498 research outputs found
Bureaucratic malaises and their remedies in Public and Nonprofit Organizations
Many experts have observed that bureaucratic malaises are endemic in public sector organizations. These so-called “diseases,” which include personnel constraints, red tape and risk avoidance, can discourage workers, damage organizational performance, and lower the quality of public services. The depth and impact of these malaises are tested across the public and nonprofit sectors using data from the third National Administrative Studies Project (NASP III). NASP III surveyed randomly selected managers in public and nonprofit organizations in Georgia and Illinois. Multiple informant data are aggregated to the organizational level resulting 47 public and 64 nonprofit organizations for further analysis. Multivariate statistical analysis suggests that most of the maladies have harmful effects on work quality in the public sector, but not on the nonprofit agencies studied in this sample. The results further show that task clarity does not mitigate the performance effects of these maladies in the public sector whereas in the nonprofit sector it is associated with higher levels of performance. The implications for theory and practice are discussed.postprin
Focal amplification of the androgen receptor gene in hormone-naive human prostate cancer.
BACKGROUND: Androgen receptor (AR)-gene amplification, found in 20-30% of castration-resistant prostate cancer (CRPCa) is proposed to develop as a consequence of hormone-deprivation therapy and be a prime cause of treatment failure. Here we investigate AR-gene amplification in cancers before hormone deprivation therapy. METHODS: A tissue microarray (TMA) series of 596 hormone-naive prostate cancers (HNPCas) was screened for chromosome X and AR-gene locus-specific copy number alterations using four-colour fluorescence in situ hybridisation. RESULTS: Both high level gain in chromosome X (≥4 fold; n=4, 0.7%) and locus-specific amplification of the AR-gene (n=6, 1%) were detected at low frequencies in HNPCa TMAs. Fluorescence in situ hybridisation mapping whole sections taken from the original HNPCa specimen blocks demonstrated that AR-gene amplifications exist in small foci of cells (≤ 600 nm, ≤1% of tumour volume). Patients with AR gene-locus-specific copy number gains had poorer prostate cancer-specific survival. CONCLUSION: Small clonal foci of cancer containing high level gain of the androgen receptor (AR)-gene develop before hormone deprivation therapy. Their small size makes detection by TMA inefficient and suggests a higher prevalence than that reported herein. It is hypothesised that a large proportion of AR-amplified CRPCa could pre-date hormone deprivation therapy and that these patients would potentially benefit from early total androgen ablation
The landscape of viral associations in human cancers
Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, for which whole-genome and—for a subset—whole-transcriptome sequencing data from 2,658 cancers across 38 tumor types was aggregated, we systematically investigated potential viral pathogens using a consensus approach that integrated three independent pipelines. Viruses were detected in 382 genome and 68 transcriptome datasets. We found a high prevalence of known tumor-associated viruses such as Epstein–Barr virus (EBV), hepatitis B virus (HBV) and human papilloma virus (HPV; for example, HPV16 or HPV18). The study revealed significant exclusivity of HPV and driver mutations in head-and-neck cancer and the association of HPV with APOBEC mutational signatures, which suggests that impaired antiviral defense is a driving force in cervical, bladder and head-and-neck carcinoma. For HBV, HPV16, HPV18 and adeno-associated virus-2 (AAV2), viral integration was associated with local variations in genomic copy numbers. Integrations at the TERT promoter were associated with high telomerase expression evidently activating this tumor-driving process. High levels of endogenous retrovirus (ERV1) expression were linked to a worse survival outcome in patients with kidney cancer
Children with Juvenile Rheumatoid Arthritis at School
Parents of 135 children with juvenile rheumatoid arthritis (JRA) completed a mailed questionnaire about problems at school. Writing was the most frequently reported difficulty, with hand involvement causing more problems than decreased mobility. Compared to children with pauciarticular JRA, those with polyarticular or systemic JRA were significantly more likely to miss school, experience problems, participate less in physical education, have an Individualized Educational Plan (IEP) developed, and receive related services. Only 39 parents had heard of PL 94-142, and only 21 of those could define the federal law. Twenty children had an IEP within the previous two years. Possible deficiencies in the implementation of PL 94-142 were discovered. This study demonstrates that the treatment of children with JRA should include efforts to: 1) identify and remediate potential performance limitations before they become problematic at school; 2) communicate this information to parents and school personnel; 3) and improve parents' awareness and understanding of PL 94-142.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/67045/2/10.1177_000992288902801104.pd
External sources of clean technology: evidence from the clean development mechanism
New technology is fundamental to sustainable development. However, inventors from industrialized countries often refuse technology transfer because they worry about reverse-engineering. When can clean technology transfer succeed? We develop a formal model of the political economy of North–South technology transfer. According to the model, technology transfer is possible if (1) the technology in focus has limited global commercial potential or (2) the host developing country does not have the capacity to absorb new technologies for commercial use. If both conditions fail, inventors from industrialized countries worry about the adverse competitiveness effects of reverse-engineering, so technology transfer fails. Data analysis of technology transfer in 4,894 projects implemented under the Kyoto Protocol’s Clean Development Mechanism during the 2004–2010 period provides evidence in support of the model
Business models for circular sanitation: lessons from India
Providing safe sanitation in the developing world is still a major hurdle to achieving Sustainable Development Goal number six, with 61% of the global population lacking safely managed sanitation services. Circular economy in the context of sanitation focuses on the whole sanitation chain which includes the provision of toilets, the collection of waste, treatment and transformation into sanitation-derived products including fertiliser, fuel and clean water. As well as potentially reducing the cost of toilet provision, a circular economy approach also has the potential to enable positive environmental and health impacts, unlike other systems where waste may be discharged untreated into the environment. The implementation of a system level transformation is not simple, considering operator capacity, lack of funding, slowly growing acceptance by local communities, and a policy landscape which can be inconsistent in its support for the circular economy. As India invests in long-term infrastructure to improve citizens’ quality of life (e.g., Swachh Bharat Mission), it could incorporate circular economy principles into the design of infrastructure, creating effective urban nutrient and material cycles, enhancing economic development and welfare. This represents a significant opportunity for government and businesses in India to develop circular sanitation infrastructure to recover and valorise biological nutrients. After collecting information from five case studies across India, covering different treatment technologies, waste-derived products, markets and contexts; this research identifies the main barriers and enablers for circular sanitation business models to succeed. Whilst there were many different institutional and technological arrangements, common issues of managing and enforcing incoming waste and competing with chemical fertilisers were found
Development and Validation of the Behavioral Tendencies Questionnaire
At a fundamental level, taxonomy of behavior and behavioral tendencies can be described
in terms of approach, avoid, or equivocate (i.e., neither approach nor avoid). While there are
numerous theories of personality, temperament, and character, few seem to take advantage
of parsimonious taxonomy. The present study sought to implement this taxonomy by
creating a questionnaire based on a categorization of behavioral temperaments/tendencies
first identified in Buddhist accounts over fifteen hundred years ago. Items were developed
using historical and contemporary texts of the behavioral temperaments, described as
“Greedy/Faithful”, “Aversive/Discerning”, and “Deluded/Speculative”. To both maintain
this categorical typology and benefit from the advantageous properties of forced-choice
response format (e.g., reduction of response biases), binary pairwise preferences for items
were modeled using Latent Class Analysis (LCA). One sample (n1 = 394) was used to estimate
the item parameters, and the second sample (n2 = 504) was used to classify the participants
using the established parameters and cross-validate the classification against
multiple other measures. The cross-validated measure exhibited good nomothetic span
(construct-consistent relationships with related measures) that seemed to corroborate the
ideas present in the original Buddhist source documents. The final 13-block questionnaire
created from the best performing items (the Behavioral Tendencies Questionnaire or BTQ)
is a psychometrically valid questionnaire that is historically consistent, based in behavioral
tendencies, and promises practical and clinical utility particularly in settings that teach and
study meditation practices such as Mindfulness Based Stress Reduction (MBSR)
Multi-level evidence of an allelic hierarchy of USH2A variants in hearing, auditory processing and speech/language outcomes.
Language development builds upon a complex network of interacting subservient systems. It therefore follows that variations in, and subclinical disruptions of, these systems may have secondary effects on emergent language. In this paper, we consider the relationship between genetic variants, hearing, auditory processing and language development. We employ whole genome sequencing in a discovery family to target association and gene x environment interaction analyses in two large population cohorts; the Avon Longitudinal Study of Parents and Children (ALSPAC) and UK10K. These investigations indicate that USH2A variants are associated with altered low-frequency sound perception which, in turn, increases the risk of developmental language disorder. We further show that Ush2a heterozygote mice have low-level hearing impairments, persistent higher-order acoustic processing deficits and altered vocalizations. These findings provide new insights into the complexity of genetic mechanisms serving language development and disorders and the relationships between developmental auditory and neural systems
Multidimensional Proteomics Analysis of Amniotic Fluid to Provide Insight into the Mechanisms of Idiopathic Preterm Birth
Though recent advancement in proteomics has provided a novel perspective on several distinct pathogenetic mechanisms leading to preterm birth (inflammation, bleeding), the etiology of most preterm births still remains elusive. We conducted a multidimensional proteomic analysis of the amniotic fluid to identify pathways related to preterm birth in the absence of inflammation or bleeding.A proteomic fingerprint was generated from fresh amniotic fluid using surface-enhanced laser desorbtion ionization time of flight (SELDI-TOF) mass spectrometry in a total of 286 consecutive samples retrieved from women who presented with signs or symptoms of preterm labor or preterm premature rupture of the membranes. Inflammation and/or bleeding proteomic patterns were detected in 32% (92/286) of the SELDI tracings. In the remaining tracings, a hierarchical algorithm was applied based on descriptors quantifying similarity/dissimilarity among proteomic fingerprints. This allowed identification of a novel profile (Q-profile) based on the presence of 5 SELDI peaks in the 10-12.5 kDa mass area. Women displaying the Q-profile (mean+/-SD, gestational age: 25+/-4 weeks, n = 40) were more likely to deliver preterm despite expectant management in the context of intact membranes and normal amniotic fluid clinical results. Utilizing identification-centered proteomics techniques (fluorescence two-dimensional differential gel electrophoresis, robotic tryptic digestion and mass spectrometry) coupled with Protein ANalysis THrough Evolutionary Relationships (PANTHER) ontological classifications, we determined that in amniotic fluids with Q-profile the differentially expressed proteins are primarily involved in non-inflammatory biological processes such as protein metabolism, signal transduction and transport.Proteomic profiling of amniotic fluid coupled with non-hierarchical bioinformatics algorithms identified a subgroup of patients at risk for preterm birth in the absence of intra-amniotic inflammation or bleeding, suggesting a novel pathogenetic pathway leading to preterm birth. The altered proteins may offer opportunities for therapeutical intervention and future drug development to prevent prematurity
Business models for circular sanitation: lessons from India
Providing safe sanitation in the developing world is still a major hurdle to achieving Sustainable Development Goal number six, with 61% of the global population lacking safely managed sanitation services. Circular economy in the context of sanitation focuses on the whole sanitation chain which includes the provision of toilets, the collection of waste, treatment and transformation into sanitation-derived products including fertiliser, fuel and clean water. As well as potentially reducing the cost of toilet provision, a circular economy approach also has the potential to enable positive environmental and health impacts, unlike other systems where waste may be discharged untreated into the environment. The implementation of a system level transformation is not simple, considering operator capacity, lack of funding, slowly growing acceptance by local communities, and a policy landscape which can be inconsistent in its support for the circular economy. As India invests in long-term infrastructure to improve citizens’ quality of life (e.g., Swachh Bharat Mission), it could incorporate circular economy principles into the design of infrastructure, creating effective urban nutrient and material cycles, enhancing economic development and welfare. This represents a significant opportunity for government and businesses in India to develop circular sanitation infrastructure to recover and valorise biological nutrients. After collecting information from five case studies across India, covering different treatment technologies, waste-derived products, markets and contexts; this research identifies the main barriers and enablers for circular sanitation business models to succeed. Whilst there were many different institutional and technological arrangements, common issues of managing and enforcing incoming waste and competing with chemical fertilisers were found
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