WHO policy development processes for a new vaccine: case study of malaria vaccines

<p>Abstract</p> <p>Background</p> <p>Recommendations from the World Health Organization (WHO) are crucial to inform developing country decisions to use, or not, a new intervention. This article analysed the WHO policy development process to predict its course for a malaria vaccine.</p> <p>Methods</p> <p>The decision-making processes for one malaria intervention and four vaccines were classified through (1) consultations with staff and expert advisors to WHO's Global Malaria Programme (GMP) and Immunization, Vaccines and Biologicals Department (IVB); (2) analysis of the procedures and recommendations of the major policy-making bodies of these groups; (3) interviews with staff of partnerships working toward new vaccine availability; and (4) review and analyses of evidence informing key policy decisions.</p> <p>Case description</p> <p>WHO policy formulation related to use of intermittent preventive treatment in infancy (IPTi) and the following vaccine interventions: <it>Haemophilus influenzae </it>type b conjugate vaccine (Hib), pneumococcal conjugate vaccine (PCV), rotavirus vaccine (RV), and human papillomavirus vaccine (HPV), five interventions which had relatively recently been through systematic WHO policy development processes as currently constituted, was analysed. Required information was categorized in three areas defined by a recent WHO publication on development of guidelines: safety and efficacy in relevant populations, implications for costs and population health, and localization of data to specific epidemiological situations.</p> <p>Discussion and evaluation</p> <p>Data needs for a malaria vaccine include safety; the demonstration of efficacy in a range of epidemiological settings in the context of other malaria prevention interventions; and information on potential rebound in which disease increases subsequent to the intervention. In addition, a malaria vaccine would require attention to additional factors, such as costs and cost-effectiveness, supply and demand, impact of use on other interventions, and distribution issues.</p> <p>Conclusions</p> <p>Although policy issues may be more complex for future vaccines, the lead-time between the date of product regulatory approval and a recommendation for its use in developing countries is decreasing. This study presents approaches to define in advance core data needs to support evidence-based decisions, to further decrease this lead-time, accelerating the availability of a malaria vaccine. Specific policy areas for which information should be collected are defined, including studying its use within the context of other malaria interventions.</p

Computer controlled music synthesis

Improvements made to a computer controlled digital music synthesizer are described. The basic elements of the synthesizer are discussed to give the background for these developments. Hardware additions have been made to extend the technical capabilities of the system and provide the user with computer control over various aspects of a musical sound including tremolo (frequency, amplitude and waveshape), the attack and decay rates of the notes and the volumes of the notes. Emphasis, however, is placed on describing the software developments, which are designed to provide the user with powerful facilities which are easy to use even if the operator has no computer training (as is likely with musicians). The software allows the user to interact with the timbres being produced by the synthesizer and to develop complete performances which can then be played by a computer. All aspects of the synthesizer are controlled by the computer

Health state utility values for diabetic retinopathy: protocol for a systematic review and meta-analysis

Background People with diabetic retinopathy tend to have lower levels of health-related quality of life than individuals with no retinopathy. Strategies for screening and treatment have been shown to be cost-effective. In order to reduce the bias in cost-effectiveness estimates, systematic reviews of health state utility values (HSUVs) are crucial for health technology assessment and the development of decision analytic models. A review and synthesis of HSUVs for the different stages of disease progression in diabetic retinopathy has not previously been conducted. Methods/Design We will conduct a systematic review of the available literature that reports HSUVs for people with diabetic retinopathy, in correspondence with current stage of disease progression and/or visual acuity. We will search Medline, EMBASE, Web of Science, Cost-Effectiveness Analysis Registry, Centre for Reviews and Dissemination Database, and EconLit to identify relevant English-language articles. Data will subsequently be synthesized using linear mixed effects modeling meta-regression. Additionally, reported disease severity classifications will be mapped to a four-level grading scale for diabetic retinopathy. Discussion The systematic review and meta-analysis will provide important evidence for future model-based economic evaluations of technologies for diabetic retinopathy. The meta-regression will enable the estimation of utility values at different disease stages for patients with particular characteristics and will also highlight where the design of the study and HSUV instrument have influenced the reported utility values. We believe this protocol to be the first of its kind to be published

Belief bias during reasoning among religious believers and skeptics

We provide evidence that religious skeptics, as compared to believers, are both more reflective and effective in logical reasoning tasks. While recent studies have reported a negative association between an analytic cognitive style and religiosity, they focused exclusively on accuracy, making it difficult to specify potential underlying cognitive mechanisms. The present study extends the previous research by assessing both performance and response times on quintessential logical reasoning problems (syllogisms). Those reporting more religious skepticism made fewer reasoning errors than did believers. This finding remained significant after controlling for general cognitive ability, time spent on the problems, and various demographic variables. Crucial for the purpose of exploring underlying mechanisms, response times indicated that skeptics also spent more time reasoning than did believers. This novel finding suggests a possible role of response slowing during analytic problem solving as a component of cognitive style that promotes overriding intuitive first impressions. Implications for using additional processing measures, such as response time, to investigate individual differences in cognitive style are discussed

It’s Still Bullshit: Reply to Dalton (2016)

In reply to Dalton (2016), the authors argue that bullshit is defined in terms of how it is produced, not how it is interpreted. They agree that it can be interpreted as profound by some readers (and assumed as much in the original paper). Nonetheless, they present additional evidence against the possibility that more reflective thinkers are more inclined to interpret bullshit statements as profound

On the Reception and Detection of Pseudo-profound Bullshit

Although bullshit is common in everyday life and has attracted attention from philosophers, its reception (critical or ingenuous) has not, to our knowledge, been subject to empirical investigation. Here we focus on pseudo-profound bullshit, which consists of seemingly impressive assertions that are presented as true and meaningful but are actually vacuous. We presented participants with bullshit statements consisting of buzzwords randomly organized into statements with syntactic structure but no discernible meaning (e.g., “Wholeness quiets infinite phenomena”). Across multiple studies, the propensity to judge bullshit statements as profound was associated with a variety of conceptually relevant variables (e.g., intuitive cognitive style, supernatural belief). Parallel associations were less evident among profundity judgments for more conventionally profound (e.g., “A wet person does not fear the rain”) or mundane (e.g., “Newborn babies require constant attention”) statements. These results support the idea that some people are more receptive to this type of bullshit and that detecting it is not merely a matter of indiscriminate skepticism but rather a discernment of deceptive vagueness in otherwise impressive sounding claims. Our results also suggest that a bias toward accepting statements as true may be an important component of pseudo-profound bullshit receptivity

On the relation of mind wandering and ADHD symptomatology

Mind wandering seems to be a prototypical feature of attention-deficit/hyperactivity disorder (ADHD). However, an important emerging distinction of mind-wandering types hinges on whether a given episode of mind wandering reflects a failure of executive control (spontaneous mind wandering) or the engagement of controlled processes for internal processing (deliberate mind wandering). Here we distinguish between spontaneous and deliberate mind wandering and test the hypothesis that symptoms of ADHD are associated with the former but not the latter. We assessed ADHD symptomatology and everyday levels of deliberate and spontaneous mind wandering in two large non-clinical samples (Ns = 1,354). In addition, to provide converging evidence, we examined rates of deliberate and spontaneous mind wandering in a clinically diagnosed ADHD sample. Results provide clear evidence that spontaneous, but not deliberate, mind wandering is a central feature of ADHD symptomatology at both the clinical and non-clinical level. We discuss the implications of these results for understanding both ADHD and mind wandering

Fast field-cycling magnetic resonance detection of intracellular ultra-small iron oxide particles in vitro: Proof-of-concept.

PurposeInflammation is central in disease pathophysiology and accurate methods for its detection and quantification are increasingly required to guide diagnosis and therapy. Here we explored the ability of Fast Field-Cycling Magnetic Resonance (FFC-MR) in quantifying the signal of ultra-small superparamagnetic iron oxide particles (USPIO) phagocytosed by J774 macrophage-like cells as a proof-of-principle.MethodsRelaxation rates were measured in suspensions of J774 macrophage-like cells loaded with USPIO (0-200 μg/ml Fe as ferumoxytol), using a 0.25 T FFC benchtop relaxometer and a human whole-body, in-house built 0.2 T FFC-MR prototype system with a custom test tube coil. Identical non-imaging, saturation recovery pulse sequence with 90° flip angle and 20 different evolution fields selected logarithmically between 80 μT and 0.2 T (3.4 kHz and 8.51 MHz proton Larmor frequency [PLF] respectively). Results were compared with imaging flow cytometry quantification of side scatter intensity and USPIO-occupied cell area. A reference colorimetric iron assay was used.ResultsThe T1 dispersion curves derived from FFC-MR were excellent in detecting USPIO at all concentrations examined (0-200 μg/ml Fe as ferumoxytol) vs. control cells, p ≤ 0.001. FFC-NMR was capable of reliably detecting cellular iron content as low as 1.12 ng/µg cell protein, validated using a colorimetric assay. FFC-MR was comparable to imaging flow cytometry quantification of side scatter intensity but superior to USPIO-occupied cell area, the latter being only sensitive at exposures ≥ 10 µg/ml USPIO.ConclusionsWe demonstrated for the first time that FFC-MR is capable of quantitative assessment of intra-cellular iron which will have important implications for the use of USPIO in a variety of biological applications, including the study of inflammation

Fast field-cycling magnetic resonance detection of intracellular ultra-small iron oxide particles in vitro : Proof-of-concept

DKD would like to declare funding from British Heart Foundation Project Grant PG/15/108/31928 with no financial conflict of interest. DJL would like to declare funding from the European Commission – ‘Improving Diagnosis by Fast Field-Cycling MRI’ grant number 668119 with no financial conflict of interest, and GE Healthcare in the form of funding for PhD studentship in radiofrequency coils for FFC-MRI, with potential financial conflict of interest. The authors have no additional financial interests.Peer reviewedPublisher PD

Assessment of perinatal anxiety: diagnostic accuracy of five measures

Background Anxiety in pregnancy and after giving birth (the perinatal period) is highly prevalent but under-recognised. Robust methods of assessing perinatal anxiety are essential for services to identify and treat women appropriately. Aims To determine which assessment measures are most psychometrically robust and effective at identifying women with perinatal anxiety (primary objective) and depression (secondary objective). Method We conducted a prospective longitudinal cohort study of 2243 women who completed five measures of anxiety and depression (Generalized Anxiety Disorder scale (GAD) two- and seven-item versions; Whooley questions; Clinical Outcomes in Routine Evaluation (CORE-10); and Stirling Antenatal Anxiety Scale (SAAS)) during pregnancy (15 weeks, 22 weeks and 31 weeks) and after birth (6 weeks). To assess diagnostic accuracy a sample of 403 participants completed modules of the Mini-International Neuropsychiatric Interview (MINI). Results The best diagnostic accuracy for anxiety was shown by the CORE-10 and SAAS. The best diagnostic accuracy for depression was shown by the CORE-10, SAAS and Whooley questions, although the SAAS had lower specificity. The same cut-off scores for each measure were optimal for identifying anxiety or depression (SAAS ≥9; CORE-10 ≥9; Whooley ≥1). All measures were psychometrically robust, with good internal consistency, convergent validity and unidimensional factor structure. Conclusions This study identified robust and effective methods of assessing perinatal anxiety and depression. We recommend using the CORE-10 or SAAS to assess perinatal anxiety and the CORE-10 or Whooley questions to assess depression. The GAD-2 and GAD-7 did not perform as well as other measures and optimal cut-offs were lower than currently recommended