Current grounding theories propose that sensory-motor brain systems are not only modulated by the comprehension of concrete but also partly of abstract language. In order to investigate whether concrete or abstract language elicits similar or distinct brain activity, neuronal synchronization patterns were investigated by means of long-range EEG coherence analysis. Participants performed a semantic judgment task with concrete and abstract sentences. EEG coherence between distant electrodes was analyzed in various frequencies before and during sentence processing using a bivariate AR-model with time-varying parameters. The theta frequency band (3–7 Hz) reflected common and different synchronization networks related to working memory processes and memory-related lexico-semantic retrieval during processing of both sentence types. In contrast, the beta1 band (13–18 Hz) showed prominent differences between both sentence types, whereby concrete sentences were associated with higher coherence implicating a more widespread range and intensity of mental simulation processes. The gamma band (35–40 Hz) reflected the sentences' congruency and indicated the more difficult integration of incongruent final nouns into the sentence context. Most importantly, findings support the notion that different cognitive operations during sentence processing are associated with multiple brain oscillations. In many of these so-called “grounding theories” the body is the focus of interest but besides this, the situated nature of actions, the importance of the experience with the environment and cultural influences are often emphasized too  with German as their native language participated in the EEG-experiment. They all had inconspicuous audiograms of both ears and reported no history of any significant neurological or psychiatric illness. All of the participants were right-handed, gave written informed consent prior to the measurements and were paid for their participation. Another 101 students participated in the various ratings and the reaction time study described in sections Stimuli and Reaction Time Data.Twenty-nine monolingual students  aged 19–28 years .The critical material analyzed in this study consisted of 100 German sentences randomly presented in four blocks. Half of the critical sentences were constructed as concrete, the other half as abstract sentences. The criteria for controlling concreteness/abstractness were as follows: At first, nouns and verbs used for sentence construction were matched on imageability and concrete-/abstractness in order to use only very concrete and very abstract words for the construction of the sentences. All nouns were matched on imageability and concreteness/abstractness according to studies of Baschek et al.  and OffeFurther, verbs, which were previously rated on a 7-point scale on imageability and concreteness/abstractness . In addition, the average number of words per sentence, the percentage of verbs used and the percentage of one−, two−, and three-syllabic words were controlled. This was undertaken to control for potential cognitive-linguistic differences between concrete and abstract sentences besides their concreteness. Univariate ANOVAs did not reveal any difference between the average number of words for concrete (10.83 ± 1.83) and abstract (10.83 ± 1.60) sentences. The mean amount of syllables also did not differ between concrete (20.5 ± 3.28) and abstract sentences (20.5 ± 3.53).t-test, 2p = 0.26). These results allow us to construct incongruent sentences by semantically violating half of the concrete and abstract sentences with the final noun. No word generated by any of the participants was used for the construction of the incongruent sentences, thus effectively making the cloze values for the incongruent sentences zero.Further, the cloze-probability for concrete and abstract sentences was equalized. Cloze probability was assessed by a separate group of 32 participants who listened to the sentences without the final noun and filled in what they thought was the most appropriate final word for each sentence. All sentences had a high cloze probability of at least 80% and the concrete and abstract sentences did not differ in cloze probability .Twenty-five concrete congruent sentences: e.g., “Sie sah gern Tiere und darum ging sie in den Zoo.” .Twenty-five concrete incongruent sentences: e.g., “Sie sah gern Tiere und darum ging sie in den Schrank.” .Twenty-five abstract congruent sentences: e.g., “Sie hatte keine Zeit und darum setzte sie ihm eine Frist.” .Twenty-five abstract incongruent sentences: e.g., “Sie hatte keine Zeit und darum setzte sie ihm eine Gunst.”  = 710.84; p = 0.000], imageability  and congruency . No interaction between any of the factors was found. As expected, post-hoc t-tests revealed significantly higher concreteness and imagery ratings for the concrete sentences. Congruent sentences were rated as being more concrete and imaginable than incongruent ones . Concreteness and imagery ratings were highly correlated  which prompted us to use only the concreteness score for further behavioral and EEG analyses. Thus, very concrete and abstract sentences were obtained and used for further analyses.Univariate ANOVAs were carried out on the rating scores revealing significant main effects for concreteness , congruence , interaction }.The final sentence stimuli were spoken by a professional male speaker (radio announcer) and recorded in a sound studio (Bielefeld University). Stimuli were digitized at 44.1 kHz, 16 bit and had a mean articulatory duration of 3902 ± 625 ms . Most importantly, ANOVA revealed no main effects or interactions for concreteness and congruence on articulatory sentence length {concreteness , congruence  and a significant interaction between congruence and concreteness  on the reaction time both for subject and item analyses. Post-hoc paired t-tests revealed that reaction time to concrete compared with abstract sentences is faster for the congruent condition only . Thus, the concreteness effect was only shown for the congruent condition, whereas in the incongruent condition the reaction time to concrete and abstract sentences did not differ significantly. One explanation concerns the overall lower concreteness of the concrete incongruent sentences suggesting that the semantic implausibility of the sentences cancelled out the concreteness's effect on the reaction time and the error rate. Holcomb et al.  = 26.95; p = 0.000; F2 = 8.29; p = 0.005], of congruence  and a significant interaction between congruence and concreteness  on the error rate. As expected, fewer errors were made during the processing of concrete sentences. However, there was also an effect of congruence on the error rate showing overall fewer errors in the incongruent condition. To summarize, abstract congruent sentences elicited slower reaction times and more errors than concrete ones and reaction time to incongruent sentences was slower than to congruent ones but incongruent sentences elicited fewer errors. Thus, participants were in need of longer decision times for the incongruent sentences but also made fewer errors. These results indicate that the participants' decision processes and task-dependent strategies heavily influence the reaction time.ANOVAs revealed a significant main effect of concreteness [b et al.  found a We applied multivariate analyses to the EEG coherence data of 29 subjects in order to test the main factors and their interactions. Repeated measures ANOVAs were calculated for EEG coherence as a dependent variable with the within-subject factors concreteness  and congruence  and the between-subject factors frequency  and topography  for the three relevant sentence intervals . The processing of concrete sentences correlated with a significantly higher mean coherence than abstract sentences. Specifically, the theta and beta1 frequency bands showed this effect (concreteness × frequency interaction), particularly at posterior sites (concreteness × topo interaction).A main effect of To determine which electrode pairs show coherence changes during the processing of concrete or abstract sentences in interval 2, paired Wilcoxon-tests were applied to all possible electrode pairs for theta and beta1 . Test results were converted to error probabilities and presented as lines between the electrodes on a schematic drawing of the brain Figure . Normallp = 0.05). Coherence changes between similar electrode pairs for both concrete and abstract sentences are mainly found between temporal, parietal and frontal electrodes as well as central electrodes. In particular, right-hemispheric and interhemispheric electrode pairs exhibit these coherence changes . Analogously as in interval 2, concrete sentences showed higher coherence than abstract ones during the processing of the final noun. However, differences were significant only for the incongruent sentences, not for the congruent ones. The differences were significant at anterior and posterior electrode pairs Figure .During the sentence interval before the final noun  there was a strong effect of concreteness on the EEG coherence and, as expected, no congruence effect, since during this interval participants did not know whether a sentence would end congruently or not. In general, concrete sentences elicited significantly more and higher coherence changes than abstract sentences during this sentence interval compared to a pre-sentence baseline. This result was most significant in the theta and beta1 frequency band at posterior sites but was also found at frontal and temporal sites determined by the single coherence analysis.to wipe) show increased brain activity in the inferior parietal lobe compared to verbs denoting a more general motor program  and abstract verbs (to ignore)  vary with episodic and/or working memory processes  and world-knowledge related processes (at anterior sites; Hagoort et al., In a recent study, it has been shown that gamma power increased only during a violation of world-knowledge in sentences, whereas theta power increased for semantic violation (Hagoort et al., To summarize, our findings on long-range EEG coherence changes indicate that processing of concrete and abstract sentences relies both on common and different neuronal networks. This supports the view proposed by grounding theories, that sensory-motor systems are not only modulated by the comprehension of concrete but also partly of abstract language (e.g., Glenberg et al., The difference of concrete and abstract language was associated with EEG coherence changes within different frequency bands. Whereas the theta band reflected an increased working memory load during sentence processing, in the beta1 band EEG activity was possibly related to different mental simulation processes for concrete and abstract sentences. Activity in the gamma2 band came along with semantic binding processes at the final noun, and the gamma1 band reflected an interaction between concreteness and congruence.There is no doubt that EEG rhythms are functionally important for cognitive-linguistic processing, but a direct relation between a single frequency and a single cognitive component during language comprehension seems unrealistic (Pulvermueller, 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 investigate whether a combination of a selected but limited number of anthropometric measurements predicts visceral adipose tissue (VAT) better than other anthropometric measurements, without resort to medical imaging.Abdominal anthropometric measurements are total abdominal adipose tissue indicators and global measures of VAT and SAAT . Therefore, subtracting the anthropometric measurement the more correlated possible with SAAT while being the least correlated possible with VAT, from the most correlated abdominal anthropometric measurement with VAT while being highly correlated with TAAT, may better predict VAT.−2. Anthropometric and abdominal adipose tissues data by computed tomography (CT-Scan) were available in 253 patients (18-78 years)  and used to develop the anthropometric VAT prediction models.BMI participants' range was from 16.3 to 52.9 kg mR2 = 0.836. Men: VAT = 6 × Waist C − 4.41 × proximal thigh C + 1.19 × Age − 213.65; R2 = 0.803) than the best single anthropometric measurement or the association of two anthropometric measurements highly correlated with VAT. Both multivariate models showed no collinearity problem. Selected models demonstrate high sensitivity . Similar predictive abilities were observed in the validation sample . Bland and Altman method showed no systematic estimation error of VAT.Subtraction of proximal thigh circumference from waist circumference, adjusted to age and/or BMI, predicts better VAT . Visceral adipose tissue (VAT) excess is a very important independent predictor, related to body composition, of metabolic syndrome, cardiovascular disease, and mortality independent of BMI -5. CompuOur aim was to investigate and validate whether association of a limited but selected number of anthropometric measurements should better predict VAT, without resort to medical imaging.Abdominal anthropometric measurements being total abdominal adipose tissue (TAAT) indicators and global measures of VAT and SAAT taken together, we hypothesized that subtracting the anthropometric measurement, the more correlated possible with SAAT while being the least correlated possible with VAT, from the most correlated abdominal anthropometric measurement with VAT while being highly correlated with TAAT, may differentiate VAT and SAAT and better predict VAT.Therefore, we aimed to:Identify distinctive anthropometric measurements of VAT and SAAT:- the abdominal anthropometric measurement the most correlated with VAT, while being highly correlated with TAAT;- the anthropometric measurement the more correlated possible with SAAT, while being the least correlated possible with VAT;Combine these measurements, according to the hypothesis, to develop the most accurate anthropometric VAT prediction in the form of the model VAT = TAAT-SAAT;Validate the concept VAT = TAAT-SAAT by DXA;Validate our anthropometric developed models in a 2nd patient's sample.n = 114, first year of the study, development of VAT anthropometric models in relation to CT-scan) and Sample 2 . DXA performed in sample 1 were useful to validate the “VAT = TAAT-SAAT” anthropometric concept. Abdominal anthropometric circumferences and diameters, limb circumferences and skinfolds thickness were evaluated within the framework of our study for each participant. BMI and age ranges were from 16.32 to 52.94 kg m−2, respectively from 18 to 78 years. The study was approved by the local committee for ethics. Informed consent was obtained from each participant.For medical reasons, body composition of 253 patients  from the Department of Endocrinology, Metabolism and Nutrition  has been assessed. Participants were metabolically settled type 1 diabetics or obese subjects but were free of diseases liable to affect body composition or influence anthropometric measures . Total and subcutaneous abdominal adipose tissues and visceral adipose tissue were available by CT-Scan for all of the patients: Sample 1 (2) were calculated with the image analysis software linked to the CT-scan equipment. To distinguish adipose tissue from muscle and bone tissues, the fixed CT-Scan attenuation range from −190 to −30 Hounsfield Units for adipose tissue was applied, as defined by Sjöstrom etal. , as previously described by Smith et al. . Patientom etal.  and Kvisom etal. .All adipose tissue pixels inside the line tracing the skin abdominal circumference were regarded as TAAT, as showed first . All adiIn addition to weight and stature, 24 anthropometric measurements were performed in all patients by a single investigator (H.S.) according to Lohmann , within Waist circumference (Waist C) was measured midway between the lower rib and the iliac crest on the midaxillary line; and at the umbilicus. The measurement of abdominal diameters was made at the same level (the approximate location was between the 4th and the 5th lumbar vertebrae). The sagittal abdominal diameter (SAD) was measured with two different types of portable calliper: straight and curved blade callipers. The transversal abdominal diameter (TAD) was measured with a straight blade calliper. All abdominal measurements were performed with the subjects standing and supine, except the curved blade calliper SAD (standing). Measurements were made at various levels to test which way of measurement is more associated with VAT. Abdominal, pectoral and subscapular skinfolds thicknesses were assessed with the thickness caliper.Thigh circumferences were measured at three levels: proximal ,  and . Hip , calf , ankle , arm , forearm , elbow  and wrist  circumferences were also performed. Tricipital, bicipital, supra-iliac, and thigh skinfolds thickness were assessed with the thickness caliper.Body mass index (BMI) and waist-to-hip ratio (WHR) were calculated.Total body fat and regional body fat measurements were measured by DXA, with the Hologic®QDR4500W densitometer:- Six conventional predefined fat areas: head, trunk (trunk fat), arms (left arm fat and right arm fat) and legs (left leg fat and right leg fat);- Six specific fat areas manually defined from skeletal landmarks and using standard cut lines, with the purpose to correlate either with visceral fat or with subcutaneous fat: 1. [abdominal + pelvic fat] area delineated by a horizontal line linking the last thoracic rib lower borders through the rachis; two vertical lines linking the shoulders (at the glenoid fossa) with the thighs and two angled lines bisecting the femoral necks below the pelvis. 2. [Thigh Fat] area delineated by the angled line bisecting the femoral neck below the pelvis, a vertical line lateral to the thigh and going on until the knee, a horizontal line going through the knee and a vertical line linking the knee with the pelvis. 3. [Central Fat] area delineated by the horizontal line linking the last thoracic rib lower borders through the rachis; a horizontal line above the pelvis (just above the crest of the ilium) and two vertical lines linking these boundaries at the level of the external edge of the rib cage. 4. [Intra-Pelvic Fat] area delineated by the triangle linking the posterior superior iliac spines with the pubis symphis. 5. The [central + intra-pelvic fat] area was defined as the sum of the [central fat] and the [intra-pelvic fat] areas. 6. The [peripheral abdominal fat] area was obtained by subtracting the [central + intra-pelvic fat] area from the [abdominal + pelvic fat] area.n = 114, first year of the study) was analyzed to identify distinctive anthropometric measurements of VAT and SAAT and to develop anthropometric VAT models against CT-scan (gold standard). Pearson correlation coefficients (R) were established between anthropometry and CT-Scan to identify distinctive anthropometric measurements of VAT and SAAT . Multiple linear regressions were developed with VAT as a dependent variable and a maximum of two anthropometric parameters as independent variables, adjusted to age, gender, weight and/or BMI. According to our hypothesis “VAT = TAAT-SAAT,” we associated, as independent variables to predict VAT, the anthropometric measurement the more correlated possible with SAAT while being the least correlated possible with VAT, with the abdominal anthropometric measurement the more correlated possible with VAT and highly associated to TAAT. R, R2, and SEE  were calculated. To be included in models, each variable required firstly not be collinear with another and secondly to significantly contribute . We also performed a no controlled stepwise regressions to verify this empirical parameters selection: a forward selection, starting with no variables in the model, trying out the variables one by one and including them if they are statistically significant.Statistical analysis was performed using SPSS® for Windows Version 17.0. All descriptive data were expressed as mean ± sd. Data of the two volunteers groups were analyzed. The first set of data . We tested the possible pair of combinations of the three single more correlated anthropometric variables with VAAT. We evaluated variances explained par models and collinearity in each of them: 1. serious collinearity problems if condition index > 30; 2. possible collinearity if condition index > 15; 3.collinearity if two or more variables with a variance proportion ≥0.5, variance inflation factor (VIF) ≥4.0 and tolerance <0.25 .2 .The same procedure was applied with conventional and specific DXA fat areas to validate the anthropometric concept. Finally, we tested, in the sample 1, the equations published in the literature (Intra- and inter observer (s) precision of anthropometric measurements in the selected models were assessed . Apart from the principal investigator, three others observers took part in the inter observers variability assessment, amongst 30 participants.”n = 139, second year of the study) was a sample to test our anthropometric models, against CT-scan .The second set of data  are presented in The characteristics of the 253 volunteers , measured with a curved blade caliper, appears to be the best single anthropometric measurement for the assessment of VAT in both genders, Waist C (measured midway between the lower rib and the iliac crest on the midaxillary line) being nearly as powerful. Both SAD and Waist C are highly correlated with TAAT but higher correlation is observed with Waist C.Proximal thigh circumference  is the anthropometric measurement the more correlated possible with SAAT, while being the least correlated possible with VATProximal thigh C is also clearly less correlated with TAAT than waist.R: Women = 0.72; Men = 0.74), whereas Waist C is rather correlated with TAAT  combined with age and/or BMI provide a good prediction of VAT . Model iR2 = 0.836; SEE = 36.88; P < 10−4. Waist C: rpartial = 0.313; P = 0.009. Proximal thigh C: rpartial = −0.463; P < 10−4. Age: rpartial = 0.433; P < 10−4. BMI: rpartial = 0.355; P = 0.003]In women: VAT = 2.15 × Waist C − 3.63 × proximal thigh C + 1.46 × age + 6.22 × BMI − 92.713 . BMI's rpartial is no significant in men, but adding BMI improves R2 in the model (0.817) (Annex B). Both selected models showed no collinearity problem .In men: VAT = 6 × Waist C − 4.41 × proximal thigh C + 1.19 × Age − 213.65 ; ; . In men: ; ; . 2.2. Each model had a condition index > 15, a variance proportion > 0.5, a VIF > 4, tolerance < 0.25, therefore a collinearity problem.Combination of the two anthropometric measurements the more correlated with VAT: 2.1. Variances explained par models, in women:  in the VAT assessment sample . The Bland/Altman limits of agreement  associated with age and BMI and without resorting to CT-scan, MRI or DXA. Despite the fact that age and BMI considerably influence body composition, and are usually collected in most epidemiological studies or in clinics, they are not frequently used in anthropometric models designed for the assessment of body composition. This concept implied the subtraction of the most correlated anthropometric measurement with SAAT, while being the least correlated possible with VAT (Thigh C), from the abdominal anthropometric measurement the most correlated to VAT while being highly correlated with TAAT (Waist C).R = 0.914; R2 = 0.836; SEE = 36.88; P < 10−4); respectively 80.3% in men  . We didn't include BMI in men because of its no significant contribution (P > 0.05), even if R2Model increased (R2 = 0.817). Indeed, our VAT anthropometric prediction models design was based on the fact that to be included in the models, variables have to be significant and no collinear.The modeling of these data in our study population explains 83.6 % of the variance of VAT in women  , R2, SEE, and Bland/Altman representations significant improvement, together with the absence of collinearity, the significant partial correlation, and hence the validity of our hypothesis, justify in our opinion, the little complexity added by performing an additional measurement in clinical or research settings. Moreover, in the clinical setting, many clinicians involved in weight management and metabolic care routinely perform the measurement of two anthropometric measurements (i.e. waist circumference and hip circumference), so that measuring both waist circumference and thigh circumference should not be off-putting so much. Furthermore, the measurement of thigh circumference is quite easy to perform. Associating two anthropometric abdominal measurements seems to be less optimal. Our anthropometric models showed a high level of accuracy to predict VAT, in the assessment and validation samples. VAT is a very important and independent predictor, related to body composition, of cardiovascular diseases ; and the size of our validation sample is more substantial. Moreover, to assess the accuracy of VAT models, we have used the Bland and Altman method   who obsen method  and 2, u007  who n method . AlthougHowever, our anthropometric model might not be optimal and could be refined by another level of CT-Scan slice, particularly between the third and fourth lumbar vertebra in men , approxiR2: 0.91), in a small postmenopausal women sample. Treuth etal. (R2 = 0.81) in a similar sample. The authors then divided the trunk into pelvic fat, upper and lower trunk but no specific section improved the precision of VAT estimation in women (R: 0.83-0.9). In another small group of obese men and women, Kamel et al. . In an elderly group, Snijder etal.  and cardiovascular morbi-mortality on the other hand, was described and explained by the health protective effect assigned to a larger Thigh C or Hip C for a given Waist C . This heIn conclusion, our anthropometric models, simple and inexpensive, improve substantially VAT prediction in Europides (in the South of France) probably because they provide an independent estimation of VAT and SAAT, helping to differentiate abdominal fat compartments, in a large range of age and BMI. These models are extremely useful for research and clinical practice. Otherwise, in other populations, our models and/or concept should indeed be re-validated against the gold standard methods before use  It will consequently be interesting to assess, as part of future studies, the ability of our models to predict metabolic and cardiovascular morbidity and mortality.


Systematic Reviews (SRs) are an essential part of evidence-based medicine, providing support for clinical practice and policy on a wide range of medical topics. However, producing SRs is resource-intensive, and progress in the research they review leads to SRs becoming outdated, requiring updates. Although the question of how and when to update SRs has been studied, the best method for determining when to update is still unclear, necessitating further research.In this work we study the potential impact of a machine learning-based automated system for providing alerts when new publications become available within an SR topic. Some of these new publications are especially important, as they report findings that are more likely to initiate a review update. To this end, we have designed a classification algorithm to identify articles that are likely to be included in an SR update, along with an annotation scheme designed to identify the most important publications in a topic area. Using an SR database containing over 70,000 articles, we annotated articles from 9 topics that had received an update during the study period. The algorithm was then evaluated in terms of the overall correct and incorrect alert rate for publications meeting the topic inclusion criteria, as well as in terms of its ability to identify important, update-motivating publications in a topic area.Our initial approach, based on our previous work in topic-specific SR publication classification, identifies over 70% of the most important new publications, while maintaining a low overall alert rate.We performed an initial analysis of the opportunities and challenges in aiding the SR update planning process with an informatics-based machine learning approach. Alerts could be a useful tool in the planning, scheduling, and allocation of resources for SR updates, providing an improvement in timeliness and coverage for the large number of medical topics needing SRs. While the performance of this initial method is not perfect, it could be a useful supplement to current approaches to scheduling an SR update. Approaches specifically targeting the types of important publications identified by this work are likely to improve results. Evidence-based medicine (EBM) is the process of applying the best available evidence gained from clinical research to the practice of medicine . While t"“…attempts to collate all empirical evidence that fits pre-specified eligibility criteria in order to answer a specific research question. It uses explicit, systematic methods that are selected with a view to minimizing bias, thus providing more reliable findings from which conclusions can be drawn and decisions made[ions made.”SRs are literature reviews designed to locate, appraise and synthesize the best-available evidence from clinical studies of diagnosis, treatment, prognosis, or etiology, and provide informative empirical answers to specific medical questions. SRs inform medical recommendations, guiding both practice and policy, such as in the creation of published practice guidelines .The process of creating and maintaining SRs is resource- and labor-intensive, typically requiring 6–12 months of effort, with the main expense being personnel time. There is ample evidence that SRs become outdated as research progresses, and thus need to be periodically updated ,5. Best when to conduct the required literature search. The machine learning method proposed here provides exactly this guidance, and fits into the SR update process ahead of review commitment decision methods such as those assessed by Shekelle.Although there exists research guidance on when and how to update SRs ,7, the pA survival analysis study of SRs by Shojania  found thBuilding on our prior work in applying automated document classification to work prioritization for SRs -11, in tNew Update Alert. The idea behind New Update Alert is that as publications become available to the SR team, an automated document classification system may be able to determine which ones are most likely to be included in the SR update. When an article is detected that is likely to be included in the SR update, the system alerts the SR leader, perhaps via an automatically generated email message, or using a custom RSS  feed. For the purposes of this work, a publication becomes available to the review team when it is indexed in MEDLINE, and therefore is findable using the search queries previously designed for the SR topic. The algorithm looks at each article meeting the original review search criteria, and notifies the team about articles that it predicts as likely to be included in an update.Here, we define a document classification task called TP), at the cost of more false alarms . Furthermore, some publications may be more important than others, in that, in addition to being included in the final SR, they may include specific novel, or higher quality evidence that could motivate the scheduling, priority, or initiation of a review update. We specifically annotate and study these important publications in the work described below. For the work described here, alerts are trigged when any potentially included publication is detected, whether this is a motivating publication or not.We define a correct alert to be one that notifies the SR team about a publication that will be included in the eventual SR report update. These are publications that include new evidence regarding interventions, populations, or study designs relevant to the report. An incorrect alert is an alert about publication that is not eventually included in the SR update; these are “false alarms”. The machine predictions are not perfect, and a range of settings trading off sensitivity and specificity are possible. Greater sensitivity means that the team will be notified about the publication of a greater fraction of articles that will be ultimately included in the review update  system, which has been described elsewhere . The colEnd of the Report Cycle occurs for a topic when an SR has had its peer review completed and it is published on the Internet (http://www.ohsu.edu/drugeffectiveness). The Report Search Begins event occurs when the first literature search for a subsequent review update is begun. We use the term Pre-Update Period to describe the time period between the End of the Report Cycle for the prior report, and the Report Search Begins. During this time, relevant studies and articles are published and new medical evidence accumulates. Some of these publications will eventually be included in the next report update for the topic. Relatively few expert resources are available to follow the SR topic during this period; the DERP conducts a yearly literature scan for each topic.We define two specific time events in the SR process. The End of the Report Cycle (for the prior report) as the classification system training data for that topic. We used the DERP review inclusion judgments for articles indexed in MEDLINE during the Pre-Update Period (after the End of the Report Cycle date and prior to the Report Search Begins for the next update) as the testing data for that topic. Note that, for this data set, these articles were retrieved and inclusion judgments assigned after the Pre-Update Period, but they apply to articles that were published, indexed in MEDLINE, and are therefore potentially available to the SR team during the pre-update period. ‘Potentially available’ means that if the SR team re-ran their MEDLINE query during this time period, they would retrieve these documents, along with many others. These events and time periods are listed in temporal order and defined in Table For each topic, we used the DERP review inclusion judgments for articles with MEDLINE entry dates prior to the New Update Alerts, as well as apply the trained models to documents made available within MEDLINE during the pre-update period. Since this work is actually being done after the report update of interest has been completed, we know which documents indexed in MEDLINE during the Pre-Update Period were actually included in the subsequent report update. This allows us to measure the performance of the classifier system on articles published during this period.In this way, we can simulate both the data available for training the machine learning system for predicting Antiplatelets and NSAIDs an insufficient number of newly included and/or excluded articles were found in the update (fewer than 10), preventing adequate analysis. Therefore we excluded these two topics from the present study, leaving us with nine topics. See Table Of course, the above-described evaluation approach requires that we have SR topics for which both a prior report and a report update have been completed by the DERP investigators, and that we have the inclusion/exclusion judgments for these topics within these periods in our data collection window. For this work we used a cross-sectional snapshot of the SYRIAC database, incorporating all inclusion decisions made up to February 12, 2010. In reviewing the DERP records, we found that 11 topics met these requirements. For two of the topics, New Update Alert, as well as how the classifier performs on the “important” publications. These important publications are the ones that are most likely to motivate SR experts to decide that a new update is needed for the topic. These publications could change or influence the conclusions or recommendations of the SR. This could be due, for example, to a new study providing additional evidence for meta-analysis, or studying a new harm, or a new indication or patient population for a drug. We term these publications update-motivating publications, realizing that it may be an individual or a collection of these publications that provide the actual motivation to the SR expert to recommend an update on a review topic.For these nine topics, we separated out the data into training and test sets, as noted above, and annotated the test collection. We wanted to understand both the overall performance of the machine learning system on identifying publications for Therefore, we designed an annotation scheme to identify the important studies in the test collection. The scheme shown in Table Pre-Update Period that were included in the report update according to these criteria. The two senior authors (AMC and MM) discussed and modified the article annotation assignments until consensus was reached. The annotations were assigned before the machine learning models were created from the training data or applied to the test data. Therefore, none of the authors had prior information about the machine learning performance on the test data that could have biased annotation assignments. Only publications meeting the specific criteria given in Table New Update Alert task. The number and types of annotations assigned for each topic in the data set are shown in Table We then annotated each of the publications from the New Update Alert for each SR, we applied the support vector machine (SVM)-based classification system that we have described in detail in our prior work [http://svmlight.joachims.org/), with a linear kernel at default settings [New Update Alert, and those classified as negative would not.To classify the samples according to whether they should be used to display a ior work . Brieflysettings . See AddNew Update Alert task, we adjusted the classification cutoff threshold in the following manner. Previously, and in ongoing work, we have studied the user preferences of systematic reviewers in terms of document classification system tradeoffs for New Update Alert. It has been determined that, in general, review experts are more willing to trade off recall for precision for the New Update Alert task, as compared to the work prioritization task that we have previously studied. In particular, the principle investigator of the DERP (one of the senior authors of this paper) consistently preferred a recall of 0.55 and the achievable precision corresponding to that level of recall over all other available levels of recall between 0.99 and 0.55. The context of DERP is important in the choice of 0.55. The team lead would be reviewing multiple topics every month for years – not just a one-off SR every now and then. The level of the continual workload is an important factor. This means that the reviewer found 0.55 as the lowest acceptable recall for this task, leading to the highest precision that the current system can deliver at an acceptable recall. We therefore targeted a recall of 0.55 to study the performance of the classification system on the important publications in each topic.For the New Update Alert and a document not predicted to raise an alert. We analyzed the performance of the trained classifiers—both overall, as well as on the designated motivating publications.For each topic, we performed 5 repetitions of two-way cross-validation on the training data, and determined the threshold that lead to a recall of 0.55 for each repetition. These thresholds were averaged together to determine the threshold to use when applying the classifier to the test data set for each topic. Then, for each topic, we trained a classification model on that topic’s training data. We next classified each document in the corresponding test collection, using the computed threshold as a cutoff between a document predicted to raise a AtypicalAntipsychotics to a high of 1.0 on NasalCorticosteroids. Precision also varied greatly, both on the training data as well as the test set, varying from a low of 0.306 on the NasalCorticosteroids test collection to a high of 0.800 on ProtonPumpInhibitors.Tables Pre-Update Period. Each annotation code is represented by a different marker shape, as indicated in the figure legend. Black, filled in markers designate important annotated publications that were correctly recognized by the classification system and therefore could be used to initiate a new update alert . White, unfilled markers represent important, annotated publications that were missed by the classification system and are therefore not able to be used to initiate a new update alert . Most of the annotated publications are identified by the classification system. Overall there are 57 out of 80 annotated publications identified by the classification system, a recall of 0.7125 on the most important publications. The vast majority of the misses are on articles in the ProtonPumpInhibitors topic.Figure ADHD, Antiemetics, and ProtonPumpInhibitors. Conversely, some topics do not rapidly accumulate new evidence motivating a review update. Sedatives and NasalCorticosteriods only have three annotated as important studies during the Pre-Update Period, and these topics each only have one publication that would be a year old at the time of the performed review update.The timeline view shows that there are important differences between the topics. From the figure it is clear that for some topics, substantial new evidence that may motivate a review update begins to accumulate essentially immediately after the prior review is published. This is especially apparent for the topics ADHD, Antiemetics, AtypicalAntipsychotics, and ProtonPumpInhibitors. For ADHD, all of the annotated publications are captured for alert. For Antiemetics, 15 of 17 motivating publications are correctly predicted. For AtypicalAntipsychotics, 8 are correctly predicted and 3 are missed (overlap in the timeline plot obscures some of the points). Finally, for ProtonPumpInhibitors, only 12 of the 26 annotated publications are captured for alert. It is interesting to note that for AEDs and ProtonPumpInhibitors the set of missed publications include not only the M category of generically motivating publications, but the more specific and perhaps more important categories of new or serious adverse events (A) and better designed or novel study (B). For the other topics, the classifier performs well on the more specific annotation categories , and it is only the more general M potentially motivating studies that are missed.The topics with the most publications annotated as motivating an SR update are ProtonPumpInhibitors to a high of 2.67 alerts per month for ADHD. The number of correct alerts exceeds the number of incorrect alerts on three topics, has about the same number of correct and incorrect alerts on one topic, and a higher number of incorrect alerts on six topics. However, the imbalance between correct and incorrect alerts is understandable, since included documents are a small percentage of documents returned by the original query. The relative frequency of excluded documents is typically vastly higher than included documents for SR topics  saves time on the part of reviewers, 2) reduces time delays in updating topics that develop faster, and 3) prevents time and effort spent on reviewing topics not yet in need of an update. The system fits in well with the current RAND and Ottawa approaches, serving as a continuous prior step before the decision is made to allocate the substantial resources required by these approaches. The authors declare that they have no competing interests.All authors contributed to the construction of the SR datasets. AMC and MM designed and applied the annotation guide. AMC and KA built the automated text processing system and ran the machine learning experiments. All authors contributed to the writing and to the editing of the manuscript. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1472-6947/12/33/prepubAppendix 1 for Studying the Potential Impact of Automated Document Classification on the Systematic Review Update Scheduling Process.Click here for file


Although Blm and Top3α are known to form a minimal dissolvasome that can uniquely undo a double Holliday junction structure, the details of the mechanism remain unknown. It was originally suggested that Blm acts first to create a hemicatenane structure from branch migration of the junctions, followed by Top3α performing strand passage to decatenate the interlocking single strands. Recent evidence suggests that Top3α may also be important for assisting in the migration of the junctions. Using a mismatch-dHJ substrate (MM-DHJS) and eukaryotic Top1 (in place of Top3α), we show that the presence of a topoisomerase is required for Blm to substantially migrate a topologically constrained Holliday junction. When investigated by electron microscopy, these migrated structures did not resemble a hemicatenane. However, when Blm is together with Top3α, the dissolution reaction is processive with no pausing at a partially migrated structure. Potential mechanisms are discussed. We found that Top3α does show preferential binding to the junction on a dHJ substrate, similar to Blm. In addition, migration of the junction requires the presence of a topoisomerase, although Top1 could substitute and allow limited migration. The migration product of Blm and Top1 was directly observed by electron microscopy, and the junctions remained 10's of base pairs (bp) apart, rather than converging at a hemicatenane. However, the dissolution reaction proceeds through both migration and decatenation with no apparent pause when both Top3α and Blm are present.Drosophila Blm and Top3α were purified as in Drosophila Top1 was purified as in Recombinant The double Holliday junction DNA substrate and the mismatch double Holliday junction DNA substrate were created as in DNA samples (∼100 ng) were incubated with Blm (30 nM) and/or Top3α (50 nM) as appropriate. The reactions were performed in dissolution buffer . For reactions looking at the binding of Blm alone on DNA, ATP was excluded. The protein-DNA complexes were fixed with 0.6% glutaraldehyde (v/v) for 10 min at room temperature followed by gel filtration using a 1 mL Bio-Gel A-5m (BioRad) column to remove free protein and fixatives. No cross-linking step was used to treat protein-free samples following the reactions. The reactions were first stopped and the reaction products were digested with proteinase K at 55°C for at least two hours prior to column purification.The samples were prepared for electron microscopy as described previously Xenopus, Xtop3α was able to localize to chromatin when replication was inhibited even in the absence of Xblm Previous studies have shown that Blm is needed to direct Top3α to nuclear foci in unperturbed cells We tested whether Top3α bound preferentially on the dHJ substrate. Due to the lack of free ends for radiolabeling and a desire to distinguish between binding on different areas of the substrate, we employed electron microscopy to directly visualize the binding. Top3α was incubated with the substrate, fixed with 0.6% glutaraldehyde, passed over a gel filtration column, and mounted onto a carbon grid. Surprisingly, visualization of 83 molecules revealed that Top3α had a distinct preference for the junction site, localizing to the junction in 71% of the protein-bound DNA molecules , Table 1As expected from previous work Dissolution of the dHJ requires that the two junctions are convergently migrated and the two conjoined duplexes are then separated. It has been suggested that Blm alone can migrate the junctions together to create a hemicatenane structure, which is then resolved by Top3α. Although Blm is very efficient at migrating HJ's with free ends Drosophila Top1, a type IB topoisomerase capable of binding to and fully relaxing duplex DNA. In the presence of Top1, Blm was able to migrate the junction past the restriction site at levels equal to Top3α and RPA, but was unable to fully dissolve the substrate. This indicates that in the presence of Top1, which is likely available in the cell, Blm can migrate a constrained HJ, but is unable to fully unlink the dHJ.Blm alone is not able to migrate the Holliday junction past a distance of 40 bp where the mismatch sites are located, as indicated by the lack of restriction digest products . As expeAs it has been suggested that the product of Blm migration is a hemicatenane, we wanted to determine if the product of Blm and Top1 migration was a hemicatenane structure. Because the product of Blm and Top1 involves migrated junctions, we refer to this DNA structure as convergently branch migrated intermediate (CBM), in accordance with previous nomenclature To determine the exact structure of the CBM, these molecules were visualized by electron microscopy. Both substrate (DHJS) and product (CBM) protein-free DNA molecules were visualized and compared. The molecules were divided into four categories based on shape: unreacted, bar, loop, and circle . The “loTo determine the inter-junction distance of the “bar” and “loop” intermediates, the distance of the arms outside of the junctions were measured  and subtracted from the length of the whole substrate. The entire length of the molecules was also measured using unreacted molecules from the starting substrate, and was found to be comparable to the predicted length. The outer-junction distances of the unreacted and circle molecules also agreed with predicted lengths .While the bar molecules displayed slightly shorter distances, the inter-junction distances of bar and loop molecules were within error of each other . AlthougDuring the course of dHJ dissolution, as the junctions approach each other, a CBM-like molecule may be created as an intermediate prior to complete dissolution. If the CBM or hemicatenane state presents a kinetic barrier and is well-populated, it should appear as a slower-migrating species on a gel during the time course of dHJ dissolution.We analyzed by agarose gel electrophoresis the reaction products from a time course of dHJ dissolution using Blm and Top3α. We found no slower-migrating species appearing prior to the formation of dissolution products , indicatThe process of dHJ dissolution presents a unique topological puzzle, and its disentanglement requires both the branch migration activity of Blm and the strand passage activity of Top3α. It was previously unclear whether these activities were required at the same time or could work sequentially.It has been suggested that Top3α is not necessary for Blm's migration of the junctions, but can arrive later to simply undo the hemicatenane that forms as the result of migration In our study, based on visualization of molecules bound to the dHJ substrate, Top3α preferentially binds at the junction. This differs from previous results using electrophoretic mobility shift assays (EMSA). To study interactions of proteins with Holliday junctions, a static-X structure is often used, which is composed of short oligonucleotides and is non-migratable due to sequence variations of the arms. Such free-ended structures typically form the stacked, antiparallel conformation Blm and Top1 could partially migrate the constrained HJ, creating four classes of DNA structures. Besides the expected starting molecule (unreacted) and minimal amounts of dissolution product (circle), the two migrated species were referred to as “bar” or “loop” depending on the observed structure of their inter-junction DNA. The collapsed structure of the inter-junction DNA seen in the “bar” molecules may be due to the homology of that region of the DNA, which has been shown to produce a paranemic structure in which the two duplexes interact The partially migrated (CBM) intermediate, created from migration of Blm and Top1, displayed a variety of inter-junction distances, ranging between 20–120 bp with an average distance of 80–90 bp, whether a “bar” or “loop” structure was formed. The relatively large range in the length distribution could be due to the resolution of the measurements by electron microscopy. In addition, it could also be due to the relatively broad length limitation for the DNA bendability. It is possible that the formation of CBM intermediates reflects constraints from DNA tension due to contorting helical segments in bringing two HJ's closer. Interestingly, the persistence length of DNA, related to the minimum length of double-strand DNA which can bend to form a complete circle, is thought to be around 50 nm, or 150 bp, in physiological salt Two models have been suggested for the mechanism of the Blm-Top3α dissolvasome


HIV AIDS is a complex scientific phenomenon of our time. Ultimately however, HIV AIDS is a public health matter of unparalleled concern . This is due to the social and economic dimension of the HIV AIDS epidemic in the public domain. Public health communication is an integral part and key instrument employed by national health systems worldwide, in the management of public health.By quantitative and qualitative method of data analysis. This paper investigates t he evolution of public health communication in Uganda related to HIV AIDS in a period covering over two decades. A period that initially placed Uganda as model country in the fight against HIV AIDS globally, as result of the country’s success in decreasing HIV AIDS prevalence rates at national level. It also examines the likely factors behind the recent resurgence in new infections and prevalence rates.This paper postulate, giving empirical evidence, that key to the initial success of the fight against HIV AIDS in Uganda were the novelty of public health messages in the face of a fatal disease hitherto unknown by the public, and the means of their delivery. It argues that with the passage of time and reduction in stigma associated with being an HIV AIDS patient, public health messages became over used and ineffective.The paper explores possible sources of new public health messages and techniques of dissemination using traditional and new media. It probes whether the on-going research on AIDS Vaccine could generate new messages vital for public health campaigns, without giving a false impression of cure, a tendency that experts concur could lead to the rise in risky behavior in the public in some countries, as has been the case with the introduction of antiretroviral drugs and medical male circumcision.


One of the most damaging actions affecting concrete is the abrupt temperature change (freeze-thaw cycles). The types of deterioration of concrete structures by cyclic freeze-thaw can be largely classified into surface scaling (characterized by the weight loss) and internal crack growth (characterized by the loss of dynamic modulus of elasticity). The present study explored the durability of concrete made with air-entraining agent subjected to 0, 100, 200, 300, and 400 cycles of freeze-thaw. The experimental study of C20, C25, C30, C40, and C50 air-entrained concrete specimens was completed according to “the test method of long-term and durability on ordinary concrete” GB/T 50082-2009. The dynamic modulus of elasticity and weight loss of specimens were measured after different cycles of freeze-thaw. The influence of freeze-thaw cycles on the relative dynamic modulus of elasticity and weight loss was analyzed. The findings showed that the dynamic modulus of elasticity and weight decreased as the freeze-thaw cycles were repeated. They revealed that the C30, C40, and C50 air-entrained concrete was still durable after 300 cycles of freeze-thaw according to the experimental results. Concrete is considered as one of the most nonhomogeneous and demanding engineering materials used by mankind. The durability –5 of conConcrete has a potential to be damaged if it is subjected to freeze-thaw cycles. The American Concrete Institute (ACI) has established specifications for protection of concrete placed during cold weather. ACI defined cold weather as the period where more than three successive days have a mean daily air temperature less than 40 F (Fahrenheit). The freeze-thaw durability of concrete is of utmost importance in countries having subzero temperature conditions, such as The Arctic Zone, Russia, Northern China, and China. Frost damage, a progressive deterioration which starts from the surface separation or scaling and ends up with complete collapse, is a major concern when concrete is used in colder regions. The deterioration proceeds as freezing and thawing cycles are repeated, and the material gradually loses its stiffness and strength. In addition, the increasing irreversible expansion is induced. So frost damage is a very complex fatigue process. It has been a significant scientific and technical problem to improve the freeze-thaw durability and to prolong the service life of concrete. Hong-Qiang et al.  and Li-k Air-entraining agent –13 was rIn this investigation, local materials were utilized. A Chinese standard (GB175-99)  Portland Concrete prisms with size of 100 mm × 100 mm × 400 mm (to determine the weight loss and the dynamic modulus of elasticity) were prepared. The specimens were cast in steel molds and compacted through external vibration and demolded 24 h later. All the specimens were cured in a condition of 20 ± 3°C and 95 percent RH for 23 days. Thereafter, the specimens were immersed in water for 4 days prior to the freeze-thaw cycles. Then when the age of the specimens was 28 days, the air-entrained concrete specimens were placed into the freeze-thaw apparatus. In this paper, the freeze-thaw test apparatus  meeting The dynamic modulus of elasticity and weight loss of each specimen were measured before placing the specimens with size of 100 mm × 100 mm × 400 mm into the freeze-thaw apparatus. One specimen with size of 100 mm × 100 mm × 400 mm was placed in a rubber container. In which, standard concrete prisms were surrounded by water. Specimens were removed for testing when they were in a thawed condition at 50-cycle or 100-cycle intervals. The dynamic modulus of elasticity and weight were recorded. Before returning the specimens into the freeze-thaw apparatus in a random order, containers were cleaned out and fresh water was added. The C20 and C25 air-entrained concrete specimens were exposed to 300 cycles of freeze-thaw, the C30, C40, and C50 air-entrained concrete specimens were exposed to 400 cycles of freeze-thaw.The surface deterioration of the C30 air-entrained concrete specimens undergoing 0, 200, and 400 cycles of freeze-thaw is shown in Figures The RDME of C20, C25, C30, C40, and C50 air-entrained concrete after different cycles of freeze-thaw was given in P is relative dynamic modulus of elasticity at n cycles of freeze-thaw, expressed as percentage, computed as the average of three specimens; fn is dynamic modulus of elasticity at n cycles of freeze-thaw; f0 is dynamic modulus of elasticity before freeze-thaw cycles.The relative dynamic modulus of elasticity is defined as follows:After 300 cycles of freeze-thaw, the C30, C40, and C50 air-entrained concrete specimens showed a small loss of RDME, while C20 and C25 air-entrained concrete specimens showed considerable loss of RDME, as shown in As seen from Sun et al.  and ZahaOne type of deterioration of concrete structures by cyclic freeze-thaw is surface scaling. Surface scaling is the loss of paste and mortar from the surface of concrete by the cyclic freeze-thaw or by an internal reaction of aggregate . In extreme cases, the loss of paste can result in loosening of coarse aggregate and gradual reduction in strength of concrete structures. The weight loss will be caused by surface scaling, so the weight loss was measured. Wn is weight loss at n cycles of freeze-thaw, expressed as percentage, computed as the average of three specimens; Gn is weight at n cycles of freeze-thaw; G0 is weight before freeze-thaw cycles.It can be seen from The test results show that the weight loss of C30 air-entrained concrete was 0.20 percent compared with 1.81 percent for plain concrete after 100 cycles of freeze-thaw . For C20The weight loss of concrete specimens is caused by surface separation or scale off. The weight variation during freeze-thaw cycles is due to movement in and out of water in the specimen and surface separation or scaling . As soon as microcracking takes place, the deteriorated zones filled with the surrounding water will cause change in the weight of the specimen. If the mass of surface separation is larger than the water absorbed by the concrete specimens, the weight of the concrete specimens will increase. The weight of the concrete specimens will decrease when the mass of surface separation is less than the water absorbed by the concrete specimens. Compared with plain concrete, the deteriorated zones filled with the surrounding water occurred in the air-entrained concrete needed much more cycles of freeze-thaw.In actual concrete structures, concrete surface scaled markedly when exposed to deicing salt and freeze-thaw cycles caused by the change of climate. The cycling rate in the laboratory conditions was much higher than that in the natural environment because of the fast change of temperature. Thus, it is reasonable that the scaling observed during the tests was more severe, and the scaling depth of concrete specimens was over 1 mm. A lot of structures, like bridges, tunnels, dams, buildings, and others, were constructed with concrete material. During the life cycle of these structures, degradations can occur because of mechanical, thermal, or chemical stresses. These often lead to the development of porosity, microcracks, and cracks in the material. Knowing the concrete structure state to prevent or repair damage is needed so the nondestructive characterisation is an important way, and the ultrasonic method is often proposed.In this work, the ultrasonic velocity of C30 air-entrained concrete was measured with ultrasonic method according to “Testing Code of Concrete for Port and Waterwog Engineering” JTJ 270-98 .  Table Concrete is a three-phase composite structure at microscopic scale, a cement matrix, aggregate, and the interfacial transition zone between the two. The microcracks will be caused by the action of freezing and thawing cycles; the direction and distribution of microcosmic cracks are stochastic. The microcosmic cracks manifold and become broad as freeze-thaw cycles are repeated. Air-entrained concrete contains billions of microscopic air cells when air-entraining agents were used in concrete. These relieve internal pressure on the concrete by providing tiny chambers for the expansion of water when it freezes. So, comparing the test results in this paper with the conclusion given by other authors , 5, the The RDME decreased as the freeze-thaw cycles were repeated. After 100 cycles of freeze-thaw, the RDME decreased to 94.35 and 98.75 percent for C25 and C30 air-entrained concrete, and 64 percent for C30 plain concrete. Therefore, the freeze-thaw durability of air-entrained concrete is much higher than that of plain concrete. After 200 cycles of freeze-thaw, the weight loss was 0.70, 0.67, and 0.25 percent for C30, C40, and C50 air-entrained concrete, and 2.35 and 3.58 percent for C20 and C25 air-entrained concrete. The weight variation during freeze-thaw cycles is due to moveming in and out of water in the specimen and surface separation or scaling. The freeze-thaw durability of plain concrete is poor, but it can be improved greatly when air-entraining agent is mixed into concrete. It demonstrates that ordinary strength concrete can also have a high freeze-thaw durability.The effects of freeze-thaw cycles on the RDME and weight loss of C20, C25, C30, C40, and C50 air-entrained concrete were investigated. Based on the experimental work in this study and the discussion about the experimental results, the results of the investigation can be summarized as follows


In advance of the September 2011 UN Summit on non-communicable diseases (NCDs), Rebecca Dirks and colleagues identify lessons from the AIDS epidemic that can inform the response to the growing epidemic of NCDs. The September 2011 UN High-Level Meeting on Noncommunicable Diseases provides an opportunity for the international community and national stakeholders to raise awareness and launch an effective global response to noncommunicable diseases (NCDs).Valuable policy lessons have been learned in the control of AIDS that can help inform the global dialogue when designing a NCD response in developing countries.The AIDS response demonstrates successes in advocacy and resource mobilization, priority setting, coalition building, strong national and community leadership, strengthening of community health infrastructures, and health systems strengthening.Weaknesses of the AIDS response to avoid when building a NCD response include creation of stove-pipe vertical programs, ineffectiveness of prevention efforts, and inefficient and uncoordinated use of resources.The lessons learned in the global response to AIDS are relevant to the likely outcomes of the UN High-Level Meeting on NCDs: (1) improvement in advocacy and recognition of the NCD burden, (2) greater attention in national planning and resource allocation, (3) a longer-term investment of donors, and (4) greater emphasis on strengthening health systems.The United Nations General Assembly Special Session (UNGASS) on HIV/AIDS in 2001 was a critical event that dramatically enhanced the global AIDS response. Ten years later, the September 2011 UN High-Level Meeting on Noncommunicable Disease Prevention and Control provides a similar opportunity for the international community and national stakeholders to raise awareness and launch an effective global response to noncommunicable diseases (NCDs). It is an opportunity that should not be missed as it will not likely occur again.Infectious diseases continue to have a devastating impact on the health and development of low- and middle-income countries (LMICs). However, NCDs have silently become “the poor world's greatest health problem” and the major causes of premature deaths in LMIC Despite the growing burden in developing countries, NCDs have received little attention and funding to date First, the success in substantially increasing funding for AIDS programs over the last decade provides lessons in resource mobilization and advocacy to the NCD community. This dramatic increase was fueled by a variety of factors, including the impact of the disease on children and women, the availability of inexpensive diagnostics, reduced treatment costs, and the disparity in access to care between developed and developing countries. The AIDS response demonstrates the need to create a committed, diverse, and broad coalition comprised of multilateral and bilateral agencies, the donor community, national and regional leadership, and those whose lives are affected by the disease. Like AIDS, NCDs should be positioned as a leading cause of morbidity and mortality in LMIC with devastating social and economic impacts.Next, policymakers must recognize that as devastating as the AIDS pandemic and other infectious diseases have been, the burden of NCDs have the potential to be much worse in LMICs. There is an urgent need to change national and international priorities and resource allocation policies to address these deficiencies. For example, Sridhar et al. propose the appointment of an NCD czar and leveraging existing high level leadership such as the UN Secretary General, Director General of World Health Organization (WHO), and the NCD Alliance to elevate and strengthen the leadership for NCD Another valuable lesson from the AIDS response is the role of strong national and community leadership. Such leadership was critical in achieving a coordinated and broad-based national response to AIDS over the course of many years. To tackle NCDs, the response must start with national leadership of country-owned and -managed strategies and programs. Just as national AIDS strategies have served as the basis for international support for AIDS funding, international and donor communities should invest in country-led NCD plans.Furthermore, the AIDS response demonstrated that in order to develop sustainable and effective programs, community health infrastructures must be strengthened. Community-based organizations have successfully reached the most-at-risk populations, and experience from AIDS treatment points to the critical role of community-based care as part of a package of essential entitlements for access to healthcare Lastly, the AIDS response has shown that a primarily vertical health infrastructure can result in improvements in the laboratory infrastructure, pharmacy, and supply chain management of drugs and other medical commodities. Some of these health systems improvements have benefited non-HIV services, such as reproductive health In addition to the successes, the response to the AIDS epidemic provides lessons as to approaches that should be avoided when building a NCD response. To begin, the emergency nature of the AIDS response and the subsequent significant increase in funding resulted in the creation of many vertical programs. While AIDS programs have strengthened related aspects of health services, they have also fueled competition between AIDS and other health programs, hampering efforts in some countries to improve the capacity of the health system to address other priority health issues. These constraints are apparent across each of the WHO's six key health-systems' components While leveraging the improvements in health systems due to AIDS programs, the NCD response should avoid the weaknesses of a vertical response and develop a diagonal or horizontal approach to address a wide range of health conditions. There is in fact increased momentum among funders, such as the US President's Emergency Plan for AIDS Relief (PEPFAR) and The Global Fund for AIDS Tuberculosis and Malaria (GFATM), to strengthen national health systems to address a variety of health issues.Second, despite some successes in AIDS prevention efforts, twice as many people are newly infected as are put on treatment. If we cannot treat ourselves out of the AIDS pandemic, it is equally unlikely that we would be able to treat ourselves out of a much larger NCD pandemic. An effective NCD response must ensure that adequate resources are allocated to comprehensive evidence-based prevention efforts.Third, the complexity of AIDS prevention was not fully appreciated early on. It took many years for the AIDS response to evolve from a limited infectious disease approach to a broader public health and developmental response. We should not be similarly naïve when it comes to NCDs; the multisectoral dimensions of NCDs must be tackled from the onset.Fourth, the urgent nature of the AIDS response and the need to rapidly implement interventions created inefficiencies and ineffective use of resources. Coordination among donors is still inadequate, limiting the ability to maximize and integrate the use of resources. The upcoming UN High-Level meeting should allow national governments and donors to synergize their efforts against NCDs.Fifth, almost 30 years into the AIDS pandemic, we are still debating which of the many interventions are most effective. We need to agree on priority and evidence-based NCD interventions that are appropriate for local needs. The focus of the high-level UN meeting in 2011 on the four key NCDs  and their key risk factors  is a step in the right direction. Prevention of chronic infections such as human papillomavirus, hepatitis B virus, and hepatitis C virus, and prevention of cook stove smoke are additional NCD risk factors to consider in some settings.Finally, the reduction in HIV treatment costs was realized late and the long-term costs of initiating and maintaining an increasing number of patients on antiretroviral treatment pose a serious challenge. This challenge is further compounded by the “treatment for prevention” debate that could result in millions of people with HIV infections being treated early and for many years. In this era of scarce resources, we need to ensure access to the most feasible, cost-effective, and sustainable NCD interventions to the populations at most risk.Noncommunicable diseases are no longer limited to industrialized countries. Many LMIC have completed their epidemiological transition with accelerated growth of NCDs, but without transitioning beyond diseases of the poor. NCDs are on the decline in high-income countries but rising rapidly in LMIC. By 2030, these chronic diseases will likely account for over two-thirds of deaths worldwide.The upcoming UN High-Level Meeting on NCDs should lead to: (1) a significant improvement in advocacy and recognition of the NCD burden at the national and global levels, (2) greater attention in national planning and resource allocation, (3) modest immediate resource commitment, but more likely a longer-term investment of donors, and (4) greater emphasis on strengthening health systems for a more horizontal response to broader disease burdens. As we have indicated, several lessons from the AIDS epidemic can inform this meeting .Position NCDs as a leading cause of morbidity and mortality in LMICs with devastating social and economic impactsAppoint czar or other high-level leadership to increase profile of NCDsInvest international and donor support in country-led NCD plansStrengthen community health infrastructuresAdopt horizontal or diagonal health infrastructure to address multiple health issues simultaneouslyFocus on prevention, not just treatmentSynergize donor and governmental efforts against NCDAgree on priority conditions, risk factors, and evidence-based interventions for NCDEnsure access to the most feasible, cost-effective, and sustainable NCD interventions to the populations at most riskThe global response to AIDS has demonstrated it is feasible to scale-up both prevention and treatment programs and drastically reduce both morbidity and mortality. Scale-up of even a limited number of interventions can have an even more dramatic reduction on NCDs. The AIDS response has taught us that efforts to address a pandemic are incremental and can take time. We need to be both opportunistic and strategic to achieve an NCD response of significant magnitude. Unless the pandemics of NCDs are addressed now, the lives of those living in developing countries will be saved from communicable diseases only to be lost prematurely from noncommunicable diseases.


Recently, the food and malnutrition issues have taken centre stage within the arena of HIV/AIDS epidemic, with several calls being made for context-specific health and nutrition interventions to deal with the emerging food insecurity and malnutrition issues in settings with high burdens of HIV/AIDS. The use of probiotics as nutritional supplements in HIV/AIDS-affected and resource-poor settings has also been advocated. This paper presents the results of a qualitative study on community knowledge and perceptions about probiotics and their potential impact on people's everyday life in the context of the HIV/AIDS epidemic. In-depth interviews (n=26) were conducted with residents in Mwanza, Tanzania. The results showed that people living with HIV/AIDS, who were using probiotic yogurt produced through a joint partnership of Western Heads East, Tanzania Medical Research Institute and the Tukwamune Women's Group, reported perceived beneficial effects, such as gain in weight and improved health and well-being. Yet, these beneficial effects might be resulting in growing misconceptions about probiotic yogurt being ‘medicine’ for the treatment of HIV/AIDS; this is leading some people living with HIV/AIDS to abandon taking their antiretroviral medications based on the view that the probiotic yogurt is making them feel much better. The findings illustrate the potential challenges with regard to the introduction of nutritional food supplements into new contexts plagued by malnutrition and infectious diseases. Public-health education and awareness programmes are needed when introducing novel foods into such contexts. In 2003, HIV/AIDS became the leading cause of death among adults in Tanzania. By early 2008, it was estimated that 1.3 million people, including adults and children aged less than 18 years, in Tanzania mainland were living with HIV .For people living with HIV/AIDS (PLWA), antiretroviral therapy improves immunity, slows down disease progression, and increases life expectancy. However, nausea, dizziness, vomiting, and contribution to a poor quality of life are often cited as reasons for non-adherence to and discontinuation of antiretrovirals (ARVs) ,6. The iMore recently, the food and malnutrition issues have taken centre stage within the arena of HIV/AIDS epidemic -18, within vitro and reduce the risk of bacterial vaginosis, a condition that predisposes women to sexually transmitted diseases and increases the risk of mother-to-child transmission of disease  used in the yogurt  aged 20-65 years. The interviews were guided by a checklist that was developed based on the overarching themes of knowledge and perceptions of probiotic yogurt ,23,29,45To ensure that the interview checklist was culturally and contextually appropriate, the WHE researchers and members of Kivulini, who have significant knowledge of the community, reviewed the interview guide before making contact with the participants. The interview checklist was also tested with members of the Mabatini community (where the current probiotic yogurt project is located) to ensure that the questions would be acceptable to the community. The feedback from test participants was taken into account, and the necessary changes were made to the interview instrument.The interviews, on average, lasted for approximately 45 minutes and were translated by a trained research assistant from the St. Augustine University in Mwanza from English to Swahili and back to English. Interviews were conducted either at the local community centre or at the participants’ homes to ensure the comfort of the participants. All the tape-recorded interviews were transcribed verbatim for analysis.The mode of analysis of the interviews was guided by the literature on conceptions and perceptions of probiotics, nutritional supplements, and HIV/AIDS -48. EachIn each segment of the data representation, we provide quotations from the data. The participant's name, represented by a pseudonym and his/her sex, are provided at the end of each quotation.Ethical approval for the study was obtained from both UWO Research and NIMR Ethics Boards. Initial contacts with the community leaders  were made through our partners. Meetings were then held with the community chairperson and gatekeepers to discuss the research objectives and to secure their support and approval of the study. Before interviews, the participants were informed that their participation was voluntary and they may withdraw from the interview anytime. The majority (61%) of the 26 participants were married  and wereTwenty-one participants reported that they had eaten the probiotic yogurt produced by the TWG. Seventeen consumed the probiotic yogurt at least three times per week. Thirteen had knowledge regarding the health benefits of probiotics. Overall, the participants indicated that their knowledge and understandings of probiotics were drawn from lay-people (Yogurt Mamas and other yogurt consumers) and from professionals, such as doctors and nurses, at the Sekou Tuore and Bugando Hospitals, who sometimes referred HIV/AIDS patients to the probiotic yogurt kitchen. Other sources of the information included ARV clinic staff, local organizations, and non-profit organizations, such as Kivulini and the Tanzanian Commission for AIDS (TACAIDS).Most (81%) participants who were eating the probiotic yogurt agreed that their knowledge about the yogurt was limited. In the following statement, a participant explained that she regularly consumed the probiotic yogurt but did not know anything about its special properties:… I take the [probiotic] yogurt about 4 or 5 times a week. I like its taste. But I must tell you, I do not know what is in the yogurt. I was told that I could register to get it [the probiotic yogurt] free of charge because I have HIV…since I started eating it, I feel so much better…but I do not know why this yogurt is so good for me…I just do not know what is put in there and why it helps…. I can cook milk at home but it does not help me feel the same way .bakteria in kishwahili language) that benefit health. The following quote describes one woman's perception about the probiotic bacteria:Those who had more in-depth knowledge  identifibakteria in it and that make you healthy. The doctor at the clinic said something about how bakteria are not always bad and the probiotic yogurt has the good bakteria in it that make us healthy .I do not know everything [about the probiotic yogurt] but I do know that it has good The lack of knowledge on probiotics did not limit the participants’ overall perceptions about the health benefits of probiotic yogurt.The participants described several perceived benefits of probiotic yogurt to their health and well-being. For instance, in the comment below, Lobbo reported that the consumption of probiotic yogurt boosts his energy and makes him feel ‘stronger’:It [the probiotic yogurt] makes me feel stronger and gives me energy. Before I used to feel so tired, and I did not want to do anything but since I started taking the yogurt, I noticed that my energy is back…. I feel strong again .Other participants specifically focused on the benefits for the PLWA and talked about the potential of probiotics to increase immunity, including the CD4 counts of PLWA who are taking the yogurt:People with HIV are the ones taking it daily…. It is good for everyone but for people like me with HIV, it really helps. It makes the immune system work better and has made my CD4 count go up to 500. I take ARVs and these help too but with the [probiotic] yogurt it works better .I was told that it would be beneficial for me to take the yogurt with my ARVs.…But the ARVs make me feel very sick sometimes, and the yogurt helps stop this…it makes me feel better. It is good for those of us with HIV. It increased my CD4 count, and now I am healthier. I think that it makes the ARVs work better too…that is why I take it .Among other nutritional benefits, the participants talked at length about how consuming probiotic yogurt causes gain in needed weight:I know this is good because I have gained weight …this is what I needed because my clothes were starting to fall off from me….HIV/AIDS makes you lose weight, and this is not good for you .My friend who eats the yogurt has gained weight from eating it, which is good because she was so skinny. You can see it in her body and face that this is good for her…she looks healthier since she has been taking the yogurt .Some respondents also talked about the impact of the probiotic yogurt on their gastrointestinal health by reporting that, since they started taking the yogurt, they experienced fewer stomach upsets and pain.When I take probiotic yogurt, I do not get stomach upsets anymore. Before my stomach would really hurt … especially with ARVs … my stomach would churn inside, and I would get a terrible pain in the lower abdomen. Now, this does not happen so much…. .It [the probiotic yogurt] stops the pain in my stomach…. It used to hurt so much…and all the time, it just did not feel right. Now, it is a lot better…so I go about my daily activities more freely .The reduction of diarrhoeal episodes as a result of eating probiotic yogurt was also reported by some participants. One participant noted that she now sees the doctor less often because she does not experience many diarrhoeal episodes:… this [the consumption of probiotic yogurt] has helped make my diarrhoea happen less often. I used to go to the clinic a lot more because of diarrhoea, and now I only have to go once in a while .The participants also mentioned other health effects of probiotic yogurt, including the ‘clearance of skin rashes’ and ‘reduced pain in lower limbs’:Well, I used to have rashes on my skin that would not go away but since I have started taking probiotic yogurt, it has almost all gone away. See this spot of rash here [points to arm] …this used to be all over my body and now it is not. The [probiotic] yogurt has cleared it up .For some reason, my legs have stopped hurting as much. I used to get such bad pain in the muscle and joints, and now that I am eating the [probiotic] yogurt, this is no longer the case .While the participants talked about the benefits of the probiotic yogurt, it also emerged in the study that 38% of the participants viewed probiotic yogurt as medicine and not just a nutritional supplement.In the following passages, the respondents conceptualized probiotic yogurt as ‘medicine’ for treating HIV/AIDS, thereby highlighting a misconception:… Now, I take the yogurt as medicine for my HIV/AIDS and lots of other things like diarrhoea and stuff like that. This medicine is making me feel good…. It is something that helps so much, and there are no side-effects when I take it .… people take it as medicine…it cures everything. Some people think that it is a miracle medicine because it is just much better than the ARVs…it does not make people feel sick, it makes me feel healthy.…I would like to know and understand what exactly the probiotic yogurt does for people who are HIV-positive… .While the overall health impacts of probiotic yogurt are acknowledged in the literature, the problem whereby some HIV/AIDS patients are abandoning their ARVs because they are eating probiotic yogurt and perceiving it as ‘medicine’ is a concern.In the following excerpt, a respondent explained why she stopped taking her ARVs:… I noticed myself, from taking the yogurt, that I felt really good. I now have energy I did not have before…. I feel strong now. So, I know that this probiotic medicine is something that is good for my health. This is why I stopped taking ARVs. The yogurt is helping me so much that I do not even have to take ARVs. This is good because they [ARVs] made me feel very sick before, and now I have energy. I also like the taste of the yogurt. It is a good meal for me .Similarly, another respondent commented on the effectiveness of probiotic yogurt and how it has resulted in an increase in her CD4 count.Probiotic yogurt is a powerful medicine … it just makes me feel healthy. I take yogurt instead of ARVs to help me feel better from the HIV. The ARVs used to make me feel very sick, and I do not like them. Also, since I have been taking the yogurt, my CD4 counts have gone up, and this is why I know that it helps my immune system. My CD4 count has gone from 235 to 315. Since this is helping me so much, I stopped taking my ARVs.… It is simple, the ARVs make me feel sick but the yogurt does not, and it tastes good .As demonstrated in the above quotations, the abandonment of ARVs in place of probiotic yogurt suggests a lack of understanding of the role of ARVs to PLWA, and the fact that probiotic yogurt is only a nutritional supplement. A summary of the interview responses are provided in The HIV/AIDS epidemic continues to present unique and severe challenges for the global health community, especially in the hardest-hit areas, such as SSA. Countries, such as Tanzania, are impacted in multidimensional ways, and the effects are exacerbated by chronic poverty, growing food insecurity, and severe malnutrition. As the local governments in SSA make attempts to provide ARVs to those infected with HIV, it is imperative that the nutritional status of PLWA is kept in mind since well-nourished individuals who use ARVs have reduced side-effects and are more likely to live longer.The importance of nutrition in both transmission and progression of HIV led to the recommendation that those infected should consume adequate quantity of foods that are high in vitamins and micronutrients and can help boost the immune system -22. The Despite the positive therapeutic benefits of probiotics, the misconception by some participants that probiotic yogurt is a ‘medicine’ for the treatment of HIV/AIDS emerged as a major concern. Understandably, those who were referring to probiotic yogurt as ‘medicine’ may have been using the term in relation to their individual perceptions and cultural constructs of health and well-being embedded in the context, to the extent that what makes people 'feel better’ becomes their ‘medicine’ . As the Most indigenous approaches to healing are principally concerned with treating illness as the human experience of sickness rather than the biological recognition and treatment of disease ,57. ConsWithin the context of the HIV/AIDS epidemic in SSA, the increasing availability of several nutritional supplements and therapies means that individual's decisions about their preferred options will frequently revolve around what makes them feel better. Some people in this category then stop taking their ARVs with the belief and hope that the probiotic yogurt is the best option for their better health and well-being. This is consistent with the literature whereby patients with non-curative diseases, such as HIV/AIDS, may be so desperate such that any treatment, medicine, procedure, or substance that make them feel better or minimize their symptoms become the best therapy for them, regardless of biological pathways and markers that may indicate otherwise . To a peWhile we acknowledge the therapeutic effects of probiotics, there is no scientific recommendation that they can be used for treating HIV or replace ARVs. However, results of several studies suggest that the combination of ARVs with probiotics is, in fact, beneficial to the patient due to the numerous therapeutic and nutritional properties of probiotic yogurt ,12,13,21This study has a number of limitations that must be acknowledged. First, with regard to the context in which the study was done, there is a possibility that interview responses were distorted by personal biases, communal motivations, or emotional states. Second, it is also possible that, given the nature of the topic, the responses were made out to be self-serving. For instance, the participants may have over-exaggerated or downplayed certain issues because they thought that it would have some impact on whether or not a current probiotic yogurt kitchen will continue to serve their needs or whether a new kitchen will be set up in their neighbourhood. Consequently, while the information gathered here will be useful in SSA and other HIV/AIDS-affected regions, the pronounced contextual differences in various regions have to be kept in mind when these findings are being generalized too broadly.With regard to the increasing availability  of probiotics and other nutritional supplements to benefit the health of the general population, policy-makers and community workers need to be forthcoming with explicit information regarding what nutritional supplements, such as probiotics, can do or cannot do, more so that these supplements are not to replace ARVs as treatment for HIV/AIDS.The authors thank the community leaders and people of Mahina, Mwanza, Tanzania, for participating in the study. Special thanks are due to the Tukwamuane Women's Group ‘Yogurt Mamas’ who have been providing probiotic yogurt to community members. The authors also thank everybody involved with Western Heads East for their relentless efforts with the entire probiotic yogurt programme in East Africa. They also thank the anonymous reviewers for their extremely-useful comments and suggestions.