Research for Policy (R4P): development of a reflection tool for researchers to improve knowledge utilization

Background: To improve knowledge utilization in policymaking, alignment between researchers and policymakers during knowledge production is essential, but difficult to maintain. In three previously reported case studies, we extensively evaluated complex research projects commissioned by policymakers to investigate how alignment is achieved in a research process and to discover ways to enhance knowledge contributions to health policy. In the present study, we investigated how the findings of these three research projects could be integrated into a practical tool for researchers to enhance their contribution to evidence-based policy. Methods: A cross-case analysis was conducted to integrate the findings of the evaluation of the three research projects and to identify important alignment areas in these projects. By means of an iterative process, we prepared a tool that includes reflection questions for researchers. The "Research for Policy" tool was tested with input from the project managers of three new research projects. Based on the findings, the final version of the Research for Policy tool was prepared. Results: By cross-case analysis of the three case studies, the following important alignment areas were identified: the goal, quality, relevance, timing, and presentation of research, the tasks and authorities of actors, the consultative structure and vertical alignment within organizations, and the organizational environment. The project managers regarded the Research for Policy tool as a useful checklist for addressing the important alignment areas in a research project. Based on their feedback, the illustrative examples from the case studies were added to the reflection questions. The project managers suggested making the tool accessible not only to researchers but also to policymakers. The format of the Research for Policy tool was further adjusted to users' needs by adding clickable links. Conclusions: Alignment between research and policymaking requires continuous efforts and a clear understanding of process issues in the research project. The Research for Policy tool offers practical alignment guidance and facilitates reflection on process issues, which supports researchers in aligning with policymakers and in acting in a context-sensitive way. © 2016 The Author(s)

Periodontitis and cognitive impairment in older adults:The mediating role of mitochondrial dysfunction

Background: Increased attention has been focused on the associations of periodontal disease with the onset and progression of cognitive impairment. Although the associations are likely to be multifactorial, few studies have explored the role of mitochondrial dysfunction in the periodontitis-dementia link. Methods: Cross-sectional data of 1,883 participants aged ≥60 years in the National Health and Nutrition Examination Survey 2011‒2014 were analyzed. The following data were collected: 1) general information on sociodemographic, behavioral, and health-related factors; 2) periodontal status (mean attachment loss [AL] and mean probing depth [PD]); 3) mitochondrion-derived biomarker of mitochondrial dysfunction (blood sample concentration of methylmalonic acid [MMA]); 4) cognitive function (Consortium to Establish a Registry for Alzheimer's disease immediate recall [CERAD-IR] and delay recall [CERAD-DR], animal fluency test, and digit symbol substitution test [DSST]). Mediation analysis weighted for complex survey design was used to assess the effect of MMA on the association of periodontal status with cognitive function after adjusting for potential confounders. Results: Participants with Stage III and IV periodontitis had lower scores on cognitive performance and higher MMA levels than those with Stages I/II periodontitis. Circulating MMA was significantly associated with CERAD-DR (weighted β [SE] = −0.076 [0.011]) and DSST (weighted β [SE] = −0.039 [0.009]), which mediated 9.9% and 6.0% of the total association of mean PD with cognitive function. Moreover, MMA mediated 11.7% and 5.8% of the association of mean AL with CERAD-DR and DSST, respectively. Conclusion: The findings suggest that MMA, a biomarker of mitochondrial dysfunction, plays a mediating role in the link between periodontitis and cognitive impairment in older adults aged ≥60 years

The acoustical and perceptual features of snore-related sounds in patients with obstructive sleep apnea sleeping with the dynamic mandibular advancement system MATRx plus®

Purpose: The effect of snoring on the bed partner can be studied through the evaluation of in situ sound records by the bed partner or unspecialized raters as a proxy of real-life snoring perception. The aim was to characterize perceptual snore events through acoustical features in patients with obstructive sleep apnea (OSA) with an advanced mandibular position. Methods: Thirty-minute sound samples of 29 patients with OSA were retrieved from overnight, in-home recordings of a study to validate the MATRx plus® dynamic mandibular advancement system. Three unspecialized raters identified sound events and classified them as noise, snore, or breathing. The raters provided ratings for classification certainty and annoyance. Data were analyzed with respect to respiratory phases, and annoyance. Results: When subdividing perceptual events based on respiratory phase, the logarithm-transformed Mean Power, Spectral Centroid, and Snore Factor differed significantly between event types, although not substantially for the spectral centroid. The variability within event type was high and distributions suggested the presence of subpopulations. The general linear model (GLM) showed a significant patient effect. Inspiration segments occurred in 65% of snore events, expiration segments in 54%. The annoyance correlated with the logarithm of mean power (r = 0.48) and the Snore Factor (0.46). Conclusion: Perceptual sound events identified by non-experts contain a non-negligible mixture of expiration and inspiration phases making the characterization through acoustical features complex. The present study reveals that subpopulations may exist, and patient-specific features need to be introduced

Optical coherence tomography: A review of clinical development from bench to bedside

Since its introduction, optical coherence tomography (OCT) technology has advanced from the laboratory bench to the clinic and back again. Arising from the fields of low coherence interferometry and optical time- and frequency-domain reflectometry, OCT was initially demonstrated for retinal imaging and followed a unique path to commercialization for clinical use. Concurrently, significant technological advances were brought about from within the research community, including improved laser sources, beam delivery instruments, and detection schemes. While many of these technologies improved retinal imaging, they also allowed for the application of OCT to many new clinical areas. As a result, OCT has been clinically demonstrated in a diverse set of medical and surgical specialties, including gastroenterology, dermatology, cardiology, and oncology, among others. The lessons learned in the clinic are currently spurring a new set of advances in the laboratory that will again expand the clinical use of OCT by adding molecular sensitivity, improving image quality, and increasing acquisition speeds. This continuous cycle of laboratory development and clinical application has allowed the OCT technology to grow at a rapid rate and represents a unique model for the translation of biomedical optics to the patient bedside. This work presents a brief history of OCT development, reviews current clinical applications, discusses some clinical translation challenges, and reviews laboratory developments poised for future clinical application

The role of structural evolution on the quantum conductance behavior of gold nanowires during stretching

Gold nanowires generated by mechanical stretching have been shown to adopt only three kinds of configurations where their atomic arrangements adjust such that either the [100], [111] or [110] zone axes lie parallel to the elongation direction. We have analyzed the relationship between structural rearrangements and electronic transport behavior during the elongation of Au nanowires for each of the three possibilities. We have used two independent experiments to tackle this problem, high resolution transmission high resolution electron microscopy to observe the atomic structure and a mechanically controlled break junction to measure the transport properties. We have estimated the conductance of nanowires using a theoretical method based on the extended H\"uckel theory that takes into account the atom species and their positions. Aided by these calculations, we have consistently connected both sets of experimental results and modeled the evolution process of gold nanowires whose conductance lies within the first and third conductance quanta. We have also presented evidence that carbon acts as a contaminant, lowering the conductance of one-atom-thick wires.Comment: 10 page

Optical biopsy of lymph node morphology using optical coherence tomography

Optical diagnostic imaging techniques are increasingly being used in the clinical environment, allowing for improved screening and diagnosis while minimizing the number of invasive procedures. Diffuse optical tomography, for example, is capable of whole-breast imaging and is being developed as an alternative to traditional X-ray mammography. While this may eventually be a very effective screening method, other optical techniques are better suited for imaging on the cellular and molecular scale. Optical Coherence Tomography (OCT), for instance, is capable of high-resolution cross-sectional imaging of tissue morphology. In a manner analogous to ultrasound imaging except using optics, pulses of near-infrared light are sent into the tissue while coherence-gated reflections are measured interferometrically to form a cross-sectional image of tissue. In this paper we apply OCT techniques for the high-resolution three-dimensional visualization of lymph node morphology. We present the first reported OCT images showing detailed morphological structure and corresponding histological features of lymph nodes from a carcinogen-induced rat mammary tumor model, as well as from a human lymph node containing late stage metastatic disease. The results illustrate the potential for OCT to visualize detailed lymph node structures on the scale of micrometastases and the potential for the detection of metastatic nodal disease intraoperatively

Neoadjuvant Systemic Therapy Use for Younger Patients with Breast Cancer Treated in Different Types of Cancer Centers Across the United States

Background Multiple clinical trials have shown that neoadjuvant systemic therapy has a benefit in women who are borderline lumpectomy candidates and in those with locally advanced breast cancers by reducing the mastectomy rate and making inoperable tumors operable. The study aim was to examine the patterns of neoadjuvant chemotherapy and endocrine therapy use among younger women in the United States treated at different types of cancer centers. Study Design Data from the National Cancer Data Base for 118,086 women younger than 65 years with clinical stage IIA (T2N0 only) to IIIC breast cancer. Following the National Comprehensive Cancer Network guideline categorization, patients were grouped into those who were borderline lumpectomy candidates (clinical stage IIA [T2N0 only], IIB, or IIIA [T3N1 only]) or those with locally advanced disease (clinical stage IIIA [T0-3N2 only], IIIB, or IIIC). The main outcome was the proportion of women who received neoadjuvant systemic therapy. Results Use of neoadjuvant chemotherapy ranged from 17% (stage IIA) to 79% (stage IIIB). Across almost all stage and receptor subtypes, the use was lower in community vs academic centers. On multivariable analysis, use of neoadjuvant chemotherapy was decreased in community vs academic centers (borderline lumpectomy candidates: adjusted risk ratio = 0.73; 95% CI, 0.69–0.77; locally advanced disease: adjusted risk ratio = 0.78; 95% CI, 0.74–0.83). Conclusions Use of guideline-concordant neoadjuvant chemotherapy is significantly higher among women treated at academic vs community centers in young and healthy women who do not commonly have contraindications to this treatment. Our study identified a potential disparity in cancer care by type of center where patients receive treatment

Evaluating the effectiveness of neoadjuvant chemotherapy in reducing mastectomy for women with breast cancer

Background: Neoadjuvant chemotherapy in breast cancer reduced mastectomy rates by 7% to 13% in randomized trials. However, the differential effects for women with different stages, receptor subtypes, and ages are unknown. We compared mastectomy rates in women who did vs did not receive neoadjuvant chemotherapy in 18 patient subgroups. The main objective was to quantify the potential benefit from neoadjuvant chemotherapy in reducing mastectomy rates for each subgroup. Methods: Our retrospective analysis used data from the National Cancer Data Base, which includes approximately 70% of incident cancers across the United States. Absolute risk reductions for mastectomy were determined for 18 subgroups of clinical stage, receptor subtype, and age group. In each subgroup, propensity score weighting balanced measured covariates between women treated with vs without neoadjuvant chemotherapy. Results: A total of 55 709 patients were analyzed. In clinical stage IIA disease, only patients with human epidermal growth factor receptor 2 (HER2)-positive tumors had reduced mastectomy rates associated with neoadjuvant chemotherapy (age < 60 years, 12%; age ≥ 60 years, 12.6%). For stage IIB cancers, neoadjuvant chemotherapy was associated with an absolute reduction in mastectomy rates of 5.9% in women younger than age 60 years with hormone receptor-positive/HER2- disease, 8.2% to 10.7% for triple-negative disease, and 11.7% to 17.4% for HER2+ disease. For stage IIIA, the reductions in mastectomy rates ranged from 6.6% to 15.9%. Conclusions: In an analysis of patients treated across the United States, we found that neoadjuvant chemotherapy was associated with a reduction in mastectomy rates to a similar magnitude overall as shown in randomized trials, but this benefit varied widely by patient subgroup. This study provides novel information to help women make informed decisions regarding treatment

Building operational research capacity in the Pacific

Operational research (OR) in public health aims to investigate strategies, interventions, tools or knowledge that can enhance the quality, coverage, effectiveness or performance of health systems. Attention has recently been drawn to the lack of OR capacity in public health programmes throughout the Pacific Islands, despite considerable investment in implementation. This lack of ongoing and critical reflection may prevent health programme staff from understanding why programme objectives are not being fully achieved, and hinder long-term gains in public health. The International Union Against Tuberculosis and Lung Disease (The Union) has been collaborating with Pacific agencies to conduct OR courses based on the training model developed by The Union and Médecins Sans Frontières Brussels-Luxembourg in 2009. The first of these commenced in 2011 in collaboration with the Fiji National University, the Fiji Ministry of Health, the World Health Organization and other partners. The Union and the Secretariat of the Pacific Community organised a second course for participants from other Pacific Island countries and territories in 2012, and an additional course for Fijian participants commenced in 2013. Twelve participants enrolled in each of the three courses. Of the two courses completed by end 2013, 18 of 24 participants completed their OR and submitted papers by the course deadline, and 17 papers have been published to date. This article describes the context, process and outputs of the Pacific courses, as well as innovations, adaptations and challenges