Idiopathic inflammatory myopathy (IIM) classification criteria have been a subject of debate for many decades. Despite several limitations, the Bohan and Peter criteria are still widely used. The aim of this review is to discuss the evolution of IIM classification criteria.New IIM classification criteria are periodically proposed. The discovery of myositis-specific and myositis-associated autoantibodies led to the development of clinico-serological criteria, while in-depth description of IIM morphological features improved histopathology-based criteria. The long-awaited European League Against Rheumatism and American College of Rheumatology (EULAR/ACR) IIM classification criteria were recently published.The Bohan and Peter criteria are outdated and validated classification criteria are necessary to improve research in IIM. The new EULAR/ACR IIM classification criteria are thus a definite improvement and an important step forward in the field. Classification criteria are meant to identify uniform and comparable groups of subjects for research purposes. In an era where international collaborations are frequent and, more than ever, needed to advance research in rare autoimmune diseases, agreement on a common set of classification criteria is critical. In 1975, Dr. Anthony Bohan and Dr. James B. Peter provided a first set of classification criteria that enabled the inflammatory idiopathic myopathy (IIM) field to evolve tremendously. They divided the IIMs into five groups: primary idiopathic polymyositis (PM), primary idiopathic dermatomyositis (DM), DM/PM associated with neoplasia, childhood DM/PM associated with vasculitis, and DM/PM with associated collagen-vascular disease . In the In 1975, the original Bohan and Peter classification proposal for both diagnosis and classification was published and remains to this day the most widely used classification criteria in the field of IIM  , 12. ThiWhile some investigators focused their efforts on linking histopathologic changes associated with each IIM subset to underlying pathologic mechanisms, others were discovering and describing myositis-specific autoantibodies (MSA). By 1990, seven MSA targeting different cytoplasmic ribonucleoproteins including helicase protein (Mi2), signal recognition particle (SRP), and five anti-aminoacyl-tRNA synthetases (histidyl (Jo1), threonyl (PL-7), alanyl (PL-12), glycyl (EJ), and isoleucyl (OJ)) were discovered and each one was found to be associated with unique clinical features , 15••. IIn 1995, Tanimoto et al. published a new set of nine criteria to classify patients as either DM or PM based on a multicenter retrospective study with questionnaires and chart review . Four ofsine myositis or amyopathic DM [For decades, clinicians, especially dermatologists, recognized an entity called DM athic DM  that refathic DM . ADM wasathic DM . Van derathic DM . Their pathic DM –26.The European Neuromuscular Center (ENMC) criteria designed on behalf of the Muscle Study Group and published in 2004 also required histopathologic confirmation in conjunction with clinical and laboratory criteria for IIM classification. These detailed criteria include MRI findings, some MSA, and specific immunohistochemical stainings that help differentiate DM and PM such as major histocompatibility complex class 1 (MHC-1) and membrane attack complex (MAC) –29. TheyIn the first decade of the twenty-first century, several new MSAs were described including three new anti-aminoacyl-tRNA synthetases (asparaginyl (KS), tyrosyl (HA), phenylalanyl (Zo)), the anti-melanoma differentiation antigen 5 (anti-MDA5), the anti-small ubiquitin-like modifier activating enzyme (anti-SAE), the anti-transcriptional intermediary factor 1 (anti-TIF1), the anti-antinuclear matrix protein (anti-NXP-2), and the anti-3-hydroxy-3-methylglutaryl coenzyme A reductase (anti-HMGCR). Some of those autoantibodies have been linked to specific phenotypes and clinical courses such as the anti-TIF1γ, strongly associated with cancer-associated DM, or anti-HMGCR, a marker of IMNM associated with statin use –33. MSAsIn 2005, Troyanov et al. approached IIM classification from a different perspective, merging IIM clinical features with MSAs and myositis-associated autoantibodies profiles . They coIIM classification has been a matter of debate for decades, and myositis experts agree on the importance of reaching a consensus to improve future clinical trials. The previous classification criteria were mainly empirically derived and not properly validated. When studies were based on patient’s data, patient cohorts were often small, single-center, and did not include controls. To palliate for this, a group of international IIM experts including adult and pediatric rheumatologists, neurologists, dermatologists, epidemiologists, and biostatisticians was assembled in 2004 to develop new IIM classification criteria following the recommendations published by the EULAR/ACR , 4. The Classification of IIM has been and will likely remain the topic of much discussion and debate. Attempts at categorizing a heterogeneous group of diseases with multiple possible organ involvement, considerable overlapping features, and different underlying pathologic molecular mechanisms that are yet to be fully deciphered are a daunting task. In addition, some IIM subsets such as sIBM are characterized by an insidious onset with characteristic histologic findings appearing late in the disease course, which may lead to misclassification of affected patients as PM in the early phase of their disease •. More cA careful evaluation of the clinical features of IIM including muscle weakness pattern is also central to classification in a research setting. When assessing muscle weakness, clinicians should be aware of the caveats of frequently used tools, such as the ceiling effect of the MMT8 •. As diaOver the years, many IIM experts have offered invaluable contributions to our knowledge of the IIM disease spectrum and have proposed various approaches to its classification. Bohan and Peter criteria continue to be used widely in medical schools and residency programs and still provide deep understanding of IIM to the trainees. In the hope of transitioning to a more contemporary classification, the EULAR/ACR criteria have been developed and validated with a robust methodology, an improvement over previous criteria sets. The new IIM classification criteria are a valuable addition to the myositis disease activity core measures endorsed by IMACS and the recently published ACR/EULAR adult PM/DM and juvenile DM response criteria ••, 58••.


FPN-to-DMN connectivity also showed a significant condition × group effect (p = 0.003), with decreased connectivity at 0-back in SZ. Across groups, connectivity within the CON and DAN were increased during the 2-back condition, while DMN connectivity with either CON or DAN were decreased during the 2-back condition. Our findings support the role of the FPN, CON, and DAN in working memory and indicate that the pattern of FPN functional connectivity differs between SZ patients and control subjects during the course of a working memory task.Task-based connectivity studies facilitate the understanding of how the brain functions during cognition, which is commonly impaired in schizophrenia (SZ). Our aim was to investigate functional connectivity during a working memory task in SZ. We hypothesized that the task-negative (default mode) network and the cognitive control  network would show dysconnectivity. Twenty-five SZ patient and 31 healthy control scans were collected using the customized 3T Siemens Skyra MRI scanner, previously used to collect data for the Human Connectome Project. Blood oxygen level dependent signal during the 0-back and 2-back conditions were extracted within a network-based parcelation scheme. Average functional connectivity was assessed within five brain networks: frontoparietal (FPN), default mode (DMN), cingulo-opercular (CON), dorsal attention (DAN), and ventral attention network; as well as between the DMN or FPN and other networks. For within-FPN connectivity, there was a significant interaction between  Schizophrenia (SZ) is among the most disabling brain disorders. Clinically, patients are characterized by the presence of hallucinations, delusions, disorganization, and/or negative symptoms. The majority of affected individuals also experience pervasive cognitive deficits, including those involving working memory function –3, whichWorking memory is a limited capacity memory system involved in temporarily storing and manipulating information. Deficits in the working memory system in SZ are commonly linked to abnormal functioning of the dorsolateral prefrontal cortex (DLPFC) , 10. A mUnlike resting-state imaging studies, task-based studies can provide direct insight into brain functional connectivity involved in working memory since imaging occurs during task performance. Most task-based SZ studies have investigated functional connectivity of the FPN, and to a lesser extent the DMN . Resultsn-back task in SZ and control participants, as well as connectivity with other known cognitive brain networks: the cingulo-opercular (CON), dorsal attention (DAN), and ventral attention (VAN). Our study contributes to the literature on working memory task-based functional connectivity in SZ, by investigating multiple cognitive networks derived using a novel network-based cortical parcelation approach  of the CPT task results.Prior to scanning, participants completed a computer-based cognitive assessment, the University of Pennsylvania Computerized Neurocognitive Battery (Penn-CNB) . Cognitin-back task and procedure used has been previously described  registration into MNI152 space and grand-mean intensity normalization. From here, the data were projected onto a surface representation and smoothing was constrained to cortical surface and subcortical gray-matter parcels as part of a “grayordinate”-based approach .n-back level (0- and 2-back), correct responses, incorrect responses, and confound regressors described above. The residuals of this regression were then specified for the five specified networks (and their constituent parcels) using the existing 333-node parcelation scheme described by Gordon et al.  and AFNI FreeSurfer (5.3.0) . To accon et al. . Brieflyn et al. . The 333n-back level, at time points corresponding to correct trials. To account for potential spurious correlations produced by high-motion frames  and n-back condition  as factors. All analyses included number of frames dropped due to head-motion censoring as a covariate. For within-network tests, p-values are Bonferroni corrected for five tests (one per network tested). For all between-network tests, p-values reported are Bonferroni corrected for seven between-network connectivity tests. Based on ANCOVA results, we performed follow-up analyses to determine whether network connections that showed an interaction between diagnosis and n-back condition correlated with clinical symptom severity  or in-scanner accuracy. We also investigated correlations of network connectivities with cognitive performance  outside the scanner. Connectivity variables for correlations were either the specific connectivity at either condition, or derived as the functional connectivity difference between conditions . We tested the effect of typical antipsychotic drugs on connectivity at either task condition by comparing SZ patients on typical antipsychotics to those on only atypical antipsychotic drugs using a Student’s t-test.All statistical analyses were performed using IBM SPSS Statistics, version 24 (SPSS Inc.). To test for average between- and within-network differences across Table n-back condition  but no main effect of diagnostic group . The FPN, also showed a significant condition-by-diagnosis interaction , driven by decreased connectivity at the 0-back condition in SZ compared to CN participants. Unlike in CN participants, SZ participants increased within-FPN connectivity with n-back difficulty. Post hoc analyses, however, did not meet significance for group effects at 0-back  and 2-back  for within-FPN connectivity.Estimated marginal means by group for each within-network functional connectivity are shown in Figure F = 5.139, p = 0.14], diagnosis  or condition-by-group interaction .Within the DMN, there was no main effect of condition  and within-DAN  connectivity, with connectivity within both the CON and DAN increasing with n-back difficulty in both SZ and CN participants. There was no group effect or condition-by-group interaction for either network. Within-VAN connectivity showed only a trend level effect of n-back condition , and no group or condition-by-group effect.There was a significant main effect of F = 0.278, p > 0.99] or group . However, there was a significant condition-by-group interaction . Notably, DMN-to-FPN connectivity with n-back difficulty, decreased in CN participants and increased in SZ participants. Post hoc analyses did not meet significance for group effects at 0-back  and 2-back .Estimated marginal mean connectivities between either FPN or DMN and other networks are depicted in Figure FPN functional connectivity with either CON, DAN or VAN did not show any significant effects of condition or group, and there were no condition-by-group interactions.F = 13.786, p = 0.003), but there was effect of group  or a significant condition-by-group interaction . Similarly, there was a significant effect of n-back condition  for DMN-to-DAN connectivity, without group  or interaction  effects. Connectivity of the DMN with either the CON or the DAN decreased with n-back difficulty, in both SZ and CN groups.DMN-to-FPN functional connectivity results are described above. DMN-to-CON connectivity showed a significant main effect for n-back condition  and at a trend level with within-FPN connectivity . Accuracy at 2-back did not correlate significantly with either FPN connectivity.Table r = −0.3; p = 0.04) and a trend level correlation with the DMN-to-FPN functional connectivity difference . However, there was no significant relationship when only SZ participants were analyzed. Attention performance did not correlate significantly with either the FPN or DMN-to-FPN connectivity difference, in either all participants or SZ participants.We also investigated the relationship of connectivities with working memory or attention performance outside the scanner. Across groups, significant correlations were observed for working memory performance with the within-FPN functional connectivity difference , and a significant correlation of positive symptoms with the DMN-to-FPN functional connectivity difference .We tested the relationship of FPN connectivity and DMN-to-FPN connectivity, with clinical symptoms . Across groups, significant correlations were observed for negative symptoms with the within-FPN functional connectivity difference (As seen in Table N = 12) and those on only atypical antipsychotics (N = 13). There were no significant effects observed for either within-FPN connectivity  or DMN-to-FPN connectivity .We investigated the effects of the major classes of antipsychotics among SZ patients, by comparing FPN connectivities in those on typical antipsychotics . In addition, we studied functional connectivity differences between SZ patients and healthy participants while performing these tasks. Connectivity was investigated across five cognitive network that were expected to be relevant to working memory. Our neuroimaging dataset was unique, being the only one obtained from SZ patients using the customized HCP primary scanner, located at Washington University.A goal of the current study was to investigate brain functional connectivity changes with increasing difficulty on an Our study found that across subjects from both groups, functional connectivity within the frontoparietal (FPN), cingulo-opercular (CON), and dorsal attention (DAN) network increased with cognitive load. However, increased connectivity within the FPN was driven by the SZ group, with control participants showing similar connectivity during the 0-back and 2-back tests. This was in contrast to within the CON and DAN, where connectivity in both control and SZ participants increased with cognitive load. The CON and DAN also showed increased decoupling from the task-negative default mode network (DMN) with increased cognitive load, suggesting that the CON and DAN are involved in task processing. Both the CON and DAN have known roles in cognition. The CON includes brain regions that include the anterior insula/operculum and dorsal anterior cingulate cortex. Unlike the FPN that has been ascribed roles in the initiation and modulation of cognitive control abilities, the CON is thought to facilitate the maintenance of task-relevant goals and the incorporation of error information to adjust behavior , 48, andOur results are supported by reports from other studies. While negative findings have been reported , the CONWe found two significant connectivity differences between SZ patients and control participants in our study. First, there was decreased within-FPN connectivity during the 0-back condition in SZ patients, compared to controls; however, during the 2-back condition, FPN connectivity was similar across groups. Second, connectivity between the FPN and the default mode network (DMN) decreased with greater working memory load in healthy participants, but increased in SZ patients. The connectivity of other cognitive networks studied tended to be lower in SZ than controls, consistent with a generalized hypoconnectivity that has been widely described , 63, altOur study results support the role of FPN cortical regions, including the DLPFC, in SZ. Meta-analytic and review studies of working memory have generally found reduced activation of the DLPFC in most studies of SZ patients compared to healthy controls , 12, 64.The underlying neurobiology of decreased functional connectivity in SZ with working memory may be related to decreased integrity of key white matter tracts within the brain. Functional connectivity is not isomorphic with structural connectivity (at least in terms of single synapse connections) and thus one cannot directly interpret alterations in functional connectivity as reflecting alterations in structural connectivity. White matter abnormalities in SZ have, however, been well described from diffusion studies , 68, incDespite the relevance of the results presented, our study does have some limitations that may influence our findings. First, as with other functional connectivity studies, potential motion-related effects may have affected data quality. While our motion-censoring is expected to minimize such influences, motion-related differences across groups may have confounded our results. The amount of data available could also have influenced the reliability of our connectivity results –74. WhilIn summary, our study focused on the connectivity of five key cognitive networks, which were defined using a validated cortical network parcelation approach, with imaging data obtained using the HCP primary scanner. We found decreased FPN functional connectivity and FPN-to-DMN functional connectivity during the 0-back condition, relative to the 2-back condition, in SZ patients compared to controls. In addition, increased CON and DAN functional connectivity was found with increased working memory load in both control and SZ participants. Normalization of FPN connectivities with increasing cognitive load, suggests that FPN dysconnectivity in SZ occurs mainly with tasks requiring low effort. These findings provide evidence for the interplay of these cognitive networks in working memory performance and for abnormal cognitive processing in SZ, supporting results from other studies. Future studies would be important to investigate the specificity of our findings to working memory tasks, and the role of other brain networks.This study was carried out in accordance with the recommendations of the Institutional Review Board (IRB) of Washington University, St. Louis with written informed consent from all subjects. All subjects gave written informed consent in accordance with the Declaration of Helsinki. The protocol was approved by the Institutional Review Board (IRB) of Washington University.DG wrote the first draft of the manuscript and conducted the majority of the analyses. AJ and SK conducted some of the analyses. DM planned and supervised the study and analyses.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.


To examine two hypotheses about the longitudinal relationship between night-time parenting behaviours in the first few postnatal weeks and infant night-time sleep-waking at five weeks, three months and six months of age in normal London home environments.Most western infants develop long night-time sleep periods by four months of age. However, around 20–30% of infants in many countries continue to sleep for short periods and cry out on waking in the night: the most common type of infant sleep behaviour problem. Preventive interventions may help families and improve services. There is evidence that ‘limit-setting’ parenting, which is common in western cultures, supports the development of settled infant night-time behaviour. However, this evidence has been challenged. The present study measures three components of limit-setting parenting , examines their stability, and assesses the predictive relationship between each of them and infant sleep-waking behaviours.n=101) group and subgroups with a Bed-Sharing (n=19) group on infra-red video, diary and questionnaire measures of parenting behaviours and infant feeding and sleep-waking at night.Longitudinal observations comparing a General-Community (Bed-Sharing parenting was highly infant-cued and stable. General-Community parenting involved more limit-setting, but was less stable, than Bed-Sharing parenting. One element of General-Community parenting – consistently introducing a short interval before feeding – was associated with the development of longer infant night-time feed intervals and longer day-time feeds at five weeks, compared with other General-Community and Bed-Sharing infants. Twice as many General-Community infants whose parents introduced these short intervals before feeding in the early weeks slept for long night-time periods at three months of age on both video and parent-report measures, compared with other General-Community and Bed-Sharing infants. The findings’ implications for our understanding of infant sleep-waking development, parenting programmes, and for practice and research, are discussed. Derived from learning theory and sleep problem treatment studies, this hypothesis posits that immediate parental response maintains infant night-time signalling until later ages, while delayed response extinguishes it. Because some parents vary their care strategies during the postnatal period (Goodlin-Jones (2)et al., Our secondary hypothesis was that implementing an interval between infant waking and feeding (rather than feeding immediately) would predict prolonged infant sleep periods, and reduced signalling, at night. This ‘feeding interval’ hypothesis was based on Wright’s  observatThe present report addresses the review’s other query by examining longitudinal relationships between limit-setting parenting and infant night-time sleeping in the first 3M of age in the same infants and parents. As well as parental reports, we used infra-red video recording methods developed by Anders The study received Riverside Medical Research Ethics Committee approval (REC 09/H0706/11).n=101) was enrolled in postnatal wards of a general community maternity hospital. We excluded multiple births, infants with birth weight <2500 g, admitted to special care, who medical staff considered unwell, and mothers with limited English. Otherwise, mothers were approached consecutively, introduced to the study, and asked to allow a telephone call to explain the research fully after returning home. Mothers who gave written informed consent completed the newborn Infant Sleep and Feeding Arrangements Questionnaire (ISFAQ), described below, when infants were <48 h old.Two groups of mothers and breast-feeding singleton infants living within the M25 motorway around London, UK were recruited. The ‘General-Community’ group  and asked parents to keep this for 3×24 h days. The Diary is a validated, real-time, parent-report measure of infant sleep, fuss/crying, and awake-settled behaviour  was coded, allowing measures of the timing, duration and frequency of each behaviour. Following earlier findings, the diary night-time was defined as 7pm to 7am, day-time from 7am to 7pm  versus limit-setting (below the median) categories for each ISFAQ measure  at each age. In step two, objective, video or Diary, methods were used to confirm these group and ISFAQ-defined subgroup differences in parenting.In step three, the parenting groups and subgroups were compared on video, diary and parental questionnaire measures of infant night waking and continuous sleeping at 3M and 6M of age.et al. .Most (63%) Bed-Sharing parents planned and implemented settling their infants when tired . General-Community parenting was again less stable, so that 30.7% of these parents reported planning and implementing settling when tired, 32.7% consistently settling infants to sleep at a regular time, and 36.6% changed from one to the other .These parent-report findings indicate that General-Community parenting was more unstable, as well as more limit-setting, compared with Bed-Sharing parenting. The General-Community group included stable and unstable parenting subgroups.et al. , diary data were used to measure these inter-feed intervals (the time between the end of one and start of the next feed). P<0.05). These subgroup differences in night-time inter-feed interval were substantial, averaging >20 min at 2W and >40 min at 5W . This was not matched by significantly more frequent feeding, but both General-Community subgroups who responded rapidly at 5W tended to have short inter-feed intervals . Nevertheless, group and subgroup differences should be similar across methods.Bed-Sharing infants had more frequent, shorter sleep periods and woke more often during the night than General-Community infants on all video, Diary and questionnaire measures .Table 4CAmong the General-Community subgroups, delayed responding predicted longer night-time sleep periods in 3M Diary, but not in video or parental questionnaire measures, or in 6M measures , providiP<0.05).Our secondary hypothesis predicted that use of feeding intervals in the early weeks would lead to longer day-time feeds at 5W to compensate for the longer feeding intervals and fewer feeds at night. As Stably implemented feeding intervals also predicted the infant outcome sleep-waking measures from all three methods at 3M, and both questionnaire measures at 6M age . Figure The parents’ bed-time settling method did not predict 3M infant sleep-waking on any measure . The preStepwise logistic regressions were used to examine whether the feeding interval predictions in et al. , et al. (et al., et al., The first finding was that around a third of London General-Community parents did not implement their planned form of parenting, or changed from an infant-cued towards a limit-setting strategy, or vice versa, in the first five postnatal weeks. This variability, initially described by Goodlin-Jones et al. , stood iet al.  by increet al., et al., The second finding was that stable limit-setting parenting led to longer infant night-time sleep periods at 3M and 6M of age. Analyses of the videos confirm that this involved increased infant sleep length over age, not variations in parents’ detection of infant waking (St James-Roberts These findings need to be interpreted in light of the methodological limitations of this study, including that participants were highly educated, largely white parents in stable relationships in London, the small size of the comparison group and General-Community subgroups, and reliance on only three 24-h diary days at each of three ages and one night of video recording at each of two ages. The use of median splits to divide the General-Community group into subgroups at each age has disadvantages, but these concern the likelihood that analyses will fail to identify subgroup differences. In contrast, our video and diary findings confirmed the validity of our median-split analyses, while the finding of highly significant differences in the group and General-Community subgroup measures of infant sleep-walking across video, diary and questionnaire methods at 3M of age, and at both 3M and 6M ages, is highly unlikely to be due to error or chance.et al., As others point out (Tikotzky et al., et al., et al., et al., et al., et al., Although we accept this limitation, four RCTs – the most powerful research method for establishing causation – have provided replicated evidence that limit-setting parenting increases the proportion of infants who have long night-time sleep periods by 3M of age (Wolfson Taken together, these findings provide substantial, but not conclusive, evidence that a short interval before feeding leads to a cascade of adaptations in infant self-regulation and sleep-waking which many infants manage successfully by 3M of age. RCT confirmation of this finding is needed, but physiological research to establish how feed spacing can alter infant metabolic self-regulation may be a useful prior step. For instance, an interval before feeding may increase wakefulness and feeding vigour, resulting in greater intake and physiological adjustments which extend sleep length and the interval before the next feed. The existing findings do not support the long-standing assumption that breast milk constituents require 3M-old infants to wake frequently at night.et al., For clinical purposes, any benefits which stem from introducing an interval before feeding need to be balanced against its disadvantages, including the evidence that this leads to increased distress in General-Community infants, relative to infants whose parents use highly infant-cued parenting including bed sharing. However, no significant differences in infant night-time distress were found between General-Community subgroups with minimal versus typical pre-feeding intervals (St James-Roberts These findings can be conveyed to parents and professionals to help them to make informed choices but, in our view, should not be incorporated prescriptively into health service recommendations. Instead, the findings should provide the basis for further research to substantiate, and refine, their use. The existing evidence implies that limit-setting parenting should result in less infant night-time distress and improved sleeping over the long-term, while improved sleeping should help to support healthy infant development (El-Sheikh and Sadeh et al., when to transition from infant-cued to limit-setting parenting so as to maintain breast-feeding, support infant self-regulation, and prevent long-term night waking and distress, seems likely to be a fruitful focus for research.‘Authoritative’ parenting, that combines warmth with limit-setting, is especially effective in supporting older children’s development (Pratt


Polybrominated diphenyl ethers (PBDEs) have been used worldwide to reduce flammability in different materials and are suspected to be EDCs. The production of the commercial Penta- and OctaBDE mixtures is banned, but DecaBDEs and existing products may leak PBDEs into the environment. Our aim was to investigate the effect of the PentaBDE mixture DE-71 on human thyroid cells Primary human thyroid cells were obtained as paraadenomatous tissue and cultured in monolayers. The influence of DE-71 on cyclic adenosine monophosphate (cAMP) and thyroglobulin (Tg) production was examined in the culture medium by competitive radioimmunoassay and enzyme-linked immunosorbent assay, respectively. Real-time quantitative PCR analysis of thyroid-specific genes was performed on the exposed cell cultures. PBDE concentrations were determined in cellular and supernatant fractions of the cultures.DE-71 inhibited Tg-release from TSH-stimulated thyrocytes. At 50 mg/L DE-71, mean Tg production was reduced by 71.9% (range: 8.5–98.7%), and cAMP by 95.1% (range: 91.5–98.8%) compared to controls). Expression of mRNA encoding Tg, TPO and TSHr were significantly inhibited . The majority of DE-71 added was found in the cell fraction. No cytotoxicity was found.DE-71 inhibited differentiated thyroid cell functions in a two phase response manner and a concentration-dependent inhibition of Tg and cAMP production, respectively, as well as expression of mRNA encoding Tg, TPO and TSHr. Our findings suggest an inhibiting effect of PBDEs on thyroid cells. Polybrominated diphenyl ethers (PBDEs) have been used as flame retardants to reduce flammability of electronic equipment, upholstery, textiles, plastics and building materials . Commercin vitro studies have also shown effects of PBDEs on the immune system , but rath PBDEs .in vitro results should be extrapolated to in vivo actions with caution. There are a limited number of target sites and toxicity pathways in cells in vitro compared to the amount of target sites in an organ/multi-organ system, with many interactions and feedback systems [In view of the above, our  systems . In addiThyrocytes leaked LDH at high DE-71 concentrations indicating a cytotoxic effect of DE-71. However, all LDH-levels from DE-71 stimulated cell supernatants were below the lowest positive Triton X-100 control, and the cells appeared viable by microscopy. Hence, we assumed that the applied concentrations of DE-71 were not toxic to thyrocytes. However, it is possible that DE-71 has cytotoxic effects at low levels, which might explain the tendency of a no-dose dependent effect at higher DE-71 concentrations. It is highly relevant for future studies to examine this issue e.g. by other methods.Although production of PBDEs is now prohibited and some studies have indicated stagnations in exposure levels and in human and animal sera , the resin vivo studies with an in vivo design are needed.DE-71 exerted a two-phase response of Tg and a concentration-dependent inhibition of cAMP production from human thyrocytes as well as inhibition of the expression of the genes encoding Tg, TSHr and TPO. Former human epidemiological studies found changed thyroid hormone levels following exposure to DE-71, while animal studies found reduced T4-concentrations. Our findings suggest an inhibiting effect of PBDEs on thyroid cells, which may explain the disturbances of thyroid homeostasis found by others. Further investigations regarding thyroid disturbances exerted by PBDEs in humans are needed. In addition, further experiments are needed at a lower concentration spectrum of DE-71 or individual PBDE congeners. To predict systemic toxicological effects,


The emergence of multi-drug resistant tuberculosis (MDR-TB) has become a major public health concern that threatens advances made in global TB control efforts. Though the problem is prevalent, it did not receive major attention to generate supportive evidence for the prevention and control of MDR-TB. The aim of this study was to identify predictors of MDR-TB in a national TB referral centre in Ethiopia.An unmatched, case-control study was conducted at St. Peter Hospital to assess risk factors associated with MDR-TB. The study included 103 culture proven, MDR-TB patients referred to the hospital during the study period (cases) and 103 randomly-selected TB patients with confirmed TB who turned negative after treatment (controls). Regressions analyses were used to determine the association of variables.The mean age among cases and controls was 30.5 (±9.26) and 34.73 (±11.28) years, respectively. The likelihood of having MDR-TB was 20.3 times higher among those who had a any previous history of TB treatment , 15.7 times higher among those who had TB more than once  compared those who had once, 6.8 times higher among those who had pulmonary TB  and 16.1 times higher for those who had experienced treatment with a Category II regimen . HIV infection was less common among cases than controls.This study concluded that special attention should be given to patients with a history of the following: TB more than once, presence of pulmonary TB, and used a Category II treatment regimen, as these were all determining factors for MDR-TB. Thus, this study urges the development and implementation of well-planned and integrated strategies for MDR-TB control and prevention in Ethiopia. The emergence of drug-resistant tuberculosis (TB) has become a serious public health threat in a number of countries . The larThe treatment of MDR-TB with second line drugs is long, complex process, and has a considerable rate of adverse effects , 5, makiDrug-resistant TB is considered to be a man-made problem resulting from the consequences of individual or combined factors related to the management of drug supply, patient management, and patient adherence. Behavioural and environmental factors, economic status, and poor infection control practices have also been identified as major contributing factors to the occurrence and spread of MDR-TB , 8, 9. NStudy design and area: a hospital-based, unmatched, case-control study design was carried out among cases (MDR-TB) and controls (TB) at St. Peter Hospital in Addis Ababa Ethiopia. St. Peter hospital is the largest TB referral center within the country. With several hundreds of patients welcomed for TB/HIV treatments, this facility has a long history of TB management. During the study period, St. Peter Hospital had about 363 MDR-TB patients and 121 TB patients being managed at inpatient and outpatient levels. St Peter Hospital has a strong collaborative partnership with the Ethiopian Health and Nutrition Research Institute (EHNRI), which hosts the TB National Reference Laboratory (NRL). Information obtained from the Health and Health Related Indicators revealed that a total of 35,002 TB and 6500 MDR-TB cases were registered within the country in the year 2013.Cases and controls: cases (MDR- TB patients) were all culture-proven to be resistant to both isoniazid and rifampicin, with or without resistance to other anti-TB drugs whereas, controls (non-MDR TB patients) were all TB patients who were either not resistant to anti-TB drugs or resistant to isoniazid or rifampicin. Both cases and controls were under treatment at St. Peter Hospital.Sample size determination and sampling: the required sample size was determined using EPI INFO software based on the assumption of a 26% of HIV exposure among controls (non-MDR-TB cases) [B cases) , 80% powB cases) , 1 to 1 Data collection: primary data were collected from cases and controls by face-to-face interview using pretested structured questionnaires, whereas secondary data were collected by reviewing patient medical charts/ registration logs for the corresponding study participants. MDR-TB trained and well-experienced nurses currently working in other health institutions conducted the subject interviews and reviewed the corresponding records. Information on level of income and other variables not recorded in the medical charts were obtained by means of interview. The questionnaire was translated into Amharic and back-translated into English to ensure phrasing accuracy and validity. Further information on history and laboratory test results were obtained by studying each patient’s medical records. During data collection, data collectors used the N-95 respiratory mask (covers both the mouth and nose and filters more than 95% of particles). Study subjects wore a surgical mask to reduce the risk of TB transmission.Data management and analysis: data were cleaned and entered using Epi Info version 3.5.1 and analyzed using SPSS version 20. Both descriptive and analytical statistical procedures were employed. Bivariate and multivariate logistic regression odds ratios, with a 95% confidence interval, were used to ascertain the association between the exposure variables and the outcome variable at the conventional 0.05 p-value level. Only exposure variables that were statistically significant variables at the bivariate level were entered into a multivariate logistic regression analysis to examine the main predictors of MDR-TB among the exposure variables. Non-significant variables were subsequently omitted in the modeling process. Once a satisfactory multivariate model was obtained, tests for interaction and confounding factors were conducted based on the likely combinations of the exposure variables. In addition, Pearson´s chi-square tests and odds ratio (OR) were used to assess the relationship between the exposure variables and MDR-TB.Ethical clearance: ethical clearance was obtained from the research ethics committee of Gambi University College. Written consent was also obtained from St. Peter Hospital research center. Verbal consent was asked from each study subject. Subjects were also informed about the purpose of the study and respectfully asked to give genuine information. Confidentiality of the collected data was also ensured. Study subjects were also advised strictly not to terminate their TB treatment and follow-up under any circumstances.Socio-demographic characteristics of study subjects: a total of 206 subjects participated in the study: 103 were cases and 103 were controls. Female study subjects constituted 52% of the cases and 38% of the controls. The mean age of respondents was 30.5 (+9.26) years among the case and 34.7 (+11.28) years among the control groups. With regard to self-reported monthly income, 42(40.8%) cases and 69 (67.0%) controls were earning less than or equal to $25. In terms of occupation, 89 (86.4%) cases and 63 (61.2%) controls were unemployed. The majority of the study subjects 141 (68.5%) were residing in Addis Ababa with their families 153 (74.3%) of cases stayed in a rented house compared to 104 (50.48%) controls. Bivariate analysis of socio- demographic characteristics showed that gender, average monthly income, occupational status, and residing place were significantly associated with MDR TB .Potential determinant factors for MDR-TB: the percentage of subjects with a history of TB treatment and pulmonary TB was greater for the cases than the controls. The percentage of subjects treated through the DOTS TB control strategy, imprisonment and with co-morbidity illness was similar between the groups. Results of bivariate analysis showed that the odds of developing MDR-TB were high among those who had previous history of TB, more than one episodes of TB, pulmonary TB, interrupted TB therapy, and been treated in category II. HIV co-infection and COPD were not associated with development of MDR-TB .Multivariate logistic analysis of determinant factors of MDR-TB: results of multiple logistic regression analysis showed that a history of more than one episode of TB, pulmonary TB, and treatment category remained significantly associated with MDR-TB. The odds of MDR-TB were higher among those who had a history of previous TB treatment and multiple episodes of TB. The odds of MDR-TB was 6.83 times higher among those who had pulmonary TB than those with extra pulmonary TB . However, HIV co-infection was not associated with development of MDR-TB. The observed association between occupational status, residence, and income with MDR-TB in the bivariate analysis was not evident in the logistic regression analysis when controlled for all other variables in the model .The emergence of drug-resistant TB, particularly MDR-TB, is threatening to destabilize global TB control in a number of countries, including Ethiopia . Either Previous treatment and episodes of TB: previous treatment has been widely recognized as the strongest risk factor for the development of MDR-TB , 16. UsuConsistent with the results of previous studies both in developed and developing countries including Ethiopia , 19, 20,Multiple episodes of TB: this study showed that having more than one TB episode significantly increased the risk of MDR-TB development. A similar study in Uganda also showed that multiple TB episodes and treatment failures were significantly associated with MDR-TB . PreviouBiological site of TB: this study also found that smear-positive pulmonary TB patients had a higher risk of developing MDR-TB. The odd of MDR-TB was found to be 6.83 times higher among those who have pulmonary TB than extra pulmonary TB. This may also be associated with the fact that patients with smear-positive pulmonary TB have a higher bacterial load and may not respond to treatment within a short period of time compared with patients who have a low bacterial load . It may Category II type of treatment: category II type of treatment is another significant variable that gives room for discussion. Multiple observational studies have examined outcomes among individuals receiving category II treatment and shown mixed results. Overall, success rates are in the 60% to 80% range , 26 withHIV and AIDS: the role of HIV infection as a risk factor for the development of drug-resistant TB is also not clear . AvailabSocio-demographic characteristics: the authors did not find any significant association between socio-demographic variables  and development of MDR-TB. However, the importance of socioeconomic determinants and other potential risk factors in the development of TB has been reiterated in numerous publications , 34. MorGenerally, in countries like Ethiopia, MDR-TB is becoming a challenge because of poor adherence to treatment and because patients stay in their communities for long periods of time without being diagnosed or seeking proper treatment. Even after diagnosis, there are few diagnostic and treatment facilities and lack of trained health professionals, and second line drugs; therefore, patients do not start treatment immediately. MDR-TB patients in rural and remote areas may not have access to health care services, may prefer consultation with traditional healers that are more readily available, and come late to health care centers. This delay potentially allows easy spread of the disease to a large number of individuals within a short time. Delayed recognition of drug resistance is one of the major factors contributing to MDR-TB .Limitations: all data on education, living and employment conditions, history of imprisonment, use of alcohol, and smoking history were reported by patients participating in the study and were not verified. The possibility of minor reporting errors and the potential of recall bias cannot be ruled out.This study showed that history of previous TB, more than one TB episode, pulmonary type of TB, and treatment with a Category II regimen were significantly associated with MDR-TB. Therefore, health professionals involved with TB management should give priority to culture and DST for patients who have any of these risk factors to control the spread of drug-resistant TB in Ethiopia. The Ministry has to include TB guideline. Existing TB control measures need to address such risk factors to significantly reduce the development of MDR-TB. More meticulous administration of anti-TB medication as well as more efficient follow-up are required to prevent development of MDR-TB in the country. Lack of a positive association between MDR-TB and HIV co-infection observed in this study does not mean that the collaboration between TB and HIV control programs to provide greater support to co-infected patients not be strengthen. Rather, countrywide studies should be done to further explore risk factors for the development of MDR-TB.Ethiopia is one of the high TB burden country and prone to MDR TB prevalence;MDR-TB is becoming a challenge because of poor adherence to treatment and because patients stay in their communities for long periods of time without being diagnosed or seeking proper treatment.Lack of a positive association between MDR-TB and HIV co-infection;History of previous TB, more than one TB episode, pulmonary type of TB, and treatment with a Category II regimen the most significantly associated with MDR-TB.


Background: Non-suicidal self-injury (NSSI) is commonly present in individuals with eating disorders (EDs) and is often employed as a maladaptive emotion regulation strategy to avoid or abate negative emotions. One of the most prevalent negative emotions experienced by self-injurers is anxiety; however, this emotion has not been extensively studied in this population. Thus, the aim of our study was to investigate the influence of anxiety on NSSI in patients with ED from two different dimensions: state anxiety and trait anxiety.Methods: The study comprised a total of 66 females: 12 ED patients with NSSI, 32 ED patients without a history of NSSI, and 22 healthy controls. State and trait anxiety were assessed by means of State-Trait Anxiety Inventory (STAI-S-T) and physiological data  were collected.Results: STAI-trait scores were significantly higher in ED patients with NSSI than ED patients without NSSI. Furthermore, when conducting logistic regression analyses higher STAI-trait scores were associated with NSSI in ED patients. However, no differences in STAI-state scores and HRV were found between ED patients with and without NSSI.Discussion: The present findings suggest that anxiety as a trait is associated with the use of maladaptive strategies  in ED patients. These results uphold the need to target trait anxiety in ED treatment in order to prevent possible NSSI behaviors. There is growing evidence indicating that patients with eating disorders (EDs) present difficulties expressing and regulating emotions . IncreasNSSI behaviors are described as deliberate self-induced harm actions on the surface of one’s body that usually cause bleeding, bruising, or pain  without suicidal intention . NotablyIn physiological terms, emotions can be framed in a body–mind interaction model where both current body state  and associated cognitions are coupled to embody the emotional state and subjective experience of the emotion, which in turn can lead to the resulting ER processes. A well-accepted way to assess autonomic nervous system state is through measuring the heart rate variability (HRV) index , a variaImportantly, anxiety is highly linked to ER capacity  and it hAs such, the main aims of the present study were the following: (1) to compare state, trait anxiety and in-task HRV (measured through a serious videogame in a biofeedback task that triggers the implementation of ER strategies) in three different groups: ED with NSSI (ED+NSSI), ED without NSSI (ED-NSSI), and healthy controls (HC), and (2) to test state-trait anxiety and in-task HRV as independent predictors of NSSI in ED+NSSI patients in a cross-sectional study. In-task HRV indices were obtained while participants were engaged in the Playmancer  biofeedbn = 19), 25% anorexia nervosa restrictive type , 12.5% anorexia nervosa binge-eating/purging type  and 3% of otherwise specified feeding or ED purging subtype . The ED+NSSI group was 50% BN (n = 6), 25% AN-R (n = 3), 17% binge ED  and 8% AN-B/P (n = 1). The prevalence of NSSI among the different ED diagnoses of our total sample was 100% in BED, 24% in BN, 20% in AN-B/P, 14% in AN-R and 0% in OSFED-P. The presence of ED were diagnosed by experienced psychologists and psychiatrists according to DSM-IV-TR criteria ; (2) Treasures of the Sea: In this swimming game, the player must find different hidden treasures while trying to regulate their oxygen consumption. Higher physiological activation causes an increase in the oxygen consumption, making the task more difficult to complete; and (3) Sign of the Magupta: In this relaxation game, the player has to complete different constellations of stars via slow, deep breathing techniques.The physiological variable employed in this study was in-task HRV. This measure was recorded while participants played a serious videogame named “Playmancer.” Serious games are games designed for a specific purpose that goes beyond that of pure entertainment. They are applied with an explicit goal in contexts such as healthcare, with educational, preventive, and/or therapeutic purposes . As descTn-1 and Tn (in seconds), then the momentary HR is (60/ΔT) where ΔT = Tn -Tn-1. HRV is the difference between momentary and average HR, averaged over the last eight beats to reduce the impact of breathing . HRV was acquired through the TMSi Mobi8 amplifier sensor system. Sensors are connected via wires to the Mobi8. The Mobi8 receives measurement data from sensors and sends them via BluetoothTM to the Playmancer desktop PC application where data is recorded. Each recording session lasts 26 min. Higher HRV reflects less physiological activation, whereas lower HRV indicates more physiological activation and, thus, increased anxiety levels  sensors are placed to measure the participants’ electrical heart activity. To do so, two skin electrodes are placed on the chest, as follows: one electrode (negative) is placed above the ninth-tenth rib, on the right side; the other electrode (positive) is also placed above the 9th to 10th rib, but on the left side. These sensors are the source for ECG lead, HR, and HRV. Thereby, from other biofeedback variables, this videogame program calculates the average HRV of the player during the session. HRV reflects the fluctuation in HR. In our videogame system, HRV is given as percentage relative to the average HR. If the last two beats found by the beat-to-beat algorithm are at times y levels . For morAll participants with EDs (ED+NSSI and ED-NSSI) were assessed with a clinical interview and completed the aforementioned questionnaires, as part of the assessment and diagnostic protocol of our Unit. All anxiety measures were completed within the same day, including questionnaires and the ER biofeedback task (Playmancer serious videogame). HC participants followed the same procedure: they first completed the diagnostic protocol and self-reported questionnaires followed by the Playmancer task. Although Playmancer treatment lasts 10 sessions (see d coefficient (|d| > 0.50 was considered moderate and |d| > 0.80 was considered high).Statistical analysis was carried out with STATA13.1 for Windows. Firstly, analysis of variance (ANOVA) adjusted for the covariates SCL-90R depression score and ED subtype compared the means for clinical variables and anxiety dimensions between the three independent groups . Regarding using the SCL-90R depression subscale as a covariable, it was included since previous studies have described that depressive state is a powerful risk factor for the presence of NSSI ; therefoSecondly, Pearson’s correlations described the relationships between the main variables of the study. The correlation matrix was stratified by diagnostic subtype  since the associations between the variables could be different depending on the diagnostic group. This correlation matrix was included with two main objectives: (a) to describe the pattern of relationships for the main variables of the study, and (b) to identify potential problems due to the presence of collinearity between variables that could affect the predictive logistic models.p > 0.05 was considered adequate fitting), the global predictive capacity with the Nagelkerke’s pseudo-R2 coefficient  and the global discriminative capacity with the area under the ROC curve (AUC).Thirdly, a logistic regression assessed the predictive capacity of STAI scales (state and trait) and HRV for the presence of the NSSI behavior (0 = absent versus 1 = present) in the ED samples. This model was programmed in two blocks/steps: (a) the first block included and set the covariates: patient’s age, BMI  comparing mean scores of clinical variables and anxiety dimensions between the three groups of the study, pairwise comparisons and effect size . Participants’ age, age of onset of the ED, duration of the ED, and BMI were equally distributed between groups, and only one mean difference in the moderate range was found: the pairwise comparison of the chronological age between the two ED groups . Considering anxiety measures, more relevant differences emerged. First, compared to both the ED-NSSI and ED+NSSI groups, HC registered lower mean scores in the STAI-state and STAI-trait scales, but no differences among groups were observed in in-task HRV indices. Second, ED+NSSI obtained higher means compared to the ED-NSSI group on the STAI-trait scale. ED severity  significantly and clinically differed comparing HC with both ED subtypes, while differences between ED-NSSI and ED+NSSI patients were non-significant.r = -0.345, p < 0.05); (b) the state and trait anxiety scores positively correlated with ED severity , and with depression ; and (c) state and trait anxiety positively inter-correlated . In the ED+NSSI group more associations and with a higher effect size emerged: (a) HRV index positively correlated with ED severity ; (b) and state anxiety correlated with age , BMI , ED severity  and depression ; and (c) trait anxiety correlated with and ED severity  and HRV . Finally, in HC: (a) HRV index negatively correlated with age  and positively with anxiety trait levels ; and (b) anxiety state correlated with depression levels ; and (c) anxiety state and trait levels positively correlated .The Pearson’s correlation-matrix for the main variables of the study, stratified by the diagnostic subtype, describes the pattern of associations in each group. In ED-NSSI patients: (a) the HRV index negatively correlated with the age  and in-task HRV indices for the presence of NSSI. Adjusted for the covariates patient’s age, BMI, SCL-90-R depression and ED subtype, the risk of presenting NSSI was increased for ED patients with higher STAI-trait scores. STAI-state scale scores and in-task HRV indices did not statistically contribute to the outcome. This model achieved adequate fit (p = 0.875) and high predictive and discriminative capacity .p values, than HC. Still, no significant differences are observed for the in-task HRV indices. Also and most importantly, results reveal that trait anxiety plays a pivotal role in the presence of NSSI behaviors among the ED patients.This study aimed to compare state/trait anxiety and in-task HRV indices (through a serious videogame in a biofeedback task that triggers the implementation of ER strategies) in three different samples: ED patients with NSSI, ED patients without NSSI and HC. We also sought to test state-trait anxiety and in-task HRV as independent predictors of NSSI in ED patients. Results show that ED patients have significantly higher trait anxiety scores and higher state anxiety scores with significant effect sizes, although without significant Individuals with ED have been widely described as a population with poor ER skills  as well Additionally, NSSI behaviors are highly prevalent among patients with disordered eating  and bothAdditionally, our logistic regression model analysis demonstrated that trait anxiety was the only variable that predicts NSSI behaviors among the ED patients in our sample. Considering that individuals with NSSI often use these behaviors as a way to manage negative emotions , it stanFinally, EDs have been associated with alterations in the autonomic nervous system ,b. In thTo our knowledge, few studies on ED patients with NSSI have exclusively focused on the role of anxiety in itself. In this regard, our study is the first that explores which dimension of anxiety (state or trait) is associated with NSSI behaviors in individuals with ED, including not only subjective (self-reported questionnaires) but also objective  measurements. Thus, this research contributes to conceptualize NSSI in ED and raises many questions worthy of further investigation.p < 0.05) or moderate to high effect sizes (|d| > 0.50) were considered as relevant in the work.Nevertheless, the generalization of the reported results is subject to certain limitations. First, based on previous studies  and giveIn conclusion, our results suggest that trait anxiety plays a larger role than state anxiety in the occurrence of NSSI in patients with ED. Anxious temperament could be a main factor in choosing maladaptive strategies  as a mechanism to regulate negative emotions. From a clinical perspective, these results uphold that special attention should be paid to those patients with ED who present high trait anxiety levels and that such patients should be provided with targeted ER interventions in order to prevent possible NSSI behaviors. Although the results of the present study are promising, further research through longitudinal studies is needed to corroborate these findings.CG-B, NM-B, IT-S, TS, RG, SJ-M, and FF-A have substantial contributions to the three following processes:(1)Conception or design of the work: CG-B, NM-B, IT-S, SJ-M, and FF-A.(2)Acquisition, analysis, or interpretation of data for the work: RG, CG-B, NM-B, IT-S, and FF-A.(3)Drafting the work or revising it critically for important intellectual content: CG-B, NM-B, IT-S, TS, RG, SJ-M, and FF-A.All authors express the agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.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.


Spatiotemporal analytics of multi-source Earth observation (EO) big data is a pre-condition for semantic content-based image retrieval (SCBIR). As a proof of concept, an innovative EO semantic querying (EO-SQ) subsystem was designed and prototypically implemented in series with an EO image understanding (EO-IU) subsystem. The EO-IU subsystem is automatically generating ESA Level 2 products  from optical satellite data. The EO-SQ subsystem comprises a graphical user interface (GUI) and an array database embedded in a client server model. In the array database, all EO images are stored as a space-time data cube together with their Level 2 products generated by the EO-IU subsystem. The GUI allows users to (a) develop a conceptual world model based on a graphically supported query pipeline as a combination of spatial and temporal operators and/or standard algorithms and (b) create, save and share within the client-server architecture complex semantic queries/decision rules, suitable for SCBIR and/or spatiotemporal EO image analytics, consistent with the conceptual world model. Vision (image understanding) is a cognitive process responsible for scene-from-image representation, ranging from local syntax of individual objects to global gist and spatial layout of objects in the 4D spatiotemporal scene domain, including multiple plausible semantic scene interpretations and even emotions  systems, including photographic image search engines such as the Google Image Search, support human–machine interaction through queries by metadata text information, by image-wide summary statistics or by either image, image–object or multi-object examples  domain, Earth observation (EO) CBIR systems support human–machine interaction through queries by either metadata text information or image-wide summary statistics  system is expected to cope with spatiotemporal semantic queries such as “retrieve all images in the database where a lake is not covered by clouds and larger than a certain area”. Such an SCBIR system must rely on image understanding as a pre-condition for SCBIR. This makes the SCBIR problem at least as difficult (or ill-posed) as vision. Since computer vision is still an open problem, this may explain why very few SCBIR system prototypes have been presented in the RS and computer vision literature  capabilities, where spatial information dominates colour information . Thus, the array database is able to perform internal optimizations, such as identifying the best access patterns using query plans, which can lead to a significant improvement in efficiency , is proposed as a proof of concept to work in series with an EO-IU subsystem, capable of multi-source EO big data spatiotemporal analytics as a pre-condition for SCBIR. The combined EO-SQ and EO-IU subsystems form an integrated EO image understanding and semantic querying (EO-IU&SQ) system. Within the EO-IU&SQ system design, the IQ system prototypical implementation in a distributed client-server architecture will be discussed in detail.In the remainder of this paper an innovative EO semantic querying (EO-SQ) system prototype, called The integrated EO-IU&SQ system architecture  atmospheric and topographic effect removal  is a well-known “prerequisite for physical model-based analysis of airborne and satellite sensor measurements in the optical domain”  EO-IUSs. To comply with the EO data Cal requirement, the proposed hybrid EO-IU subsystem employs a battery of sensor-specific EO image radiometric calibrators, for example, Landsat-5 to Landsat-8, MeteoSat, RapidEye, WorldView, etc., to transform digital numbers into physical units of measure, for example, top-of-atmosphere reflectance values.Sensory data calibration  terms by an mDMI set of planar shape indexes, such as area, characteristic scale, scale-invariant roundness, elongatedness, straightness of boundaries, simple connectivity and rectangularity , where the 4-tuple  is the location in space and time of the observation, and the attribute “theme” identifies the real-world phenomenon or object being observed  can be represented by objects/continuants and events/occurrence derived from the three spatiotemporal data types time series, coverage and trajectory. In EO applications, a real-world object can be (a) a periodic object whose identity is fixed while its attributes change with a cyclic behaviour, that is, the object’s identity comprises a given sequence of different states in a fixed time periodicity, for example, a corn agricultural field whose growth cycle is decided by agricultural practices specific to a geographic region spatiotemporal c region  or (b) pc region . An evenc region . It exiss Growe,  and 5.A graphical user interface (GUI) allows users to easily select existing semantic queries/decision rules or to intuitively generate new ones. Each query instantiation is associated with an information pair, specifically, spatiotemporal scene-domain knowledge (e.g. target LC classes) and one set of sensor-specific transfer functions required to map scene-domain knowledge into image-domain knowledge. A query pipeline is considered a combination of spatial and temporal operators and/or standard algorithms whose inputs are qualitative/categorical information layers (e.g. SCMs) or quantitative/numeric variables  available in the fact base. There are two types of semantic queries: (a) to accomplish SCBIR operations, where the fact base is investigated for EO image retrieval purposes, for example, retrieve EO images that are cloud-free across the selected geographic AOI and (b) to infer new information layers from the fact base, for example, detect flooded areas as a post-classification combination through time of available single-date SCMs.To accomplish efficient geospatial data querying and analysis through space and time within a user-defined AOI and a target time interval, a fact base stores multi-sensor multi-temporal EO images, for example, Landsat-5/7/8 and Sentinel-2A time-series, together with their information products, either numeric, such as spectral indexes, or categorical, such as SCMs. This is realized within an array database  with the same dimensionality. Each partition is then stored as separate file on the hard disk. Additionally, large data cubes can be distributed on multiple servers. This distributed system can be scaled horizontally using the capability of the Rasdaman database to deploy multiple worker units coordinated by a management unit. Associated metadata, for example, for the spatial reference, are stored in an object-relational PostgreSQL database.The main application tier is accessible over the internet using an Apache http webserver. It was written in python and developed in-house . The purEO big data require scalable and efficient processes to store, process and visualize EO images and products, but also affect quality assurance (QA). Besides automatic QA of sensory data, QA has to guarantee validity of a user’s semantic query/decision rule, whose input variables are images and products available in the fact base and whose functions are operators and processes available in the rule base. To enforce QA of decision rules, the EO-SQ subsystem delivers quality-ensuring metadata for each query, in agreement with the available 4D world model. Query-specific metadata are the possible target AOI, time interval and spatial, temporal, radiometric and spectral resolution of the imaging sensor, the name of the user who created the query and the time when the query was created. Query performance metrics are collected during each execution and updated regularly.The IQ’s GUI allows a user (1) to select the AOI and (2) the target time period and (3) to create or select via graphical elements the decision-rule pipeline for semantic querying the fact base. Once a decision rule is executed, the query results are shown in the image domain and/or as summary statistics. The following sections discuss four examples of semantic spatiotemporal queries instantiated by users through the IQ’s GUI.A snow cover analysis through time is conducted across an alpine area, specifically, the Hohe Tauern National Park in Austria , point 1high  – Land Cover Classification System (LCCS)  is found across the AOI, based on the available Level 2 SCMs. In the implemented IQ prototype, image retrieval queries turn back the matching image IDs and associated coverages which are accessible using the OGC Web Coverage Service (WCS). Other examples for such an AOI-based SCBIR are searching for images showing flooded areas/burnt areas/deforested areas or similar in the selected AOI.For a test area in Somalia, all 78 available Landsat 8 scenes between 2013 and September 2016 were pre-processed and fed into the database allowing queries to detect flood events and their recorded extent as well as a spatial aggregation of flooded areas as an indicator for flood-prone areas through time  plugged-in an innovative EO-IU&SQ system was proposed as a proof of concept. Capable of providing every EO image stored in the database with EO Level 2 products generated automatically (without user interaction) and in near real time, the EO-IU subsystem is preliminary to IQ. Within the proposed EO-IU&SQ system architecture, the EO-IU and EO-SQ subsystems, their algorithms and their implementations can be modified or replaced to accomplish SCBIR capabilities in operating mode.Further research and development will be focused on six areas: (1) increase the 4D spatiotemporal world model; (2) develop and implement an algebra to describe spatiotemporal data types and operations in a language-independent and formal way inspired to Reis Ferreira et al. ; (3) aug


The application of the sensor optical fibers in the areas of scientific instrumentation and industrial instrumentation is very attractive due to its numerous advantages. In the industry of civil engineering for example, quasi-distributed sensors made with optical fiber are used for reliable strain and temperature measurements. Here, a quasi-distributed sensor in the frequency domain is discussed. The sensor consists of a series of low-finesse Fabry-Perot interferometers where each Fabry-Perot interferometer acts as a local sensor. Fabry-Perot interferometers are formed by pairs of identical low reflective Bragg gratings imprinted in a single mode fiber. All interferometer sensors have different cavity length, provoking frequency-domain multiplexing. The optical signal represents the superposition of all interference patterns which can be decomposed using the Fourier transform. The frequency spectrum was analyzed and sensor’s properties were defined. Following that, a quasi-distributed sensor was numerically simulated. Our sensor simulation considers sensor properties, signal processing, noise system, and instrumentation. The numerical results show the behavior of resolution vs. signal-to-noise ratio. From our results, the Fabry-Perot sensor has high resolution and low resolution. Both resolutions are conceivable because the Fourier Domain Phase Analysis (FDPA) algorithm elaborates two evaluations of Bragg wavelength shift.  Bragg grating has a very particular peak in its reflection spectrum; the peak is centered at the Bragg wavelength λBG=2nΛ , where n system , and dirn system . Bragg gratings play an important role in fiber-optic sensor technology. Such sensors are very attractive for quasi-distributed sensing, employing only one optical fiber with many gratings printed along a fiber length. The conventional Bragg grating sensors use a broadband light source and a direct spectrometric detection technique. Their principal problem concerns the detection of relatively small shifts in the resonant wavelength of grating arrays exposed to strain or slow temperature changes. An additional application of Bragg gratings in sensor technology is to build interferometers within a single path fiber. In this case, Bragg gratings act as selective mirrors. The positions of gratings along the fiber length define the optical path difference. Frequency-division multiplexing, wavelength-division multiplexing, and time-division multiplexing can be implemented ,10,11,12The low-finesse Fabry-Perot interferometer has low reflectivity and it can be built with the end-faces of the lead-in/out and the target fibers , polymerThe twin-grating fiber optic sensor was used for the temperature measurement. The optical sensor acts as a low-finesse Fabry-Perot interferometer and it consists of two identical Bragg gratings separated by a short distance. The Fourier Domain Phase Analysis (FDPA) algorithm was used for its signal demodulation. The FDPA algorithm evaluates the Bragg wavelength shift at the frequency domain. The algorithm is based on the evaluation of the phase of the interference pattern produced by light reflected from both gratings and on the determination of the Bragg wavelength shift. The wavelength shift sensitivity was measured to 0.00985 nm/°C . This fiIn reference , a quasiTo our knowledge, the quasi-distributed sensor described in  does notWhen the quasi-distributed sensor does not have external perturbations, the optical signal itten as (2)RT, the frequency spectrum For all quasi-distributed sensors based on interferometers , the cavity length is a very important parameter since it defines the sensor characteristics. Their limits depend of instrumentation, local sensor characteristics, and signal demodulation. In the following sections, we determine minimum and maximum cavities where the low-finesse Fabry-Perot interferometer can be applied. The Fourier Domain Phase Analysis (FDPA) algorithm was developed for the twin-grating fiber optic sensor . This alThe condition (14) eliminates the overlapping between components, As It is not possible to have smaller cavities because the FDPA algorithm cannot demodulate the optical signal.The optical sensing system applies the direct spectroscopic detection . This teFrom Combining Equations (17)–(19), the maximum cavity length isEquation (20) indicates the maximum cavity length where OSA spectrometer can detect the optical signal. It is not possible to have bigger cavities because the instrumentation cannot detect the optical signal. Using Equations (16) and (20), the cavity length can be within the interval ofmth Fabry-Perot sensor. From In the quasi-distributed sensor, each low-finesse Fabry-Perot interferometer generates an interference pattern and then each pattern produces a channel in the frequency domain. The enveloped function produces the bandwidth In other words, the capacity of frequency-division multiplexing Finally, substituting the Equations (16) and (20) into Equation (22), we haveThis expression gives the limit for the multiplexing capacity within one wavelength channel.When the optical spectrometer analyzer instrument acquires the optical signal, the reflection spectrum is recorded as a series of digital samples. If a minimum and maximum wavelength within a working interval Since Finally, the number of samples isThe number of samples depends of optical system parameters.M filters. The FDPA algorithm was described in [M filters isThe demodulation is the complete signal processing algorithm developed for a quasi-distributed sensor based on the low-finesse Fabry-Perot interferometers. The complete processing algorithm combines the Fourier Domain Phase Analysis (FDPA) algorithm and a bank of ribed in  while thM filters is a series of rect functions where The bank filter of The digital demodulation consists of two phases: calibration and measurements. In the calibration, there are four steps: (1)  applied .Due to the presence of the noise in the original signal, the calculated phase will be fluctuating. To minimize the noise influence and provide the best estimate, the absolute phase is multiplied with a set of coefficients. Those coefficients act as an adaptive filter. 1/2. A Laptop Toshiba 45C was used, with 512 Mb of RAM memory and a velocity of 1.7 GHz.To test and compare our theoretical analysis, we performed a numerical simulation of a quasi-distributed sensor based on low-finesse Fabry-Perot interferometers. Three Fabry-Perot sensors were simulated. Their physical parameters can be observed in If the OSA spectrometer has From ferences ,38.1/2. If the demodulation error is denominated resolution, then low-finesse Fabry-Perot has two resolutions: low resolution and high resolution. Two resolutions are possible because the FDPA algorithm does two evaluations of the Bragg wavelength shift [th shift ,37. All Based on our theoretical analysis and numerical simulation, the quasi-distributed sensor would be built on the low-finesse Fabry-Perot interferometer. Our theoretical analysis optimizes its implementation. Instrumentation, local sensor properties, noise (Gaussian distribution), and signal processing were considered. The quasi-distributed sensor has good sensitivity and excellent resolution. All Fabry-Perot sensors have two resolutions: low resolution and high resolution See . Low resWhen the noise is big, signal-to-noise ratio (SNR) is small. In this case, the FDPA algorithm cannot evaluate the Bragg wavelength shift, causing the transition from high resolution to low resolution. This can be observed in From Equation (33), each low-finesse Fabry-Perot interferometer has its own thresholding value. This one depends on the cavity length, Bragg wavelength, and refraction index. For example: our Fabry-Perot sensors have next thresholding values, S1 → 0.033 nm, S2 → 0.016 nm, and S3 → 0.008 nm. The thresholding value is smaller if the cavity length is bigger. In the quasi-distributed sensor, ghost interferometers are eliminated if the separation between any two interferometers satisfies the expression Our future research work is in the following direction: wavelength-division multiplexing (WDM) can be implemented based on the low-finesse Fabry-Perot interferometers. The theoretical resolution is another direction. Technical applications are possible, for example: temperature, strain, humidity, force measurement, and oil detection. The quasi-distributed optical fiber sensor based on the low-finesse Fabry-Perot interferometer was studied theoretically and simulated numerically. Theory and simulation are in concordance. Our study considers quasi-distributed sensor properties, local sensor properties, signal processing, noise source, frequency-division multiplexing, and instrumentation. Our numerical results showed that all Fabry-Perot sensors have two resolutions: low resolution and high resolution. Low resolution is similar for all sensors, however, each Fabry-Perot sensor has its own high resolution. The thresholding value (from high resolution to low resolution) was defined in terms of low resolution and physical parameters. The quasi-distributed sensor has potential industrial applications, for example: structure monitoring, security system, humidity sensing, and level sensing.


Introduction: Despite improved efficacy of, and access to, combination antiretroviral therapy (cART), HIV-associated cognitive impairments remain prevalent in both children and adults. Neuropsychological tests that detect such impairment can help clinicians formulate effective treatment plans. The Kaufman Assessment Battery for Children (KABC), although developed and standardized in the United States, is used frequently in many different countries and cultural contexts to assess paediatric performance across various cognitive domains. This systematic review investigated the cross-cultural utility of the original KABC, and its 2nd edition (KABC-II), in detecting HIV-associated cognitive impairment in children and adolescents.Methods: We entered relevant keywords and MeSH terms into the PubMed, PsycInfo, EBSCOHost, ProQuest, and Scopus databases, with search limits set from 1983–2017. Two independent reviewers evaluated the retrieved abstracts and manuscripts. Studies eligible for inclusion in the review were those that (a) used the KABC/KABC-II to assess cognitive function in children/adolescents aged 2–18 years, (b) featured a definition of cognitive impairment (e.g. >2 SD below the mean) or compared the performance of HIV-infected and uninfected control groups, and (c) used a sample excluded from population on which the instruments were normed.Results and discussion: We identified nine studies  to comprise the review’s sample. All studies detected cognitive impairment in HIV-infected children, including those who were cART-naïve or who were cART treated and clinically stable. KABC/KABC-II subtests assessing simultaneous processing appeared most sensitive. Evaluation of the methodological quality of the selected studies by two independent reviews suggested that shortcomings included reporting and selection biases.Conclusions: This systematic review provides evidence for the cross-cultural utility of the KABC/KABC-II, particularly the simultaneous processing subtests, in detecting cognitive impairment in HIV-infected children . Although the current results suggest there is justification for using the KABC/KABC-II primarily in East Africa, further investigation is required to explore the instrument’s utility in other HIV-prevalent regions of the globe. Recent global estimates suggest that 3.2 million children under 15 years of age are living with HIV. Ninety-one per cent (more than 2.9 million) of those children reside in Sub-Saharan Africa .Research investigating the cognitive development of African, Indian, Asian, European, and South American HIV-infected children has reported a high (up to 90%) prevalence of cognitive and neurodevelopmental delays –11. DespClinicians weighing the appropriateness of a cognitive measure for their particular context must consider whether a test developed and standardized on a specific population continues to measure the same construct when applied in a different setting ,16. MeasThe Kaufman Assessment Battery for Children (KABC), and its revised second edition, the KABC-II, are measures of intellectual functioning, developed and standardized in the United States, with strong psychometric characteristics ,25. As FBoth the KABC and KABC-II have been used across the globe to assess cognitive functioning comprehensively ,30. TheiDespite the KABC/KABC-II’s popularity, and its widespread use in regions where HIV is highly prevalent (e.g. sub-Saharan Africa), no study has formally evaluated whether these instruments are suited to identify cognitive impairment, across distinct and independent domains, in HIV-infected children.  Hence, this systematic review aimed to determine whether the KABC/KABC-II identifies HIV-associated cognitive impairment in children who reside in cultural contexts outside of that in which the instrument was developed, standardized, and validated.We used electronic databases  to search for published and unpublished studies, posters, PowerPoints, and abstracts. The search limits were set from 1983 (the year the KABC was published) to February 2017. Keywords were MeSH and non-MeSH search terms covering HIV/AIDS, children, HIV medication (e.g. HAART), KABC, and cognitive development/functioning . The search identified 38 studies. We then conducted a manual search of the references from the identified articles and published conference proceedings to ensure all relevant articles were identified. This arm of the search strategy yielded an additional 28 articles.Two authors (KvW and TvdW) screened abstracts (and full text if needed) to determine inclusion status. Disagreements were resolved by discussion. We included studies that met the following criteria: (1) Used a sample that comprised HIV-infected children ; (2) used a sample consisting of children between the ages of 2 and 18 years, inclusive; (3) used (a subtest of) the KABC/KABC-II; (4) provided a method to indicate cognitive impairment in the HIV-infected sample ; and (5) used a sample excluded from the original normative data on which the KABC was standardized .There were no exclusion criteria based on language or format of publication. All study designs were included, with the exception of reviews. The latter were used to search for any other studies that could be included. If a full text was unavailable online, we emailed the authors and followed up weekly. If there was no response after 3 months, the article was considered excluded/missing data. Items coded as “not specified” (NS) indicates that we did not receive a response .Nine studies  fulfilled the inclusion criteria and were reviewed –47. Two We set out to determine, via systematic review, whether a popular, widely used, and psychometrically sound cognitive test battery, the Kaufman Assessment Battery for Children, identifies HIV-associated cognitive impairment in children who reside in cultural contexts outside of that in which the instrument was developed, standardized, and validated.As M for HIV-infected participants = 7.9 years; M for controls, across the seven studies that reported this statistic, was 7.4 years). Regarding the sex distribution across the comparison groups, in the six studies that reported this statistic 369 of the 720 HIV-infected participants (51%) were female, as were 473 of the 842 uninfected controls (56%).As Four studies ,41,43,44Overall, our review suggests that the KABC/KABC-II can be used successfully across different countries and cultural contexts to identify cognitive impairment in HIV-infected children and adolescents. Hence, although there is no current consensus regarding whether adult diagnostic criteria for HIV-associated neurocognitive disorders (HAND) might be applied to children and adolescents , it appeIn each of the reviewed studies, the KABC/KABC-II successfully identified cognitive impairment in HIV-infected children, either relative to uninfected counterparts or to their own baseline. Eight of the nine studies used local normative data, or a local reference group, against which to compare cognitive performance of HIV-infected children. These studies identified impairment at the group level . Gosling et al.  reportedAcross all studies, there was no single KABC/KABC-II subtest or scale on which HIV-infected children performed consistently poorly. Hence, this review suggests that no single subtest offers the potential to be adapted into a stand-alone screening tool. This conclusion is consistent with research indicating that numerous independent cognitive domains are affected in HIV-infected children ,53. ApprOur review also demonstrates that the KABC/KABC-II is sensitive to cognitive impairment in HIV-infected children, with and without cART, when compared to controls. This finding is promising because a growing body of research demonstrates that subtle cognitive impairments may persist even in HIV-infected children who are well controlled on cART –56.To improve the culture-fairness of the instrument, researchers across the reviewed studies typically implemented a three-part strategy: (1) They translated it into the local language; (2) they excluded either or both the Knowledge and Achievement components ; and (3) where local normative data were unavailable, they applied either conventional cutoffs (1 SD below the standardization sample mean), or stricter cutoffs , to classify impairment, depending on whether standardization sample data were judged applicable or not.Finally, we identified an interesting trend in the reviewed studies: The KABC/KABC-II was not always administered by a registered or licensed clinical psychologist or neuropsychologist. Rather, administration fell to local teachers, research assistants, or psychometrists. Although not all of the manuscripts make it clear, perusal of the author lists and acknowledgements suggests that these test administrators all operated under appropriate supervision. In light of the scarcity of highly-trained professionals in low- and middle-income countries where HIV is prevalent ,57, it iThe strength of the conclusions one might draw from this systematic review are limited by the characteristics of the reviewed studies and by the nature of the reviewed instrument. We therefore offer the following caveats.First, although authors of the included studies noted that they had translated the instrument from English into the local language, most did not describe their translation procedures in detail. So, for example, it is unknown whether rigorous back-translations procedures were in place, and whether community members were consulted about idiomatic aspects of the translation. The absence of this information raises questions around linguistic equivalence of the various translated versions of the KABC/KABC-II.Second, no KABC/KABC-II subtest measures the cognitive construct of information processing speed directly. This limits the value of the instrument in assessment of HIV-infected children in different countries and cultural contexts, given that (a) strong recent evidence suggests that processing speed is an important component of HANI , and (b)Third, HIV-1 subtype distribution is not consistent across the globe , and so The findings of this review suggest that the KABC/KABC-II has cross-cultural utility. It appears that the instrument can provide comprehensive information regarding cognitive impairment in HIV-infected children, regardless of the country or cultural context in which it is administered. The instrument is especially useful because it can be administered by laypersons, and because it is sensitive enough to identify impairment in children who are otherwise well managed . However, the review also highlights the need for more cross-cultural validity studies of the KABC/KABC-II, and, particularly, for research investigating whether the instrument is sensitive to clade-specific variations in cognitive impairment. In such future research , we suggest that the adaptation procedures described in the studies reviewed here be used as a baseline to ensure culture-fair testing. We further recommend that, when adapting test material, researchers apply the standard procedures set out by the International Test Commission ,62, and