Adaptive sampling method to monitor low-risk pathways with limited surveillance resources

The rise of globalisation has led to a sharp increase in international trade, with high volumes of containers, goods and items moving across the world. Unfortunately, these trade pathways also facilitate the movement of unwanted pests, weeds, diseases, and pathogens. Each item could contain biosecurity risk material, but it is impractical to inspect every item. Instead, inspection efforts typically focus on high risk items. However, low risk does not imply no risk. It is crucial to monitor the low risk pathways to ensure that they are and remain low risk. To do so, many approaches would seek to estimate the risk to some precision, but the lower the risk, the more samples needed to estimate the risk. On a low-risk pathway that can be afforded more limited inspection resources, it makes more sense to assign fewer samples to the lower risk activities. We approach the problem by introducing two thresholds. Our method focuses on letting us know whether the risk is below certain thresholds, rather than estimating the risk precisely. This method also allows us to detect a significant change in risk. Our approach typically requires less sampling than previous methods, while still providing evidence to regulators to help them efficiently and effectively allocate inspection effort.Comment: 12 + 2 pages, 8 figures, 2 table

Adipocyte-specific protein tyrosine phosphatase 1B deletion increases lipogenesis, adipocyte cell size and is a minor regulator of glucose homeostasis

Peer reviewedPublisher PD

Membrane Tension Orchestrates Rear Retraction in Matrix-Directed Cell Migration.

In development, wound healing, and cancer metastasis, vertebrate cells move through 3D interstitial matrix, responding to chemical and physical guidance cues. Protrusion at the cell front has been extensively studied, but the retraction phase of the migration cycle is not well understood. Here, we show that fast-moving cells guided by matrix cues establish positive feedback control of rear retraction by sensing membrane tension. We reveal a mechanism of rear retraction in 3D matrix and durotaxis controlled by caveolae, which form in response to low membrane tension at the cell rear. Caveolae activate RhoA-ROCK1/PKN2 signaling via the RhoA guanidine nucleotide exchange factor (GEF) Ect2 to control local F-actin organization and contractility in this subcellular region and promote translocation of the cell rear. A positive feedback loop between cytoskeletal signaling and membrane tension leads to rapid retraction to complete the migration cycle in fast-moving cells, providing directional memory to drive persistent cell migration in complex matrices

Terminal osteoblast differentiation, mediated by runx2 and p27KIP1, is disrupted in osteosarcoma

The molecular basis for the inverse relationship between differentiation and tumorigenesis is unknown. The function of runx2, a master regulator of osteoblast differentiation belonging to the runt family of tumor suppressor genes, is consistently disrupted in osteosarcoma cell lines. Ectopic expression of runx2 induces p27KIP1, thereby inhibiting the activity of S-phase cyclin complexes and leading to the dephosphorylation of the retinoblastoma tumor suppressor protein (pRb) and a G1 cell cycle arrest. Runx2 physically interacts with the hypophosphorylated form of pRb, a known coactivator of runx2, thereby completing a feed-forward loop in which progressive cell cycle exit promotes increased expression of the osteoblast phenotype. Loss of p27KIP1 perturbs transient and terminal cell cycle exit in osteoblasts. Consistent with the incompatibility of malignant transformation and permanent cell cycle exit, loss of p27KIP1 expression correlates with dedifferentiation in high-grade human osteosarcomas. Physiologic coupling of osteoblast differentiation to cell cycle withdrawal is mediated through runx2 and p27KIP1, and these processes are disrupted in osteosarcoma

Trends in Incidence of Hospitalized Acute Myocardial Infarction in the Cardiovascular Research Network (CVRN)

Monitoring trends in cardiovascular events can provide key insights into the effectiveness of prevention efforts. Leveraging data from electronic health records provides a unique opportunity to examine contemporary, community-based trends in acute myocardial infarction hospitalizations

Use of a mixed tissue RNA design for performance assessments on multiple microarray formats

The comparability and reliability of data generated using microarray technology would be enhanced by use of a common set of standards that allow accuracy, reproducibility and dynamic range assessments on multiple formats. We designed and tested a complex biological reagent for performance measurements on three commercial oligonucleotide array formats that differ in probe design and signal measurement methodology. The reagent is a set of two mixtures with different proportions of RNA for each of four rat tissues (brain, liver, kidney and testes). The design provides four known ratio measurements of >200 reference probes, which were chosen for their tissue-selectivity, dynamic range coverage and alignment to the same exemplar transcript sequence across all three platforms. The data generated from testing three biological replicates of the reagent at eight laboratories on three array formats provides a benchmark set for both laboratory and data processing performance assessments. Close agreement with target ratios adjusted for sample complexity was achieved on all platforms and low variance was observed among platforms, replicates and sites. The mixed tissue design produces a reagent with known gene expression changes within a complex sample and can serve as a paradigm for performance standards for microarrays that target other species

Endurance, resistance and resilience in the South African health care system: case studies to demonstrate mechanisms of coping within a constrained system

BACKGROUND: South Africa is at present undertaking a series of reforms to transform public health services to make them more effective and responsive to patient and provider needs. A key focus of these reforms is primary care and its overburdened, somewhat dysfunctional and hierarchical nature. This comparative case study examines how patients and providers respond in this system and cope with its systemic demands through mechanisms of endurance, resistance and resilience, using coping and agency literatures as the theoretical lenses. METHODS: As part of a larger research project carried out between 2009 and 2010, this study conducted semi-structured interviews and observations at health facilities in three South African provinces. This study explored patient experiences of access to health care, in particular, ways of coping and how health care providers cope with the health care system’s realities. From this interpretive base, four cases (two patients, two providers) were selected as they best informed on endurance, resistance and resilience. Some commentary from other respondents is added to underline the more ubiquitous nature of these coping mechanisms. RESULTS: The cases of four individuals highlight the complexity of different forms of endurance and passivity, emotion- and problem-based coping with health care interactions in an overburdened, under-resourced and, in some instances, poorly managed system. Patients’ narratives show the micro-practices they use to cope with their treatment, by not recognizing victimhood and sometimes practising unhealthy behaviours. Providers indicate how they cope in their work situations by using peer support and becoming knowledgeable in providing good service. CONCLUSIONS: Resistance and resilience narratives show the adaptive power of individuals in dealing with difficult illness, circumstances or treatment settings. They permit individuals to do more than endure (itself a coping mechanism) their circumstances, though resistance and resilience may be limited. These are individual responses to systemic forces. To transform health care, mutually supportive interactions are required among and between both patients and providers but their nature, as micro-practices, may show a way forward for system change

Mapping Drug Physico-Chemical Features to Pathway Activity Reveals Molecular Networks Linked to Toxicity Outcome

The identification of predictive biomarkers is at the core of modern toxicology. So far, a number of approaches have been proposed. These rely on statistical inference of toxicity response from either compound features (i.e., QSAR), in vitro cell based assays or molecular profiling of target tissues (i.e., expression profiling). Although these approaches have already shown the potential of predictive toxicology, we still do not have a systematic approach to model the interaction between chemical features, molecular networks and toxicity outcome. Here, we describe a computational strategy designed to address this important need. Its application to a model of renal tubular degeneration has revealed a link between physico-chemical features and signalling components controlling cell communication pathways, which in turn are differentially modulated in response to toxic chemicals. Overall, our findings are consistent with the existence of a general toxicity mechanism operating in synergy with more specific single-target based mode of actions (MOAs) and provide a general framework for the development of an integrative approach to predictive toxicology

Knowledge ‘Translation’ as Social Learning: Negotiating the Uptake of Research-Based Knowledge in Practice

BACKGROUND: Knowledge translation and evidence-based practice have relied on research derived from clinical trials, which are considered to be methodologically rigorous. The result is practice recommendations based on a narrow view of evidence. We discuss how, within a practice environment, in fact individuals adopt and apply new evidence derived from multiple sources through ongoing, iterative learning cycles. DISCUSSION: The discussion is presented in four sections. After elaborating on the multiple forms of evidence used in practice, in section 2 we argue that the practitioner derives contextualized knowledge through reflective practice. Then, in section 3, the focus shifts from the individual to the team with consideration of social learning and theories of practice. In section 4 we discuss the implications of integrative and negotiated knowledge exchange and generation within the practice environment. Namely, how can we promote the use of research within a team-based, contextualized knowledge environment? We suggest support for: 1) collaborative learning environments for active learning and reflection, 2) engaged scholarship approaches so that practice can inform research in a collaborative manner and 3) leveraging authoritative opinion leaders for their clinical expertise during the shared negotiation of knowledge and research. Our approach also points to implications for studying evidence-informed practice: the identification of practice change (as an outcome) ought to be supplemented with understandings of how and when social negotiation processes occur to achieve integrated knowledge. SUMMARY: This article discusses practice knowledge as dependent on the practice context and on social learning processes, and suggests how research knowledge uptake might be supported from this vantage point

Patient safety culture in care homes for older people: a scoping review

Background: In recent years, there has been an increasing focus on the role of safety culture in preventing incidents such as medication errors and falls. However, research and developments in safety culture has predominantly taken place in hospital settings, with relatively less attention given to establishing a safety culture in care homes. Despite safety culture being accepted as an important quality indicator across all health and social care settings, the understanding of culture within social care settings remains far less developed than within hospitals. It is therefore important that the existing evidence base is gathered and reviewed in order to understand safety culture in care homes. Methods: A scoping review was undertaken to describe the availability of evidence related to care homes’ patient safety culture, what these studies focused on, and identify any knowledge gaps within the existing literature. Included papers were each reviewed by two authors for eligibility and to draw out information relevant to the scoping review. Results: Twenty-four empirical papers and one literature review were included within the scoping review. The collective evidence demonstrated that safety culture research is largely based in the USA, within Nursing Homes rather than Residential Home settings. Moreover, the scoping review revealed that empirical evidence has predominantly used quantitative measures, and therefore the deeper levels of culture have not been captured in the evidence base. Conclusions: Safety culture in care homes is a topic that has not been extensively researched. The review highlights a number of key gaps in the evidence base, which future research into safety culture in care home should attempt to address