Towards an interoperable healthcare information infrastructure - working from the bottom up

Historically, the healthcare system has not made effective use of information technology. On the face of things, it would seem to provide a natural and richly varied domain in which to target benefit from IT solutions. But history shows that it is one of the most difficult domains in which to bring them to fruition. This paper provides an overview of the changing context and information requirements of healthcare that help to explain these characteristics.First and foremost, the disciplines and professions that healthcare encompasses have immense complexity and diversity to deal with, in structuring knowledge about what medicine and healthcare are, how they function, and what differentiates good practice and good performance. The need to maintain macro-economic stability of the health service, faced with this and many other uncertainties, means that management bottom lines predominate over choices and decisions that have to be made within everyday individual patient services. Individual practice and care, the bedrock of healthcare, is, for this and other reasons, more and more subject to professional and managerial control and regulation.One characteristic of organisations shown to be good at making effective use of IT is their capacity to devolve decisions within the organisation to where they can be best made, for the purpose of meeting their customers' needs. IT should, in this context, contribute as an enabler and not as an enforcer of good information services. The information infrastructure must work effectively, both top down and bottom up, to accommodate these countervailing pressures. This issue is explored in the context of infrastructure to support electronic health records.Because of the diverse and changing requirements of the huge healthcare sector, and the need to sustain health records over many decades, standardised systems must concentrate on doing the easier things well and as simply as possible, while accommodating immense diversity of requirements and practice. The manner in which the healthcare information infrastructure can be formulated and implemented to meet useful practical goals is explored, in the context of two case studies of research in CHIME at UCL and their user communities.Healthcare has severe problems both as a provider of information and as a purchaser of information systems. This has an impact on both its customer and its supplier relationships. Healthcare needs to become a better purchaser, more aware and realistic about what technology can and cannot do and where research is needed. Industry needs a greater awareness of the complexity of the healthcare domain, and the subtle ways in which information is part of the basic contract between healthcare professionals and patients, and the trust and understanding that must exist between them. It is an ideal domain for deeper collaboration between academic institutions and industry

Optimizing the scale of markets for water quality trading

Applying market approaches to environmental regulations requires establishing a spatial scale for trading. Spatially large markets usually increase opportunities for abatement cost savings but increase the potential for pollution damages (hot spots), vice versa for spatially small markets. We develop a coupled hydrologic-economic modeling approach for application to point source emissions trading by a large number of sources and apply this approach to the wastewater treatment plants (WWTPs) within the watershed of the second largest estuary in the U.S. We consider two different administrative structures that govern the trade of emission permits: one-for-one trading (the number of permits required for each unit of emission is the same for every WWTP) and trading ratios (the number of permits required for each unit of emissions varies across WWTP). Results show that water quality regulators should allow trading to occur at the river basin scale as an appropriate first-step policy, as is being done in a limited number of cases via compliance associations. Larger spatial scales may be needed under conditions of increased abatement costs. The optimal scale of the market is generally the same regardless of whether one-for-one trading or trading ratios are employed

Connectionist perspectives on language learning, representation and processing.

The field of formal linguistics was founded on the premise that language is mentally represented as a deterministic symbolic grammar. While this approach has captured many important characteristics of the world\u27s languages, it has also led to a tendency to focus theoretical questions on the correct formalization of grammatical rules while also de-emphasizing the role of learning and statistics in language development and processing. In this review we present a different approach to language research that has emerged from the parallel distributed processing or \u27connectionist\u27 enterprise. In the connectionist framework, mental operations are studied by simulating learning and processing within networks of artificial neurons. With that in mind, we discuss recent progress in connectionist models of auditory word recognition, reading, morphology, and syntactic processing. We argue that connectionist models can capture many important characteristics of how language is learned, represented, and processed, as well as providing new insights about the source of these behavioral patterns. Just as importantly, the networks naturally capture irregular (non-rule-like) patterns that are common within languages, something that has been difficult to reconcile with rule-based accounts of language without positing separate mechanisms for rules and exceptions

Perturbation with Intrabodies Reveals That Calpain Cleavage Is Required for Degradation of Huntingtin Exon 1

Background: Proteolytic processing of mutant huntingtin (mHtt), the protein that causes Huntington's disease (HD), is critical for mHtt toxicity and disease progression. mHtt contains several caspase and calpain cleavage sites that generate N-terminal fragments that are more toxic than full-length mHtt. Further processing is then required for the degradation of these fragments, which in turn, reduces toxicity. This unknown, secondary degradative process represents a promising therapeutic target for HD. Methodology/Principal Findings: We have used intrabodies, intracellularly expressed antibody fragments, to gain insight into the mechanism of mutant huntingtin exon 1 (mHDx-1) clearance. Happ1, an intrabody recognizing the proline-rich region of mHDx-1, reduces the level of soluble mHDx-1 by increasing clearance. While proteasome and macroautophagy inhibitors reduce turnover of mHDx-1, Happ1 is still able to reduce mHDx-1 under these conditions, indicating Happ1-accelerated mHDx-1 clearance does not rely on these processes. In contrast, a calpain inhibitor or an inhibitor of lysosomal pH block Happ1-mediated acceleration of mHDx-1 clearance. These results suggest that mHDx-1 is cleaved by calpain, likely followed by lysosomal degradation and this process regulates the turnover rate of mHDx-1. Sequence analysis identifies amino acid (AA) 15 as a potential calpain cleavage site. Calpain cleavage of recombinant mHDx-1 in vitro yields fragments of sizes corresponding to this prediction. Moreover, when the site is blocked by binding of another intrabody, V_L12.3, turnover of soluble mHDx-1 in living cells is blocked. Conclusions/Significance: These results indicate that calpain-mediated removal of the 15 N-terminal AAs is required for the degradation of mHDx-1, a finding that may have therapeutic implications

Pastoral Herding Strategies and Governmental Management Objectives: Predation Compensation as a Risk Buffering Strategy in the Saami Reindeer Husbandry

Previously it has been found that an important risk buffering strategy in the Saami reindeer husbandry in Norway is the accumulation of large herds of reindeer as this increases long-term household viability. Nevertheless, few studies have investigated how official policies, such as economic compensation for livestock losses, can influence pastoral strategies. This study investigated the effect of received predation compensation on individual husbandry units’ future herd size. The main finding in this study is that predation compensation had a positive effect on husbandry units’ future herd size. The effect of predation compensation, however, was nonlinear in some years, indicating that predation compensation had a positive effect on future herd size only up to a certain threshold whereby adding additional predation compensation had little effect on future herd size. More importantly, the effect of predation compensation was positive after controlling for reindeer density, indicating that for a given reindeer density husbandry units receiving more predation compensation performed better (measured as the size of future herds) compared to husbandry units receiving less compensation

Analysis of factors influencing the ultrasonic fetal weight estimation

Objective: The aim of our study was the evaluation of sonographic fetal weight estimation taking into consideration 9 of the most important factors of influence on the precision of the estimation. Methods: We analyzed 820 singleton pregnancies from 22 to 42 weeks of gestational age. We evaluated 9 different factors that potentially influence the precision of sonographic weight estimation ( time interval between estimation and delivery, experts vs. less experienced investigator, fetal gender, gestational age, fetal weight, maternal BMI, amniotic fluid index, presentation of the fetus, location of the placenta). Finally, we compared the results of the fetal weight estimation of the fetuses with poor scanning conditions to those presenting good scanning conditions. Results: Of the 9 evaluated factors that may influence accuracy of fetal weight estimation, only a short interval between sonographic weight estimation and delivery (0-7 vs. 8-14 days) had a statistically significant impact. Conclusion: Of all known factors of influence, only a time interval of more than 7 days between estimation and delivery had a negative impact on the estimation

Effects of mesenchymal stromal cells versus serum on tendon healing in a controlled experimental trial in an equine model

Abstract Background Mesenchymal stromal cells (MSC) have shown promising results in the treatment of tendinopathy in equine medicine, making this therapeutic approach seem favorable for translation to human medicine. Having demonstrated that MSC engraft within the tendon lesions after local injection in an equine model, we hypothesized that they would improve tendon healing superior to serum injection alone. Methods Quadrilateral tendon lesions were induced in six horses by mechanical tissue disruption combined with collagenase application 3 weeks before treatment. Adipose-derived MSC suspended in serum or serum alone were then injected intralesionally. Clinical examinations, ultrasound and magnetic resonance imaging were performed over 24 weeks. Tendon biopsies for histological assessment were taken from the hindlimbs 3 weeks after treatment. Horses were sacrificed after 24 weeks and forelimb tendons were subjected to macroscopic and histological examination as well as analysis of musculoskeletal marker expression. Results Tendons injected with MSC showed a transient increase in inflammation and lesion size, as indicated by clinical and imaging parameters between week 3 and 6 (p < 0.05). Thereafter, symptoms decreased in both groups and, except that in MSC-treated tendons, mean lesion signal intensity as seen in T2w magnetic resonance imaging and cellularity as seen in the histology (p < 0.05) were lower, no major differences could be found at week 24. Conclusions These data suggest that MSC have influenced the inflammatory reaction in a way not described in tendinopathy studies before. However, at the endpoint of the current study, 24 weeks after treatment, no distinct improvement was observed in MSC-treated tendons compared to the serum-injected controls. Future studies are necessary to elucidate whether and under which conditions MSC are beneficial for tendon healing before translation into human medicine

Sensitive Detection of Chromosomal Segments of Distinct Ancestry in Admixed Populations

Identifying the ancestry of chromosomal segments of distinct ancestry has a wide range of applications from disease mapping to learning about history. Most methods require the use of unlinked markers; but, using all markers from genome-wide scanning arrays, it should in principle be possible to infer the ancestry of even very small segments with exquisite accuracy. We describe a method, HAPMIX, which employs an explicit population genetic model to perform such local ancestry inference based on fine-scale variation data. We show that HAPMIX outperforms other methods, and we explore its utility for inferring ancestry, learning about ancestral populations, and inferring dates of admixture. We validate the method empirically by applying it to populations that have experienced recent and ancient admixture: 935 African Americans from the United States and 29 Mozabites from North Africa. HAPMIX will be of particular utility for mapping disease genes in recently admixed populations, as its accurate estimates of local ancestry permit admixture and case-control association signals to be combined, enabling more powerful tests of association than with either signal alone

Online, Group-Based Psychological Support for Adolescent and Young Adult Cancer Survivors: Results from the Recapture Life Randomized Trial

Telehealth interventions offer a practical platform to support adolescent and young adult (AYA) cancer survivors' mental health needs after treatment, yet efficacy data are lacking. We evaluated an online, group-based, videoconferencing-delivered cognitive-behavioral therapy (CBT) intervention ('Recapture Life') in a 3-arm randomized-controlled trial comparing Recapture Life with an online peer-support group, and a waitlist control, with the aim of testing its impact on quality of life, emotional distress and healthcare service use. Forty AYAs (Mage = 20.6 years) within 24-months of completing treatment participated, together with 18 support persons. No groupwise impacts were measured immediately after the six-week intervention. However, Recapture Life participants reported using more CBT skills at the six-week follow-up (OR = 5.58, 95% CI = 2.00-15.56, p = 0.001) than peer-support controls. Recapture Life participants reported higher perceived negative impact of cancer, anxiety and depression at 12-month follow-up, compared to peer-support controls. Post-hoc analyses suggested that AYAs who were further from completing cancer treatment responded better to Recapture Life than those who had completed treatment more recently. While online telehealth interventions hold promise, recruitment to this trial was challenging. As the psychological challenges of cancer survivorship are likely to evolve with time, different support models may prove more or less helpful for different sub-groups of AYA survivors at different times