Additional Clinical Value for PET/MRI in Oncology: Moving Beyond Simple Diagnosis

Initial clinical research comparing the diagnostic performance of PET/MRI and PET/CT has largely shown equivalent diagnostic capabilities for these modalities in oncology. These uncertainties about the magnitude of diagnostic benefit are compounded by the considerable health economic challenges associated with clinical implementation. Therefore, there is a need to identify ways to extend the use of this technology beyond simple diagnosis so that PET/MRI can add sufficient clinical value beyond PET/CT or MRI alone and become a cost-effective imaging modality in clinical practice. A major advantage of PET/MRI over other imaging modalities is the ability to generate multiple quantitative images from a single examination. This article describes how a multiparametric PET/MRI approach not only can add clinical value through contributing to precision medicine but also can establish PET/MRI as a potentially cost-effective imaging modality in oncology

CT-based texture analysis potentially provides prognostic information complementary to interim fdg-pet for patients with hodgkin's and aggressive non-hodgkin's lymphomas

OBJECTIVES: The purpose of this study was to investigate the ability of computed tomography texture analysis (CTTA) to provide additional prognostic information in patients with Hodgkin's lymphoma (HL) and high-grade non-Hodgkin's lymphoma (NHL). METHODS: This retrospective, pilot-study approved by the IRB comprised 45 lymphoma patients undergoing routine 18F-FDG-PET-CT. Progression-free survival (PFS) was determined from clinical follow-up (mean-duration: 40 months; range: 10-62 months). Non-contrast-enhanced low-dose CT images were submitted to CTTA comprising image filtration to highlight features of different sizes followed by histogram-analysis using kurtosis. Prognostic value of CTTA was compared to PET FDG-uptake value, tumour-stage, tumour-bulk, lymphoma-type, treatment-regime, and interim FDG-PET (iPET) status using Kaplan-Meier analysis. Cox regression analysis determined the independence of significantly prognostic imaging and clinical features. RESULTS: A total of 27 patients had aggressive NHL and 18 had HL. Mean PFS was 48.5 months. There was no significant difference in pre-treatment CTTA between the lymphoma sub-types. Kaplan-Meier analysis found pre-treatment CTTA (medium feature scale, p=0.010) and iPET status (p<0.001) to be significant predictors of PFS. Cox analysis revealed that an interaction between pre-treatment CTTA and iPET status was the only independent predictor of PFS (HR: 25.5, 95% CI: 5.4-120, p<0.001). Specifically, pre-treatment CTTA risk stratified patients with negative iPET. CONCLUSION: CTTA can potentially provide prognostic information complementary to iPET for patients with HL and aggressive NHL

Structure of the C-terminal domain of the Prokaryotic Sodium Channel Orthologue NsvBa

Crystallographic and electrophysiological studies have recently provided insight into the structure, function and drug binding of prokaryotic sodium channels. These channels exhibit significant sequence identities, especially in their transmembrane regions, with human voltage-gated sodium channels. However, rather than being single polypeptides with four homologous domains, they are tetramers of single domain polypeptides, with a C-terminal domain (CTD) composed of an inter-subunit four helix coiled-coil. The structures of the CTDs differ between orthologues. In NavBh and NavMs, the C-termini form a disordered region adjacent to the final transmembrane helix, followed by a coiled-coil region, as demonstrated by synchrotron radiation circular dichroism (SRCD) and double electron-electron resonance electron paramagnetic resonance spectroscopic measurements. In contrast, in the crystal structure of the NavAe orthologue, the entire C-terminus is comprised of a helical region followed by a coiled-coil. In this study we have examined the CTD of the NsvBa from Bacillus alcalophilus, which unlike other orthologues is predicted by different methods to have different types of structures: either a disordered adjacent to the transmembrane region, followed by a helical coiled-coil, or a fully helical CTD. To discriminate between the two possible structures we have used SRCD spectroscopy to experimentally determine the secondary structure of the C-terminus of this orthologue and used the results as the basis for modelling the transition between open and closed conformations of the channel

The braincase and jaws of a Devonian 'acanthodian' and modern gnathostome origins.

Modern gnathostomes (jawed vertebrates) emerged in the early Palaeozoic era, but this event remains unclear owing to a scant early fossil record. The exclusively Palaeozoic acanthodians are possibly the earliest gnathostome group and exhibit a mosaic of shark- and bony fish-like characters that has long given them prominence in discussions of early gnathostome evolution. Their relationships with modern gnathostomes have remained mysterious, partly because their un-mineralized endoskeletons rarely fossilized. Here I present the first-known braincase of an Early Devonian (approximately 418-412 Myr bp) acanthodian, Ptomacanthus anglicus, and re-evaluate the interrelationships of basal gnathostomes. Acanthodian braincases have previously been represented by a single genus, Acanthodes, which occurs more than 100 million years later in the fossil record. The braincase of Ptomacanthus differs radically from the osteichthyan-like braincase of Acanthodes in exhibiting several plesiomorphic features shared with placoderms and some early chondrichthyans. Most striking is its extremely short sphenoid region and its jaw suspension, which displays features intermediate between some Palaeozoic chondrichthyans and osteichthyans. Phylogenetic analysis resolves Ptomacanthus as either the most basal chondrichthyan or as the sister group of all living gnathostomes. These new data alter earlier conceptions of basal gnathostome phylogeny and thus help to provide a more detailed picture of the acquisition of early gnathostome characters

A Qualitative Study of Perceived Risk for HIV Transmission among Police Officers in Dar es Salaam, Tanzania.

Understanding people's views about HIV transmission by investigating a specific population may help to design effective HIV prevention strategies. In addition, knowing the inherent sexual practices of such a population, as well as the risky circumstances that may facilitate HIV transmission, is crucial for the said strategies to become effective. In this article, we report how police officers in Dar es Salaam, Tanzania, perceived the problem of HIV and AIDS in their local context, particularly in relation to unsafe sexual practices. The study was done with the view to recommending ways by which HIV transmission could be minimised within the police force. The study was conducted among members of the police force in Dar es Salaam, Tanzania. Eight focus group discussions (FGDs) were conducted, with a total of 66 participants who were mixed in terms of age, gender, and marital status. Some of these were caregivers to patients with AIDS. Data were analysed using the interpretive description approach. The participants believed that both individual sexual behaviour and work-related circumstances were sources of HIV infection. They also admitted that they were being tempted to engage in risky sexual practices because of the institutional rules that prohibit officers from getting married during their training and for three years after. Nevertheless, as members of the Police Force, they stressed the fact that the risky sexual behaviour that exposes them to HIV is not limited to the force; it is rather a common problem that is faced by the general population. However, they complained, the nature of their job exposes them to road accident victims, subjecting them further to possible infection, especially when they have to handle these road accident casualties without proper protective gear. Individual sexual behaviour and job-related circumstances are worth investigating if proper advice is to be given to the police regarding HIV prevention strategies. In order to improve the lives of these police officers, there is a need to review the existing institutional rules and practices to accommodate individual sexual needs. In addition, improving their working environment may minimize the risk of HIV transmission from handling casualties in emergency situations

Reporting accuracy of packed lunch consumption among Danish 11-year-olds differ by gender.

Background: Packed lunch is the dominant lunch format in many countries including Denmark. School lunch is consumed unsupervised, and self-reported recalls are appropriate in the school setting. However, little is known about the accuracy of recalls in relation to packed lunch. Objective: To assess the qualitative recall accuracy of self-reported consumption of packed lunch among Danish 11-year-old children in relation to gender and dietary assessment method. Design: A cross-sectional dietary recall study of packed lunch consumption. Digital images (DIs) served as an objective reference method to determine food items consumed. Recalls were collected with a lunch recall questionnaire (LRQ) comprising an open-ended recall (OE-Q) and a pre-coded food group prompted recall (PC-Q). Individual interviews (INTs) were conducted successively. The number of food items was identified and accuracy was calculated as match rates (% identified by DIs and reported correctly) and intrusion rates (% not identified by DIs but reported) were determined. Setting and subjects: Three Danish public schools from Copenhagen. A total of 114 Danish 11-year-old children, mean (SE) age=11.1 (0.03), and body mass index=18.2 (0.26). Results: The reference (DIs) showed that girls consumed a higher number of food items than boys [mean (SE) 5.4 (0.25) vs. 4.6 (0.29) items (p=0.05)]. The number of food items recalled differed between genders with OE-Q recalls (p=0.005) only. Girls&#x2019; interview recalls were more accurate than boys&#x2019; with higher match rates (p=0.04) and lower intrusion rates (p=0.05). Match rates ranged from 67&#x2013;90% and intrusion rates ranged from 13&#x2013;39% with little differences between girls and boys using the OE-Q and PC-Q methods. Conclusion: Dietary recall validation studies should not only consider match rates as an account of accuracy. Intrusions contribute to over-reporting in non-validation studies, and future studies should address recall accuracy and inaccuracies in relation to gender and recall method

Isatuximab plus pomalidomide and dexamethasone in relapsed/refractory multiple myeloma patients with renal impairment: ICARIA-MM subgroup analysis

The randomized, phase 3 ICARIA-MM study investigated isatuximab (Isa) with pomalidomide and dexamethasone (Pd) versus Pd in patients with relapsed/refractory multiple myeloma and ≥2 prior lines. This prespecified subgroup analysis examined efficacy in patients with renal impairment (RI; estimated glomerular filtration rate <60 mL/min/1.73 m²). Isa 10 mg/kg was given intravenously once weekly in cycle 1, and every 2 weeks in subsequent 28-day cycles. Patients received standard doses of Pd. Median progression-free survival (PFS) for patients with RI was 9.5 months with Isa-Pd (n = 55) and 3.7 months with Pd (n = 49; hazard ratio [HR] 0.50; 95% confidence interval [CI], 0.30–0.85). Without RI, median PFS was 12.7 months with Isa-Pd (n = 87) and 7.9 months with Pd (n = 96; HR 0.58; 95% CI, 0.38–0.88). The overall response rate (ORR) with and without RI was higher with Isa-Pd (56 and 68%) than Pd (25 and 43%). Complete renal response rates were 71.9% (23/32) with Isa-Pd and 38.1% (8/21) with Pd; these lasted ≥60 days in 31.3% (10/32) and 19.0% (4/21) of patients, respectively. Isa pharmacokinetics were comparable between the subgroups, suggesting no need for dose adjustment in patients with RI. In summary, the addition of Isa to Pd improved PFS, ORR and renal response rates

Roadmaps to Utopia: Tales of the Smart City

Notions of the Smart City are pervasive in urban development discourses. Various frameworks for the development of smart cities, often conceptualized as roadmaps, make a number of implicit claims about how smart city projects proceed but the legitimacy of those claims is unclear. This paper begins to address this gap in knowledge. We explore the development of a smart transport application, MotionMap, in the context of a £16M smart city programme taking place in Milton Keynes, UK. We examine how the idealized smart city narrative was locally inflected, and discuss the differences between the narrative and the processes and outcomes observed in Milton Keynes. The research shows that the vision of data-driven efficiency outlined in the roadmaps is not universally compelling, and that different approaches to the sensing and optimization of urban flows have potential for empowering or disempowering different actors. Roadmaps tend to emphasize the importance of delivering quick practical results. However, the benefits observed in Milton Keynes did not come from quick technical fixes but from a smart city narrative that reinforced existing city branding, mobilizing a growing network of actors towards the development of a smart region. Further research is needed to investigate this and other smart city developments, the significance of different smart city narratives, and how power relationships are reinforced and constructed through them

Critical research gaps and translational priorities for the successful prevention and treatment of breast cancer

INTRODUCTION Breast cancer remains a significant scientific, clinical and societal challenge. This gap analysis has reviewed and critically assessed enduring issues and new challenges emerging from recent research, and proposes strategies for translating solutions into practice. METHODS More than 100 internationally recognised specialist breast cancer scientists, clinicians and healthcare professionals collaborated to address nine thematic areas: genetics, epigenetics and epidemiology; molecular pathology and cell biology; hormonal influences and endocrine therapy; imaging, detection and screening; current/novel therapies and biomarkers; drug resistance; metastasis, angiogenesis, circulating tumour cells, cancer 'stem' cells; risk and prevention; living with and managing breast cancer and its treatment. The groups developed summary papers through an iterative process which, following further appraisal from experts and patients, were melded into this summary account. RESULTS The 10 major gaps identified were: (1) understanding the functions and contextual interactions of genetic and epigenetic changes in normal breast development and during malignant transformation; (2) how to implement sustainable lifestyle changes (diet, exercise and weight) and chemopreventive strategies; (3) the need for tailored screening approaches including clinically actionable tests; (4) enhancing knowledge of molecular drivers behind breast cancer subtypes, progression and metastasis; (5) understanding the molecular mechanisms of tumour heterogeneity, dormancy, de novo or acquired resistance and how to target key nodes in these dynamic processes; (6) developing validated markers for chemosensitivity and radiosensitivity; (7) understanding the optimal duration, sequencing and rational combinations of treatment for improved personalised therapy; (8) validating multimodality imaging biomarkers for minimally invasive diagnosis and monitoring of responses in primary and metastatic disease; (9) developing interventions and support to improve the survivorship experience; (10) a continuing need for clinical material for translational research derived from normal breast, blood, primary, relapsed, metastatic and drug-resistant cancers with expert bioinformatics support to maximise its utility. The proposed infrastructural enablers include enhanced resources to support clinically relevant in vitro and in vivo tumour models; improved access to appropriate, fully annotated clinical samples; extended biomarker discovery, validation and standardisation; and facilitated cross-discipline working. CONCLUSIONS With resources to conduct further high-quality targeted research focusing on the gaps identified, increased knowledge translating into improved clinical care should be achievable within five years

Organizational factors and depression management in community-based primary care settings

Abstract Background Evidence-based quality improvement models for depression have not been fully implemented in routine primary care settings. To date, few studies have examined the organizational factors associated with depression management in real-world primary care practice. To successfully implement quality improvement models for depression, there must be a better understanding of the relevant organizational structure and processes of the primary care setting. The objective of this study is to describe these organizational features of routine primary care practice, and the organization of depression care, using survey questions derived from an evidence-based framework. Methods We used this framework to implement a survey of 27 practices comprised of 49 unique offices within a large primary care practice network in western Pennsylvania. Survey questions addressed practice structure (e.g., human resources, leadership, information technology (IT) infrastructure, and external incentives) and process features (e.g., staff performance, degree of integrated depression care, and IT performance). Results The results of our survey demonstrated substantial variation across the practice network of organizational factors pertinent to implementation of evidence-based depression management. Notably, quality improvement capability and IT infrastructure were widespread, but specific application to depression care differed between practices, as did coordination and communication tasks surrounding depression treatment. Conclusions The primary care practices in the network that we surveyed are at differing stages in their organization and implementation of evidence-based depression management. Practical surveys such as this may serve to better direct implementation of these quality improvement strategies for depression by improving understanding of the organizational barriers and facilitators that exist within both practices and practice networks. In addition, survey information can inform efforts of individual primary care practices in customizing intervention strategies to improve depression management.http://deepblue.lib.umich.edu/bitstream/2027.42/78269/1/1748-5908-4-84.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78269/2/1748-5908-4-84-S1.PDFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78269/3/1748-5908-4-84.pdfPeer Reviewe