Measuring horizontal integration among health care providers in the community: An examination of a collaborative process within a palliative care network

In many countries formal or informal palliative care networks (PCNs) have evolved to better integrate community-based services for individuals with a life-limiting illness. We conducted a cross-sectional survey using a customized tool to determine the perceptions of the processes of palliative care delivery reflective of horizontal integration from the perspective of nurses, physicians and allied health professionals working in a PCN, as well as to assess the utility of this tool. The process elements examined were part of a conceptual framework for evaluating integration of a system of care and centred on interprofessional collaboration. We used the Index of Interdisciplinary Collaboration (IIC) as a basis of measurement. The 86 respondents (85% response rate) placed high value on working collaboratively and most reported being part of an interprofessional team. The survey tool showed utility in identifying strengths and gaps in integration across the network and in detecting variability in some factors according to respondent agency affiliation and profession. Specifically, support for interprofessional communication and evaluative activities were viewed as insufficient. Impediments to these aspects of horizontal integration may be reflective of workload constraints, differences in agency operations or an absence of key structural features.

Hirschsprung's disease prevalence in Europe: A register based study

Background: Hirschsprung's disease is a congenital gut motility disorder, characterised by the absence of the enteric ganglion cells along the distal gut. The aim of this study was to describe the epidemiology of Hirschsprung's disease, including additional congenital anomalies, total prevalence, trends, and association with maternal age. Methods: Cases of Hirschsprung's disease delivered during 1980 to 2009 notified to 31 European Surveillance of Congenital Anomaly registers formed the population-based case-series. Prevalence rates and 95% confidence intervals were calculated as the number of cases per 10,000 births. Multilevel Poisson regression was performed to investigate trends in prevalence, geographical variation and the association with maternal age. Results: There were 1,322 cases of Hirschsprung's disease among 12,146,210 births. The total prevalence was 1.09 (95% confidence interval, 1.03–1.15) per 10,000 births and there was a small but significant increase in prevalence over time (relative risk = 1.01; 95% credible interval, 1.00–1.02; p = 0.004). There was evidence of geographical heterogeneity in prevalence (p < 0.001). Excluding 146 (11.0%) cases with chromosomal anomalies or genetic syndromes, there were 1,176 cases (prevalence = 0.97; 95% confidence interval, 0.91–1.03 per 10,000 births), of which 137 (11.6%) had major structural anomalies. There was no evidence of a significant increased risk of Hirschsprung's disease in cases born to women aged ≥35 years compared with those aged 25 to 29 (relative risk = 1.09; 95% credible interval, 0.91–1.31; p = 0.355). Conclusion: This large population-based study found evidence of a small increasing trend in Hirschsprung's disease and differences in prevalence by geographic location. There was also no evidence of an association with maternal age.

Downregulation of the Wnt inhibitor CXXC5 predicts a better prognosis in acute myeloid leukemia

The gene CXXC5 on 5q31 is frequently deleted in acute myeloid leukemia (AML) with del(5q), suggesting that inactivation of CXXC5 might play a role in leukemogenesis. Here, we investigated the functional and prognostic implications of CXXC5 expression in AML. CXXC5 mRNA was downregulated in AML with MLL rearrangements, t(8;21) and GATA2 mutations. As a mechanism of CXXC5 inactivation, we found evidence for epigenetic silencing by promoter methylation. Patients with CXXC5 expression below the median level had a lower relapse rate (45% vs 59%; P = .007) and a better overall survival (OS, 46% vs 28%; P < .001) and event-free survival (EFS, 36% vs 21%; P < .001) at 5 years, independent of cytogenetic risk groups and known molecular risk factors. In gene-expression profiling, lower CXXC5 expression was associated with upregulation of cell-cycling genes and codownregulation of genes implicated in leukemogenesis (WT1, GATA2, MLL, DNMT3B, RUNX1). Functional analyses demonstrated CXXC5 to inhibit leukemic cell proliferation and Wnt signaling and to affect the p53-dependent DNA damage response. In conclusion, our data suggest a tumor suppressor function of CXXC5 in AML. Inactivation of CXXC5 is associated with different leukemic pathways and defines an AML subgroup with better outcome.

Orthogonal targeting of EGFRvIII expressing glioblastomas through simultaneous EGFR and PLK1 inhibition

We identified a synthetic lethality between PLK1 silencing and the expression of an oncogenic Epidermal Growth Factor Receptor, EGFRvIII. PLK1 promoted homologous recombination (HR), mitigating EGFRvIII induced oncogenic stress resulting from DNA damage accumulation. Accordingly, PLK1 inhibition enhanced the cytotoxic effects of the DNA damaging agent, temozolomide (TMZ). This effect was significantly more pronounced in an Ink4a/Arf(-/-) EGFRvIII glioblastoma model relative to an Ink4a/Arf(-/-) PDGF-β model. The tumoricidal and TMZ-sensitizing effects of BI2536 were uniformly observed across Ink4a/Arf(-/-) EGFRvIII glioblastoma clones that acquired independent resistance mechanisms to EGFR inhibitors, suggesting these resistant clones retain oncogenic stress that required PLK1 compensation. Although BI2536 significantly augmented the anti-neoplastic effect of EGFR inhibitors in the Ink4a/Arf(-/-) EGFRvIII model, durable response was not achieved until TMZ was added. Our results suggest that optimal therapeutic effect against glioblastomas requires a "multi-orthogonal" combination tailored to the molecular physiology associated with the target cancer genome.

WHIRLBOB, the Whirlpool Based Variant of STRIBOB: Lighter, Faster, and Constant Time

WHIRLBOB, also known as STRIBOBr2, is an AEAD (Authenticated Encryption with Associated Data) algorithm derived from STRIBOBr1 and the Whirlpool hash algorithm. WHIRLBOB/STRIBOBr2 is a second round candidate in the CAESAR competition. As with STRIBOBr1, the reduced-size Sponge design has a strong provable security link with a standardized hash algorithm. The new design utilizes only the LPS or ρ component of Whirlpool in flexibly domain-separated BLNK Sponge mode. The number of rounds is increased from 10 to 12 as a countermeasure against Rebound Distinguishing attacks. The 8 ×8 - bit S-Box used by Whirlpool and WHIRLBOB is constructed from 4 ×4 - bit “MiniBoxes”. We report on fast constant-time Intel SSSE3 and ARM NEON SIMD WHIRLBOB implementations that keep full miniboxes in registers and access them via SIMD shuffles. This is an efficient countermeasure against AES-style cache timing side-channel attacks. Another main advantage of WHIRLBOB over STRIBOBr1 (and most other AEADs) is its greatly reduced implementation footprint on lightweight platforms. On many lower-end microcontrollers the total software footprint of π+BLNK = WHIRLBOB AEAD is less than half a kilobyte. We also report an FPGA implementation that requires 4,946 logic units for a single round of WHIRLBOB, which compares favorably to 7,972 required for Keccak / Keyak on the same target platform. The relatively small S-Box gate count also enables efficient 64-bit bitsliced straight-line implementations. We finally present some discussion and analysis on the relationships between WHIRLBOB, Whirlpool, the Russian GOST Streebog hash, and the recent draft Russian Encryption Standard Kuznyechik.

VentBase:Developing a consensus among stakeholders in the deep-sea regarding environmental impact assessment for deep-sea mining-A workshop report

Mining seafloor massive sulfides for metals is an emergent industry faced with environmental management challenges. These revolve largely around limits to our current understanding of biological variability in marine systems, a challenge common to all marine environmental management. VentBase was established as a forum where academic, commercial, governmental, and non-governmental stakeholders can develop a consensus regarding the management of exploitative activities in the deep-sea. Participants advocate a precautionary approach with the incorporation of lessons learned from coastal studies. This workshop report from VentBase encourages the standardization of sampling methodologies for deep-sea environmental impact assessment. VentBase stresses the need for the collation of spatial data and importance of datasets amenable to robust statistical analyses. VentBase supports the identification of set-asides to prevent the local extirpation of vent-endemic communities and for the post-extraction recolonization of mine sites. © 2013.

Introducing the CTA concept

The Cherenkov Telescope Array (CTA) is a new observatory for very high-energy (VHE) gamma rays. CTA has ambitions science goals, for which it is necessary to achieve full-sky coverage, to improve the sensitivity by about an order of magnitude, to span about four decades of energy, from a few tens of GeV to above 100 TeV with enhanced angular and energy resolutions over existing VHE gamma-ray observatories. An international collaboration has formed with more than 1000 members from 27 countries in Europe, Asia, Africa and North and South America. In 2010 the CTA Consortium completed a Design Study and started a three-year Preparatory Phase which leads to production readiness of CTA in 2014. In this paper we introduce the science goals and the concept of CTA, and provide an overview of the project. © 2013 Elsevier B.V. All rights reserved.

Measuring healthcare integration: Operationalization of a framework for a systems evaluation of palliative care structures, processes, and outcomes

BACKGROUND: Healthcare integration is a priority in many countries, yet there remains little direction on how to systematically evaluate this construct to inform further development. The examination of community-based palliative care networks provides an ideal opportunity for the advancement of integration measures, in consideration of how fundamental provider cohesion is to effective care at end of life.

AIM: This article presents a variable-oriented analysis from a theory-based case study of a palliative care network to help bridge the knowledge gap in integration measurement.

DESIGN: Data from a mixed-methods case study were mapped to a conceptual framework for evaluating integrated palliative care and a visual array depicting the extent of key factors in the represented palliative care network was formulated.

SETTING/PARTICIPANTS: The study included data from 21 palliative care network administrators, 86 healthcare professionals, and 111 family caregivers, all from an established palliative care network in Ontario, Canada.

RESULTS: The framework used to guide this research proved useful in assessing qualities of integration and functioning in the palliative care network. The resulting visual array of elements illustrates that while this network performed relatively well at the multiple levels considered, room for improvement exists, particularly in terms of interventions that could facilitate the sharing of information.

CONCLUSION: This study, along with the other evaluative examples mentioned, represents important initial attempts at empirically and comprehensively examining network-integrated palliative care and healthcare integration in general.

C Dupré, The Age of Dignity (Hart 2015)

Bob Dylan famously searched high and low for it and left us wondering ‘what it’s gonna take’ to find it. These days, the elusive dignity – and her equally, if not more, elusive cousin human dignity – has captured the imagination of not just the poet and philosopher, but also, in light of its increasing prominence in an array of legal contexts, the legal scholar. Catherine Dupré’s The Age of Dignity comes at a high point in (human) dignity scholarship, with the publication of numerous texts in the English language emerging on the subject, and with interest in it looking unlikely to dissipate any time soon. In this review, I consider (human) dignity’s promise and pitfalls as it transpires in Dupré’s wide-ranging and ambitious monograph.