Meet the Tutors: Student Expectations, Tutor Perspectives, and Some Recommendations for Sharing Information about Tutors Online

This article presents findings from an IRB-approved study about tutors’ online information on writing center websites, scheduling systems, and social media. The study used surveys to investigate students’ responses to tutors’ online information and focus groups to investigate tutors’ rationale for the information they shared. While many researchers have studied how writing centers are presented online, little research considers how tutors are represented. The authors argue that such representation merits attention, as tutor profiles can affect students’ comfort with the writing center staff and their microdecisions about who to see and how to interact with them (Salem, 2016). The authors share advice for making decisions about how tutors are presented online and for using the process of creating meet the staff and similar pages to study and improve their centers

Regulation of Brain Primary Cilia Length by MCH Signaling: Evidence from Pharmacological, Genetic, Optogenetic, and Chemogenic Manipulations

The melanin-concentrating hormone (MCH) system is involved in numerous functions, including energy homeostasis, food intake, sleep, stress, mood, aggression, reward, maternal behavior, social behavior, and cognition. In rodents, MCH acts on MCHR1, a G protein-coupled receptor, which is widely expressed in the brain and abundantly localized to neuronal primary cilia. Cilia act as cells’ antennas and play crucial roles in cell signaling to detect and transduce external stimuli to regulate cell differentiation and migration. Cilia are highly dynamic in terms of their length and morphology; however, it is not known if cilia length is causally regulated by MCH system activation in vivo. In the current work, we examined the effects of activation and inactivation of MCH system on cilia lengths by using different experimental models and methodologies, including organotypic brain slice cultures from rat prefrontal cortex (PFC) and caudate–putamen (CPu), in vivo pharmacological (MCHR1 agonist and antagonist GW803430), germline and conditional genetic deletion of MCHR1 and MCH, optogenetic, and chemogenetic (designer receptors exclusively activated by designer drugs (DREADD)) approaches. We found that stimulation of MCH system either directly through MCHR1 activation or indirectly through optogenetic and chemogenetic-mediated excitation of MCH-neuron, caused cilia shortening, detected by the quantification of the presence of ADCY3 protein, a known primary cilia marker. In contrast, inactivation of MCH signaling through pharmacological MCHR1 blockade or through genetic manipulations — germline deletion of MCHR1 and conditional ablation of MCH neurons — induced cilia lengthening. Our study is the first to uncover the causal effects of the MCH system in the regulation of the length of brain neuronal primary cilia. These findings place MCH system at a unique position in the ciliary signaling in physiological and pathological conditions and implicate MCHR1 present at primary cilia as a potential therapeutic target for the treatment of pathological conditions characterized by impaired primary cilia function associated with the modification of its length

MTN-001: Randomized Pharmacokinetic Cross-Over Study Comparing Tenofovir Vaginal Gel and Oral Tablets in Vaginal Tissue and Other Compartments

Background: Oral and vaginal preparations of tenofovir as pre-exposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) infection have demonstrated variable efficacy in men and women prompting assessment of variation in drug concentration as an explanation. Knowledge of tenofovir concentration and its active form, tenofovir diphosphate, at the putative vaginal and rectal site of action and its relationship to concentrations at multiple other anatomic locations may provide key information for both interpreting PrEP study outcomes and planning future PrEP drug development. Objective: MTN-001 was designed to directly compare oral to vaginal steady-state tenofovir pharmacokinetics in blood, vaginal tissue, and vaginal and rectal fluid in a paired cross-over design. Methods and Findings: We enrolled 144 HIV-uninfected women at 4 US and 3 African clinical research sites in an open label, 3-period crossover study of three different daily tenofovir regimens, each for 6 weeks (oral 300 mg tenofovir disoproxil fumarate, vaginal 1% tenofovir gel [40 mg], or both). Serum concentrations after vaginal dosing were 56-fold lower than after oral dosing (p<0.001). Vaginal tissue tenofovir diphosphate was quantifiable in ≥90% of women with vaginal dosing and only 19% of women with oral dosing. Vaginal tissue tenofovir diphosphate was ≥130-fold higher with vaginal compared to oral dosing (p<0.001). Rectal fluid tenofovir concentrations in vaginal dosing periods were higher than concentrations measured in the oral only dosing period (p<0.03). Conclusions: Compared to oral dosing, vaginal dosing achieved much lower serum concentrations and much higher vaginal tissue concentrations. Even allowing for 100-fold concentration differences due to poor adherence or less frequent prescribed dosing, vaginal dosing of tenofovir should provide higher active site concentrations and theoretically greater PrEP efficacy than oral dosing; randomized topical dosing PrEP trials to the contrary indicates that factors beyond tenofovir's antiviral effect substantially influence PrEP efficacy. Trial Registration: ClinicalTrials.gov NCT00592124

Implementing Provider‐based Sampling for the National Children's Study: Opportunities and Challenges

Background:  The National Children's Study (NCS) was established as a national probability sample of births to prospectively study children's health starting from in utero to age 21. The primary sampling unit was 105 study locations (typically a county). The secondary sampling unit was the geographic unit (segment), but this was subsequently perceived to be an inefficient strategy. Methods and Results:  This paper proposes that second‐stage sampling using prenatal care providers is an efficient and cost‐effective method for deriving a national probability sample of births in the US. It offers a rationale for provider‐based sampling and discusses a number of strategies for assembling a sampling frame of providers. Also presented are special challenges to provider‐based sampling pregnancies, including optimising key sample parameters, retaining geographic diversity, determining the types of providers to include in the sample frame, recruiting women who do not receive prenatal care, and using community engagement to enrol women. There will also be substantial operational challenges to sampling provider groups. Conclusion:  We argue that probability sampling is mandatory to capture the full variation in exposure and outcomes expected in a national cohort study, to provide valid and generalisable risk estimates, and to accurately estimate policy (such as screening) benefits from associations reported in the NCS.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94504/1/ppe12005.pd

Dopamine D2-like receptor stimulation blocks negative feedback in visual and spatial reversal learning in the rat: behavioural and computational evidence

Abstract: Rationale: Dopamine D2-like receptors (D2R) are important drug targets in schizophrenia and Parkinson’s disease, but D2R ligands also cause cognitive inflexibility such as poor reversal learning. The specific role of D2R in reversal learning remains unclear. Objectives: We tested the hypotheses that D2R agonism impairs reversal learning by blocking negative feedback and that antagonism of D1-like receptors (D1R) impairs learning from positive feedback. Methods: Male Lister Hooded rats were trained on a novel visual reversal learning task. Performance on “probe trials”, during which the correct or incorrect stimulus was presented with a third, probabilistically rewarded (50% of trials) and therefore intermediate stimulus, revealed individual learning curves for the processes of positive and negative feedback. The effects of D2R and D1R agonists and antagonists were evaluated. A separate cohort was tested on a spatial probabilistic reversal learning (PRL) task after D2R agonism. Computational reinforcement learning modelling was applied to choice data from the PRL task to evaluate the contribution of latent factors. Results: D2R agonism with quinpirole dose-dependently impaired both visual reversal and PRL. Analysis of the probe trials on the visual task revealed a complete blockade of learning from negative feedback at the 0.25 mg/kg dose, while learning from positive feedback was intact. Estimated parameters from the model that best described the PRL choice data revealed a steep and selective decrease in learning rate from losses. D1R antagonism had a transient effect on the positive probe trials. Conclusions: D2R stimulation impairs reversal learning by blocking the impact of negative feedback

Estimating prevalence of overweight and obesity at the neighborhood level: the value of maternal height and weight data available on birth certificate records

<p>Abstract</p> <p>Objective</p> <p>To determine the value of maternal height and weight data on birth certificate records when estimating prevalence of overweight and obese adults at the neighborhood level.</p> <p>Research Design and Methods</p> <p>Regression analysis was used to determine how much variation in the percentage of the adult population with a body mass index (BMI) of ≥ 25 (based on survey data) could be accounted for by the percentage of mothers with BMI ≥ 25 (based on birth certificate data) -- alone and in combination with other sociodemographic characteristics of census tracts.</p> <p>Results</p> <p>Alone, the percentage of mothers with BMI ≥ 25 explained more than half (R²= .52) of the variation in the percentage of all residents in census tracts with BMI ≥ 25; in combination with several measures of the sociodemographic characteristics of the census tracts, 75% ( R²= 75.2) of the variation is explained.</p> <p>Conclusions</p> <p>Maternal height and weight data available from birth certificate records may be useful for identifying neighborhoods with relatively high or low prevalence of adult residents who are overweight or obese. This is especially true if used in combination with readily available census data.</p

Screening Low-Income Women of Reproductive Age for Cardiovascular Disease Risk Factors

Identifying and treating chronic diseases, their precursors, and other cardiovascular disease (CVD) risk factors during family planning visits may improve long-term health and reproductive outcomes among low-income women. A cross-sectional study design was used to describe the prevalence of chronic diseases (hypertension, high cholesterol, and diabetes), their precursors (pre-hypertension, borderline high cholesterol, and pre-diabetes), and related CVD risk factors (such as obesity, smoking, and physical inactivity) among low-income women of reproductive age

Cardiovascular comorbidities among public health clinic patients with diabetes: the Urban Diabetics Study

BACKGROUND: We sought to determine the frequency and distribution of cardiovascular comorbidities in a large cohort of low-income patients with diabetes who had received primary care for diabetes at municipal health clinics. METHODS: Outpatient data from the Philadelphia Health Care Centers was linked with hospital discharge data from all Pennsylvania hospitals and death certificates. RESULTS: Among 10,095 primary care patients with diabetes, with a mean observation period of 4.6 years (2.8 after diabetes diagnosis), 2,693 (14.3%) were diagnosed with heart disease, including 270 (1.4%) with myocardial infarction and 912 (4.8%) with congestive heart failure. Cerebrovascular disease was diagnosed in 588 patients (3.1%). Over 77% of diabetic patients were diagnosed with hypertension. Incidence rates of new complications ranged from 0.6 per 100 person years for myocardial infarction to 26.5 per 100 person years for hypertension. Non-Hispanic whites had higher rates of myocardial infarction, and Hispanics and Asians had fewer comorbid conditions than African Americans and non-Hispanic whites. CONCLUSION: Cardiovascular comorbidities were common both before and after diabetes diagnosis in this low-income cohort, but not substantially different from mixed-income managed care populations, perhaps as a consequence of access to primary care and pharmacy services

Biological and clinical characteristics of gene carriers far from predicted onset in the Huntington's disease Young Adult Study (HD-YAS): a cross-sectional analysis.

BACKGROUND: Disease-modifying treatments are in development for Huntington's disease; crucial to their success is to identify a timepoint in a patient's life when there is a measurable biomarker of early neurodegeneration while clinical function is still intact. We aimed to identify this timepoint in a novel cohort of young adult premanifest Huntington's disease gene carriers (preHD) far from predicted clinical symptom onset. METHODS: We did the Huntington's disease Young Adult Study (HD-YAS) in the UK. We recruited young adults with preHD and controls matched for age, education, and sex to ensure each group had at least 60 participants with imaging data, accounting for scan fails. Controls either had a family history of Huntington's disease but a negative genetic test, or no known family history of Huntington's disease. All participants underwent detailed neuropsychiatric and cognitive assessments, including tests from the Cambridge Neuropsychological Test Automated Battery and a battery assessing emotion, motivation, impulsivity and social cognition (EMOTICOM). Imaging (done for all participants without contraindications) included volumetric MRI, diffusion imaging, and multiparametric mapping. Biofluid markers of neuronal health were examined using blood and CSF collection. We did a cross-sectional analysis using general least-squares linear models to assess group differences and associations with age and CAG length, relating to predicted years to clinical onset. Results were corrected for multiple comparisons using the false discovery rate (FDR), with FDR 0·16). CSF neurofilament light protein (NfL), plasma NfL, and CSF YKL-40 were elevated in this far-from-onset preHD cohort compared with controls (FDR<0·0001, =0·01, and =0·03, respectively). CSF NfL elevations were more likely in individuals closer to expected clinical onset (FDR <0·0001). INTERPRETATION: We report normal brain function yet a rise in sensitive measures of neurodegeneration in a preHD cohort approximately 24 years from predicted clinical onset. CSF NfL appears to be a more sensitive measure than plasma NfL to monitor disease progression. This preHD cohort is one of the earliest yet studied, and our findings could be used to inform decisions about when to initiate a potential future intervention to delay or prevent further neurodegeneration while function is intact. FUNDING: Wellcome Trust, CHDI Foundation

The Soft Power of Anglia: British Cold War Cultural Diplomacy in the USSR

This article contributes to the growing literature on the cultural Cold War through an exploration of the British national projection magazine Anglia, produced by the Foreign Office for distribution in the USSR from 1962 to 1992. As well as drawing attention to the significance of national magazines in general, the article sheds light on Britain's distinctive approach to propaganda and cultural diplomacy during the Cold War. It considers why the magazine was set up and endured for so long, despite considerable reservations about its value. It examines how Britain was projected in a manner that accorded with British understandings about the need for ‘subtle’ propaganda. Finally, it addresses the question of the magazine's impact in the USSR