Pathways to Impact: Insights from Research Partnerships in Uganda and India

This article sets out a perspective from the United Kingdom’s Department for International Development (DFID) on the challenges of achieving research uptake. Two country case studies are presented from India and Uganda, which explore research projects under the Economic and Social Research Council ESRC-DFID-funded Raising Learning Outcomes programme. These case studies focus on relationships between the key stakeholders that enable policy debate relevant to the funded research. They are not a direct assessment of the impact that this research has had. Rather, this article explores the messy and iterative processes that DFID advisers are engaged in within the networks that they are embedded (and those that they are not), the way that they use partnerships to access evidence and promote it into policy debate, and the other drivers that matter. This article is important as a contribution to ongoing efforts to improve the quality and usage of education evidence in low-income contexts.Department for International Development (DFID)Economic and Social Research Council (ESRC

Global policy mobilities in federal education systems

As an introduction to this special issue, this paper presents a discussion of different theoretical and methodological challenges in analyzing the ways in which global policy flows are shaping education policies and practices within and across federal systems. We argue that the dynamics between the global and the federal systems are complex, non-linear, multi-directional and ever changing. We start by discussing the notion of global policy mobilities and the kinds of theoretical approaches that we suggest can be productive in understanding the flows of power in education across spaces. We then move on to conceptualize “the federal” in education. While global flows do not lead toward universal results or linear policy convergence across nations, we also stress the necessity to think about federalism not as singular but in the plural, as federalisms, given the different configurations and historical developments of federal systems of education. To conclude, we highlight four analytic tensions and new directions for future research on global policy mobilities in federal education systems

More Than Skin Deep: Detection of subclinical enthesopathy and early psoriatic arthritis in patients with psoriasis in primary and secondary care and assessment of the response to anti-IL-12/IL-23p40 monoclonal antibody skin-directed therapy using ultrasound and whole-body MRI

Objectives: Primary care cohort: To determine the rates of undiagnosed psoriatic arthritis (PsA) amongst patients with psoriasis using clinical examination and screening questionnaires, and test the performance a new PsA screening questionnaire alongside the current standard (Psoriasis Epidemiology Screening Tool, PEST). Secondary care cohort: To develop novel ultrasound and whole body magnetic resonance imaging (WBMRI) protocols to facilitate the comprehensive assessment of subclinical abnormalities within the peripheral and axial skeleton of immunomodulatory therapy-naïve patients with psoriasis referred to secondary care, and to use these protocols to assess the imaging response of abnormalities over 52 weeks of skin- directed treatment with a licensed IL-12/23p40 inhibitor (ustekinumab). Methods: Primary care cohort: 932 patients, across five diverse primary care practices, who were coded as having a diagnosis of psoriasis, were invited by their General Practitioner to attend an evening appointment at their surgery for a consultation with a dermatologist and a rheumatologist. Half of patients were sent an educational leaflet regarding PsA with their invitation letter. Attendees were examined and asked to complete a PEST questionnaire and a new PsA screening questionnaire (CONTEST). Secondary care cohort: 73 immunomodulatory therapy-naive patients, without musculoskeletal disease or symptoms, who were referred to dermatology for treatment of moderate to severe psoriasis were screened using an extensive ultrasound protocol to assess for the presence of subclinical enthesitis. Patients who had at least one inflammatory abnormality, and in whom biologic therapy was not contraindicated, were invited to receive standard-dose skin directed therapy with ustekinumab for 52 weeks. Ultrasound examination of 13 entheses and structures within the adjacent synovio- entheseal complex were performed at weeks 0, 12, 24 and 52. WBMRI was performed at week 0, 24 and 52, to assess the axial skeleton and sites in the peripheral skeleton inaccessible by ultrasound. 23 healthy volunteers had one ultrasound scan and WBMRI using the same protocols, for comparison. Results: Primary care cohort: 20.5% of patients invited for screening attended. The provision of an educational leaflet did not have an impact on attendance for screening, except in the most deprived areas. 191 patients were examined, of which 169 had current or previous psoriasis (11.5% misdiagnosis rate). 17 patients were newly diagnosed with PsA (10.1%). The best sensitivity and specificity of the CONTEST questionnaires were 76.5% and 56.5% respectively, without the joint mannequin (cut off 33), and 70.6% and 63.3% respectively, with the joint mannequin (cut off 34). The sensitivity and specificity of the PEST questionnaire in this cohort, using the validated cut off 33, was 52.9% and 66.0%. Lowering the cut off 32, the sensitivity improved to 82.4% with a specificity of 44.9%. Secondary care cohort: 36 patients (49.3%) had at least inflammatory subclinical abnormality on screening ultrasound. 28 of these 36 were eligible for a biologic therapy and agreed to undergo a more detailed ultrasound scan and WBMRI. 5 patients subsequently chose conventional therapy, and 23 patients consented to treatment with ustekinumab and long-term review. 23 patients reached the primary end point of week 24, and 20 reached week 52. Inflammatory and chronic damage abnormalities were seen with greater frequency in the peripheral rather than axial skeleton, mostly involving the larger entheses of the knee, foot, ankle and elbows. Healthy volunteers exhibited a similar pattern of abnormalities but at a significantly lower frequency (inflammatory lesions 4.5% vs. 31.1%, chronic damage lesions 6.0% vs. 27.0%, both p<0.00001). Synovitis was seen in 82.1% of patients, while bursitis and tenosynovitis were uncommon. Following treatment with ustekinumab, ultrasound inflammation scores reduced by 42.2% at the primary end point (week 24, p<0.001), and by 51.5% after 52 weeks (p=0.01). Chronic damage scores remain unchanged (p=0.082 week 24, p=0.512 week 52). In the axial skeleton, more patients than volunteers had vertebral unit bone marrow oedema (64.3% vs. 30.4%, p<0.00001). Sacroiliac joint inflammation was minimal in both groups. Axial structural changes occurred in 14.3% in patients and were absent in volunteers. No significant change in spine or SIJ osteitis (p=0.656 week 24, p=0.627 week 52), or structural abnormalities were observed after ustekinumab therapy. Conclusions: A proportion of patients with psoriasis have undiagnosed PsA in primary care, even with signs and symptoms of inflammatory arthritis. Screening questionnaires are useful to detect some, but not all patients and further measures are required to capture all cases of PsA. Early identification and treatment is essential to prevent future pain, functional limitation and disability. Treating patients for psoriasis with a therapeutic agent that is effective at reducing the development of PsA is one means of addressing the failings of clinical examination and screening questionnaires, although the evolution from subclinical enthesitis (a common finding in patients with psoriasis) to PsA is not understood. This thesis provides preliminary data to suggest that anti-IL-12/23p40 therapy may reduce the burden of subclinical inflammation at the primary site of lesion development in PsA (the enthesis), and further longitudinal studies are now encouraged to confirm these observations with ustekinumab and other immunomodulatory therapies

Spitzer IRAC Imaging of the Relativistic Jet from Superluminal Quasar PKS 0637-752

Emission from the relativistic jet located at hundreds of kpc from the core of the superluminal quasar PKS 0637-752 was detected at 3.6 and 5.8 microns with the Infrared Array Camera (IRAC) on the Spitzer Space Telescope. The unprecedented sensitivity and arcsecond resolution of IRAC allows us to explore the mid-infrared emission from kiloparsec-scale quasar jets for the first time. The mid-infrared flux from the jet knots, when combined with radio and optical fluxes, confirms a synchrotron origin of the radio-to-optical emission and constrains very well the high energy end of the nonthermal electron distribution. Assuming the X-rays are produced in the relativistically moving knots via inverse Compton scattering of cosmic microwave background (CMB) radiation, the infrared observation puts constraints on the matter content of the quasar extended jet. Specifically, pure electron-positoron pair jet models are unfavorable based on the lack of an infrared bump associated with ``bulk Comptonization'' of CMB photons by an ultrarelativistic jet.Comment: 4 pages, 3 figures; accepted for publication in ApJ Letter

Winning and losing: differences in reward and punishment sensitivity between smokers and nonsmokers

Background: Smokers show increased brain activation in reward processing regions in response to smoking-related cues, yet few studies have examined secondary rewards not associated with smoking (i.e., money). Inconsistencies exist in the studies that do examine secondary rewards with some studies showing increased brain activation in reward processing brain regions, while others show decreased activation or no difference in activation between smokers and nonsmokers. Aims: The goal of the current study is to see if smokers process the evaluation and delivery of equally salient real world rewards similarly or differently than nonsmokers. Methods: The current study employed functional magnetic resonance imaging (fMRI) to examine brain responses in smokers and nonsmokers during the evaluation and delivery of monetary gains and losses. Results: In comparison to nonsmokers, smokers showed increased activation in the ventromedial prefrontal cortex to the evaluation of anticipated monetary losses and the brain response. Moreover, smokers compared to nonsmokers showed decreased activation in the inferior frontal gyrus to the delivery of expected monetary gains. Brain activations to both the evaluation of anticipated monetary losses and the delivery of expected monetary gains correlated with increased self-reported smoking craving to relieve negative withdrawal symptoms and craving related to positive aspects of smoking, respectively. Discussion: Together these results indicate that smokers are hyperresponsive to the evaluation of anticipated punishment and hyporesponsive to the delivery of expected rewards. Although further research is needed, this hypersensitivity to punishments coupled with increased craving may negatively impact quit attempts as smokers anticipate the negative withdrawal symptoms associated with quitting

Pre–post intervention exploring cognitive function and relationships with weight loss, intervention adherence and dropout

Objective: To evaluate the association between baseline cognitive function, intervention dropout, adherence and 3-month weight loss (WL) when controlling for confounding demographic variables. Methods: 107 (Mage = 40.9 yrs.), BMI in the overweight and obese range (BMI = 35.6 kg/m2), men (N = 17) and women (N = 90) completed a 3-month WL intervention. Participants attended weekly behavioral sessions, comply with a reduced calorie diet, and complete 100 min of physical activity (PA)/wk. Cognitive function tasks at baseline included Flanker (attention), Stroop (executive control) and working memory, demographics, body weight and cardiovascular fitness were assessed at baseline. Session attendance, adherence to PA and diet were recorded weekly. Results: Baseline attention was positively correlated with age (p \u3c .05), education (p \u3c .05), attendance (p \u3c .05), diet (p \u3c .05) and PA (p \u3c .05). Baseline executive control (p \u3c .05) and working memory (p \u3c .05) were each associated with % WL. Baseline executive control (p \u3c .01) and working memory (p \u3c .001) were also each associated with education. ANOVA indicated that baseline attention (p \u3c .01) was associated with WL, specifically for comparing those who achieved 5–10% WL (p \u3c .01) and those who achieved greater than 10% WL (p \u3c .01) to those who dropped. Significance: Results suggest that stronger baseline attention is associated with completion of a 3-mo. WL intervention. Executive control and working memory are associated with amount of WL achieved. NCT registration: US NIH Clinical Trials, NCT0166471

Novel Biomarkers of Physical Activity Maintenance in Midlife Women: Preliminary Investigation

The precision health initiative is leading the discovery of novel biomarkers as important indicators of biological processes or responses to behavior, such as physical activity. Neural biomarkers identified by magnetic resonance imaging (MRI) hold promise to inform future research, and ultimately, for transfer to the clinical setting to optimize health outcomes. This study investigated resting-state and functional brain biomarkers between midlife women who were maintaining physical activity in accordance with the current national guidelines and previously acquired age-matched sedentary controls. Approval was obtained from the Human Subjects Committee. Participants included nondiabetic, healthy weight to overweight (body mass index 19–29.9 kg/m2) women (n = 12) aged 40–64 years. Control group data were used from participants enrolled in our previous functional MRI study and baseline resting-state MRI data from a subset of sedentary (week) midlife women who were enrolled in a 9-month exercise intervention conducted in our imaging center. Differential activation of the inferior frontal gyrus (IFG) and greater connectivity with the dorsolateral prefrontal cortex (dlPFC) was identified between physically active women and sedentary controls. After correcting for multiple comparisons, these differences in biomarkers of physical activity maintenance did not reach statistical significance. Preliminary evidence in this small sample suggests that neural biomarkers of physical activity maintenance involve activations in the brain region associated with areas involved in implementing goal-directed behavior. Specifically, activation of the IFG and connectivity with the dlPFC is identified as a neural biomarker to explain and predict long-term physical activity maintenance for healthy aging. Future studies should evaluate these biomarker links with relevant clinical correlations

The effects of moderate prenatal alcohol exposure on the organization of exploratory behavior by adult female rats

A large body of research has indicated that moderate Prenatal Alcohol Exposure (PAE - 60 mg/dl peak BAC) can produce impairments on cognitive processes, such as spatial learning and memory. The neurobiological basis of these impairments is poorly understood but is frequently linked to alterations in hippocampal functioning. Although the hippocampus has a central role in learning and memory, damage to the hippocampus can also produce impairments in locomotor and exploratory behaviors by rodents (reviewed in Thompson et al., 2018). Rodent exploratory behavior is organized around home bases, which serves as central points of attraction from which rats and mice organize their exploratory trips into the remaining environment. We are unaware of studies investigating the relationship between moderate prenatal alcohol exposure and exploratory behavior. Thus, in the present study, we tested adult female rats in two experiments where they were allowed to freely explore a circular open field for ~30min. Here, we report that, with respect to home base behavior, exploratory movements were largely intact in rats exposed to alcohol prenatally. Specifically, animals rapidly established home bases within 5min of the beginning of testing and the bases were established in one or two locations in the environment. They made exploratory trips away and back to the home base and made several stops at this location along with bouts of grooming behavior. The results are discussed with respect to theories of hippocampal function and the impact of moderate prenatal alcohol on spatial behavior

Pilot Study of Endurance Runners and Brain Responses Associated with Delay Discounting

International Journal of Exercise Science 10(5): 690-701, 2017. High levels of endurance training have been associated with potentially negative health outcomes and addictive-like symptoms such as exercise in the presence of injury and higher levels of impulsivity. This pilot study examined the relationships among self-report measures of addictive symptoms related to exercise and behavioral and neural measures of impulsivity in endurance runners. We hypothesized endurance runners would have increased preference for immediate rewards and greater activation of cognitive control regions when making decisions involving delayed rewards. Twenty endurance runners (at least 20 miles/week) were recruited to undergo measures of self-report exercise addiction symptoms, impulsive decision-making (delay discounting) and functional magnetic resonance imaging (fMRI). During behavioral and fMRI examinations, participants chose between a small hypothetical amount of money given immediately ($0 – 100) compared to a larger hypothetical amount of money ($100) given after a delay (2-12 weeks). On half of the trials participants were instructed that if they chose the delayed reward they would not be able to exercise during the delay period. Eighteen participants were included in the analysis. Results indicated that 94% of endurance runners reported high levels of exercise addiction symptoms, and 44% were “at-risk” for exercise addiction. In addition, endurance runners demonstrated increased preference for immediately available compared to delayed rewards (p \u3c 0.001) and greater recruitment of cognitive control regions (dorsomedial prefrontal cortex and anterior cingulate) when making decisions involving rewards when exercise was delayed (p \u3c 0.05). Together, these results indicate that endurance runners not only report addictive symptoms related to exercise, but also demonstrate addictive-like behaviors