PRODROMAL SYMPTOMS OF RECURRENT MAJOR DEPRESSIVE EPISODES: A Qualitative Analysis

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75396/1/h0080234.pd

Lesinurad, a novel, oral compound for gout, acts to decrease serum uric acid through inhibition of urate transporters in the kidney.

BackgroundExcess body burden of uric acid promotes gout. Diminished renal clearance of uric acid causes hyperuricemia in most patients with gout, and the renal urate transporter (URAT)1 is important for regulation of serum uric acid (sUA) levels. The URAT1 inhibitors probenecid and benzbromarone are used as gout therapies; however, their use is limited by drug-drug interactions and off-target toxicity, respectively. Here, we define the mechanism of action of lesinurad (Zurampic®; RDEA594), a novel URAT1 inhibitor, recently approved in the USA and Europe for treatment of chronic gout.MethodssUA levels, fractional excretion of uric acid (FEUA), lesinurad plasma levels, and urinary excretion of lesinurad were measured in healthy volunteers treated with lesinurad. In addition, lesinurad, probenecid, and benzbromarone were compared in vitro for effects on urate transporters and the organic anion transporters (OAT)1 and OAT3, changes in mitochondrial membrane potential, and human peroxisome proliferator-activated receptor gamma (PPARγ) activity.ResultsAfter 6 hours, a single 200-mg dose of lesinurad elevated FEUA 3.6-fold (p < 0.001) and reduced sUA levels by 33 % (p < 0.001). At concentrations achieved in the clinic, lesinurad inhibited activity of URAT1 and OAT4 in vitro, did not inhibit GLUT9, and had no effect on ABCG2. Lesinurad also showed a low risk for mitochondrial toxicity and PPARγ induction compared to benzbromarone. Unlike probenecid, lesinurad did not inhibit OAT1 or OAT3 in the clinical setting.ConclusionThe pharmacodynamic effects and in vitro activity of lesinurad are consistent with inhibition of URAT1 and OAT4, major apical transporters for uric acid. Lesinurad also has a favorable selectivity and safety profile, consistent with an important role in sUA-lowering therapy for patients with gout

Chronic Stress, Sense of Belonging, and Depression Among Survivors of Traumatic Brain Injury

To test whether chronic stress, interpersonal relatedness, and cognitive burden could explain depression after traumatic brain injury (TBI). Design : A nonprobability sample of 75 mild-to-moderately injured TBI survivors and their significant others, were recruited from five TBI day-rehabilitation programs. All participants were within 2 years of the date of injury and were living in the community. Methods : During face-to-face interviews, demographic information, and estimates of brain injury severity were obtained and participants completed a cognitive battery of tests of directed attention and short-term memory, responses to the Perceived Stress Scale, Interpersonal Relatedness Inventory, Sense of Belonging Instrument, Neurobehavioral Functioning Inventory, and Center for Epidemiological Studies Depression Scale;. Findings : Chronic stress was significantly and positively related to post-TBI depression. Depression and postinjury sense of belonging were negatively related. Social support and results from the cognitive battery did not explain depression. Conclusions : Postinjury chronic stress and sense of belonging were strong predictors of post-injury depression and are variables amenable to interventions by nurses in community health, neurological centers, or rehabilitation clinics. Future studies are needed to examine how these variables change over time during the recovery process.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72593/1/j.1547-5069.2002.00221.x.pd

Phenotype-specific association of the TGFBR3 locus with nonsyndromic cryptorchidism

PURPOSE: Based on a genome-wide association study of testicular dysgenesis syndrome showing a possible association with TGFBR3, we analyzed data from a larger, phenotypically restricted cryptorchidism population for potential replication of this signal. MATERIALS AND METHODS: We excluded samples based on strict quality control criteria, leaving 844 cases and 2,718 controls of European ancestry that were analyzed in 2 separate groups based on genotyping platform (ie Illumina® HumanHap550, version 1 or 3, or Human610-Quad, version 1 BeadChip in group 1 and Human OmniExpress 12, version 1 BeadChip platform in group 2). Analyses included genotype imputation at the TGFBR3 locus, association analysis of imputed data with correction for population substructure, subsequent meta-analysis of data for groups 1 and 2, and selective genotyping of independent cases (330) and controls (324) for replication. We also measured Tgfbr3 mRNA levels and performed TGFBR3/betaglycan immunostaining in rat fetal gubernaculum. RESULTS: We identified suggestive (p ≤ 1× 10(-4)) association of markers in/near TGFBR3, including rs9661103 (OR 1.40; 95% CI 1.20, 1.64; p = 2.71 × 10(-5)) and rs10782968 (OR 1.58; 95% CI 1.26, 1.98; p = 9.36 × 10(-5)) in groups 1 and 2, respectively. In subgroup analyses we observed strongest association of rs17576372 (OR 1.42; 95% CI 1.24, 1.60; p = 1.67 × 10(-4)) with proximal and rs11165059 (OR 1.32; 95% CI 1.15, 1.38; p = 9.42 × 10(-4)) with distal testis position, signals in strong linkage disequilibrium with rs9661103 and rs10782968, respectively. Association of the prior genome-wide association study signal (rs12082710) was marginal (OR 1.13; 95% CI 0.99, 1.28; p = 0.09 for group 1), and we were unable to replicate signals in our independent cohort. Tgfbr3/betaglycan was differentially expressed in wild-type and cryptorchid rat fetal gubernaculum. CONCLUSIONS: These data suggest complex or phenotype specific association of cryptorchidism with TGFBR3 and the gubernaculum as a potential target of TGFβ signaling

From Composite Indicators to Partial Orders: Evaluating Socio-Economic Phenomena Through Ordinal Data

In this paper we present a new methodology for the statistical evaluation of ordinal socio-economic phenomena, with the aim of overcoming the issues of the classical aggregative approach based on composite indicators. The proposed methodology employs a benchmark approach to evaluation and relies on partially ordered set (poset) theory, a branch of discrete mathematics providing tools for dealing with multidimensional systems of ordinal data. Using poset theory and the related Hasse diagram technique, evaluation scores can be computed without performing any variable aggregation into composite indicators. This way, ordinal scores need not be turned into numerical values, as often done in evaluation studies, inconsistently with the real nature of the phenomena at hand. We also face the problem of \u201cweighting\u201d evaluation dimensions, to account for their different relevance, and show how this can be handled in pure ordinal terms. A specific focus is devoted to the binary variable case, where the methodology can be specialized in a very effective way. Although the paper is mainly methodological, all of the basic concepts are illustrated through real examples pertaining to material deprivation

Improving Automatic Melanoma Diagnosis using Deep Learning-Based Segmentation of Irregular Networks

Deep Learning Has Achieved Significant Success in Malignant Melanoma Diagnosis. These Diagnostic Models Are Undergoing a Transition into Clinical Use. However, with Melanoma Diagnostic Accuracy in the Range of Ninety Percent, a Significant Minority of Melanomas Are Missed by Deep Learning. Many of the Melanomas Missed Have Irregular Pigment Networks Visible using Dermoscopy. This Research Presents an Annotated Irregular Network Database and Develops a Classification Pipeline that Fuses Deep Learning Image-Level Results with Conventional Hand-Crafted Features from Irregular Pigment Networks. We Identified and Annotated 487 Unique Dermoscopic Melanoma Lesions from Images in the ISIC 2019 Dermoscopic Dataset to Create a Ground-Truth Irregular Pigment Network Dataset. We Trained Multiple Transfer Learned Segmentation Models to Detect Irregular Networks in This Training Set. a Separate, Mutually Exclusive Subset of the International Skin Imaging Collaboration (ISIC) 2019 Dataset with 500 Melanomas and 500 Benign Lesions Was Used for Training and Testing Deep Learning Models for the Binary Classification of Melanoma Versus Benign. the Best Segmentation Model, U-Net++, Generated Irregular Network Masks on the 1000-Image Dataset. Other Classical Color, Texture, and Shape Features Were Calculated for the Irregular Network Areas. We Achieved an Increase in the Recall of Melanoma Versus Benign of 11% and in Accuracy of 2% over DL-Only Models using Conventional Classifiers in a Sequential Pipeline based on the Cascade Generalization Framework, with the Highest Increase in Recall Accompanying the Use of the Random Forest Algorithm. the Proposed Approach Facilitates Leveraging the Strengths of Both Deep Learning and Conventional Image Processing Techniques to Improve the Accuracy of Melanoma Diagnosis. Further Research Combining Deep Learning with Conventional Image Processing on Automatically Detected Dermoscopic Features is Warranted

Factors associated with depression in navy recruits

The age of onset for depression is decreasing and seems to be linked with major life events. This study examined predisposing and concomitant factors related to Navy recruit basic training, and consisted of 443 recruits (200 with depressive symptoms and 243 matched comparison subjects). Two hypotheses were proposed, and both were supported by results of the study. Depressed recruits were more likely to be separated from the Navy and not complete training. They had significantly more predisposing factors than comparison recruits including family history of mental illness, family history of alcohol abuse, and history of psychiatric problems. They also had significantly more concomitant factors such as higher levels of stress, more loneliness, more life-change events, lower sense of belonging, more emotion-oriented coping, and less task-oriented coping. Although the study examined Navy recruits, the findings are applicable to depression in young people. This study adds to understanding the role of lifestressors, interpersonal functioning, and development of depressive symptoms. © 2002 Wiley Periodicals, Inc. J Clin Psychol 58: 323–337, 2002.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34445/1/1146_ftp.pd

The challenges of communicating research evidence in practice: perspectives from UK health visitors and practice nurses

<p>Background: Health practitioners play a pivotal role in providing patients with up-to-date evidence and health information. Evidence-based practice and patient-centred care are transforming the delivery of healthcare in the UK. Health practitioners are increasingly balancing the need to provide evidence-based information against that of facilitating patient choice, which may not always concur with the evidence base. There is limited research exploring how health practitioners working in the UK, and particularly those more autonomous practitioners such as health visitors and practice nurses working in community practice settings, negotiate this challenge. This research provides a descriptive account of how health visitors and practice nurses negotiate the challenges of communicating health information and research evidence in practice.</p> <p>Methods: A total of eighteen in-depth telephone interviews were conducted in the UK between September 2008 and May 2009. The participants comprised nine health visitors and nine practice nurses, recruited via adverts on a nursing website, posters at a practitioner conference and through recommendation. Thematic analysis, with a focus on constant comparative method, was used to analyse the data.</p> <p>Results: The data were grouped into three main themes: communicating evidence to the critically-minded patient; confidence in communicating evidence; and maintaining the integrity of the patient-practitioner relationship. These findings highlight some of the daily challenges that health visitors and practice nurses face with regard to the complex and dynamic nature of evidence and the changing attitudes and expectations of patients. The findings also highlight the tensions that exist between differing philosophies of evidence-based practice and patient-centred care, which can make communicating about evidence a daunting task.</p> <p>Conclusions: If health practitioners are to be effective at communicating research evidence, we suggest that more research and resources need to be focused on contextual factors, such as how research evidence is negotiated, appraised and communicated within the dynamic patient-practitioner relationship.</p&gt

Apparent quality-of-life in nations : how long and happy people live

Quality-of-life in nations can be measured by how long and happy people live. This is assessed by combining data on life expectancy drawn from civil registration with survey data on subjective enjoyment of life as a whole. This measure of 'apparent' quality-of-life is a good alternative to current indexes of 'assumed' quality-of-life such as the Human Development Index. Data are available for 67 nations in the 1990s. The number of Happy-Life-Years varies considerably across nations. Switzerland is at the top with 63.0 years and Moldavia at the bottom with 20.5 years. China is in the middle with an average of 46.7. Happy lifetime has risen considerably in advanced nations over the last decade. People live longer and happier in nations characterised by economic affluence, freedom and justice. Together these three societal qualities explain 66% of the cross-national variance in Happy-Life-Years. Income equality and generous social security do not appear to be required for a long and happy life