their environment through the design and reflection of practice tasks that invite, guide and regulate the actions and behaviours of teammates.As in other design features, a multidisciplinary team of practitioners could use questions such as The ‘Football Interactions’ concept emerged from an ecological realism perspective, with talent development practices not being based on deterministic models of behaviour , but founded upon high-quality athletic experiences and continuous interactions with practice and competitive environments. Accordingly, in April 2017, with the support of a newly-formed Research and Development department comprised of researchers and coaches, AIK (Allmänna Idrottsklubben) youth football made the decision to build a player development framework guided by (i) the well-being of the child; (ii) supporting documents from the United Nations Convention on the Rights of the Child and Swedish Sports Confederation, and (iii) the promotion of more youth players to participate in the under 16, under 17 and under 19 years teams. After implementation, this approach saw the disbanding of AIK’s traditional early talent selection policy, in which the club had selected the ‘best’ early performers to form an academy team at < 9 years of age.form of life, that acknowledged the many values, beliefs and different socio-cultural practices (e.g. in practice task design and coach education) that shaped player development, and especially, Gibson’s [Whilst coined by the Research and Development department, the Football Interactions concept was predicated on Wittgenstein’s  notion oGibson’s  and RietGibson’s  accountsGibson’s . Specifipath dependency underpinned by inherited beliefs sheltered by more traditional ideological inertia [Integrating an ecological dynamics framework for player development in a youth football club can be a challenging task, which can be compounded by a  inertia . In this inertia –48. AccoThrough biographical examination, it was identified that coaching skill was being developed and shaped by the landscape of traditional coaching practices and coach education programmes, with these being recognised as key constraints on the emergence of new, more contemporary epistemologies. A further revelation was how attributes and skills appreciated in players at AIK youth football were culturally embedded in traditional pedagogical approaches, organisational settings and structural mechanisms founded upon specific socio-cultural and historical constraints. For instance, training designs in Swedish youth football have typically been underpinned by a culturally dominant planning paradigm pervasive in traditional educational approaches . Within the younger teams at AIK youth football, it was revealed that coaches’ planning and practice designs were aimed at shaping self-organising tendencies of players and teams at a global-to-local scale by explicitly imposing a game model . Put simTo initiate this liberation, the framework ‘AIK Base’ was introduced by AIK Research and Development in late 2018 . Football interactions are tuned by environmental information to function specifically in each unique situation, emphasising the need to understand the nature of the information that constrains movement. In stark contrast to predetermined passing patterns, practice should highlight informational constraints that allow players to learn new ways of acting adaptively through exploration . The praA central component of football performance is being able to ‘dribble’ the ball . Thus, performance preparation within developmental programmes framed by ecological dynamics should educate players of opportunities to dribble that may emerge, as opposed to the repetition of the ‘football action’ (dribbling) itself. This example draws upon a 4v4 game, in which affordances orienting start positions were designed in to initially educate the player’s attention towards relevant information sources to exploit gaps and utilise space whilst in possession of the ball. To further promote the utilisation of gaps and space via dribbling, as opposed to passing, a coach could manipulate the task in such a way that promotes the utility of dribbling. To do so, careful task constraint manipulation could be used, such as awarding a point to the team who is able to intercept a pass, thus placing a risk associated with passing the ball, but not excluding its utility. This increased risk could invite players both with and without the ball to self-organise their individual and collective behaviours by attending to local information through utilisation of football interactions . Whilst the targeted task constraint manipulation to increase risk or uncertainty associated with passing emphasises the need to identify opportunities to exploit gaps and space through dribbling, it additionally invites teammates to continuously adapt their position in relation to local information . This example yields stark contrast to more traditional ways of ‘teaching’ dribbling, which would typically involve the reproduction of predetermined dribbling patterns.A key aim of the Football Interaction concept was that the affordance landscape was to be co-designed between the coach and player(s). In other words, practice tasks were co-designed between players  and coaches (through observation of these interactions and reflection). Through co-design, coaches could become better informed with regards to designing in present and future opportunities or affordances for interaction . In thishow the player is performing the shooting action.It is quite common in youth football to see shooting exercises in which the coach drives the action of the player, as opposed to exercises in which the football interaction is preserved . Thus, to co-design a shooting practice task that places the football interaction at its core, a coach could observe how the player is adapting his/her shooting behaviour in relation to the information present . Through this observation, and subsequent player reflection, a coach could better understand the information sources players use to guide their shooting behaviour, being able to design in these information sources to promote richer football interactions through careful constraint manipulation . This is in direct contrast to traditionally focusing on In summary, this case example sought to offer readers a basis of how practitioners could integrate key features of ecological dynamics in the development of youth footballers. Specifically, it emphasised the evolution of more historical coaching practice, with practitioners transitioning towards learning environment designers that placed the individual-environment  interaction at the core of the learning design.As timelessly captured by the psychologist Kurt Lewin, a good theory should be practical. Thus, an important current and future challenge for the theory of ecological dynamics resides within its practical integration. We sought to provide insights into how high-level organisations have attempted to integrate ecological dynamics for performance preparation. It was not our intention to prescribe a universal solution for performance preparation, but rather offer the readership an overview on how some professional sporting organisations are seeking to challenge traditional ideologies of performance preparation. More specifically, these case examples were intended as models exemplifying how practitioners and organisations could challenge themselves to adapt strategies to design contemporary practice tasks within their ecosystem. To continually assist this process, we encourage the sport science community to promote the sharing and scientific publication of exemplars and/or case studies that afford opportunities to accept, reject or adapt practical approaches used by others. We perceive that it is this continued sharing, offering and discussion of application and methodological ideas in the sport sciences that will advance the application of (good) theory.


Comparative psychology assesses cognitive abilities and capacities of non-human animals and humans. Based on performance differences and similarities in various species in cognitive tests, it is inferred how their minds work and reconstructed how cognition might have evolved. Critically, such species comparisons are only valid and meaningful if the tasks truly capture individual and inter-specific variation in cognitive abilities rather than contextual variables that might affect task performance. Unlike in human test psychology, however, cognitive tasks for non-human primates  have been rarely evaluated regarding their measurement validity. We review recent studies that address how non-cognitive factors affect performance in a set of commonly used cognitive tasks, and if cognitive tests truly measure individual variation in cognitive abilities. We find that individual differences in emotional and motivational factors primarily affect performance via attention. Hence, it is crucial to systematically control for attention during cognitive tasks to obtain valid and reliable results. Aspects of test design, however, can also have a substantial effect on cognitive performance. We conclude that non-cognitive factors are a minor source of measurement error if acknowledged and properly controlled for. It is essential, however, to validate and eventually re-design several primate cognition tasks in order to ascertain that they capture the cognitive abilities they were designed to measure. This will provide a more solid base for future cognitive comparisons within primates but also across a wider range of non-human animal species. Comparative psychologists design and use cognitive tests to investigate and compare cognitive performance and capacities of extant non-human animal species and humans (mainly children). The ultimate goal is to better understand how animal minds are organized and to reconstruct the evolution of mind, including the human one. To date, a variety of animal species has been compared in cognitive studies, ranging from mammals  to birds e.g., , fish e, reptileG) across a set of diverse tasks and this performance score increases from humans’ evolutionary most distant primate relatives (lowest scores in strepsirrhines) to their closest primate relatives  and increasing evidence in non-human animals suggests considerable evolutionary continuity of g , at least within the mammalian lineage , several non-cognitive biases may affect the outcomes of both original studies and their replications. Human cognitive test batteries are regularly evaluated regarding psychometric criteria such as their validity , and reliability . In comparative psychology with non-human primates and other animals, however, such evaluations are currently largely missing. This might be problematic, especially in light of the recent replication crisis in human psychology highlighting that many original research findings, even from studies using established experimental paradigms, cannot be replicated by fellow researchers . One conThe few primate studies that assessed the re-test reliability of primate cognition tests include one that used different test sessions within single cognitive tasks of the Tamarin Test Battery (TTB) as a proxy for repeated testing and found a relatively low correlation between performance scores . In an ag: In comparative psychology, large samples, particularly of non-human primates, are often not available , b, whicg), the main question is whether individual performance is correlated across tasks, and such correlations can be the result of confounds rather than a true positive manifold  the sensory  abilities to easily perceive the test apparatus and distinguish the test stimuli, (ii) the motor skills to easily handle the test apparatus and (iii) sufficient motivation to participate in and attend to the cognitive task at hand . The firEven when conducting cognitive species comparisons within the primate order, some differences in sensory-motor skills remain that might affect individual test performance if not considered when constructing test apparatuses. For instance, many strepsirrhines (lemurs and lorises) are nocturnal and possess limited color vision  and dexterity, while they appear to rely more on olfaction than haplorrhines (monkeys and apes), most of whom are diurnal and have excellent stereoscopic color vision. Yet different haplorrhine primate species, and even different individuals within a single species, also vary to some degree in perception and dexterity . ImportaWhile test designers and experimenters can largely control sensory-motor confounding factors by using appropriate test apparatuses, they may have limited control over several other non-cognitive factors during testing. For instance, motivational aspects remain a potential source of bias on cognitive performance. Examples are inner states and predispositions that affect how individuals approach and attend to their non-social (including cognitive tasks) and social environment (including the human experimenter and the cognitive test situation). However, deliberate test designs and analytical methods might alleviate some of these issues e.g., .Starting from primate cognition studies, we here review recent studies that exemplary address (1) how individual differences in several non-cognitive factors affect participation and performance in cognitive tasks commonly used for within and between-species comparisons and (2) how aspects of test design and human-induced biases directly or indirectly affect cognitive performance. Finally, we evaluate (3) how recent studies that used cognitive test batteries may be affected by such effects.Individuals can differ considerably in terms of non-cognitive factors  and different species differ in social factors  that might affect their cognitive task performance. Recent comparative cognition studies have started to assess a number of such internal (subject-related) and external (test design-related) non-cognitive factors and their potential effects on cognitive performance. Here, we review several relevant studies and their findings regarding whether they affected cognitive task performance or not see also .(Sapajus apella) in two training tasks that preceded cognitive testing. Subjects with more open or less assertive personalities and particularly those exhibiting a combination of both trait expressions were more motivated to participate and also performed better in the training tasks than less open and highly assertive subjects  and orang-utans (Pongo pygmaeus) approached such novel situations more quickly and performed better in some physical subtests of the PCTB than their shyer conspecifics. In the social subtests, however, individual differences in temperament were not associated with the apes’ cognitive performance in either domain  subjects who showed a strong spontaneous emotional reaction to the experimenter and the test situation participated in fewer trials of an object permanence task than their less emotionally reactive conspecifics , is able to acquire a larger set of cognitive skills than an individual who is deprived of this opportunity  than their mother-raised conspecifics  and in several inhibitory control tasks from other sources  exhibit generally high levels of social tolerance, which appears to facilitate performance in socio-cognitive tasks such as social learning or cooperative problem solving compared to their less tolerant sister taxa  mental processes and maintaining information such as executive functions  are also predicted to decrease with increasing age in non-human primates e.g., . CognitiTask format, i.e., the way in which a cognitive task is designed and how (many) test stimuli are presented to the subject, not only generally affected cognitive performance in several empirical comparative cognition studies but it sometimes did so in different ways in different species.trap-tube task, originally designed by rake-in the reward (thereby pulling it away from the trap) rather than having to push the reward away from the trap . Through the transparent front of the box, the subject had visual access to the test apparatus and could use its finger to move the reward away from the trap without requiring a tool, which made the task easier for chimpanzees , two Old World monkey species, olive baboons (Papio anubis) and long-tailed macaques (Macaca fascicularis) performed better when the test stimuli were inedible  as opposed to edible items . Interestingly, the same monkeys performed equally well with edible test stimuli when the food type of the edible items they were rewarded with differed from the food type of the test stimuli (Cebus sapajus apella) performed better with edible stimuli than tokens (Saimiri sciureus). When the quality of food rewards was modulated, both New World monkey species performed better with higher quality rewards independent of how long they had to wait to be rewarded . They were more successful at distinguishing between two objects when they had access to haptic in addition to purely visual information by being allowed to touch and manipulate the objects suggesting they benefited from this multimodal exploration  or not . Initial findings by Other modifications to the original object choice task, such as increasing the distance between the containers in which the food item is hidden, have also been shown to positively affect the performance of bonobos, chimpanzees, and orangutans in object choice tasks e.g., . The disAlthough it is effortful to establish eye contact with some non-human primate subjects and this is not possible with all species , ensuring in this way that the subject is attentive to the experimenter’s cues has been shown to improve the performance of bonobos, chimpanzees, and orangutans in the object choice task .One specific issue of comparative psychology is that not all species and not all individuals within a given species are equally motivated to continually participate in cognitive tasks. An individual’s lack of motivation to do so can critically affect the course of a study because the individual will require substantially more than the allocated or available testing time to complete the cognitive tasks. This can be particularly problematic in cognitive studies with non-human primates because access to respective testing facilities is often temporally limited, which constrains the time available for a study. Researchers often deal with this constraint by following an opportunistic approach of only testing individuals who readily participate and are most likely to complete the tasks in the available testing time and excluding those who are not. However, such opportunistic testing might bias a study’s outcome if the excluded individuals not only differ from the selected ones in motivational factors but also in terms of cognitive abilities.testing time to those who were consistently motivated showed that both groups performed equally well in all tasks. This suggests that opportunistic testing and the selection bias that results from it does not necessarily affect a study’s outcome. Whether this also applies to other species still needs to be established.In a recent study with common marmosets and common squirrel monkeys, this issue has been addressed by including less consistently motivated individuals and allowing them additional time to complete the six tasks of a cognitive test battery at their own pace . A direcWhen using test batteries to assess individual differences within a species, priority is given to the same individuals completing all tasks. This is because obtaining a complete data set enables researchers to conduct factor-analytical performance analysis whereas dropouts would complicate this approach. A second goal is to obtain large enough sample sizes to reach sufficient statistical power. As current data suggest, using an opportunistic (as opposed to a randomized) approach by only selecting those individuals as subjects who are most likely to stay consistently motivated and complete all tasks is not a major issue. At least not as long as researchers report that and why this approach was followed and as long as dropouts and their performance in the few tasks they completed are also reported in detail.However, some individuals (or species) might also require more time to get used to a new task because they are neophobic and more cautious when approaching the test apparatus for the first time. It is therefore advisable to allow every subject to familiarize itself with the basic test apparatus and to only start testing when the subject appears comfortable with all components. Highly neophilic individuals, on the other hand, tend to approach and get used to the test apparatus much more quickly with the risk that some of these individuals might also more quickly lose interest once the task is not novel anymore. In order to enable later replications of a study, it is therefore important to describe in detail how subjects were familiarized with the tasks prior to testing, how their motivation was regained if necessary, and which criteria were used to objectively decide when a test session started and when it had to be aborted.Besides opportunistic testing, using several experimenters rather than just one is another way to test as many subjects as possible with all tasks in a limited testing period. Although training different experimenters to use the same standardized methods helps reducing experimenter effects that might bias the subjects’ cognitive performance, a certain risk of such unintended biases remains. Another issue is that not all subjects are equally motivated to participate in food-reward tasks and different food types do not have the same value for all individuals. One way of limiting such individual differences is to use tokens as test stimuli rather than food items e.g., . However, five Old World monkey species  the tested species do not differ in terms of cognitive abilities (which would be in line with Macphail’s null hypothesis), (ii) small differences in task designs rather than cognitive ability masked species differences in cognitive performance, or (iii) the levels of task sensitivity were not appropriate to identify between-species variation and instead led to ceiling  or floor effects . While the first possibility appears unlikely to explain the primate and parrot findings based on what is known about their cognitive abilities, the two other two possibilities or a combination of the two (depending on the tasks and species) appear more plausible.The lack of clear-cut performance differences between the different primate taxa points to ceiling effects in most tasks of the PCTB with relatively good performance levels in all species most likely owing to the relatively low task sensitivity . MoreoveCacatua goffiniana) having been shown to be skillful at using a stick to retrieve food in previous experiments. According to Comparably to the primates, all tested macaw species also performed relatively poorly in the tool-use task despite other parrot species  and parrots received up to six trials per subtest. In the object-permanence tasks of the physical scale, for instance, the monkeys and lemurs received six trials so that all spatial positions and combinations of the baited cups were evenly distributed. In principal, participating in the double amount of trials might have given them an advantage over the great apes in that they had the opportunity to learn and perform better across trials. However, the monkey and lemur results were stable and there were no learning effects from the first to the second half of trials, which makes it unlikely that they had a substantial learning advantage over the great apes .Therefore, the most plausible explanation for the apparent lack of cognitive differences between various primate species based on individual performance scores in the PCTB, is that some of the tasks are not valid or sensitive enough to reveal differences between species . For insThe floor effects in the primates’ and parrots’ performance demonstrate that researchers are facing a trade-off when constructing cognitive test batteries. While the test set-ups need to be sufficiently abstract to also identify a putative domain-general cognitive ability rather than only capturing narrow domain-specific adaptations, the task apparatuses also need to be ecologically valid enough to be easily perceived and handled by all individuals. While closely related species can be largely tested with the same test apparatuses and setups with only minor adjustments, large-scale species comparisons might require more changes. This might particularly be the case for species with low dexterity levels or those who have to use their beaks (birds) or noses  to handle the test apparatus and make responses. As the parrot results suggest, validated tasks should be used that can be adjusted for as many species as possible while keeping the cognitive task itself as similar as possible. This is an immense challenge for comparative psychology that yet needs to be accomplished.One task that may be promising for meaningful species comparisons is the reversal learning task  in whichMost importantly, however, our findings illustrate the importance of conducting basic validations of cognitive tasks and test batteries in comparative psychology before applying them to a broader range of different species. This can be achieved by establishing that the cognitive tasks truly measure differences and similarities in aspects of cognition rather than other aspects that are not primarily cognitive in nature. One possible way of doing so is to first establish that each cognitive task (of a future test battery) identifies intra- and inter-individual cognitive variation in one species by assessing which potentially confounding factors can be ruled out or have to be controlled as far as possible. In a second step this species could then be compared to its closest evolutionary relatives and then to more distant ones. Another way is to use one or a small number of established and validated cognitive tasks to compare the cognitive abilities of a wide range of different species  non-cognitive factors that may confound the outcomes of primate cognition tasks in general and primate test batteries in particular. In order to take into account sensory-motor species-differences, we have largely focused on studies with primates rather than other mammals or birds . Our findings from these typical comparative cognition tasks suggest that individual differences in non-cognitive internal (subject-related) factors  affected cognitive performance primarily via attention, which in principle can be controlled or at least quantified. Depending on the individuals and species tested, differences in social and demographic factors may positively or negatively affect performance. Unless cognitive comparisons specifically account for the influence of such factors on cognitive performance, it is therefore essential to report these potential sources of variation and control them if possible.per se, the more specific issue of construct validity remains. Since all cognitive abilities represent constructs and as such have to be inferred from cognitive test performance, each construct needs to be carefully defined before its validity can be established. Although establishing construct validity in a top-down (theory-based) rather than a bottom-up approach  would be ideal, doing so is extremely challenging (but see We conclude that non-cognitive factors are a minor issue if experimenters ensure they only test attentive individuals who are motivated to use appropriate response strategies. This is best achieved by either presenting more than two choice options to the subjects whenever possible or by using modified two-choice task versions that prevent motivational issues. Since relatively small differences in task format and test procedures can have major effects on the outcomes of comparative cognition studies, it is essential to report the testing procedure and individual results in detail, ideally supplemented with video clips. While basic aspects of internal task validity can thus be improved by establishing that the tasks measure at least cognition In sum, test design remains the major issue of contemporary comparative psychology and it is essential that researchers validate and redesign cognitive tests, if needed, in order to ascertain that the tasks accurately capture cognitive abilities. Once the sensitivity, reliability, and internal validity of cognitive tasks have been established, these tasks can then be integrated into test batteries and applied to an increasingly wide range of species. This will also help establishing their external validity, i.e., if they measure the same cognitive abilities in different species. Such evaluated test batteries that only include tasks with established internal and external validity will then hopefully provide a solid base for future cognitive comparisons and further our understanding of the evolution of mind, including the human mind.MS, CF, and JB wrote the review together. All authors contributed to the article and approved the submitted version.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.