The organophosphate cholinesterase inhibitor paraoxon is hydrolysed by serum paraoxonase/arylesterase. A genetic polymorphism of paraoxonase (PON) activity which determines high versus low paraoxon hydrolysis in human populations, may determine sensitivity to parathion poisoning. We demonstrate that arginine at position 192 specifies high activity PON whereas a glutamine specifies the low activity variant. Allele-specific probes or restriction enzyme analysis of amplified DNA allow for the genotyping of individuals. PON maps to chromosome 7q21-22, proximal to the cystic fibrosis gene, in agreement with previous genetic linkage studies.

In addition to helping employees with depression obtain high-quality depression treatment, new interventions may be needed to help them to overcome the substantial job upheaval that this population experiences.

Objective-This study assessed the relationship between depression severity and job performance among employed primary care patients.Method-In a 2001-2004 longitudinal observational study of depression's affect on work productivity, 286 patients with DSM-IV major depressive disorder and/or dysthymia were compared to 93 individuals with rheumatoid arthritis, a condition associated with work disability, and 193 depression-free healthy control subjects. Participants were employed at least 15 hours per week, did not plan to stop working, and had no major medical co-morbidities. Measures at baseline, six, 12, and 18 months included the Work Limitations Questionnaire for work outcomes, and the Patient Health Questionnaire-9 for depression.Results-At baseline and each follow-up, the depression group had significantly greater deficits in managing mental-interpersonal, time, and output tasks, as measured by the Work Limitations Questionnaire: The rheumatoid arthritis group's deficits in managing physical job demands surpassed those of either the depression or comparison groups. Improvements in job performance were predicted by symptom severity. However, the job performance of even the "clinically improved" subset of depressed patients remained consistently worse than the control groups.Conclusions-Multiple dimensions of job performance are impaired by depression. This impact persisted after symptoms have improved. Efforts to reduce work-impairment secondary to depression are needed.Research in community-based and primary care populations documents that depression has an adverse affect on employment, resulting in job loss, absenteeism, and "presenteeism" (reduced at-work job performance and productivity) (1-18) and generally an estimated national productivity cost of $44-$51 billion in U.S. dollars annually (19,20). Despite these large human and economic costs, research on the work impact of depression is a topic in a nascent stage. Most available studies have included work outcomes as secondary endpoints, using samples chosen without regard to employment characteristics (e.g., baseline employment status) and omitting appropriate comparison groups. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript before 2000 frequently measured work outcomes using role disability scales not specifically addressing paid employment (21). Generally, the results of such treatment suggest that treatment can reduce the disorder's adverse work impact and that functioning improves relatively soon after treatment is initiated (9, 13). Furthermore, high-quality depression detection and treatment has been shown to be superior to usual care, thus, increasing the number of days employed (9,10,12,13,17). However, no study has used nondepressed comparison groups to judge the impact of depression on work performance. This prospective study builds on prior research by considering job performance as its primary endpoint, including two employed comparison groups. Specifically, we 1) enrolled individuals who were working at b...

We present a modular convolutional architecture for denoising rendered images. We expand on the capabilities of kernel-predicting networks by combining them with a number of task-specific modules, and optimizing the assembly using an asymmetric loss. The source-aware encoder---the first module in the assembly---extracts low-level features and embeds them into a common feature space, enabling quick adaptation of a trained network to novel data. The spatial and temporal modules extract abstract, high-level features for kernel-based reconstruction, which is performed at three different spatial scales to reduce low-frequency artifacts. The complete network is trained using a class of asymmetric loss functions that are designed to preserve details and provide the user with a direct control over the variance-bias trade-off during inference. We also propose an error-predicting module for inferring reconstruction error maps that can be used to drive adaptive sampling. Finally, we present a theoretical analysis of convergence rates of kernel-predicting architectures, shedding light on why kernel prediction performs better than synthesizing the colors directly, complementing the empirical evidence presented in this and previous works. We demonstrate that our networks attain results that compare favorably to state-of-the-art methods in terms of detail preservation, low-frequency noise removal, and temporal stability on a variety of production and academic datasets.

Glutamic acid decarboxylase (GAD; glutamate decarboxylase, L-glutamate 1-carboxy-lyase, EC 4.1.1.15), which catalyzes formation of gamma-aminobutyric acid from L-glutamic acid, is detectable in different isoforms with distinct electrophoretic and kinetic characteristics. GAD has also been implicated as an autoantigen in the vastly differing autoimmune disease stiff-man syndrome and insulin-dependent diabetes mellitus. Despite the differing GAD isoforms, only one type of GAD cDNA (GAD-1), localized to a syntenic region of chromosome 2, has been isolated from rat, mouse, and cat. Using sequence information from GAD-1 to screen a human pancreatic islet cDNA library, we describe the isolation of an additional GAD cDNA (GAD-2), which was mapped to the short arm of human chromosome 10. Genomic Southern blotting with GAD-2 demonstrated a hybridization pattern different from that detected by GAD-1. GAD-2 recognizes a 5.6-kilobase transcript in both islets and brain, in contrast to GAD-1, which detects a 3.7-kilobase transcript in brain only. The deduced 585-amino acid sequence coded for by GAD-2 shows less than 65% identity to previously published, highly conserved GAD-1 brain sequences, which show greater than 96% deduced amino acid sequence homology among the three species. The function of this additional islet GAD isoform and its importance as an autoantigen in insulin-dependent diabetes remain to be determined.

Summary The importance of miRNAs during development and disease processes is well established. However, most studies have been done in cells or with patient tissues, and therefore the physiological roles of miRNAs are not well understood. To unravel in vivo functions of miRNAs, we have generated conditional, reporter-tagged knockout-first mice for numerous evolutionarily conserved miRNAs. Here we report the generation of 162 miRNA targeting vectors, 64 targeted ES cell lines, and 46 germline-transmitted miRNA knockout mice. In vivo lacZ reporter analysis in 18 lines revealed highly tissue-specific expression patterns and their miRNA expression profiling matched closely with published expression data. Most miRNA knockout mice tested were viable, supporting a mechanism by which miRNAs act redundantly with other miRNAs or other pathways. These data and collection of resources will be of value for the in vivo dissection of miRNA functions in mouse models.

Employers who are developing strategies to reduce health-related productivity loss may benefit from aiming their interventions at the employees who need them most. We determined whether depression's negative productivity impact varied with the type of work employees performed. Subjects (246 with depression and 143 controls) answered the Work Limitations Questionnaire and additional work questions. Occupational requirements were measured objectively. In multiple regression analyses, productivity was most influenced by depression severity (P < 0.01 in 5/5 models). However, certain occupations also significantly increased employee vulnerability to productivity loss. Losses increased when employees had occupations requiring proficiency in decision-making and communication and/or frequent customer contact (P < 0.05 in 3/5 models). The Work Limitations Questionnaire can help employers to reduce productivity loss by identifying health and productivity improvement priorities.A wealth of research now shows that depression can exact a heavy economic toll on businesses and their employees. [1][2][3][4] Depression in the working-age population is estimated to cost this nation at least $12.4 billion annually in medical care and at least another $44 billion annually in lost productive work time. 4,5 Researchers estimate that approximately half of the employers' total costs for depression are the result of employee work absences and disability claims. 3 One of the main reasons for these staggering costs is that one in eight working-age adults, 18 to 54 years of age, is estimated to be clinically depressed, and half will experience a recurrence within 1 year of remission. 6 Employers have relied mainly on medical care for help in treating their employees' depression. By doing so, some companies have hoped to minimize the condition's secondary Copyright © by American College of Occupational and Environmental Medicine Address correspondence to: Debra Lerner, MS, PhD, The Health Institute, Tufts-New England Medical Center, 750 Washington Street, NEMC #345, Boston, MA 02111; dlerner@tufts-nemc.org.. NIH Public AccessAuthor Manuscript J Occup Environ Med. Author manuscript; available in PMC 2015 January 05. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript impact on employee work performance and productivity. There is some rationale for this approach. In addition to the depression impact studies cited previously, 1-4 studies suggest that patients whose symptoms improve subsequently have less work impairment. [7][8][9][10] Recently, a few treatment trials have found that compared with patients receiving usual care, those getting high-quality depression treatment have fewer work absences and less unemployment (Rost K, Smith JL, Elliott CE, Dickinson M, Duan N, submitted). 11In previous depression research, productivity loss has been included as a secondary outcome and few explanatory variables, other than depression symptoms or depression treatment, were included. This study addresses productivity loss...

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