Systems intervention to promote colon cancer screening in safety net settings: Protocol for a community-based participatory randomized controlled trial

BACKGROUND: Colorectal cancer is a leading cause of cancer mortality. Screening can be effective but is underutilized. System- or multi-level interventions could be effective at increasing screening, but most have been implemented and evaluated in higher-resource settings such as health maintenance organizations. Given the disparities evident for colorectal cancer and the potential for screening to improve outcomes, there is a need to expand this work to include diverse settings, including those who treat economically disadvantaged patients. This paper describes the study protocol for a trial designed to increase colorectal cancer screening in those ‘safety-net’ health centers that serve underinsured and uninsured patients. This trial was designed and is being implemented using a community-based participatory approach. METHODS/DESIGN: We developed a practical clinical cluster-randomized controlled trial. We will recruit 16 community health centers to this trial. This systems-level intervention consists of a menu of evidence-based implementation strategies for increasing colorectal cancer screening. Health centers in the intervention arm then collaborate with the study team to tailor strategies to their own setting in order to maximize fit and acceptability. Data are collected at the organizational level through interviews, and at the provider and patient levels through surveys. Patients complete a survey about their healthcare and screening utilization at baseline, six months, and twelve months. OUTCOMES: The primary outcome is colorectal cancer screening by patient self-report, supplemented by a chart-audit in a subsample of patients. Implementation outcomes informed by the Reach, Efficacy/Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) conceptual framework will be measured at patient, provider, and practice levels. DISCUSSION: Our study is one of the first to integrate community participatory strategies to a randomized controlled trial in a healthcare setting. The multi-level approach will support the ability of the intervention to affect screening through multiple avenues. The participatory approach will strengthen the chance that implementation strategies will be maintained after study completion and, supports external validity by increasing health center interest and willingness to participate. TRIAL REGISTRATION: NCT0129949

Evidence of Embodied Social Competence During Conversation in High Functioning Children with Autism Spectrum Disorder

Even high functioning children with Autism Spectrum Disorder (ASD) exhibit impairments that affect their ability to carry out and maintain effective social interactions in multiple contexts. One aspect of subtle nonverbal communication that might play a role in this impairment is the whole-body motor coordination that naturally arises between people during conversation. The current study aimed to measure the time-dependent, coordinated whole-body movements between children with ASD and a clinician during a conversational exchange using tools of nonlinear dynamics. Given the influence that subtle interpersonal coordination has on social interaction feelings, we expected there to be important associations between the dynamic motor movement measures introduced in the current study and the measures used traditionally to categorize ASD impairment (ADOS-2, joint attention and theory of mind). The study found that children with ASD coordinated their bodily movements with a clinician, that these movements were complex and that the complexity of the children’s movements matched that of the clinician’s movements. Importantly, the degree of this bodily coordination was related to higher social cognitive ability. This suggests children with ASD are embodying some degree of social competence during conversations. This study demonstrates the importance of further investigating the subtle but important bodily movement coordination that occurs during social interaction in children with ASD

Understanding the structure and processes of primary health care for young indigenous children

INTRODUCTION: Primary health care organisations need to continuously reform to more effectively address current health challenges, particularly for vulnerable populations. There is growing evidence that optimal health service structures are essential for producing positive outcomes. AIM: To determine if there is an association between process of care indicators (PoCIs) for important young indigenous child health and social issues and: (i) primary health-care service and child characteristics; and (ii) organisational health service structures. METHODS: This was a cross-sectional study of 1554 clinical child health audits and associated system assessments from 74 primary care services from 2012 to 2014. Composite PoCIs were developed for social and emotional wellbeing, child neurodevelopment and anaemia. Crude and adjusted logistic regression models were fitted, clustering for health services. Odds ratios and 95% confidence intervals were derived. RESULTS: Overall, 32.0% (449) of records had a social and emotional wellbeing PoCI, 56.6% (791) had an anaemia PoCI and 49.3% (430) had a child neurodevelopment PoCI. Children aged 12–23 months were significantly more likely to receive all PoCIs compared to children aged 24–59 months. For every one point increase in assessment scores for team structure and function (aOR 1.14, 95% CI 1.01–1.27) and care planning (aOR 1.14, 95% CI 1.01–1.29) items, there was a 14% greater odds of a child having an anaemia PoCI. Social and emotional wellbeing and child neurodevelopment PoCIs were not associated with system assessment scores. DISCUSSION: Ensuring young indigenous children aged 24–59 months are receiving quality care for important social and health indicators is a priority. Processes of care and organisational systems in primary care services are important for the optimal management of anaemia in indigenous children

Rapamycin Rescues Vascular, Metabolic and Learning Deficits in Apolipoprotein E4 Transgenic Mice with Pre-Symptomatic Alzheimer’s Disease

Apolipoprotein E ɛ4 allele is a common susceptibility gene for late-onset Alzheimer\u27s disease. Brain vascular and metabolic deficits can occur in cognitively normal apolipoprotein E ɛ4 carriers decades before the onset of Alzheimer\u27s disease. The goal of this study was to determine whether early intervention using rapamycin could restore neurovascular and neurometabolic functions, and thus impede pathological progression of Alzheimer\u27s disease-like symptoms in pre-symptomatic Apolipoprotein E ɛ4 transgenic mice. Using in vivo, multimodal neuroimaging, we found that apolipoprotein E ɛ4 mice treated with rapamycin had restored cerebral blood flow, blood–brain barrier integrity and glucose metabolism, compared to age- and gender-matched wild-type controls. The preserved vasculature and metabolism were associated with amelioration of incipient learning deficits. We also found that rapamycin restored the levels of the proinflammatory cyclophilin A in vasculature, which may contribute to the preservation of cerebrovascular function in the apolipoprotein E ɛ4 transgenics. Our results show that rapamycin improves functional outcomes in this mouse model and may have potential as an effective intervention to block progression of vascular, metabolic and early cognitive deficits in human Apolipoprotein E ɛ4 carriers. As rapamycin is FDA-approved and neuroimaging is readily used in humans, the results of the present study may provide the basis for future Alzheimer\u27s disease intervention studies in human subjects

Inhibition of mTOR by Rapamycin Abolishes Cognitive Deficits and Reduces Amyloid-β Levels in a Mouse Model of Alzheimer's Disease

extends lifespan in mice, possibly by delaying aging. Whether inhibition of the mTOR pathway would delay or prevent age-associated disease such as AD remained to be determined. and block or delay AD in mice. As expected from the inhibition of mTOR, autophagy was increased in neurons of rapamycin-treated transgenic, but not in non-transgenic, PDAPP mice, suggesting that the reduction in Aβ and the improvement in cognitive function are due in part to increased autophagy, possibly as a response to high levels of Aβ.Our data suggest that inhibition of mTOR by rapamycin, an intervention that extends lifespan in mice, can slow or block AD progression in a transgenic mouse model of the disease. Rapamycin, already used in clinical settings, may be a potentially effective therapeutic agent for the treatment of AD

Proposal for Austere Light Attack Aircraft – Project Aardvark

The WickedAir senior design team at the University of Alabama in Huntsville is developing the preliminary design of an aircraft for the AIAA Undergraduate Team Aircraft Design Competition. The RFP calls for an affordable light attack aircraft capable of executing missions currently only feasible with attack helicopters. The aircraft must be able to operate from short austere fields and accommodate a crew of two. Additional design goals include enhanced survivability and the ability for deploying a variety of weapons including an integrated gun for ground targets. The aircraft must accomplish an attack mission with a full weapons load and a long-range ferry mission with a 60% weapons load. Through evaluation of existing attack aircraft and helicopters and initial trade studies, the team has produced a conceptual design for the ZA-13 “Aardvark”. The 12,000 lbf Aardvark has twin turboprop engines mounted on a 6.9 aspect ratio swept wing. Two sponsons offer weapons attachment points similar to those of a helicopter. This design offers low speed performance, a high payload capacity, and a short takeoff length. Specific consideration was given to the effects of foreign object debris and particulate matter pollution with regards to the lifespan and vulnerability of the aircraft in various austere environments. This paper summarizes the detailed design, cost analysis, and mission capabilities behind the current aircraft

The Pain in Dystonia Scale (PIDS)—Development and Validation in Cervical Dystonia

BACKGROUND: A better understanding of pain in adult-onset idiopathic dystonia (AOID) is needed to implement effective therapeutic strategies. OBJECTIVE: To develop a new rating instrument for pain in AOID and validate it in cervical dystonia (CD). METHODS: Development and validation of the Pain in Dystonia Scale (PIDS) comprised three phases. In phase 1, international experts and participants with AOID generated and evaluated the preliminary items for content validity. In phase 2, the PIDS was drafted and revised by the experts, followed by cognitive interviews to ensure self-administration suitability. In phase 3, the PIDS psychometric properties were assessed in 85 participants with CD and retested in 40 participants. RESULTS: The final version of PIDS evaluates pain severity (by body-part), functional impact, and external modulating factors. Test-retest reliability showed a high-correlation coefficient for the total score (0.9, P < 0.001), and intraclass correlation coefficients were 0.7 or higher for all items in all body-parts subscores. The overall PIDS severity score showed high internal consistency (Cronbach's α, 0.9). Convergent validity analysis revealed a strong correlation between the PIDS severity score and the Toronto Western Spasmodic Torticollis Rating Scale pain subscale (0.8, P < 0.001) and the Brief Pain Inventory-short form items related to pain at time of the assessment (0.7, P < 0.001) and impact of pain on daily functioning (0.7, P < 0.001). CONCLUSION: The PIDS is the first specific questionnaire developed to evaluate pain in all patients with AOID, here, demonstrating high-level psychometric properties in people with CD. Future work will validate PIDS in other forms of AOID. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

The Thermal Infrared Sensor on the Landsat Data Continuity Mission

The Landsat Data Continuity Mission (LDCM), a joint NASA and USGS mission, is scheduled for launch in December, 2012. The LDCM instrument payload will consist of the Operational Land Imager (OLI), provided by Ball Aerospace and Technology Corporation (BATC} under contract to NASA and the Thermal Infrared Sensor (TIRS), provided by NASA's Goddard Space Flight Center (GSFC). This paper outlines the design of the TIRS instrument and gives an example of its application to monitoring water consumption by measuring evapotranspiration

The renal lineage factor PAX8 controls oncogenic signalling in kidney cancer

Large-scale human genetic data(1-3) have shown that cancer mutations display strong tissue-selectivity, but how this selectivity arises remains unclear. Here, using experimental models, functional genomics and analyses of patient samples, we demonstrate that the lineage transcription factor paired box 8 (PAX8) is required for oncogenic signalling by two common genetic alterations that cause clear cell renal cell carcinoma (ccRCC) in humans: the germline variant rs7948643 at 11q13.3 and somatic inactivation of the von Hippel-Lindau tumour suppressor (VHL)(4-6). VHL loss, which is observed in about 90% of ccRCCs, can lead to hypoxia-inducible factor 2 alpha (HIF2A) stabilization(6,7). We show that HIF2A is preferentially recruited to PAX8-bound transcriptional enhancers, including a pro-tumorigenic cyclin D1 (CCND1) enhancer that is controlled by PAX8 and HIF2A. The ccRCC-protective allele Cat rs7948643 inhibits PAX8 binding at this enhancer and downstream activation of CCND1 expression. Co-option of a PAX8-dependent physiological programme that supports the proliferation of normal renal epithelial cells is also required for MYC expression from the ccRCC metastasis-associated amplicons at 8q21.3-q24.3 (ref. (8)). These results demonstrate that transcriptional lineage factors are essential for oncogenic signalling and that they mediate tissue-specific cancer risk associated with somatic and inherited genetic variants.Peer reviewe