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Using interview and observational data from an in-depth case study, this article analyzes outcomes associated with a participative approach to work for non-unionized, white-collar service workers. It describes the organizational basis for business-service workers' limited self-management, and the way consent to self-management was constructed in the context of a decentralized, unpredictable, and often interpersonally stressful work environment. Workers' constrained mobility opportunities and work biographies are also considered as part of the explanation for consent to chaotic work arrangements.

Within the basolateral membrane of thyroid follicular epithelial cells, two transporter proteins are central to thyroid hormone (TH) biosynthesis and secretion. The sodium iodide symporter (NIS) delivers iodide from the bloodstream into the thyroid, and after TH biosynthesis, monocarboxylate transporter 8 (MCT8) mediates TH secretion from the thyroid gland. Pituitary tumor-transforming gene-binding factor (PBF; PTTG1IP) is a protooncogene that is up-regulated in thyroid cancer and that binds NIS and modulates its subcellular localization and function. We now show that PBF binds MCT8 in vitro, eliciting a marked shift in MCT8 subcellular localization and resulting in a significant reduction in the amount of MCT8 at the plasma membrane as determined by cell surface biotinylation assays. Colocalization and interaction between PBF and Mct8 was also observed in vivo in a mouse model of thyroid-specific PBF overexpression driven by a bovine thyroglobulin (Tg) promoter (PBF-Tg). Thyroidal Mct8 mRNA and protein expression levels were similar to wild-type mice. Critically, however, PBF-Tg mice demonstrated significantly enhanced thyroidal TH accumulation and reduced TH secretion upon TSH stimulation. Importantly, Mct8-knockout mice share this phenotype. These data show that PBF binds and alters the subcellular localization of MCT8 in vitro, with PBF overexpression leading to an accumulation of TH within the thyroid in vivo. Overall, these studies identify PBF as the first protein to interact with the critical TH transporter MCT8 and modulate its function in vivo. Furthermore, alongside NIS repression, PBF may thus represent a new regulator of TH biosynthesis and secretion.

This article uses in-depth case study research to examine one set of organizational and staffing arrangements designed to facilitate flexible service delivery. “Institutionalized flexibility” incorporated multiple contingent bases of employment and concealed hidden hierarchies in workplaces within and across organizations. It also relied on the combined efforts of permanent, moderately skilled workers and temporary, deskilled workers. The article analyzes how these multitiered organizational settings created unique opportunities and costs for the individuals working within them, and introduced new intraorganizational and interorganizational complexities.

The rate of cat flea, Ctenocephalides felis (Bouché), pupal development and the stimuli responsible for successful cocoon formation were investigated by rearing flea pupae without an enclosing cocoon. Female larvae pupated an average 12.1 h earlier than males, and female pupae developed to the adult stage an average 1.6 d earlier than males. When larvae were not allowed to orient against a perpendicular structure, only 2.2% of these larvae were able to spin an enclosing cocoon. Although these naked flea pupae had no enveloping cocoon, 96.5% survived to become adults. Gentle sifting of the larval medium 0-12 and 12-24 h after cocoons were formed resulted in 13.7 and 3.5% of the larvae emerging, respectively. Over 40% of those larvae did not spin a second cocoon, but developed as naked flea pupae.

Background Two studies were conducted to evaluate and compare the efficacy of imidacloprid + moxidectin and selamectin topical solutions against the KS1 flea strain infesting cats. In both studies the treatment groups were comprised of non-treated controls, 6% w/v selamectin (Revolution®; Pfizer Animal Health) topical solution and 10% w/v imidacloprid + 1% w/v moxidectin (Advantage Multi® for Cats, Bayer Animal Health) topical solution. All cats were infested with 100 fleas on Days -2, 7, 14, 21, and 28. The difference in the studies was that in study #1 efficacy evaluations were conducted at 24 and 48 hours post-treatment or post-infestation, and in study #2 evaluations were conducted at 12 and 24 hours. Results In study #1 imidacloprid + moxidectin and the selamectin formulation provided 99.8% and 99.0% efficacy at 24 hours post-treatment. On day 28, the 24 hour efficacy of the selamectin formulation dropped to 87.1%, whereas the imidacloprid + moxidectin formulation provided 98.9% efficacy. At the 48 hour assessments following the 28 day infestations, efficacy of the imidacloprid + moxidectin and selamectin formulations was 96.8% and 98.3% respectively. In study # 2 the efficacy of the imidacloprid + moxidectin and selamectin formulations 12 hours after treatment was 100% and 69.4%, respectively. On day 28, efficacy of the imidacloprid + moxidectin and selamectin formulations 12 hours after infestation was 90.2% and 57.3%, respectively. In study #2 both formulations provided high levels of efficacy at the 24 hour post-infestation assessments, with selamectin and imidacloprid + moxidectin providing 95.3% and 97.5% efficacy, following infestations on day 28. Conclusions At the 24 and 48 hour residual efficacy assessments, the imidacloprid + moxidectin and selamectin formulations were similarly highly efficacious. However, the imidacloprid + moxidectin formulation provided a significantly higher rate of flea kill against the KS1 flea strain infesting cats at every 12 hour post-infestation residual efficacy assessment. Both formulations should provide excellent flea control for an entire month on cats.

Pituitary tumor-transforming gene (PTTG)-binding factor (PBF; PTTG1IP) was initially identified through its interaction with the human securin, PTTG. Like PTTG, PBF is upregulated in multiple endocrine tumours including thyroid cancer. PBF is believed to induce the translocation of PTTG into the cell nucleus where it can drive tumourigenesis via a number of different mechanisms. However, an independent transforming ability has been demonstrated both in vitro and in vivo, suggesting that PBF is itself a proto-oncogene. Studied in only a limited number of publications to date, PBF is emerging as a protein with a growing repertoire of roles. Recent data suggest that PBF possesses a complex multifunctionality in an increasing number of tumour settings. For example, PBF is upregulated by oestrogen and mediates oestrogen-stimulated cell invasion in breast cancer cells. In addition to a possible role in the induction of thyroid tumourigenesis, PBF overexpression in thyroid cancers inhibits iodide uptake. PBF has been shown to repress sodium iodide symporter (NIS) activity by transcriptional regulation of NIS expression through the human NIS upstream enhancer and further inhibits iodide uptake via a post-translational mechanism of NIS governing subcellular localisation. This review discusses the current data describing PBF expression and function in thyroid cancer and highlights PBF as a novel target for improving radioiodine uptake and thus prognosis in thyroid cancer.

Review on PTTG1IP (pituitary tumor-transforming 1 interacting protein), with data on DNA, on the protein encoded, and where the gene is implicated.

Pituitary tumor transforming gene (PTTG)-binding factor (PBF or PTTG1IP) is a little characterized proto-oncogene that has been implicated in the etiology of breast and thyroid tumors. In this study, we created a murine transgenic model to target PBF expression to the thyroid gland (PBF-Tg mice) and found that these mice exhibited normal thyroid function, but a striking enlargement of the thyroid gland associated with hyperplastic and macrofollicular lesions. Expression of the sodium iodide symporter (NIS), a gene essential to the radioiodine ablation of thyroid hyperplasia, neoplasia, and metastasis, was also potently inhibited in PBF-Tg mice. Critically, iodide uptake was repressed in primary thyroid cultures from PBF-Tg mice, which could be rescued by PBF depletion. PBF-Tg thyroids exhibited upregulation of Akt and the TSH receptor (TSHR), each known regulators of thyrocyte proliferation, along with upregulation of the downstream proliferative marker cyclin D1. We extended and confirmed findings from the mouse model by examining PBF expression in human multinodular goiters (MNG), a hyperproliferative thyroid disorder, where PBF and TSHR was strongly upregulated relative to normal thyroid tissue. Furthermore, we showed that depleting PBF in human primary thyrocytes was sufficient to increase radioiodine uptake. Together, our findings indicate that overexpression of PBF causes thyroid cell proliferation, macrofollicular lesions, and hyperplasia, as well as repression of the critical therapeutic route for radioiodide uptake. Cancer Res; 71(19); 6153–64. ©2011 AACR.

The pituitary tumor-transforming gene (PTTG1) encodes a multifunctional protein (PTTG) that is overexpressed in numerous tumours, including pituitary, thyroid, breast and ovarian carcinomas. PTTG induces cellular transformation in vitro and tumourigenesis in vivo, and several mechanisms by which PTTG contributes to tumourigenesis have been investigated. Also known as the human securin, PTTG is involved in cell cycle regulation, controlling the segregation of sister chromatids during mitosis. This review outlines current information regarding PTTG structure, expression, regulation and function in the pathogenesis of neoplasia. Recent progress concerning the use of PTTG as a prognostic marker or therapeutic target will be considered. In addition, the PTTG binding factor (PBF), identified through its interaction with PTTG, has also been established as a proto-oncogene that is upregulated in several cancers. Current knowledge regarding PBF is outlined and its role both independently and alongside PTTG in endocrine and related cancers is discussed.

Under recent conditions of economic competition, customer/worker interactions increasingly are a source of profitability in service firms. Companies may employ refined methods for making these interactions a source of information about workers' performance. This paper investigates how managers and employers use customer feedback to monitor, evaluate and discipline service workers. We argue that management by customers may deepen and complicate authority and power relations in the workplace, and may also give rise to new forms of workplace conflict.

This paper applies concepts and methods developed in management to translate efficacious prevention programs into effective prevention services. The paper describes Quality Function Deployment (QFD) as a method for structured planning and development that connects the needs and wants of the consumer with the design of the product or service. The paper describes basic tools used in quality management, and discusses how they might be applied to prepare a prevention program for implementation by community agencies. Prevention programs are conceptualized as having multiple consumers (i.e., stakeholders), including the participants who receive the service, the service providers, the organizations that deliver the program, and the researchers who evaluate the programs. As an illustration of one step in the application of QFD to translate efficacious prevention programs into effective prevention services, analysis of the needs and preferences of Family Courts for the implementation of an the New Beginnings Program is presented.

A study was conducted to evaluate the efficacy of selamectin and fipronil-(S)-methoprene against adult cat fleas (Ctenocephalides felis), flea egg production, and the viability of flea eggs collected from treated cats. Cats were infested with approximately 50 adult fleas 2 days before treatment and weekly thereafter; flea eggs were collected and counted on days 0, 1, 2, and 3 and 48 and 72 hours after each weekly flea infestation. Live fleas were collected approximately 72 hours after treatment or infestation. Compared with fipronil-(S)-methoprene, selamectin provided significantly greater control of adult fleas from days 24 to 31 and significantly greater reduction in egg production from days 16 to 45. For the most part, both products significantly impacted larval and adult emergence for the entire 6-week study, with fipronil-(S)-methoprene providing significantly greater reduction in larval and adult emergence at week 6.

Though ampicillin is no longer recommended as first-line therapy for infections caused by Neisseria gonorrhoeae, the cost and efficacy of this policy in low prevalence areas has not been investigated. The problem was highlighted by an outbreak of penicillin-resistant N. gonorrhoeae in an area where the proportion of resistance had previously been only 0.14%. A decision analysis was performed to determine the cost-effectiveness of beta-lactamase screening and alternative therapies for patients attending sexually transmitted diseases clinics. Empiric therapy with an inexpensive agent active against resistant strains, such as ciprofloxacin, was the most cost-effective approach and remained more cost-effective than alternative strategies whenever the proportion of resistant isolates exceeded 3%. Ceftriaxone was less cost-effective. In low prevalence areas, and in areas where the return rate of recalled patients is high, ampicillin therapy was cost-effective, but beta-lactamase screening should be performed routinely.

A spot-on metaflumizone formulation was evaluated to determine its adulticidal efficacy, effect upon egg production, and ovicidal activity when applied to flea infested cats. Eight male and eight female adult domestic shorthair cats were randomly assigned to either serve as non-treated controls or were treated topically with a minimum of 40mg/kg metaflumizone in single spot-on Day 0. On Days -2, 7, 14, 21, 28, 35, 42, 49, and 56, each cat was infested with approximately 100 unfed cat fleas, Ctenocephalides felis felis. On Days 1, 2, and 3, and at 48 and 72h after each post-treatment reinfestation, flea eggs were collected and counted. At approximately 72h after treatment or infestation, each cat was combed to remove and count live fleas. Egg viability was determined by examining hatched eggs after 5 days and adult emergence was determined 28 days after egg collection. Metaflumizone provided >/=99.6% efficacy against adult fleas from Days 3 to 45 following a single application. Following treatment, egg production fell by 51.6% within 24h and 99.2% within 48h. Following subsequent weekly infestations egg production from treated cats was negligible out to Day 38, with >/=99.5% reduction relative to non-treated cats. Where there were eggs to evaluate, metaflumizone treatment did not have any apparent effect on the hatching of eggs or on the development and emergence of adult fleas from the eggs produced by fleas from treated animals.

A spot-on metaflumizone formulation was evaluated in adult domestic short hair cats to determine its adultidical efficacy against a flea strain that has reduced susceptibility to a number of insecticides. Eight cats served as non-treated controls, eight cats were treated with a metaflumizone formulation at 0.2 ml/kg (40 mg metaflumizone/kg) and eight cats were treated with fipronil 10% w/v–(s)-methoprene 12% w/v at 0.075 ml/kg (7.5–7.7 mg fipronil/kg:9.0–9.2 mg (s)-methoprene/kg). On days −1, 7, 14, 21, 28, 35, and 42 each cat was infested with approximately 100 unfed KS1 cat fleas, Ctenocephalides felis. At approximately 48 h after treatment or infestation, each cat was combed to remove and count live fleas. Treatment with metaflumizone provided ≥99.3% efficacy for 3 weeks post-treatment and then 97.4, 91.4 and 86.2% efficacy at 4, 5 and 6 weeks post-treatment, respectively. Fipronil–(s)-methoprene provided 99.6% efficacy at 1 week post-treatment and then 97.6, 96.4, 71.3, 22.0 and 13.1% efficacy at weeks 2, 3, 4, 5 and 6, respectively. The reductions in flea numbers were significantly greater for the metaflumizone treatment than for fipronil–(s)-methoprene from 3 to 6 weeks after treatment.

The ability of the thyroid to accumulate iodide provides the basis for radioiodine ablation of differentiated thyroid cancers and their metastases. Most thyroid tumours exhibit reduced iodide uptake, although the mechanisms accounting for this remain poorly understood. Pituitary tumour transforming gene (PTTG) is a proto-oncogene implicated in the pathogenesis of thyroid tumours. We now show that PTTG and its binding factor PBF repress expression of sodium iodide symporter (NIS) messenger RNA (mRNA), and inhibit iodide uptake. This process is mediated at least in part through fibroblast growth factor-2. In detailed studies of the NIS promoter in rat FRTL-5 cells, PTTG and PBF demonstrated specific inhibition of promoter activity via the human upstream enhancer element (hNUE). Within this approximately 1 kb element, a complex PAX8-upstream stimulating factor 1 (USF1) response element proved critical both to basal promoter activity and to PTTG and PBF repression of NIS. In particular, repression by PTTG was contingent upon the USF1, but not the PAX8, site. Finally, in human primary thyroid cells, PTTG and PBF similarly repressed the NIS promoter via hNUE. Taken together, our data suggest that the reported overexpression of PTTG and PBF in differentiated thyroid cancer has profound implications for activity of the NIS gene, and hence significantly impacts upon the efficacy of radioiodine treatment.

Although not detectable in normal breast tissue, the sodium iodide symporter (NIS) has been found to be expressed in 70-80% of breast cancers. However, the majority of NIS is intracellular, leaving only 20-30% functional at the plasma membrane. Whilst radioiodine therapy has been proposed as a potential treatment for breast cancer, effective therapy would require increased levels of membranous NIS localisation in tumours. Previous work revealed that overexpression of pituitary tumor transforming gene binding factor (PBF) in thyroid cells leads to the redistribution of NIS from the plasma membrane into intracellular vesicles, thereby reducing radioiodide uptake, a process modulated by Src phosphorylation of PBF. Here we show that PBF and NIS have a consistent relationship in breast cancer, with phosphorylation of PBF at residue Y174 being critical for the association. Immunofluorescent microscopy revealed co-localisation between NIS and PBF in co-transfected MDA-MB-231, MCF-7 and T47D cells, with increased intracellular staining for NIS compared to cells transfected with NIS alone. Phosphorylated PBF was also observed to co-localise with NIS in T47D cells. Treatment with PP1, a Src inhibitor which modulates the phosphorylation of PBF, led to increased NIS plasma membrane staining and less intracellular co-localisation with PBF. Functional studies in MCF-7 and MDA-MB-231 cells demonstrated that PBF significantly repressed radioiodide uptake in cells expressing exogenous NIS (25% and 30% reduction respectively; n=3, p Citation Format: Vikki L Poole, Martin L Read, Rachel J Watkins, Bhavika Modasia, Waraporn Imruetaicharoenchoke, Kristien Boelaert, Vicki E Smith, Christopher J McCabe. Inhibition of Src increases radioiodide uptake in breast cancer cells by inhibiting phosphorylation of pituitary tumor transforming gene binding factor (PBF) [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-03-13.

Genetic instability (GI) is a hallmark feature of tumor development. Securin, also known as pituitary tumor transforming gene (PTTG), is a mitotic checkpoint protein which is highly expressed in numerous cancers, is associated with tumor invasiveness, and induces GI in thyroid cells. We used fluorescence inter-simple sequence repeat PCR to assess GI caused primarily by DNA breakage events in 19 colorectal tumors. GI values ranged significantly, with Dukes' stage C&D colorectal tumors exhibiting greater GI and higher securin expression than Dukes' stage A&B tumors. Consistent with these findings, we observed a dose-dependent increase in GI in HCT116 cells in response to securin overexpression, as well as in non-transformed human fibroblasts. As securin has been implicated in a novel DNA repair pathway in fission yeast, we investigated its potential role in chemotoxic DNA damage response pathways in mammalian cells, using host cell reactivation assays. Securin overexpression in HCT116 cells inhibited etoposide-induced double-stranded DNA damage repair activity, and repressed Ku heterodimer function. Additionally, we observed that securin and Ku70 showed a reciprocal cytosol-nuclear translocation in response to etoposide-induced dsDNA damage. Our data suggest that, by repressing Ku70 activity and inhibiting the non-homologous end-joining dsDNA repair pathway, securin may be a critical gene in the development of GI in colorectal cancer.

The first cluster of papers in this volume studies the effect of worker participation on individuals, group processes, and organizations. This topic mirrors the predominant emphasis in the literature wherein worker participation, broadly defined, has been regressed against nearly every conceivable outcome in diverse work settings. Quite reasonably, a driving question for social scientists is what happens when worker participation is introduced. What are the consequences of top-down participation schemes and are they meaningful? Do they change the distribution of rewards and opportunities, or reconfigure dynamics between workers? The study of outcomes is significant because it touches on whether worker participation programs genuinely change the nature of work, improve workers’ jobs, strengthen workers’ hand or merely perpetuate traditional power structures.

Endometriosis is a common gynecological disease that affects up to 10% of women in their reproductive years. It causes pelvic pain, severe dysmenorrhea, and subfertility. The disease is defined as the presence of tissue resembling endometrium in sites outside the uterus. Its cause remains uncertain despite >50 years of hypothesis-driven research, and thus the therapeutic options are limited. Disease predisposition is inherited as a complex genetic trait, which provides an alternative route to understanding the disease. We seek to identify susceptibility loci, using a positional-cloning approach that starts with linkage analysis to identify genomic regions likely to harbor these genes. We conducted a linkage study of 1,176 families (931 from an Australian group and 245 from a U.K. group), each with at least two members--mainly affected sister pairs--with surgically diagnosed disease. We have identified a region of significant linkage on chromosome 10q26 (maximum LOD score [MLS] of 3.09; genomewide P = .047) and another region of suggestive linkage on chromosome 20p13 (MLS = 2.09). Minor peaks (with MLS > 1.0) were found on chromosomes 2, 6, 7, 8, 12, 14, 15, and 17. This is the first report of linkage to a major locus for endometriosis. The findings will facilitate discovery of novel positional genetic variants that influence the risk of developing this debilitating disease. Greater understanding of the aberrant cellular and molecular mechanisms involved in the etiology and pathophysiology of endometriosis should lead to better diagnostic methods and targeted treatments.

A Prevention Service Development Model (PSDM) is presented as an approach to develop, prevention programs that are both effective and that are readily adopted for implementation in community settings. The model is an integration of concepts and methods from two fields, prevention research and marketing research as applied to new service development. Questions that are posed at each stage of the PSDM are described. Studies from the development of two preventive interventions are presented to illustrate research at several of the stages of the model.

ErbB2 is overexpressed in 25-30% of breast and ovarian cancers, correlates with poor prognosis and lower survival and has also been associated with chemoresistance. We have established an isogenic pair of human ovarian cells that differ only in the expression of erbB2 protein in order to elucidate the role of the protein in determining cellular sensitivity to various drugs and agents. These included cisplatin and paclitaxel, the main drugs used in the treatment of ovarian cancer, and also various signal transduction inhibitors affecting the ras and P13K pathways. Transfection of erbB2 resulted in cells stably overexpressing the protein and showing increased motility compared to the empty vector control cells. In cells overexpressing erbB2, the most notable effect on chemosensitivity was that of significantly increased (5-fold) sensitivity to the heat shock protein 90 (HSP90) molecular chaperone inhibitor geldanamycin. In contrast, erbB2-overexpressing cells showed statistically significant resistance to cisplatin, the P13K inhibitor LY294002 and the tyrosine kinase inhibitor emodin. No significant difference in growth inhibition was observed after exposure to paclitaxel, two additional HSP90 inhibitors radicicol and 17AAG, the cyclin-dependent kinase inhibitor flavopiridol, the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor PD153035, the mek inhibitor U0126 or the famesyl transferase inhibitor R115777. Exposure of cells to geldanamycin, 17AAG, emodin, LY294002 and cisplatin led to depletion of erbB2 in the transfected cells. These data suggest that erbB2 status in ovarian cancr may contribute to chemosensitivity, in some cases leading to increased sensitivity (as with geldanamycin) but in other cases leading to resistance (as with cisplatin).

To evaluate the ability of the CatanDog's tag to eliminate fleas, inhibit egg production and prevent flea infestations, six domestic shorthaired cats were randomly allocated to two treatment groups and housed individually in stainless steel metabolic cages. Three cats were each fitted with a CatanDog's tag; the other three cats were not fitted with tags and served as controls. Following a 42-day acclimation period, each of the six cats was infested with 100, 1-3 day post-emergence, adult Ctenocephalides felis felis (Bouche) on days 0, 7, 14, 21, and 27. Flea egg production was determined by collecting and enumerating eggs 2, 4 and 6 days after each infestation. Viability of eggs was determined by placing 100 eggs recovered from each cat in rearing media in an insect rearing chamber and determining adult emergence at 28 days. Adult fleas were recovered from cats 6 days post-infestation by thoroughly combing each cat to remove fleas. To determine if the tags provided protection from infestation, the six cats were placed into a 8.53mx4.36 m room with 400 cat fleas for 3h. Cats were then combed to remove and enumerate fleas. The CatanDog's tags had no significant effect upon egg production, egg viability, or adult fleas infesting cats. In addition there was no difference in the numbers of fleas recovered from the cats placed in the flea-infested room.

Nissan's vehicle assembly plant in Smyrna, Tennessee, is testing a hydrogen fuel cell forklift.