651 research outputs found

    Work-Unit Absenteeism: Effects of Satisfaction, Commitment, Labor Market Conditions, and Time

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    Prior research is limited in explaining absenteeism at the unit level and over time. We developed and tested a model of unit-level absenteeism using five waves of data collected over six years from 115 work units in a large state agency. Unit-level job satisfaction, organizational commitment, and local unemployment were modeled as time-varying predictors of absenteeism. Shared satisfaction and commitment interacted in predicting absenteeism but were not related to the rate of change in absenteeism over time. Unit-level satisfaction and commitment were more strongly related to absenteeism when units were located in areas with plentiful job alternatives

    Tips to Advance Business Writing Skills at EFL Classes (Through the Example of "Letter of Complaint")

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    Writing is a creative communicative skill to express thoughts. It is cognitively complex, requires much practice and is best learned through experience. Writing is one of the most challenging, time-consuming tasks in acquiring a foreign language. To improve students’ writing skills and accuracy, a teacher should encourage writing-thinking, provide instructions and examples of good writing in the target language, and give feedback focusing both on error correction (cohesion) and organization of writing (clarity, idea development, coherence). This paper explores difficulties of the development of business writing skills and gives recommendations on writing a letter of complaint at English as a foreign language classes

    ABCC1: a gateway for pharmacological compounds to the ischaemic brain

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    By preventing access of drugs to the CNS, the blood-brain barrier hampers developments in brain pharmacotherapy. Strong efforts are currently being made to identify drugs that accumulate more efficaciously in ischaemic brain tissue. We identified an ATP-binding cassette (ABC) transporter, ABCC1, which is expressed on the abluminal surface of the brain capillary endothelium and mildly downregulated in response to focal cerebral ischaemia, induced by intraluminal middle cerebral artery occlusion. In biodistribution studies we show that ABCC1 promotes the accumulation of known neuroprotective and neurotoxic compounds in the ischaemic and non-ischaemic brain, ABCC1 deactivation reducing tissue concentrations by up to two orders of magnitude. As such, ABCC1's expression and functionality in the brain differs from the liver, spleen and testis, where ABCC1 is strongly expressed on parenchymal cells, resulting -- in case of liver and testis -- in directed transport from the tissue into the blood. After focal cerebral ischaemia, ABCC1 deactivation abolished the efficacy of both neuroprotective and neurotoxic compounds. Our data indicate that ABCC1 acts as gateway for pharmacological compounds to the stroke brain. We suggest that the tailoring of compounds binding to abluminal but not luminal ABC transporters may facilitate stroke pharmacotherap

    Multi‐gene metabolic engineering of tomato plants results in increased fruit yield up to 23%.

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    The capacity to assimilate carbon and nitrogen, to transport the resultant sugars and amino acids to sink tissues, and to convert the incoming sugars and amino acids into storage compounds in the sink tissues, are key determinants of crop yield. Given that all of these processes have the potential to co‐limit growth, multiple genetic interventions in source and sink tissues, plus transport processes may be necessary to reach the full yield potential of a crop. We used biolistic combinatorial co‐transformation (up to 20 transgenes) for increasing C and N flows with the purpose of increasing tomato fruit yield. We observed an increased fruit yield of up to 23%. To better explore the reconfiguration of metabolic networks in these transformants, we generated a dataset encompassing physiological parameters, gene expression and metabolite profiling on plants grown under glasshouse or polytunnel conditions. A Sparse Partial Least Squares regression model was able to explain the combination of genes that contributed to increased fruit yield. This combinatorial study of multiple transgenes targeting primary metabolism thus offers opportunities to probe the genetic basis of metabolic and phenotypic variation, providing insight into the difficulties in choosing the correct combination of targets for engineering increased fruit yield

    Interdisciplinary evidence-based recommendations for the follow-up of testicular cancer patients: a joint effort

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    Detailed recommendations for the treatment of testicular cancer exist and due to the stringent application of the standard therapies, most patients can nowadays be cured. Moreover in the treatment of early stage disease, active surveillance is now a cornerstone of treatment. Hence there is a clear need for recommendations regarding the long term follow-up of these young patients. These have to be safe, feasible and the intensity of procedures have to reflect the known risk of recurrence. Different proposals have been published but they differ widely especially in terms of frequency and modality of imaging. In the last few years, new evidence has become available regarding the relapse pattern of different disease stages of testicular cancer, the use of imaging in follow-up and the risks of excessive radiation due to imaging, in particular with CT scans. In this article, an interdisciplinary, multinational working group has reviewed the evidence and based on this has formulated practical recommendations for the follow-up of patients with testicular cancer

    Multimodality Treatment with Conventional Transcatheter Arterial Chemoembolization and Radiofrequency Ablation for Unresectable Hepatocellular Carcinoma

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    Background/Aims: To evaluate the efficacy of multimodality treatment consisting of conventional transcatheter arterial chemoembolization (TACE) and radiofrequency ablation (RFA) in patients with non-resectable and non-ablatable hepatocellular carcinoma (HCC). Methods: In this retrospective study, 85 consecutive patients with HCC (59 solitary, 29 multifocal HCC) received TACE followed by RFA between 2001 and 2010. The mean number of tumors per patient was 1.6 +/- 0.7 with a mean size of 3.0 +/- 0.9 cm. Both local efficacy and patient survival were evaluated. Results: Of 120 treated HCCs, 99 (82.5%) showed a complete response (CR), while in 21 HCCs (17.5%) a partial response was depicted. Patients with solitary HCC revealed CR in 91% (51/56); in patients with multifocal HCC (n = 29) CR was achieved in 75% (48 of 64 HCCs). The median survival for all patients was 25.5 months. The 1-, 2-, 3- and 5-year survival rates were 84.6, 58.7, 37.6 and 14.6%, respectively. Statistical analysis revealed a significant difference in survival between Barcelona Clinic Liver Cancer (BCLC) A (73.4 months) and B (50.3 months) patients, while analyses failed to show a difference for Child-Pugh score, Cancer of Liver Italian Program (CLIP) score and tumor distribution pattern. Conclusion: TACE combined with RFA provides an effective treatment approach with high local tumor control rates and promising survival data, especially for BCLC A patients. Randomized trials are needed to compare this multimodality approach with a single modality approach for early-stage HCC. Copyright (C) 2011 S. Karger AG, Base

    Structure-guided design and optimization of small molecules targeting the protein-protein interaction between the von hippel-lindau (VHL) E3 ubiquitin ligase and the hypoxia inducible factor (HIF) alpha subunit with in vitro nanomolar affinities

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    E3 ubiquitin ligases are attractive targets in the ubiquitin-proteasome system, however, the development of small-molecule ligands has been rewarded with limited success. The von Hippel-Lindau protein (pVHL) is the substrate recognition subunit of the VHL E3 ligase that targets HIF-1α for degradation. We recently reported inhibitors of the pVHL:HIF-1α interaction, however they exhibited moderate potency. Herein, we report the design and optimization, guided by X-ray crystal structures, of a ligand series with nanomolar binding affinities

    Sirolimus and kidney growth in autosomal dominant polycystic kidney disease

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    BACKGROUND: In autosomal dominant polycystic kidney disease (ADPKD), aberrant activation of the mammalian target of rapamycin (mTOR) pathway is associated with progressive kidney enlargement. The drug sirolimus suppresses mTOR signaling. METHODS: In this 18-month, open-label, randomized, controlled trial, we sought to determine whether sirolimus halts the growth in kidney volume among patients with ADPKD. We randomly assigned 100 patients between the ages of 18 and 40 years to receive either sirolimus (target dose, 2 mg daily) or standard care. All patients had an estimated creatinine clearance of at least 70 ml per minute. Serial magnetic resonance imaging was performed to measure the volume of polycystic kidneys. The primary outcome was total kidney volume at 18 months on blinded assessment. Secondary outcomes were the glomerular filtration rate and urinary albumin excretion rate at 18 months. RESULTS: At randomization, the median total kidney volume was 907 cm(3) (interquartile range, 577 to 1330) in the sirolimus group and 1003 cm(3) (interquartile range, 574 to 1422) in the control group. The median increase over the 18-month period was 99 cm(3) (interquartile range, 43 to 173) in the sirolimus group and 97 cm(3) (interquartile range, 37 to 181) in the control group. At 18 months, the median total kidney volume in the sirolimus group was 102% of that in the control group (95% confidence interval, 99 to 105; P=0.26). The glomerular filtration rate did not differ significantly between the two groups; however, the urinary albumin excretion rate was higher in the sirolimus group. CONCLUSIONS: In adults with ADPKD and early chronic kidney disease, 18 months of treatment with sirolimus did not halt polycystic kidney growth. (ClinicalTrials.gov number, NCT00346918.

    Point-of-contact interactive record linkage (PIRL) between demographic surveillance and health facility data in rural Tanzania

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    Introduction: Health and demographic surveillance systems (HDSS) have been an invaluable resource for monitoring the health status of populations, but often contain self-reported health service utilisation, which are subject to reporting bias. Objective: To implement point-of-contact interactive record linkage (PIRL) between demographic and health facility systems data, characterise attributes associated with (un)successful record linkage, and compare findings with a fully automated retrospective linkage approach. Methods: Individuals visiting the Kisesa Health Centre were matched to their HDSS records during a short up-take interview in the waiting area of the health facility. The search algorithm was used to rank potential matches, from which the true match(es) were selected after consultation with the patient. Multivariable logistic regression models were used to identify characteristics associated with being matched to an HDSS record. Records matched based on respondent's clarifications were subsequently used as the gold-standard to evaluate fully automated retrospective record linkage by calculating sensitivity and positive predictive value (PPV). Results: Among 2,624 individuals who reportedly lived in the HDSS coverage area, we matched 2,206 (84.1%) to their HDSS records. Characteristics associated with a higher odds of being matched were increased age (OR 1.07, 95% CI 1.02, 1.12; per 5-year increment), a later consent into the study (OR 2.07, 95% CI 1.37, 3.12; in the most recent six-month period), and fieldworker level of experience. The main drivers of the linkage algorithm were name, sex, year of birth, village, sub-village, and household member name. At the lowest match score threshold, automated retrospective linkage would have only correctly identified and linked 55% (1440/2612) of the records with a PPV of 55% (1440/2612). Conclusion: Where resources are available, PIRL is a viable approach to link HDSS and other administrative data sources that outperforms purely retrospective approaches
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