Quid pro quo:reflections on the value of problem structuring workshops

Attracting clients who are willing to invest in using a problem structuring method (PSM) can be particularly difficult for the emerging generation of modellers. There are many reasons for this, not least that the benefits of a problem structuring intervention are vague and evidence of benefits are often anecdotal for example, claims of constructing a deeper understanding of the problem or building the commitment of a group to implementing an outcome. This paper contributes to the evaluation of problem structuring methods by reflecting on the quid pro quo that a client and problem structuring modeller can enjoy from collaboration. The paper reflects on 21 cases, where Journey Making (a problem structuring method) was used with 16 organizations to help managers agree a suite of actions to tackle a complex strategic issue. The reflections are clustered around those benefits that pertain to: PSMs in general; PSMs that use computer-supported workshops; the Journey Making methodology

DNA replication stress restricts ribosomal DNA copy number

Ribosomal RNAs (rRNAs) in budding yeast are encoded by ~100–200 repeats of a 9.1kb sequence arranged in tandem on chromosome XII, the ribosomal DNA (rDNA) locus. Copy number of rDNA repeat units in eukaryotic cells is maintained far in excess of the requirement for ribosome biogenesis. Despite the importance of the repeats for both ribosomal and non-ribosomal functions, it is currently not known how “normal” copy number is determined or maintained. To identify essential genes involved in the maintenance of rDNA copy number, we developed a droplet digital PCR based assay to measure rDNA copy number in yeast and used it to screen a yeast conditional temperature-sensitive mutant collection of essential genes. Our screen revealed that low rDNA copy number is associated with compromised DNA replication. Further, subculturing yeast under two separate conditions of DNA replication stress selected for a contraction of the rDNA array independent of the replication fork blocking protein, Fob1. Interestingly, cells with a contracted array grew better than their counterparts with normal copy number under conditions of DNA replication stress. Our data indicate that DNA replication stresses select for a smaller rDNA array. We speculate that this liberates scarce replication factors for use by the rest of the genome, which in turn helps cells complete DNA replication and continue to propagate. Interestingly, tumors from mini chromosome maintenance 2 (MCM2)-deficient mice also show a loss of rDNA repeats. Our data suggest that a reduction in rDNA copy number may indicate a history of DNA replication stress, and that rDNA array size could serve as a diagnostic marker for replication stress. Taken together, these data begin to suggest the selective pressures that combine to yield a “normal” rDNA copy number

Selecting information technology for physicians' practices: a cross-sectional study

BACKGROUND: Many physicians are transitioning from paper to electronic formats for billing, scheduling, medical charts, communications, etc. The primary objective of this research was to identify the relationship (if any) between the software selection process and the office staff's perceptions of the software's impact on practice activities. METHODS: A telephone survey was conducted with office representatives of 407 physician practices in Oregon who had purchased information technology. The respondents, usually office managers, answered scripted questions about their selection process and their perceptions of the software after implementation. RESULTS: Multiple logistic regression revealed that software type, selection steps, and certain factors influencing the purchase were related to whether the respondents felt the software improved the scheduling and financial analysis practice activities. Specifically, practices that selected electronic medical record or practice management software, that made software comparisons, or that considered prior user testimony as important were more likely to have perceived improvements in the scheduling process than were other practices. Practices that considered value important, that did not consider compatibility important, that selected managed care software, that spent less than $10,000, or that provided learning time (most dramatic increase in odds ratio, 8.2) during implementation were more likely to perceive that the software had improved the financial analysis process than were other practices. CONCLUSION: Perhaps one of the most important predictors of improvement was providing learning time during implementation, particularly when the software involves several practice activities. Despite this importance, less than half of the practices reported performing this step

Spinning strings and integrable spin chains in the AdS/CFT correspondence

In this introductory review we discuss dynamical tests of the AdS_5 x S^5 string/N=4 super Yang-Mills duality. After a brief introduction to AdS/CFT we argue that semiclassical string energies yield information on the quantum spectrum of the string in the limit of large angular momenta on the S^5. The energies of the folded and circular spinning string solutions rotating on a S^3 within the S^5 are derived, which yield all loop predictions for the dual gauge theory scaling dimensions. These follow from the eigenvalues of the dilatation operator of N=4 super Yang-Mills in a minimal SU(2) subsector and we display its reformulation in terms of a Heisenberg s=1/2 spin chain along with the coordinate Bethe ansatz for its explicit diagonalization. In order to make contact to the spinning string energies we then study the thermodynamic limit of the one-loop gauge theory Bethe equations and demonstrate the matching with the folded and closed string result at this loop order. Finally the known gauge theory results at higher-loop orders are reviewed and the associated long-range spin chain Bethe ansatz is introduced, leading to an asymptotic all-loop conjecture for the gauge theory Bethe equations. This uncovers discrepancies at the three-loop order between gauge theory scaling dimensions and string theory energies and the implications of this are discussed. Along the way we comment on further developments and generalizations of the subject and point to the relevant literature.Comment: 40 pages, invited contribution to Living Reviews in Relativity. v2: improvements in the text and references adde

Altered Neurocircuitry in the Dopamine Transporter Knockout Mouse Brain

The plasma membrane transporters for the monoamine neurotransmitters dopamine, serotonin, and norepinephrine modulate the dynamics of these monoamine neurotransmitters. Thus, activity of these transporters has significant consequences for monoamine activity throughout the brain and for a number of neurological and psychiatric disorders. Gene knockout (KO) mice that reduce or eliminate expression of each of these monoamine transporters have provided a wealth of new information about the function of these proteins at molecular, physiological and behavioral levels. In the present work we use the unique properties of magnetic resonance imaging (MRI) to probe the effects of altered dopaminergic dynamics on meso-scale neuronal circuitry and overall brain morphology, since changes at these levels of organization might help to account for some of the extensive pharmacological and behavioral differences observed in dopamine transporter (DAT) KO mice. Despite the smaller size of these animals, voxel-wise statistical comparison of high resolution structural MR images indicated little morphological change as a consequence of DAT KO. Likewise, proton magnetic resonance spectra recorded in the striatum indicated no significant changes in detectable metabolite concentrations between DAT KO and wild-type (WT) mice. In contrast, alterations in the circuitry from the prefrontal cortex to the mesocortical limbic system, an important brain component intimately tied to function of mesolimbic/mesocortical dopamine reward pathways, were revealed by manganese-enhanced MRI (MEMRI). Analysis of co-registered MEMRI images taken over the 26 hours after introduction of Mn^(2+) into the prefrontal cortex indicated that DAT KO mice have a truncated Mn^(2+) distribution within this circuitry with little accumulation beyond the thalamus or contralateral to the injection site. By contrast, WT littermates exhibit Mn^(2+) transport into more posterior midbrain nuclei and contralateral mesolimbic structures at 26 hr post-injection. Thus, DAT KO mice appear, at this level of anatomic resolution, to have preserved cortico-striatal-thalamic connectivity but diminished robustness of reward-modulating circuitry distal to the thalamus. This is in contradistinction to the state of this circuitry in serotonin transporter KO mice where we observed more robust connectivity in more posterior brain regions using methods identical to those employed here

Ralstonia syzygii, the Blood Disease Bacterium and Some Asian R. solanacearum Strains Form a Single Genomic Species Despite Divergent Lifestyles

The Ralstonia solanacearum species complex includes R. solanacearum, R. syzygii, and the Blood Disease Bacterium (BDB). All colonize plant xylem vessels and cause wilt diseases, but with significant biological differences. R. solanacearum is a soilborne bacterium that infects the roots of a broad range of plants. R. syzygii causes Sumatra disease of clove trees and is actively transmitted by cercopoid insects. BDB is also pathogenic to a single host, banana, and is transmitted by pollinating insects. Sequencing and DNA-DNA hybridization studies indicated that despite their phenotypic differences, these three plant pathogens are actually very closely related, falling into the Phylotype IV subgroup of the R. solanacearum species complex. To better understand the relationships among these bacteria, we sequenced and annotated the genomes of R. syzygii strain R24 and BDB strain R229. These genomes were compared to strain PSI07, a closely related Phylotype IV tomato isolate of R. solanacearum, and to five additional R. solanacearum genomes. Whole-genome comparisons confirmed previous phylogenetic results: the three phylotype IV strains share more and larger syntenic regions with each other than with other R. solanacearum strains. Furthermore, the genetic distances between strains, assessed by an in-silico equivalent of DNA-DNA hybridization, unambiguously showed that phylotype IV strains of BDB, R. syzygii and R. solanacearum form one genomic species. Based on these comprehensive data we propose a revision of the taxonomy of the R. solanacearum species complex. The BDB and R. syzygii genomes encoded no obvious unique metabolic capacities and contained no evidence of horizontal gene transfer from bacteria occupying similar niches. Genes specific to R. syzygii and BDB were almost all of unknown function or extrachromosomal origin. Thus, the pathogenic life-styles of these organisms are more probably due to ecological adaptation and genomic convergence during vertical evolution than to the acquisition of DNA by horizontal transfer

Increasing efficacy of primary care-based counseling for diabetes prevention: Rationale and design of the ADAPT (Avoiding Diabetes Thru Action Plan Targeting) trial

<p>Abstract</p> <p>Background</p> <p>Studies have shown that lifestyle behavior changes are most effective to prevent onset of diabetes in high-risk patients. Primary care providers are charged with encouraging behavior change among their patients at risk for diabetes, yet the practice environment and training in primary care often do not support effective provider counseling. The goal of this study is to develop an electronic health record-embedded tool to facilitate shared patient-provider goal setting to promote behavioral change and prevent diabetes.</p> <p>Methods</p> <p>The ADAPT (Avoiding Diabetes Thru Action Plan Targeting) trial leverages an innovative system that integrates evidence-based interventions for behavioral change with already-existing technology to enhance primary care providers' effectiveness to counsel about lifestyle behavior changes. Using principles of behavior change theory, the multidisciplinary design team utilized in-depth interviews and <it>in vivo </it>usability testing to produce a prototype diabetes prevention counseling system embedded in the electronic health record.</p> <p>Results</p> <p>The core element of the tool is a streamlined, shared goal-setting module within the electronic health record system. The team then conducted a series of innovative, "near-live" usability testing simulations to refine the tool and enhance workflow integration. The system also incorporates a pre-encounter survey to elicit patients' behavior-change goals to help tailor patient-provider goal setting during the clinical encounter and to encourage shared decision making. Lastly, the patients interact with a website that collects their longitudinal behavior data and allows them to visualize their progress over time and compare their progress with other study members. The finalized ADAPT system is now being piloted in a small randomized control trial of providers using the system with prediabetes patients over a six-month period.</p> <p>Conclusions</p> <p>The ADAPT system combines the influential powers of shared goal setting and feedback, tailoring, modeling, contracting, reminders, and social comparisons to integrate evidence-based behavior-change principles into the electronic health record to maximize provider counseling efficacy during routine primary care clinical encounters. If successful, the ADAPT system may represent an adaptable and scalable technology-enabled behavior-change tool for all primary care providers.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov Identifier <a href="http://www.clinicaltrials.gov/ct2/show/NCT01473654">NCT01473654</a></p

Incidence and survival of childhood bone cancer in northern England and the West Midlands, 1981–2002

There is a paucity of population-based studies examining incidence and survival trends in childhood bone tumours. We used high quality data from four population-based registries in England. Incidence patterns and trends were described using Poisson regression. Survival trends were analysed using Cox regression. There were 374 cases of childhood (ages 0–14 years) bone tumours (206 osteosarcomas, 144 Ewing sarcomas, 16 chondrosarcomas, 8 other bone tumours) registered in the period 1981–2002. Overall incidence (per million person years) rates were 2.63 (95% confidence interval (CI) 2.27–2.99) for osteosarcoma, 1.90 (1.58–2.21) for Ewing sarcoma and 0.21 (0.11–0.31) for chondrosarcoma. Incidence of Ewing sarcoma declined at an average rate of 3.1% (95% CI 0.6–5.6) per annum (P=0.04), which may be due to tumour reclassification, but there was no change in osteosarcoma incidence. Survival showed marked improvement over the 20 years (1981–2000) for Ewing sarcoma (hazard ratio (HR) per annum=0.95 95% CI 0.91–0.99; P=0.02). However, no improvement was seen for osteosarcoma patients (HR per annum=1.02 95% CI 0.98–1.05; P=0.35) over this time period. Reasons for failure to improve survival including potential delays in diagnosis, accrual to trials, adherence to therapy and lack of improvement in treatment strategies all need to be considered