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2.  Time to Update and Quantitative Changes in the Results of Cochrane Pregnancy and Childbirth Reviews 
PLoS ONE  2010;5(7):e11553.
Background
The recommended interval between updates for systematic reviews included in The Cochrane Library is 2 years. However, it is unclear whether this interval is always appropriate. Whereas excessive updating wastes time and resources, insufficient updating allows out-of-date or incomplete evidence to guide clinical decision-making. We set out to determine, for Cochrane pregnancy and childbirth reviews, the frequency of updates, factors associated with updating, and whether updating frequency was appropriate.
Methodology/Principal Findings
Cochrane pregnancy and childbirth reviews published in Issue 3, 2007 of the Cochrane Database of Systematic Reviews were retrieved, and data were collected from their original and updated versions. Quantitative changes were determined for one of the primary outcomes (mortality, or the outcome of greatest clinical significance). Potential factors associated with time to update were assessed using the Cox proportional hazard model. Among the 101 reviews in our final sample, the median time before the first update was 3.3 years (95% CI 2.7–3.8). Only 32.7% had been updated within the recommended interval of 2 years. In 75.3% (76/101), a median of 3 new trials with a median of 576 additional participants were included in the updated versions. There were quantitative changes in 71% of the reviews that included new trials (54/76): the median change in effect size was 18.2%, and the median change in 95% CI width was 30.8%. Statistical significance changed in 18.5% (10/54) of these reviews, but conclusions were revised in only 3.7% (2/54). A shorter time to update was associated with the same original review team at updating.
Conclusions/Significance
Most reviews were updated less frequently than recommended by Cochrane policy, but few updates had revised conclusions. Prescribed time to update should be reconsidered to support improved decision-making while making efficient use of limited resources.
doi:10.1371/journal.pone.0011553
PMCID: PMC2903478  PMID: 20644625
3.  Assessment of a method to detect signals for updating systematic reviews 
Systematic Reviews  2014;3:13.
Background
Systematic reviews are a cornerstone of evidence-based medicine but are useful only if up-to-date. Methods for detecting signals of when a systematic review needs updating have face validity, but no proposed method has had an assessment of predictive validity performed.
Methods
The AHRQ Comparative Effectiveness Review program had produced 13 comparative effectiveness reviews (CERs), a subcategory of systematic reviews, by 2009, 11 of which were assessed in 2009 using a surveillance system to determine the degree to which individual conclusions were out of date and to assign a priority for updating each report. Four CERs were judged to be a high priority for updating, four CERs were judged to be medium priority for updating, and three CERs were judged to be low priority for updating. AHRQ then commissioned full update reviews for 9 of these 11 CERs. Where possible, we matched the original conclusions with their corresponding conclusions in the update reports, and compared the congruence between these pairs with our original predictions about which conclusions in each CER remained valid. We then classified the concordance of each pair as good, fair, or poor. We also made a summary determination of the priority for updating each CER based on the actual changes in conclusions in the updated report, and compared these determinations with the earlier assessments of priority.
Results
The 9 CERs included 149 individual conclusions, 84% with matches in the update reports. Across reports, 83% of matched conclusions had good concordance, and 99% had good or fair concordance. The one instance of poor concordance was partially attributable to the publication of new evidence after the surveillance signal searches had been done. Both CERs originally judged as being low priority for updating had no substantive changes to their conclusions in the actual updated report. The agreement on overall priority for updating between prediction and actual changes to conclusions was Kappa = 0.74.
Conclusions
These results provide some support for the validity of a surveillance system for detecting signals indicating when a systematic review needs updating.
doi:10.1186/2046-4053-3-13
PMCID: PMC3937021  PMID: 24529068
Methods; Systematic reviews; Updating
4.  Updated recommendations: an assessment of NICE clinical guidelines 
Background
Updating is important to ensure clinical guideline (CG) recommendations remain valid. However, little research has been undertaken in this field. We assessed CGs produced by the National Institute for Health and Care Excellence (NICE) to identify and describe updated recommendations and to investigate potential factors associated with updating. Also, we evaluated the reporting and presentation of recommendation changes.
Methods
We performed a descriptive analysis of original and updated CGs and recommendations, and an assessment of presentation formats and methods for recording information. We conducted a case-control study, defining cases as original recommendations that were updated (‘new-replaced’ recommendations), and controls as original recommendations that were considered to remain valid (‘not changed’ recommendations). We performed a comparison of main characteristics between cases and controls, and we planned a multiple regression analysis to identify potential predictive factors for updating.
Results
We included nine updated CGs (1,306 recommendations) and their corresponding original versions (1,106 recommendations). Updated CGs included 812 (62%) recommendations ‘not reviewed’, 368 (28.1%) ‘new’ recommendations, 104 (7.9%) ‘amended’ recommendations, and 25 (1.9%) recommendations reviewed but unchanged. The presentation formats used to indicate the changes in recommendations varied widely across CGs. Changes in ‘amended’, ‘deleted’, and ‘new-replaced’ recommendations (n = 296) were reported infrequently, mostly in appendices. These changes were recorded in 167 (56.4%) recommendations; and were explained in 81 (27.4%) recommendations. We retrieved a total of 7.1% (n = 78) case recommendations (‘new-replaced’) and 2.4% (n = 27) control recommendations (‘not changed’) in original CGs. The updates were mainly from ‘Fertility CG’, about ‘gynaecology, pregnancy and birth’ topic, and ‘treatment’ or ‘prevention’ purposes. We did not perform the multiple regression analysis as originally planned due to the small sample of recommendations retrieved.
Conclusion
Our study is the first to describe and assess updated CGs and recommendations from a national guideline program. Our results highlight the pressing need to standardise the reporting and presentation of updated recommendations and the research gap about the optimal way to present updates to guideline users. Furthermore, there is a need to investigate updating predictive factors.
doi:10.1186/1748-5908-9-72
PMCID: PMC4067507  PMID: 24919856
Clinical practice guidelines; Information dissemination; Evidence-based medicine; Knowledge translation; Methods; Updating
5.  Updating Systematic Reviews: An International Survey 
PLoS ONE  2010;5(4):e9914.
Background
Systematic reviews (SRs) should be up to date to maintain their importance in informing healthcare policy and practice. However, little guidance is available about when and how to update SRs. Moreover, the updating policies and practices of organizations that commission or produce SRs are unclear.
Methodology/Principal Findings
The objective was to describe the updating practices and policies of agencies that sponsor or conduct SRs. An Internet-based survey was administered to a purposive non-random sample of 195 healthcare organizations within the international SR community. Survey results were analyzed using descriptive statistics. The completed response rate was 58% (n = 114) from across 26 countries with 70% (75/107) of participants identified as producers of SRs. Among responders, 79% (84/107) characterized the importance of updating as high or very-high and 57% (60/106) of organizations reported to have a formal policy for updating. However, only 29% (35/106) of organizations made reference to a written policy document. Several groups (62/105; 59%) reported updating practices as irregular, and over half (53/103) of organizational respondents estimated that more than 50% of their respective SRs were likely out of date. Authors of the original SR (42/106; 40%) were most often deemed responsible for ensuring SRs were current. Barriers to updating included resource constraints, reviewer motivation, lack of academic credit, and limited publishing formats. Most respondents (70/100; 70%) indicated that they supported centralization of updating efforts across institutions or agencies. Furthermore, 84% (83/99) of respondents indicated they favoured the development of a central registry of SRs, analogous to efforts within the clinical trials community.
Conclusions/Significance
Most organizations that sponsor and/or carry out SRs consider updating important. Despite this recognition, updating practices are not regular, and many organizations lack a formal written policy for updating SRs. This research marks the first baseline data available on updating from an organizational perspective.
doi:10.1371/journal.pone.0009914
PMCID: PMC2848577  PMID: 20376338
6.  NEURAL SYSTEM FOR UPDATING OBJECT WORKING MEMORY FROM DIFFERENT SOURCES: SENSORY STIMULI OR LONG TERM MEMORY 
NeuroImage  2007;38(3):617-630.
Working memory (WM) is the active maintenance of currently relevant information so that it is available for use. A crucial component of WM is the ability to update the contents when new information becomes more relevant than previously maintained information. New information can come from different sources, including from sensory stimuli (SS) or from long-term memory (LTM). Updating WM may involve a single neural system regardless of source, distinct systems for each source, or a common network with additional regions involved specifically in sensory or LTM processes. The current series of experiments indicates that a single fronto-parietal network (including Supplementary Motor Area, Parietal, Left Inferior Frontal Junction, Middle Frontal Gyrus) is active in updating WM regardless of the source of information. Bilateral Cuneus was more active during updating WM from LTM than updating from SS, but the activity in this region was attributable to recalling information from LTM regardless of whether that information was to be entered into WM for future use or not. No regions were found to be more active during updating from SS than updating from LTM. Functional connectivity analysis revealed that different regions within this common update network were differentially more correlated with visual processing regions when participants updated from SS, and more correlated with LTM processing regions when participants updated from the contents of LTM. These results suggest a single neural mechanism is responsible for controlling the contents of WM regardless of whether that information originates from a sensory stimulus or from LTM. This network of regions involved in updating WM interacts with the rest of the brain differently depending on the source of newly-relevant information.
doi:10.1016/j.neuroimage.2007.06.037
PMCID: PMC2080868  PMID: 17888688
fMRI; frontal; attention; cognitive control; parietal; working memory; long term memory
7.  Human Visuospatial Updating After Passive Translations In Three-Dimensional Space 
Journal of neurophysiology  2008;99(4):10.1152/jn.01091.2007.
To maintain a stable representation of the visual environment as we move, the brain must update the locations of targets in space using extra-retinal signals. Humans can accurately update after intervening active whole-body translations. But can they also update for passive translations (i.e., without efference copy signals of an outgoing motor command)? We asked six head-fixed subjects to remember the location of a briefly flashed target (five possible targets were located at depths of 23, 33, 43, 63 and 150cm in front of the cyclopean eye) as they moved 10cm left, right, up, down, forward or backward, while fixating a head-fixed target at 53cm. After the movement, the subjects made a saccade to the remembered location of the flash with a combination of version and vergence eye movements. We computed an updating ratio where 0 indicates no updating and 1 indicates perfect updating. For lateral and vertical whole-body motion, where updating performance is judged by the size of the version movement, the updating ratios were similar for leftward and rightward translations, averaging 0.84±0.28 (mean±SD), as compared to 0.51±0.33 for downward and 1.05±0.50 for upward translations. For forward/backward movements, where updating performance is judged by the size of the vergence movement, the average updating ratio was 1.12±0.45. Updating ratios tended to be larger for far targets than near targets, although both intra- and inter-subject variabilities were smallest for near targets. Thus, in addition to self-generated movements, extra-retinal signals involving otolith and proprioceptive cues can also be used for spatial constancy.
doi:10.1152/jn.01091.2007
PMCID: PMC3835451  PMID: 18256164
8.  Guidance for updating clinical practice guidelines: a systematic review of methodological handbooks 
Background
Updating clinical practice guidelines (CPGs) is a crucial process for maintaining the validity of recommendations. Methodological handbooks should provide guidance on both developing and updating CPGs. However, little is known about the updating guidance provided by these handbooks.
Methods
We conducted a systematic review to identify and describe the updating guidance provided by CPG methodological handbooks and included handbooks that provide updating guidance for CPGs. We searched in the Guidelines International Network library, US National Guidelines Clearinghouse and MEDLINE (PubMed) from 1966 to September 2013. Two authors independently selected the handbooks and extracted the data. We used descriptive statistics to analyze the extracted data and conducted a narrative synthesis.
Results
We included 35 handbooks. Most handbooks (97.1%) focus mainly on developing CPGs, including variable degrees of information about updating. Guidance on identifying new evidence and the methodology of assessing the need for an update is described in 11 (31.4%) and eight handbooks (22.8%), respectively. The period of time between two updates is described in 25 handbooks (71.4%), two to three years being the most frequent (40.0%). The majority of handbooks do not provide guidance for the literature search, evidence selection, assessment, synthesis, and external review of the updating process.
Conclusions
Guidance for updating CPGs is poorly described in methodological handbooks. This guidance should be more rigorous and explicit. This could lead to a more optimal updating process, and, ultimately to valid trustworthy guidelines.
doi:10.1186/1748-5908-9-3
PMCID: PMC3904688  PMID: 24383701
Clinical practice guidelines; Evidence-based medicine; Handbooks; Methodology; Systematic review
9.  Does updating improve the methodological and reporting quality of systematic reviews? 
Background
Systematic reviews (SRs) must be of high quality. The purpose of our research was to compare the methodological and reporting quality of original versus updated Cochrane SRs to determine whether updating had improved these two quality dimensions.
Methods
We identifed updated Cochrane SRs published in issue 4, 2002 of the Cochrane Library. We assessed the updated and original versions of the SRs using two instruments: the 10 item enhanced Overview Quality Assessment Questionnaire (OQAQ), and an 18-item reporting quality checklist and flow chart based upon the Quality of Reporting of Meta-analyses (QUOROM) statement. At least two reviewers extracted data and assessed quality. We calculated the percentage (with a 95% confidence interval) of 'yes' answers to each question. We calculated mean differences in percentage, 95% confidence intervals and p-values for each of the individual items and the overall methodological quality score of the updated and pre-updated versions using OQAQ.
Results
We assessed 53 SRs. There was no significant improvement in the global quality score of the OQAQ (mean difference 0.11 (-0.28; 0.70 p = 0.52)). Updated reviews showed a significant improvement of 18.9 (7.2; 30.6 p < .01) on the OQAQ item assessing whether the conclusions drawn by the author(s) were supported by the data and/or analysis presented in the SR. The QUOROM statement showed that the quality of reporting of Cochrane reviews improved in some areas with updating. Improvements were seen on the items relating to data sources reported in the abstract, with a significant difference of 17.0 (9.8; 28.7 p = 0.01), review methods, reported in the abstract 35 (24.1; 49.1 p = 0.00), searching methods 18.9 (9.7; 31.6 p = 0.01), and data abstraction 18.9 (11.7; 30.9 p = 0.00).
Conclusion
The overall quality of Cochrane SRs is fair-to-good. Although reporting quality improved on certain individual items there was no overall improvement seen with updating and methodological quality remained unchanged. Further improvement of quality of reporting is possible. There is room for improvement of methodological quality as well. Authors updating reviews should address identified methodological or reporting weaknesses. We recommend to give full attention to both quality domains when updating SRs.
doi:10.1186/1471-2288-6-27
PMCID: PMC1569863  PMID: 16772030
10.  Studying the potential impact of automated document classification on scheduling a systematic review update 
Background
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.
Methods
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.
Results
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.
Conclusions
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.
doi:10.1186/1472-6947-12-33
PMCID: PMC3420236  PMID: 22515596
11.  Investing in updating: how do conclusions change when Cochrane systematic reviews are updated? 
Background
Cochrane systematic reviews aim to provide readers with the most up-to-date evidence on the effects of healthcare interventions. The policy of updating Cochrane reviews every two years consumes valuable time and resources and may not be appropriate for all reviews. The objective of this study was to examine the effect of updating Cochrane systematic reviews over a four year period.
Methods
This descriptive study examined all completed systematic reviews in the Cochrane Database of Systematic Reviews (CDSR) Issue 2, 1998. The latest version of each of these reviews was then identified in CDSR Issue 2, 2002 and changes in the review were described. For reviews that were updated within this time period and had additional studies, we determined whether their conclusion had changed and if there were factors that were predictive of this change.
Results
A total of 377 complete reviews were published in CDSR Issue 2, 1998. In Issue 2, 2002, 14 of these reviews were withdrawn and one was split, leaving 362 reviews to examine for the purpose of this study. Of these reviews, 254 (70%) were updated. Of these updated reviews, 23 (9%) had a change in conclusion. Both an increase in precision and a change in statistical significance of the primary outcome were predictive of a change in conclusion of the review.
Conclusion
The concerns around a lack of updating for some reviews may not be justified considering the small proportion of updated reviews that resulted in a changed conclusion. A priority-setting approach to the updating of Cochrane systematic reviews may be more appropriate than a time-based approach. Updating all reviews as frequently as every two years may not be necessary, however some reviews may need to be updated more often than every two years.
doi:10.1186/1471-2288-5-33
PMCID: PMC1274326  PMID: 16225692
12.  Many family physicians will not manually update PDA software: an observational study 
Informatics in primary care  2009;17(4):225-230.
Background
In a prospective study to explore connections between clinical information delivery and information retrieval, 41 Canadian family physicians searched an Electronic Knowledge Resource as needed for practice. Research software, called the Information Assessment Method prompted family physicians to report on the situational relevance, perceived cognitive impact, and application of their retrieved information hits. Both the Information Assessment Method and the Electronic Knowledge Resource needed periodic updating to properly address our research questions.
Objective
To determine the frequency of software updates when manual or semi-automatic approaches are used by family physicians.
Methods
Each family physician received a handheld computer (PDA) that ran the Windows Mobile 6 operating system. For technical reasons, the Information Assessment Method and the Electronic Knowledge Resource were accessed offline on PDA. To update the Electronic Knowledge Resource and the Information Assessment Method, family physicians were asked to synchronize their PDA to their PC. Updating the Information Assessment Method was a manual process, whereas updating the Electronic Knowledge Resource was semi-automatic.
Results
We found: (1) about 25% of family physicians never or rarely updated PDA software on their own (2) a large number of software updates were never installed, and (3) the semi-automatic method was associated with a small increase in the proportion of installed software updates (58.9% versus 48.6% for the manual method).
Conclusions
When a wireless Internet connection is not used to update PDA software, sociotechnical issues complicate mobile data collection and data transfer.
PMCID: PMC2878612  PMID: 20359400 CAMSID: cams799
Computers handheld; software; family practice
13.  The updating of clinical practice guidelines: insights from an international survey 
Background
Clinical practice guidelines (CPGs) have become increasingly popular, and the methodology to develop guidelines has evolved enormously. However, little attention has been given to the updating process, in contrast to the appraisal of the available literature. We conducted an international survey to identify current practices in CPG updating and explored the need to standardize and improve the methods.
Methods
We developed a questionnaire (28 items) based on a review of the existing literature about guideline updating and expert comments. We carried out the survey between March and July 2009, and it was sent by email to 106 institutions: 69 members of the Guidelines International Network who declared that they developed CPGs; 30 institutions included in the U.S. National Guideline Clearinghouse database that published more than 20 CPGs; and 7 institutions selected by an expert committee.
Results
Forty-four institutions answered the questionnaire (42% response rate). In the final analysis, 39 completed questionnaires were included. Thirty-six institutions (92%) reported that they update their guidelines. Thirty-one institutions (86%) have a formal procedure for updating their guidelines, and 19 (53%) have a formal procedure for deciding when a guideline becomes out of date. Institutions describe the process as moderately rigorous (36%) or acknowledge that it could certainly be more rigorous (36%). Twenty-two institutions (61%) alert guideline users on their website when a guideline is older than three to five years or when there is a risk of being outdated. Twenty-five institutions (64%) support the concept of "living guidelines," which are continuously monitored and updated. Eighteen institutions (46%) have plans to design a protocol to improve their guideline-updating process, and 21 (54%) are willing to share resources with other organizations.
Conclusions
Our study is the first to describe the process of updating CPGs among prominent guideline institutions across the world, providing a comprehensive picture of guideline updating. There is an urgent need to develop rigorous international standards for this process and to minimize duplication of effort internationally.
doi:10.1186/1748-5908-6-107
PMCID: PMC3191352  PMID: 21914177
14.  How Do We Update Faces? Effects of Gaze Direction and Facial Expressions on Working Memory Updating 
The aim of the study was to investigate how the biological binding between different facial dimensions, and their social and communicative relevance, may impact updating processes in working memory (WM). We focused on WM updating because it plays a key role in ongoing processing. Gaze direction and facial expression are crucial and changeable components of face processing. Direct gaze enhances the processing of approach-oriented facial emotional expressions (e.g., joy), while averted gaze enhances the processing of avoidance-oriented facial emotional expressions (e.g., fear). Thus, the way in which these two facial dimensions are combined communicates to the observer important behavioral and social information. Updating of these two facial dimensions and their bindings has not been investigated before, despite the fact that they provide a piece of social information essential for building and maintaining an internal ongoing representation of our social environment. In Experiment 1 we created a task in which the binding between gaze direction and facial expression was manipulated: high binding conditions (e.g., joy-direct gaze) were compared to low binding conditions (e.g., joy-averted gaze). Participants had to study and update continuously a number of faces, displaying different bindings between the two dimensions. In Experiment 2 we tested whether updating was affected by the social and communicative value of the facial dimension binding; to this end, we manipulated bindings between eye and hair color, two less communicative facial dimensions. Two new results emerged. First, faster response times were found in updating combinations of facial dimensions highly bound together. Second, our data showed that the ease of the ongoing updating processing varied depending on the communicative meaning of the binding that had to be updated. The results are discussed with reference to the role of WM updating in social cognition and appraisal processes.
doi:10.3389/fpsyg.2012.00362
PMCID: PMC3459018  PMID: 23060832
biological binding; social cognition; appraisal; gaze direction; facial expression; facial dimensions; working memory
15.  Strategies for monitoring and updating clinical practice guidelines: a systematic review 
Background
Scientific knowledge is in constant change. The flow of new information requires a frequent re-evaluation of the available research results. Clinical practice guidelines (CPGs) are not exempted from this phenomenon and need to be kept updated to maintain the validity of their recommendations. The objective of our review is to systematically identify, describe and assess strategies for monitoring and updating CPGs.
Study design and setting
We conducted a systematic review of studies evaluating one or more methods of updating (with or without monitoring) CPGs or recommendations. We searched MEDLINE (PubMed) and The Cochrane Methodology Register (The Cochrane Library) from 1966 to June 2012. Additionally, we hand-searched reference lists of the included studies and the Guidelines International Network book of abstracts. If necessary, we contacted study authors to obtain additional information.
Results
We included a total of eight studies. Four evaluated if CPGs were out of date, three updated CPGs, and one continuously monitored and updated CPGs. The most detailed reported phase of the process was the identification of new evidence. As opposed to studies updating guidelines, studies evaluating if CPGs were out of date applied restricted searches. Only one study compared a restricted versus an exhaustive search suggesting that a restricted search is sufficient to assess recommendations’ Validity. One study analyzed the survival time of CPGs and suggested that these should be reassessed every three years.
Conclusions
There is limited evidence about the optimal strategies for monitoring and updating clinical practice guidelines. A restricted search is likely to be sufficient to monitor new evidence and assess the need to update, however, more information is needed about the timing and type of search. Only the exhaustive search strategy has been assessed for the update of CPGs. The development and evaluation of more efficient strategies is needed to improve the timeliness and reduce the burden of maintaining the validity of CPGs.
doi:10.1186/1748-5908-7-109
PMCID: PMC3520818  PMID: 23164220
Clinical practice guidelines; Diffusion of innovation; Evidence-based medicine; Information storage and retrieval; Methodology; Updating; Implementation science; Dissemination and implementation; Knowledge translation
16.  Working Memory and Anticipatory Set Modulate Midbrain and Putamen Activity 
The Journal of Neuroscience  2013;33(35):14040-14047.
To behave adaptively, an organism must balance the accurate maintenance of information stored in working memory with the ability to update that information when the context changes. This trade-off between fidelity and flexibility may depend upon the anticipated likelihood that updating will be necessary. To address the neurobiological basis of anticipatory optimization, we acquired functional magnetic resonance imaging data, while healthy human subjects performed a modified delayed-response task. This task used cues that predicted memory updating, with high or low probability, followed by a contingent updating or maintenance event. This enabled us to compare behavior and neuronal activity during conditions in which updating was anticipated with high and low probability, and measure responses to expected and unexpected memory updating. Based on the known role of dopamine in cognitive flexibility and working memory updating, we hypothesized that differences in anticipatory set would be manifest in the dopaminergic midbrain and striatum. Consistent with our predictions, we identified sustained activation in the dopaminergic midbrain and the striatum, associated with anticipations of high versus low updating probability. We also found that this anticipatory factor affected neural responses to subsequent updating processes, which suppressed, rather than elevated, midbrain and striatal activity. Our study addresses for the first time an important and hitherto understudied aspect of working memory.
doi:10.1523/JNEUROSCI.1176-13.2013
PMCID: PMC3756752  PMID: 23986240
17.  Right-hand-side updating for fast computing of genomic breeding values 
Background
Since both the number of SNPs (single nucleotide polymorphisms) used in genomic prediction and the number of individuals used in training datasets are rapidly increasing, there is an increasing need to improve the efficiency of genomic prediction models in terms of computing time and memory (RAM) required.
Methods
In this paper, two alternative algorithms for genomic prediction are presented that replace the originally suggested residual updating algorithm, without affecting the estimates. The first alternative algorithm continues to use residual updating, but takes advantage of the characteristic that the predictor variables in the model (i.e. the SNP genotypes) take only three different values, and is therefore termed “improved residual updating”. The second alternative algorithm, here termed “right-hand-side updating” (RHS-updating), extends the idea of improved residual updating across multiple SNPs. The alternative algorithms can be implemented for a range of different genomic predictions models, including random regression BLUP (best linear unbiased prediction) and most Bayesian genomic prediction models. To test the required computing time and RAM, both alternative algorithms were implemented in a Bayesian stochastic search variable selection model.
Results
Compared to the original algorithm, the improved residual updating algorithm reduced CPU time by 35.3 to 43.3%, without changing memory requirements. The RHS-updating algorithm reduced CPU time by 74.5 to 93.0% and memory requirements by 13.1 to 66.4% compared to the original algorithm.
Conclusions
The presented RHS-updating algorithm provides an interesting alternative to reduce both computing time and memory requirements for a range of genomic prediction models.
doi:10.1186/1297-9686-46-24
PMCID: PMC4036606  PMID: 24708180
18.  Factors influencing infants’ ability to update object representations in memory 
Cognitive development  2013;28(3):272-289.
Remembering persisting objects over occlusion is critical to representing a stable environment. Infants remember hidden objects at multiple locations and can update their representation of a hidden array when an object is added or subtracted. However, the factors influencing these updating abilities have received little systematic exploration. Here we examined the flexibility of infants’ ability to update object representations. We tested 11-month-olds in a looking-time task in which objects were added to or subtracted from two hidden arrays. Across five experiments, infants successfully updated their representations of hidden arrays when the updating occurred successively at one array before beginning at the other. But when updating required alternating between two arrays, infants failed. However, simply connecting the two arrays with a thin strip of foam-core led infants to succeed. Our results suggest that infants’ construal of an event strongly affects their ability to update memory representations of hidden objects. When construing an event as containing multiple updates to the same array, infants succeed, but when construing the event as requiring the revisiting and updating of previously attended arrays, infants fail.
doi:10.1016/j.cogdev.2013.04.002
PMCID: PMC3773368  PMID: 24049245
memory; cognitive development; memory and attention; infants; objects
19.  Updating action domain descriptions☆ 
Artificial Intelligence  2010;174(15):1172-1221.
Incorporating new information into a knowledge base is an important problem which has been widely investigated. In this paper, we study this problem in a formal framework for reasoning about actions and change. In this framework, action domains are described in an action language whose semantics is based on the notion of causality. Unlike the formalisms considered in the related work, this language allows straightforward representation of non-deterministic effects and indirect effects of (possibly concurrent) actions, as well as state constraints; therefore, the updates can be more general than elementary statements. The expressivity of this formalism allows us to study the update of an action domain description with a more general approach compared to related work. First of all, we consider the update of an action description with respect to further criteria, for instance, by ensuring that the updated description entails some observations, assertions, or general domain properties that constitute further constraints that are not expressible in an action description in general. Moreover, our framework allows us to discriminate amongst alternative updates of action domain descriptions and to single out a most preferable one, based on a given preference relation possibly dependent on the specified criteria. We study semantic and computational aspects of the update problem, and establish basic properties of updates as well as a decomposition theorem that gives rise to a divide and conquer approach to updating action descriptions under certain conditions. Furthermore, we study the computational complexity of decision problems around computing solutions, both for the generic setting and for two particular preference relations, viz. set-inclusion and weight-based preference. While deciding the existence of solutions and recognizing solutions are PSPACE-complete problems in general, the problems fall back into the polynomial hierarchy under restrictions on the additional constraints. We finally discuss methods to compute solutions and approximate solutions (which disregard preference). Our results provide a semantic and computational basis for developing systems that incorporate new information into action domain descriptions in an action language, in the presence of additional constraints.
doi:10.1016/j.artint.2010.07.004
PMCID: PMC2978003  PMID: 21151324
Knowledge representation; Reasoning about actions and change; Theory change; Action languages; Preference-based semantics
20.  The Cognitive Building Blocks of Emotion Regulation: Ability to Update Working Memory Moderates the Efficacy of Rumination and Reappraisal on Emotion 
PLoS ONE  2013;8(7):e69071.
The ability to regulate emotions is a critical component of healthy emotional functioning. Therefore, it is important to determine factors that contribute to the efficacy of emotion regulation. The present article examined whether the ability to update emotional information in working memory is a predictor of the efficacy of rumination and reappraisal on affective experience both at the trait level (Study 1) and in daily life (Study 2). In both studies, results revealed that the relationship between use of reappraisal and high arousal negative emotions was moderated by updating ability. Specifically, use of reappraisal was associated with decreased high arousal negative emotions for participants with high updating ability, while no significant relationship was found for those with low updating ability. In addition, both studies also revealed that the relationship between rumination and high arousal negative emotions was moderated by updating ability. In general, use of rumination was associated with elevated high arousal negative emotions. However, this relationship was blunted for participants with high updating ability. That is, use of rumination was associated with less elevated high arousal negative emotions for participants with high updating ability. These results identify the ability to update emotional information in working memory as a crucial process modulating the efficacy of emotion regulation efforts.
doi:10.1371/journal.pone.0069071
PMCID: PMC3715480  PMID: 23874872
21.  A surveillance system to assess the need for updating systematic reviews 
Systematic Reviews  2013;2:104.
Background
Systematic reviews (SRs) can become outdated as new evidence emerges over time. Organizations that produce SRs need a surveillance method to determine when reviews are likely to require updating. This report describes the development and initial results of a surveillance system to assess SRs produced by the Agency for Healthcare Research and Quality (AHRQ) Evidence-based Practice Center (EPC) Program.
Methods
Twenty-four SRs were assessed using existing methods that incorporate limited literature searches, expert opinion, and quantitative methods for the presence of signals triggering the need for updating. The system was designed to begin surveillance six months after the release of the original review, and thenceforth every six months for any review not classified as being a high priority for updating. The outcome of each round of surveillance was a classification of the SR as being low, medium or high priority for updating.
Results
Twenty-four SRs underwent surveillance at least once, and ten underwent surveillance a second time during the 18 months of the program. Two SRs were classified as high, five as medium, and 17 as low priority for updating. The time lapse between the searches conducted for the original reports and the updated searches (search time lapse - STL) ranged from 11 months to 62 months: The STL for the high priority reports were 29 months and 54 months; those for medium priority reports ranged from 19 to 62 months; and those for low priority reports ranged from 11 to 33 months. Neither the STL nor the number of new relevant articles was perfectly associated with a signal for updating. Challenges of implementing the surveillance system included determining what constituted the actual conclusions of an SR that required assessing; and sometimes poor response rates of experts.
Conclusion
In this system of regular surveillance of 24 systematic reviews on a variety of clinical interventions produced by a leading organization, about 70% of reviews were determined to have a low priority for updating. Evidence suggests that the time period for surveillance is yearly rather than the six months used in this project.
doi:10.1186/2046-4053-2-104
PMCID: PMC3874670  PMID: 24225065
Systematic review; Updating; Surveillance
22.  Comparative evaluation of open source software for mapping between metabolite identifiers in metabolic network reconstructions: application to Recon 2 
Background
An important step in the reconstruction of a metabolic network is annotation of metabolites. Metabolites are generally annotated with various database or structure based identifiers. Metabolite annotations in metabolic reconstructions may be incorrect or incomplete and thus need to be updated prior to their use. Genome-scale metabolic reconstructions generally include hundreds of metabolites. Manually updating annotations is therefore highly laborious. This prompted us to look for open-source software applications that could facilitate automatic updating of annotations by mapping between available metabolite identifiers. We identified three applications developed for the metabolomics and chemical informatics communities as potential solutions. The applications were MetMask, the Chemical Translation System, and UniChem. The first implements a “metabolite masking” strategy for mapping between identifiers whereas the latter two implement different versions of an InChI based strategy. Here we evaluated the suitability of these applications for the task of mapping between metabolite identifiers in genome-scale metabolic reconstructions. We applied the best suited application to updating identifiers in Recon 2, the latest reconstruction of human metabolism.
Results
All three applications enabled partially automatic updating of metabolite identifiers, but significant manual effort was still required to fully update identifiers. We were able to reduce this manual effort by searching for new identifiers using multiple types of information about metabolites. When multiple types of information were combined, the Chemical Translation System enabled us to update over 3,500 metabolite identifiers in Recon 2. All but approximately 200 identifiers were updated automatically.
Conclusions
We found that an InChI based application such as the Chemical Translation System was better suited to the task of mapping between metabolite identifiers in genome-scale metabolic reconstructions. We identified several features, however, that could be added to such an application in order to tailor it to this task.
doi:10.1186/1758-2946-6-2
PMCID: PMC3917611  PMID: 24468196
Metabolic network reconstruction; Metabolite identifiers; Automation; MetMask; The Chemical Translation System; UniChem; Recon 2
23.  A Synchronous-Asynchronous Particle Swarm Optimisation Algorithm 
The Scientific World Journal  2014;2014:123019.
In the original particle swarm optimisation (PSO) algorithm, the particles' velocities and positions are updated after the whole swarm performance is evaluated. This algorithm is also known as synchronous PSO (S-PSO). The strength of this update method is in the exploitation of the information. Asynchronous update PSO (A-PSO) has been proposed as an alternative to S-PSO. A particle in A-PSO updates its velocity and position as soon as its own performance has been evaluated. Hence, particles are updated using partial information, leading to stronger exploration. In this paper, we attempt to improve PSO by merging both update methods to utilise the strengths of both methods. The proposed synchronous-asynchronous PSO (SA-PSO) algorithm divides the particles into smaller groups. The best member of a group and the swarm's best are chosen to lead the search. Members within a group are updated synchronously, while the groups themselves are asynchronously updated. Five well-known unimodal functions, four multimodal functions, and a real world optimisation problem are used to study the performance of SA-PSO, which is compared with the performances of S-PSO and A-PSO. The results are statistically analysed and show that the proposed SA-PSO has performed consistently well.
doi:10.1155/2014/123019
PMCID: PMC4121262  PMID: 25121109
24.  OligoRAP – an Oligo Re-Annotation Pipeline to improve annotation and estimate target specificity 
BMC Proceedings  2009;3(Suppl 4):S4.
Background
High throughput gene expression studies using oligonucleotide microarrays depend on the specificity of each oligonucleotide (oligo or probe) for its target gene. However, target specific probes can only be designed when a reference genome of the species at hand were completely sequenced, when this genome were completely annotated and when the genetic variation of the sampled individuals were completely known. Unfortunately there is not a single species for which such a complete data set is available. Therefore, it is important that probe annotation can be updated frequently for optimal interpretation of microarray experiments.
Results
In this paper we present OligoRAP, a pipeline to automatically update the annotation of oligo libraries and estimate oligo target specificity. OligoRAP uses a reference genome assembly with Ensembl and Entrez Gene annotation supplemented with a set of unmapped transcripts derived from RefSeq and UniGene to handle assembly gaps. OligoRAP produces alignments of each oligo with the reference assembly as well as with unmapped transcripts. These alignments are re-mapped to the annotation sources, which results in a concise, as complete as possible and up-to-date annotation of the oligo library. The building blocks of this pipeline are BioMoby web services creating a highly modular and distributed system with a robust, remote programmatic interface.
OligoRAP was used to update the annotation for a subset of 791 oligos from the ARK-Genomics 20 K chicken array, which were selected as starting material for the oligo annotation session of the EADGENE/SABRE Post-analysis workshop. Based on the updated annotation about one third of these oligos is problematic with regard to target specificity. In addition, the accession numbers or ids the oligos were originally designed for no longer exist in the updated annotation for almost half of the oligos.
Conclusion
As microarrays are designed on incomplete data, it is important to update probe annotation and check target specificity regularly. OligoRAP provides both and due to its design based on BioMoby web services it can easily be embedded as an oligo annotation engine in customised applications for microarray data analysis. The dramatic difference in updated annotation and target specificity for the ARK-Genomics 20 K chicken array as compared to the original data emphasises the need for regular updates.
doi:10.1186/1753-6561-3-S4-S4
PMCID: PMC2712747  PMID: 19615117
25.  Spatial Updating and the Maintenance of Visual Constancy 
Neuroscience  2008;156(4):801-818.
Spatial updating is the means by which we keep track of the locations of objects in space even as we move. Four decades of research have shown that humans and non-human primates can take the amplitude and direction of intervening movements into account, including saccades (both head-fixed and head-free), pursuit, whole-body rotations and translations. At the neuronal level, spatial updating is thought to be maintained by receptive field locations that shift with changes in gaze and evidence for such shifts have been shown in several cortical areas. These regions receive information about the intervening movement from several sources including motor efference copies when a voluntary movement is made and vestibular/somatosensory signals when the body is in motion. Many of these updating signals arise from brainstem regions that monitor our ongoing movements and subsequently transmit this information to the cortex via pathways that likely include the thalamus. Several issues of debate include (1) the relative contribution of extra-retinal sensory and efference copy signals to spatial updating, (2) the source of an updating signal for real life, three-dimensional motion that cannot arise from brain areas encoding only two-dimensional commands, and (3) the reference frames used by the brain to integrate updating signals from various sources. This review highlights the relevant spatial updating studies and provides a summary of the field today. We find that spatial constancy is maintained by a highly evolved neural mechanism that keeps track of our movements, transmits this information to relevant brain regions, and then uses this information to change the way in which single neurons respond. In this way, we are able to keep track of relevant objects in the outside world and interact with them in meaningful ways.
doi:10.1016/j.neuroscience.2008.07.079
PMCID: PMC2677727  PMID: 18786618
oculomotor; efference copy; reference frame; pursuit; vestibular; gaze

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