Mosaic effectiveness: measuring the impact of novel PrEP methods

Various ongoing trials seek to evaluate long-acting pre-exposure prophylaxis (PrEP) agents by showing that they are non-inferior to daily oral tenofovir disoproxil fumarate and emtricitabine. Trials comparing oral PrEP to new methods examine effectiveness in a setting where only one or the other is provided; however, a new product will probably be delivered in a context where oral PrEP is also available. The effectiveness of a new PrEP product is best measured by its potential effect in a context that also includes oral tenofovir disoproxil fumarate and emtricitabine as an option. We offer an alternative standard for long-acting products—a measure of the effectiveness of the new product in addition to oral tenofovir disoproxil fumarate and emtricitabine as compared with oral PrEP alone. We term this measure mosaic effectiveness. We illustrate scenarios where a novel product can fail to show non-inferiority but show substantial mosaic effectiveness, thus implying the public health value of the novel product even if it is less effective than oral PrEP. Regulatory standards should consider mosaic effectiveness, not just comparative effectiveness. We assert that measurements that combine rigor with public health relevance can accelerate progress against the HIV epidemic

Reprocessable thermosets for sustainable three-dimensional printing

Among all three-dimensional (3D) printing materials, thermosetting photopolymers claim almost half of the market, and have been widely used in various fields owing to their superior mechanical stability at high temperatures, excellent chemical resistance as well as good compatibility with high-resolution 3D printing technologies. However, once these thermosetting photopolymers form 3D parts through photopolymerization, the covalent networks are permanent and cannot be reprocessed, i.e., reshaped, repaired, or recycled. Here, we report a two-step polymerization strategy to develop 3D printing reprocessable thermosets (3DPRTs) that allow users to reform a printed 3D structure into a new arbitrary shape, repair a broken part by simply 3D printing new material on the damaged site, and recycle unwanted printed parts so the material can be reused for other applications. These 3DPRTs provide a practical solution to address environmental challenges associated with the rapid increase in consumption of 3D printing materials

Options for early breast cancer follow-up in primary and secondary care : a systematic review

Background Both incidence of breast cancer and survival have increased in recent years and there is a need to review follow up strategies. This study aims to assess the evidence for benefits of follow-up in different settings for women who have had treatment for early breast cancer. Method A systematic review to identify key criteria for follow up and then address research questions. Key criteria were: 1) Risk of second breast cancer over time - incidence compared to general population. 2) Incidence and method of detection of local recurrence and second ipsi and contra-lateral breast cancer. 3) Level 1–4 evidence of the benefits of hospital or alternative setting follow-up for survival and well-being. Data sources to identify criteria were MEDLINE, EMBASE, AMED, CINAHL, PSYCHINFO, ZETOC, Health Management Information Consortium, Science Direct. For the systematic review to address research questions searches were performed using MEDLINE (2011). Studies included were population studies using cancer registry data for incidence of new cancers, cohort studies with long term follow up for recurrence and detection of new primaries and RCTs not restricted to special populations for trials of alternative follow up and lifestyle interventions. Results Women who have had breast cancer have an increased risk of a second primary breast cancer for at least 20 years compared to the general population. Mammographically detected local recurrences or those detected by women themselves gave better survival than those detected by clinical examination. Follow up in alternative settings to the specialist clinic is acceptable to women but trials are underpowered for survival. Conclusions Long term support, surveillance mammography and fast access to medical treatment at point of need may be better than hospital based surveillance limited to five years but further large, randomised controlled trials are needed

Chaste: an open source C++ library for computational physiology and biology

Chaste - Cancer, Heart And Soft Tissue Environment - is an open source C++ library for the computational simulation of mathematical models developed for physiology and biology. Code development has been driven by two initial applications: cardiac electrophysiology and cancer development. A large number of cardiac electrophysiology studies have been enabled and performed, including high performance computational investigations of defibrillation on realistic human cardiac geometries. New models for the initiation and growth of tumours have been developed. In particular, cell-based simulations have provided novel insight into the role of stem cells in the colorectal crypt. Chaste is constantly evolving and is now being applied to a far wider range of problems. The code provides modules for handling common scientific computing components, such as meshes and solvers for ordinary and partial differential equations (ODEs/PDEs). Re-use of these components avoids the need for researchers to "re-invent the wheel" with each new project, accelerating the rate of progress in new applications. Chaste is developed using industrially-derived techniques, in particular test-driven development, to ensure code quality, re-use and reliability. In this article we provide examples that illustrate the types of problems Chaste can be used to solve, which can be run on a desktop computer. We highlight some scientific studies that have used or are using Chaste, and the insights they have provided. The source code, both for specific releases and the development version, is available to download under an open source Berkeley Software Distribution (BSD) licence at http://www.cs.ox.ac.uk/chaste, together with details of a mailing list and links to documentation and tutorials

Delayed self-recognition in children with autism spectrum disorder.

This study aimed to investigate temporally extended self-awareness (awareness of one’s place in and continued existence through time) in autism spectrum disorder (ASD), using the delayed self-recognition (DSR) paradigm (Povinelli et al., Child Development 67:1540–1554, 1996). Relative to age and verbal ability matched comparison children, children with ASD showed unattenuated performance on the DSR task, despite showing significant impairments in theory-of-mind task performance, and a reduced propensity to use personal pronouns to refer to themselves. The results may indicate intact temporally extended self-awareness in ASD. However, it may be that the DSR task is not an unambiguous measure of temporally extended self-awareness and it can be passed through strategies which do not require the possession of a temporally extended self-concept

Validation of the diabetes, hypertension and hyperlipidemia (DHL) knowledge instrument in Malaysia

BACKGROUND: Patient's knowledge on diabetes, hypertension and hyperlipidaemia and its medications can be used as one of the outcome measures to assess the effectiveness of educational intervention. To date, no such instrument has been validated in Malaysia. Therefore, the aim of this study was to evaluate the validity and reliability of the Diabetes, Hypertension and Hyperlipidemia (DHL) knowledge instrument for assessing the knowledge of patients with type 2 diabetes in Malaysia. METHODS: A 28-item instrument which comprised of 5 domains: diabetes, hypertension, hyperlipidemia, medications and general issues was designed and tested. One point was given for every correct answer, whilst zero was given for incorrect answers. Scores ranged from 0 to 28, which were then converted into percentage. This was administered to 77 patients with type 2 diabetes in a tertiary hospital, who were on medication(s) for diabetes and who could understand English (patient group), and to 40 pharmacists (professional group). The DHL knowledge instrument was administered again to the patient group after one month. Excluded were patients less than 18 years old. RESULTS: Flesch reading ease was 60, which is satisfactory, while the mean difficulty factor(SD) was 0.74(0.21), indicating that DHL knowledge instrument was moderately easy. Internal consistency of the instrument was good, with Cronbach's alpha = 0.791. The test-retest scores showed no significant difference for 26 out of the 28 items, indicating that the questionnaire has achieved stable reliability. The overall mean(SD) knowledge scores was significantly different between the patient and professional groups 74.35(14.88) versus 93.84(6.47), p < 0.001. This means that the DHL knowledge instrument could differentiate the knowledge levels of participants. The DHL knowledge instrument shows similar psychometric properties as other validated questionnaires. CONCLUSIONS: The DHL knowledge instrument shows good promise to be adopted as an instrument for assessing diabetic patients' knowledge concerning their disease conditions and medications in Malaysia

Harnessing Naturally Occurring Tumor Immunity: A Clinical Vaccine Trial in Prostate Cancer

International audienceBACKGROUND:Studies of patients with paraneoplastic neurologic disorders (PND) have revealed that apoptotic tumor serves as a potential potent trigger for the initiation of naturally occurring tumor immunity. The purpose of this study was to assess the feasibility, safety, and immunogenicity of an apoptotic tumor-autologous dendritic cell (DC) vaccine.METHODS AND FINDINGS:We have modeled PND tumor immunity in a clinical trial in which apoptotic allogeneic prostate tumor cells were used to generate an apoptotic tumor-autologous dendritic cell vaccine. Twenty-four prostate cancer patients were immunized in a Phase I, randomized, single-blind, placebo-controlled study to assess the safety and immunogenicity of this vaccine. Vaccinations were safe and well tolerated. Importantly, we also found that the vaccine was immunogenic, inducing delayed type hypersensitivity (DTH) responses and CD4+ and CD8+ T cell proliferation, with no effect on FoxP3+ regulatory T cells. A statistically significant increase in T cell proliferation responses to prostate tumor cells in vitro (p = 0.002), decrease in prostate specific antigen (PSA) slope (p = 0.016), and a two-fold increase in PSA doubling time (p = 0.003) were identified when we compared data before and after vaccination.CONCLUSIONS:An apoptotic cancer cell vaccine modeled on naturally occurring tumor immune responses in PND patients provides a safe and immunogenic tumor vaccine

Artificial intelligence in cancer imaging: Clinical challenges and applications

Judgement, as one of the core tenets of medicine, relies upon the integration of multilayered data with nuanced decision making. Cancer offers a unique context for medical decisions given not only its variegated forms with evolution of disease but also the need to take into account the individual condition of patients, their ability to receive treatment, and their responses to treatment. Challenges remain in the accurate detection, characterization, and monitoring of cancers despite improved technologies. Radiographic assessment of disease most commonly relies upon visual evaluations, the interpretations of which may be augmented by advanced computational analyses. In particular, artificial intelligence (AI) promises to make great strides in the qualitative interpretation of cancer imaging by expert clinicians, including volumetric delineation of tumors over time, extrapolation of the tumor genotype and biological course from its radiographic phenotype, prediction of clinical outcome, and assessment of the impact of disease and treatment on adjacent organs. AI may automate processes in the initial interpretation of images and shift the clinical workflow of radiographic detection, management decisions on whether or not to administer an intervention, and subsequent observation to a yet to be envisioned paradigm. Here, the authors review the current state of AI as applied to medical imaging of cancer and describe advances in 4 tumor types (lung, brain, breast, and prostate) to illustrate how common clinical problems are being addressed. Although most studies evaluating AI applications in oncology to date have not been vigorously validated for reproducibility and generalizability, the results do highlight increasingly concerted efforts in pushing AI technology to clinical use and to impact future directions in cancer care

Utility of clinical parameters to identify HIV infection in infants below ten weeks of age in South Africa: a prospective cohort study

<p>Abstract</p> <p>Background</p> <p>As HIV-infected infants have high mortality, the World Health Organization now recommends initiating antiretroviral therapy as early as possible in the first year of life. However, in many settings, laboratory diagnosis of HIV in infants is not readily available. We aimed to develop a clinical algorithm for HIV presumptive diagnosis in infants < 10 weeks old using screening data from the Children with HIV Early Antiretroviral therapy (CHER) study in South Africa.</p> <p>HIV-infected and HIV-uninfected exposed infants < 10 weeks of age were identified through Vertical Transmission Prevention programs. Clinical and laboratory data were systematically recorded, groups were compared using Kruskal-Wallis, analysis of variance (ANOVA), and Fisher's exact tests. Receiver Operating Characteristic (ROC) curves were compiled using combinations of clinical findings.</p> <p>Results</p> <p>417 HIV-infected and 125 HIV-exposed, uninfected infants, median age 46 days (IQR 38-55), were included. The median CD4 percentage in HIV-infected infants was 34 (IQR 28-41)%. HIV-infected infants had lower weight-for-age, more lymphadenopathy, oral thrush, and hepatomegaly than exposed uninfected infants (Adjusted Odds Ratio 0.51, 8.8, 5.6 and 23.5 respectively; p < 0.001 for all). Sensitivity of individual signs was low (< 20%) but specificity high (98-100%). If any one of oral thrush, hepatomegaly, splenomegaly, lymphadenopathy, diaper dermatitis, weight < 50^thcentile are present, sensitivity for HIV infection amongst HIV-exposed infants was 86%. These algorithms performed similarly when used to predict severe immune suppression.</p> <p>Conclusions</p> <p>A combination of physical findings is helpful in identifying infants most likely to be HIV-infected. This may inform management algorithms and provide guidance for focused laboratory testing in some settings, and should be further validated in these settings and elsewhere.</p