Two alternative methods for the retrieval of somatic cell populations from the mouse ovary.

Many modern techniques employed to uncover the molecular fundamentals underlying biological processes require dissociated cells as their starting point/substrate. Investigations into ovarian endocrinology or folliculogenesis, therefore, necessitate robust protocols for dissociating the ovary into its constituent cell populations. While in the mouse, methods to obtain individual, mature follicles are well-established, the separation and isolation of single cells of all types from early mouse follicles, including somatic cells, has been more challenging. Herein we present two methods for the isolation of somatic cells in the ovary. These methods are suitable for a range of applications relating to the study of folliculogenesis and mouse ovarian development. First, an enzymatic dissociation utilising collagenase and a temporary, primary cell culture step using neonatal mouse ovaries which yields large quantities of granulosa cells from primordial, activating, and primary follicles. Second, a rapid papain dissociation resulting in a high viability single cell suspension of ovarian somatic cells in less than an hour, which can be applied from embryonic to adult ovarian samples. Collectively these protocols can be applied to a broad array of investigations with unique advantages and benefits pertaining to both.

Signal transducer and activator of transcription (STAT) 1 and STAT3 are expressed in the human ovary and have Janus kinase 1-independent functions in the COV434 human granulosa cell line.

Ovarian granulosa cells are fundamental for oocyte maintenance and maturation. Recent studies have demonstrated the importance of members of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signalling pathway in the granulosa cell population of mouse and horse ovaries, with perturbation of JAK1 signalling in the mouse shown to impair oocyte maintenance and accelerate primordial follicle activation. The presence and role of the JAK/STAT pathway in human granulosa cells has yet to be elucidated. In this study, expression of JAK1, STAT1 and STAT3 was detected in oocytes and granulosa cells of human ovarian sections from fetal (40 weeks gestation) and premenopausal ovaries (34-41 years of age; n=3). To determine the effects of JAK1 signalling in granulosa cells, the human granulosa-like cell line COV434 was used, with JAK1 inhibition using ruxolitinib. Chemical inhibition of JAK1 in COV434 cells with 100nM ruxolitinib for 72h resulted in significant increases in STAT3 mRNA (P=0.034) and p-Y701-STAT1 protein (P=0.0117), demonstrating a role for JAK1 in modulating STAT in granulosa cells. This study implicates a conserved role for JAK/STAT signalling in human ovary development, warranting further investigation of this pathway in human granulosa cell function.

Constraints on Light Dark Matter Particles Interacting with Electrons from DAMIC at SNOLAB.

We report direct-detection constraints on light dark matter particles interacting with electrons. The results are based on a method that exploits the extremely low levels of leakage current of the DAMIC detector at SNOLAB of 2-6×10^{-22} A cm^{-2}. We evaluate the charge distribution of pixels that collect <10e^{-} for contributions beyond the leakage current that may be attributed to dark matter interactions. Constraints are placed on so-far unexplored parameter space for dark matter masses between 0.6 and 100 MeV c^{-2}. We also present new constraints on hidden-photon dark matter with masses in the range 1.2-30 eV c^{-2}.

Odor tracking flight of male Manduca sexta moths along plumes of different cross-sectional area.

Males of the hawkmoth, Manduca sexta, track wind-borne plumes of female sex pheromone by flying upwind, while continuously turning from side-to-side and changing altitude. Their characteristic "zigzagging" trajectory has long been thought to result from the interaction of two mechanisms, an odor-modulated orientation to wind and a built-in central nervous system turning program. An interesting and as of yet unanswered question about this tracking behavior is how the cross-section of an odor plume or its clean-air "edges" affects moths' odor tracking behavior. This study attempts to address this question by video recording and analyzing the behavior of freely flying M. sexta males tracking plumes from pheromone sources of different lengths and orientations with equal odor concentration per unit area. Our results showed that moths generated significantly wider tracks in wide plumes from the longest horizontally-oriented sources as compared to narrower point-source plumes, but had relatively unaltered tracks when orienting to plumes from the same length sources oriented vertically. This suggests that in addition to wind and the presence of pheromones, the area of the plume's cross section or its edges may also play an important role in the plume tracking mechanisms of M. sexta.

Prevalence and risk factors for metabolic syndrome in Medellin and surrounding municipalities, Colombia, 2008-2010.

OBJECTIVE: We assessed the prevalence of and risk factors for metabolic syndrome (MetS) among adults 25-64 years of age from Medellin and surrounding municipalities, Colombia. METHOD: We used 2008-2010 data from the Antioquia STEPwise approach to Surveillance (STEPS), a multi-stage complex cross-sectional survey designed according to World Health Organization guidelines. The revised 2005 International Diabetes Federation definition of MetS was used. RESULTS: There were a total of 3000 participants. Of these, 21.4% had high blood pressure (HBP) and 64% had abdominal obesity (AO). In the subsample with serum data (n = 943), 19.8% had high fasting serum glucose, 43.9% had high triglycerides (HTG), and 56.6% had low HDL cholesterol (L-HDL). Among those with data to define MetS (n = 901), 41% had MetS. Older age was associated with MetS and all components except L-HDL. Female sex [odds ratio (OR) = 2.85, 95% confidence interval (CI): 2.20-3.70], being married (OR = 1.40, CI: 1.09-1.82), and high physical activity (OR = 0.59, CI: 0.39-0.91) were associated with AO, smoking with HTG (OR = 1.76, CI: 1.16-2.67) and L-HDL (OR = 1.67, CI: 1.10-2.51) and rural residence with HBP (OR = 3.42, CI: 1.83-6.37) and L-HDL (OR = 1.18, CI: 1.10-2.51). CONCLUSION: The prevalence of MetS and AO was high in this Colombian region. Targeted strategies for promoting healthy behaviors are needed.

Optical coherence tomography segmentation reveals ganglion cell layer pathology after optic neuritis.

Post-mortem ganglion cell dropout has been observed in multiple sclerosis; however, longitudinal in vivo assessment of retinal neuronal layers following acute optic neuritis remains largely unexplored. Peripapillary retinal nerve fibre layer thickness, measured by optical coherence tomography, has been proposed as an outcome measure in studies of neuroprotective agents in multiple sclerosis, yet potential swelling during the acute stages of optic neuritis may confound baseline measurements. The objective of this study was to ascertain whether patients with multiple sclerosis or neuromyelitis optica develop retinal neuronal layer pathology following acute optic neuritis, and to systematically characterize such changes in vivo over time. Spectral domain optical coherence tomography imaging, including automated retinal layer segmentation, was performed serially in 20 participants during the acute phase of optic neuritis, and again 3 and 6 months later. Imaging was performed cross-sectionally in 98 multiple sclerosis participants, 22 neuromyelitis optica participants and 72 healthy controls. Neuronal thinning was observed in the ganglion cell layer of eyes affected by acute optic neuritis 3 and 6 months after onset (P < 0.001). Baseline ganglion cell layer thicknesses did not demonstrate swelling when compared with contralateral unaffected eyes, whereas peripapillary retinal nerve fibre layer oedema was observed in affected eyes (P = 0.008) and subsequently thinned over the course of this study. Ganglion cell layer thickness was lower in both participants with multiple sclerosis and participants with neuromyelitis optica, with and without a history of optic neuritis, when compared with healthy controls (P < 0.001) and correlated with visual function. Of all patient groups investigated, those with neuromyelitis optica and a history of optic neuritis exhibited the greatest reduction in ganglion cell layer thickness. Results from our in vivo longitudinal study demonstrate retinal neuronal layer thinning following acute optic neuritis, corroborating the hypothesis that axonal injury may cause neuronal pathology in multiple sclerosis. Further, these data provide evidence of subclinical disease activity, in both participants with multiple sclerosis and with neuromyelitis optica without a history of optic neuritis, a disease in which subclinical disease activity has not been widely appreciated. No pathology was seen in the inner or outer nuclear layers of eyes with optic neuritis, suggesting that retrograde degeneration after optic neuritis may not extend into the deeper retinal layers. The subsequent thinning of the ganglion cell layer following acute optic neuritis, in the absence of evidence of baseline swelling, suggests the potential utility of quantitative optical coherence tomography retinal layer segmentation to monitor neuroprotective effects of novel agents in therapeutic trials.

Consensus recommendations for incident learning database structures in radiation oncology.

PURPOSE: Incident learning plays a key role in improving quality and safety in a wide range of industries and medical disciplines. However, implementing an effective incident learning system is complex, especially in radiation oncology. One current barrier is the lack of technical standards to guide users or developers. This report, the product of an initiative by the Work Group on Prevention of Errors in Radiation Oncology of the American Association of Physicists in Medicine, provides technical recommendations for the content and structure of incident learning databases in radiation oncology. METHODS: A panel of experts was assembled and tasked with developing consensus recommendations in five key areas: definitions, process maps, severity scales, causality taxonomy, and data elements. Experts included representatives from all major North American radiation oncology organizations as well as users and developers of public and in-house reporting systems with over two decades of collective experience. Recommendations were developed that take into account existing incident learning systems as well as the requirements of outside agencies. RESULTS: Consensus recommendations are provided for the five major topic areas. In the process mapping task, 91 common steps were identified for external beam radiation therapy and 88 in brachytherapy. A novel feature of the process maps is the identification of "safety barriers," also known as critical control points, which are any process steps whose primary function is to prevent errors or mistakes from occurring or propagating through the radiotherapy workflow. Other recommendations include a ten-level medical severity scale designed to reflect the observed or estimated harm to a patient, a radiation oncology-specific root causes table to facilitate and regularize root-cause analyses, and recommendations for data elements and structures to aid in development of electronic databases. Also presented is a list of key functional requirements of any reporting system. CONCLUSIONS: Incident learning is recognized as an invaluable tool for improving the quality and safety of treatments. The consensus recommendations in this report are intended to facilitate the implementation of such systems within individual clinics as well as on broader national and international scales.

Improving the Quality of Care in Radiation Oncology using Artificial Intelligence.

Radiation therapy is a complex process involving multiple professionals and steps from simulation to treatment planning to delivery, and these procedures are prone to error. Additionally, the imaging and treatment delivery equipment in radiotherapy is highly complex and interconnected and represents another risk point in the quality of care. Numerous quality assurance tasks are carried out to ensure quality and to detect and prevent potential errors in the process of care. Recent developments in artificial intelligence provide potential tools to the radiation oncology community to improve the efficiency and performance of quality assurance efforts. Targets for artificial intelligence enhancement include the quality assurance of treatment plans, target and tissue structure delineation used in the plans, delivery of the plans and the radiotherapy delivery equipment itself. Here we review recent developments of artificial intelligence applications that aim to improve quality assurance processes in radiation therapy and discuss some of the challenges and limitations that require further development work to realise the potential of artificial intelligence for quality assurance.

Clinicians' attitudes towards clinical trials of cancer therapy.

BACKGROUND: Patient accrual into cancer clinical trials remains at low levels. This survey elicited attitudes and practices of cancer clinicians towards clinical trials. METHOD: The 43-item Clinicians Attitudes to Clinical Trials Questionnaire was completed by participants in an intervention study aimed at improving multi-disciplinary involvement in randomised trials. Responses from 13 items were summed to form a research-orientation score. RESULTS: Eighty-seven clinicians (78%) returned questionnaires. Physicians, more often than surgeons, chose to prioritise prolonging a patient's life, recruited ≥50% of patients into trials and attended more research-focussed conferences. Clinicians at specialist centres were more positive about trials with no-treatment arms than those at district general hospitals, more likely to believe clinician, rather than patient reluctance to participate was the greater obstacle to trial accrual, and preferred national and international to local recognition. Clinicians belonging to breast and colorectal teams were less disappointed about not enrolling patients in trials and more accepting of no-treatment arm trials. Research orientation was higher in physicians than surgeons and higher in specialist centres than district hospitals. CONCLUSIONS: This study provides greater understanding of clinicians' attitudes to trials. Results have been used to inform training interventions for clinicians targeting the problem of low and selective accrual.

Trends in obesity and abdominal obesity among adults in the United States from 1999-2008.

BACKGROUND AND OBJECTIVE: The United States has experienced a large increase in the prevalence of obesity since the 1970s. Our objective was to describe recent trends in obesity and abdominal obesity among adults in the United States. DESIGN: Trend study of cross-sectional studies. SUBJECTS: We used data from up to 22,872 men and non-pregnant women aged ≥ 20 years from the National Health and Nutrition Examination Survey (NHANES) 1999-2008. MAIN OUTCOME MEASURES: Main outcome measures are mean body mass index and waist circumference, percentages of obesity and abdominal obesity. Obesity was defined as a body mass index ≥ 30 kg m(-2), and abdominal obesity was defined as a waist circumference ≥ 102 cm in men and ≥ 88 cm in women. RESULTS: In men, the age-adjusted mean body mass index, mean waist circumference, and prevalence of obesity and abdominal obesity were 27.8 kg m(-2), 99.1 cm, and 26.9 and 37.8%, respectively, during 1999-2000 and 28.5 kg m(-2) (P (trend) = 0.001), 100.8 cm (P (trend) = 0.002), and 32.0 (P (trend) = 0.001) and 43.7% (P (trend) = 0.002), respectively, during 2007-2008. In women, the age-adjusted mean body mass index, mean waist circumference, and prevalence of obesity and abdominal obesity were 28.2 kg m(-2), 92.2 cm, and 33.2 and 55.8%, respectively, during 1999-2000 and 28.6 kg m(-2) (P (trend) = 0.181), 94.9 cm (P (trend) = 0.006), and 35.2 (P (trend) = 0.180) and 61.8% (P (trend) = 0.036), respectively, during 2007-2008. Significant linear trends for increasing prevalence of obesity were noted among men with the least and most education. CONCLUSION: Between 1999 and 2008, both obesity and abdominal obesity increased in men, and abdominal obesity increased in women.

Assessment of uncertainty in functional-structural plant models.

BACKGROUND AND AIMS: Constructing functional-structural plant models (FSPMs) is a valuable method for examining how physiology and morphology interact in determining plant processes. However, such models always have uncertainty concerned with whether model components have been selected and represented effectively, with the number of model outputs simulated and with the quality of data used in assessment. We provide a procedure for defining uncertainty of an FSPM and how this uncertainty can be reduced. METHODS: An important characteristic of FSPMs is that typically they calculate many variables. These can be variables that the model is designed to predict and also variables that give indications of how the model functions. Together these variables are used as criteria in a method of multi-criteria assessment. Expected ranges are defined and an evolutionary computation algorithm searches for model parameters that achieve criteria within these ranges. Typically, different combinations of model parameter values provide solutions achieving different combinations of variables within their specified ranges. We show how these solutions define a Pareto Frontier that can inform about the functioning of the model. KEY RESULTS: The method of multi-criteria assessment is applied to development of BRANCHPRO, an FSPM for foliage reiteration on old-growth branches of Pseudotsuga menziesii. A geometric model utilizing probabilities for bud growth is developed into a causal explanation for the pattern of reiteration found on these branches and how this pattern may contribute to the longevity of this species. CONCLUSIONS: FSPMs should be assessed by their ability to simulate multiple criteria simultaneously. When different combinations of parameter values achieve different groups of assessment criteria effectively a Pareto Frontier can be calculated and used to define the sources of model uncertainty.

Detecting bimodality in plant size distributions and its significance for stand development and competition.

Bimodal distributions in plant size, with a major mode of small and minor mode of large-size plants, have been reported for a range of single species stands in different growing conditions. The occurrence of bimodality has implications for the dynamics of competition within a stand and potentially for stand productivity. However, deduction of the existence of bimodality has been by visual assessment of histograms of a single measure of plant size which can lead to differences of opinion about its existence. We show that the bivariate distribution of plant height and weight is more informative about stand structure than univariate distributions. We demonstrate how sub-populations of small- and large-size plants can be identified using a bivariate mixture distribution fitted using evolutionary computation. For the multiple datasets we analyse, a bimodal distribution fits in preference to unimodal or trimodal distributions. Small- and large-plant sub-populations, respectively, form a lower and upper canopy. The numbers of plants in these canopies change during stand development and vary with initial spacing, contrary to reports for other species. Early in stand development, large plants show spatial separation between themselves but spatial association with small plants, and as stands develop the number of large plants declines markedly but they remain spatially separated between each other. Bivariate analysis of height and weight, and spatial analysis of individuals of different sizes, provides a more comprehensive description of stand structure than that obtained in previous studies.

Re-Validation of the COmprehensive Score for Financial Toxicity (COST): Assessing the Scale's Utility in Chronic Disease Populations.

OBJECTIVE: To report the psychometric properties of the COmprehensive Score for financial Toxicity (COST) patient-reported outcome measure (PROM), an 11-item scale previously validated among patients diagnosed with cancer and receiving chemotherapy. METHODS: Data come from a cross-sectional survey (n = 2755 response rate of 87%) of participants in a remote digital health coaching intervention collected between January 2017 and February 2019. RESULTS: COST demonstrated very good internal consistency (Cronbach's alpha = .89) and good convergent validity. Lower financial toxicity was associated with improved physical and mental well-being HRQOL measures after controlling for covariates (b = 0.13, P < .0001; b = 0.28, P < .0001, respectively). Supplemental analyses indicated that the COST instrument loaded on 2 factors. CONCLUSIONS: The COST measure of financial toxicity has good internal consistency and predictive validity in a sample of patients with chronic conditions. However, contrary to previous research examining the psychometric properties of COST in a sample of individuals with cancer, which found COST to be unidimensional, our analyses indicated that the COST measure of financial toxicity is multidimensional in a sample of individuals with chronic conditions. In particular, the items that asked about "general financial wellbeing" loaded on the second factor while "illness-related financial wellbeing" loaded on the first.

Polarization synthesis by computer-generated holography using orthogonally polarized and correlated speckle patterns.

An interlaced polarization computer-generated hologram (PCGH) is designed to produce specific irradiance and polarization states in the image plane. The PCGH produces a tangentially polarized annular pattern with correlated speckle, which is achieved by a novel application of the diffuser optimization method. Alternating columns of orthogonal linear polarizations illuminate an interlaced PCGH, producing a ratio of polarization of 88% measured on a fabricated sample. The demonstrated technique can be applied to designs for arbitrary irradiance and polarization states in the image plane.

Defining how aging Pseudotsuga and Abies compensate for multiple stresses through multi-criteria assessment of a functional-structural model.

Many hypotheses have been advanced about factors that control tree longevity. We use a simulation model with multi-criteria optimization and Pareto optimality to determine branch morphologies in the Pinaceae that minimize the effect of growth limitations due to water stress while simultaneously maximizing carbohydrate gain. Two distinct branch morphologies in the Pareto optimal space resemble Pseudotsuga menziesii (Mirb.) Franco and Abies grandis (Dougl. ex D. Don) Lindl., respectively. These morphologies are distinguished by their performance with respect to two pathways of compensation for hydraulic limitation: minimizing the mean path length to terminal foliage (Pseudotsuga) and minimizing the mean number of junction constrictions to terminal foliage (Abies). Within these two groups, we find trade-offs between the criteria for foliage display and the criteria for hydraulic functioning, which shows that an appropriate framework for considering tree longevity is how trees compensate, simultaneously, for multiple stresses. The diverse morphologies that are found in a typical old-growth conifer forest may achieve compensation in different ways. The method of Pareto optimization that we employ preserves all solutions that are successful in achieving different combinations of criteria. The model for branch development that we use simulates the process of delayed adaptive reiteration (DAR), whereby new foliage grows from suppressed buds within the established branch structure. We propose a theoretical synthesis for the role of morphology in the persistence of old Pseudotsuga based on the characteristics of branch morphogenesis found in branches simulated from the optimal set. (i) The primary constraint on branch growth for Pseudotsuga is the mean path length; (ii) as has been previously noted, DAR is an opportunistic architecture; and (iii) DAR is limited by the number of successive reiterations that can form. We show that Pseudotsuga morphology is not the only solution to old-growth constraints, and we suggest how the model results should be used to guide future empirical investigation based on the two contrasting morphologies and how the morphological contrast may relate to physiological processes. Our results show that multi-criteria optimization with Pareto optimality has promise to advance the use of models in theory development and in exploration of functional-structural trade-offs, particularly in complex biological systems with multiple limiting factors.

Common mental disorders, unemployment and welfare benefits in England.

OBJECTIVES: Individuals who are out of work have a higher rate of common mental disorders (CMD) than individuals who are employed. People who are unemployed in the UK are entitled to welfare benefits to alleviate financial strain. This study examined rates of CMD in individuals who were employed, unemployed and receiving various UK benefits. It also investigated associations between duration of unemployment, gender and CMD. STUDY DESIGN: An analysis of 5090 working-age participants from the Adult Psychiatric Morbidity Survey 2007, a stratified probability sample survey conducted among adults aged 16 years and over living in private households in England. METHODS: CMD was assessed using the Clinical Interview Schedule (Revised). Information was gathered on sociodemographics, employment, income, benefits and debt. Data were analysed using logistic regression. RESULTS: Risk of CMD was significantly greater in individuals classified as: unemployed; economically inactive; not working due to physical health reasons; unable to find a suitable job; receiving housing, care or sickness benefit; and receiving income support. However, risk of CMD was not significantly greater in individuals receiving jobseeker's allowance. Individuals unemployed for less than 1 year or more than 3 years had a higher risk of CMD. Some interactions with gender were significant, with associations being greater in men than women. CONCLUSIONS: Job loss events are not the only reason for unemployed people to develop CMD. The state of unemployment itself may be detrimental to mental health. Risk of CMD is increased in those who have been out of work for 3 years or more. Associations between benefits and mental health are likely to be due to social, health or economic circumstances associated with benefit eligibility.

Depression and anxiety among US adults: associations with body mass index.

BACKGROUND: Obesity is associated with an increased risk of developing a variety of chronic diseases, most of which are associated with psychiatric disorders. We examined the associations of depression and anxiety with body mass index (BMI) after taking into consideration the obesity-related comorbidities (ORCs) and other psychosocial or lifestyle factors. METHODS: We analyzed the data collected from 177,047 participants (aged>or=18 years) in the 2006 Behavioral Risk Factor Surveillance System. Current depression was assessed by the Patient Health Questionnaire-8 diagnostic algorithm. Lifetime diagnoses of depression, anxiety and ORCs were self-reported. The prevalence of the three psychiatric disorders was age standardized to the 2000 US population. Multivariate-adjusted prevalence ratios were computed to test associations of depression and anxiety with BMI using SUDAAN software. RESULTS: The age-adjusted prevalence of current depression, lifetime diagnosed depression and anxiety varied significantly by gender. Within each gender, the prevalence of the three psychiatric disorders was significantly higher in both men and women who were underweight (BMI<18.5 kg/m(2)), in women who were overweight (BMI: 25-<30 kg/m(2)) or obese (BMI>or=30 kg/m(2)), and in men who had class III obesity (BMI>or=40 kg/m(2)) than in those with a normal BMI (18.5-<25 kg/m(2)). After adjusting for demographics, ORCs, lifestyle or psychosocial factors, compared with men with a normal BMI, men with a BMI>or=40 kg/m(2) were significantly more likely to have current depression or lifetime diagnosed depression and anxiety; men with a BMI<18.5 kg/m(2) were also significantly more likely to have lifetime diagnosed depression. Women who were either overweight or obese were significantly more likely than women with a normal BMI to have all the three psychiatric disorders. CONCLUSIONS: Our results demonstrate that disparities in the prevalence of depression and anxiety exist among people with different BMI levels independent of their disease status or other psychosocial or lifestyle factors.

Recruitment and retention strategies and methods in the HEALTHY study.

HEALTHY was a 3-year middle school-based primary prevention trial to reduce modifiable risk factors for type 2 diabetes in youth. The study was conducted at seven centers across the country. This paper describes the recruitment and retention activities employed in the study. Schools and students were the focus of recruitment and retention. Each center was responsible for the recruitment of six schools; eligibility was based on ability to enroll a sufficient number of predominately minority and lower socioeconomic status students. Study staff met with district superintendents and school principals to verify the eligibility of schools, and to ascertain how appropriate the school would be for conducting the trial. Sixth grade students were recruited employing a variety of techniques; students and their parents did not know whether their school was randomized to the intervention or control arm. This cohort was followed through sixth, seventh and eighth grades. In the eighth grade, an additional sample of students who were not originally enrolled in the study was recruited in a similar manner to participate in data collection to allow for cross-sectional and dose-response secondary analyses. Parents signed informed consent forms and children signed informed assent forms, as per the needs of the local Institutional Review Board. Parents received a letter describing the results of the health screening for their children after data collection in sixth and eighth grades. Retention of schools and students was critical for the success of the study and was encouraged through the use of financial incentives and other strategies. To a large extent, student withdrawal due to out-migration (transfer and geographical relocation) was beyond the ability of the study to control. A multi-level approach that proactively addressed school and parent concerns was crucial for the success of recruitment and retention in the HEALTHY study.

Social marketing-based communications to integrate and support the HEALTHY study intervention.

The HEALTHY study was a randomized, controlled, multicenter, middle school-based, multifaceted intervention designed to reduce risk factors for the development of type 2 diabetes. The study randomized 42 middle schools to intervention or control, and followed students from the sixth to the eighth grades. Participants were a racially, ethnically and geographically diverse cohort from across the United States. Here, we describe the conceptual underpinnings and design of the social marketing-based communications component of the HEALTHY study intervention that combined changes in the school nutrition and physical education (PE) environment with behavior change initiatives. The communications intervention component coordinated multiple elements to deliver campaigns that served to integrate and support all aspects of the HEALTHY intervention. The campaigns unfolded across five semesters of middle school, each targeting a specific theme related to the HEALTHY objectives. Communications campaigns comprised (1) core elements such as branding, posters, banners and visual and verbal messaging, (2) student events supporting the nutrition, PE and behavior intervention components through the application of social marketing and communications strategies, including the incorporation of student-generated media and (3) distribution of premiums and theme enhancers to extend the visibility of the study beyond the intervention environment. Formative research conducted with students, parents and school administrators was used to refine the communications strategy. Student peer communicators selected from the student body were involved to influence the normative student environment. Marketing and creative design experts developed a brand, logo, activities and materials. In the latter half of the study, student-generated messages and media were used to reflect local interests and culture and enhance peer influence. The HEALTHY intervention delivery and impact were strengthened by the communications strategies. The HEALTHY experience provides practical considerations for systematically incorporating a social marketing-based communications approach within future school-based health behavior interventions.

Monocyte infiltration and kidney allograft dysfunction during acute rejection.

Multiple cell types infiltrate acutely rejecting renal allografts. Typically, monocytes and T cells predominate. Although T cells are known to be required for acute rejection, the degree to which monocytes influence this process remains incompletely defined. Specifically, it has not been established to what degree monocytes impact the clinical phenotype of rejection or how their influence compares to that of T cells. We therefore investigated the relative impact of T cells and monocytes by correlating their presence as measured by immunohistochemical staining with the magnitude of the acute change in renal function at the time of biopsy in 78 consecutive patients with histological acute rejection. We found that functional impairment was strongly associated with the degree of overall cellular infiltration as scored using Banff criteria. However, when cell types were considered, monocyte infiltration was quantitatively associated with renal dysfunction while T-cell infiltration was not. Similarly, renal tubular stress, as indicated by HLA-DR expression, increased with monocyte but not T-cell infiltration. These data suggest that acute allograft dysfunction is most closely related to monocyte infiltration and that isolated T-cell infiltration has less acute functional impact. This relationship may be useful in assigning acute clinical relevance to biopsy findings.