Comparing different versions of Undercover Boss reveals how an assemblage of TV producers, camera crews, businesses, and broadcasters choose to portray corporate hierarchies during the financial ...crisis of 2008 when corporations seemed like especially vulnerable forms of social organization for workers to rely upon. This article approaches the same show done in two different countries as a natural experiment that can reveal national differences through a textual comparison. The US show relies upon a sentimental imagination such that knowledge of the other is based on an emotional connection to the past. The UK show relies upon an organizational imagination in which the structural roles one plays in a company shape what one knows of how the company functions. Each version portrays distinctive approaches to three issues: (1) what can be known about people as social actors; (2) what is portrayed as ethical or appropriate workplace relationships; and (3) what kinds of tacit critiques of contemporary capitalism are possible.
In every US city or college campus, it is possible to attend workshops designed to teach job seekers how to fashion the genre repertoire required to apply for a job. Over the past 15 years, these ...workshops are arenas for hailing the neoliberal subject, teaching different genres as forms that interpellate job applicants as authors of their own ever improving and quantifiable chronological achievements. These workshops condense three paradoxes that neoliberal logics compel practitioners to grapple with. First, the workshops exist because of the presupposition that job seeking has changed radically in the past five or ten years, that job seeking in itself is a skill that one must always learn anew. That is, the very act of entering into an alliance involves a set of skills that must be regularly enhanced. Second, that it is possible to create a standardised genre repertoire demonstrating employability that will be successful regardless of the specific requirements of different types of jobs and workplaces. Third, the self that is being interpellated is also an ever-failing one, creating a veritable army of experts who provide a plethora of advice on how to perfect one's standardised genre repertoire so as to be employable.
We report a first-in-human trial evaluating safety and immunogenicity of a recombinant BCG, AERAS-422, over-expressing TB antigens Ag85A, Ag85B, and Rv3407 and expressing mutant perfringolysin.
This ...was a randomized, double-blind, dose-escalation trial in HIV-negative, healthy adult, BCG-naïve volunteers, negative for prior exposure to Mtb, at one US clinical site. Volunteers were randomized 2:1 at each dose level to receive a single intradermal dose of AERAS-422 (>105–<106CFU=low dose, ≥106–<107CFU=high dose) or non-recombinant Tice BCG (1–8×105CFU). Randomization used an independently prepared randomly generated sequence of treatment assignments. The primary and secondary outcomes were safety and immunogenicity, respectively, assessed in all participants through 182days post-vaccination. ClinicalTrials.gov registration number: NCT01340820.
Between Nov 2010 and Aug 2011, 24 volunteers were enrolled (AERAS-422 high dose, n=8; AERAS-422 low dose, n=8; Tice BCG, n=8); all were included in the safety and immunogenicity analyses. All 24 subjects had at least one adverse event, primarily expected local reactions. High dose AERAS-422 vaccination induced Ag85A- and Ag85B-specific lymphoproliferative responses and marked anti-mycobacterial activity in a whole blood bactericidal activity culture assay (WBA), but was associated with varicella zoster virus (VZV) reactivation in two vaccinees. These volunteers displayed high BCG-specific IFN-γ responses pre- and post-vaccination possibly predisposing them to autocrine/paracrine negative regulation of immune control of latent VZV. A systems biology transcriptomal approach identified positive correlations between post-vaccination T cell expression modules and WBA, and negative correlations between post-vaccination monocyte expression modules and WBA. The expression of one key macrophage marker (F4/80) was constitutively elevated in the two volunteers with zoster.
The unexpected development of VZV in two of eight healthy adult vaccine recipients resulted in discontinuation of AERAS-422 vaccine development. Immunological and transcriptomal data identified correlations with the development of TB immunity and VZV that require further investigation.
Aeras, FDA, Bill and Melinda Gates Foundation.
•Novel rBCG first-in-human trial overexpressing 3Mtb Ags induces a more potent human immune response than standard BCG.•Transcriptomal studies demonstrated correlations between mycobacterial growth inhibition growth and potent T cell responses.•rBCG was associated with varicella-zoster reactivation and associated with high interferon gamma and EMR1 expression.A first-in-human trial evaluating safety and immune responses of a recombinant BCG vaccine was reported. The new vaccine expresses additional TB antigens and escapes from seclusion to induce a better immune response in CD8 T cells. The immune response produced in humans could inhibit the growth of the TB pathogen. Unfortunately the vaccine was associated with shingles and studies were done to explore the reasons why that occurred.
Among individuals with COPD and/or lung cancer, to describe end-of-life health service utilization, costs, and place of death; to identify predictors of home palliative care use, and to assess ...benefits associated with palliative care use.
We conducted a retrospective population-based study using provincial linked health administrative data (Ontario, Canada) between 2010 and 2015. We examined health care use in the last 90 days of life in adults 35 years and older with physician-diagnosed COPD and/or lung cancer identified using a validated algorithm and the Ontario Cancer Registry, respectively. Four mutually exclusive groups were considered: (i) COPD only, (ii) lung cancer only, (iii) COPD and lung cancer, and (iv) neither COPD nor lung cancer. Multivariable generalized linear models were employed.
Of 445,488 eligible deaths, 34% had COPD only, 4% had lung cancer only, 5% had both and 57% had neither. Individuals with COPD only received less palliative care (20% vs 57%) than those with lung cancer only. After adjustment, people with lung cancer only were far more likely to receive palliative care (OR=4.22, 4.08-4.37) compared to those with neither diagnosis, while individuals with COPD only were less likely to receive palliative care (OR=0.82, 0.81-0.84). Home palliative care use was associated with reduced death and fewer days in acute care, and less cost, regardless of the diagnosis.
Although individuals with lung cancer were much more likely to receive palliative care than those with COPD, both populations were underserviced. Results suggest greater involvement of palliative care may improve the dying experience of these populations and reduce costs.
There is a need for valid self-report measures of core health-related quality of life (HRQoL) domains.
To derive brief, reliable and valid health profile measures from the Patient Reported Outcomes ...Measurement Information System® (PROMIS®) item banks.
Literature review, investigator consensus process, item response theory (IRT) analysis, and expert review of scaling results from multiple PROMIS data sets. We developed 3 profile measures ranging in length from 29 to 57 questions. These profiles assess important HRQoL domains with highly informative subsets of items from respective item banks and yield reliable information across mild-to-severe levels of HRQoL experiences. Each instrument assesses the domains of pain interference, fatigue, depression, anxiety, sleep disturbance, physical function, and social function using 4-, 6-, and 8-item short forms for each domain, and an average pain intensity domain score, using a 0-10 numeric rating scale.
With few exceptions, all domain short forms within the profile measures were highly reliable across at least 3 standard deviation (30 T-score) units and were strongly correlated with the full bank scores. Construct validity with ratings of general health and quality of life was demonstrated. Information to inform statistical power for clinical and general population samples is also provided.
Although these profile measures have been used widely, with summary scoring routines published, description of their development, reliability, and initial validity has not been published until this article. Further evaluation of these measures and clinical applications are encouraged.
Intestinal peristalsis is a dynamic physiologic process influenced by dietary and microbial changes. It is tightly regulated by complex cellular interactions; however, our understanding of these ...controls is incomplete. A distinct population of macrophages is distributed in the intestinal muscularis externa. We demonstrate that, in the steady state, muscularis macrophages regulate peristaltic activity of the colon. They change the pattern of smooth muscle contractions by secreting bone morphogenetic protein 2 (BMP2), which activates BMP receptor (BMPR) expressed by enteric neurons. Enteric neurons, in turn, secrete colony stimulatory factor 1 (CSF1), a growth factor required for macrophage development. Finally, stimuli from microbial commensals regulate BMP2 expression by macrophages and CSF1 expression by enteric neurons. Our findings identify a plastic, microbiota-driven crosstalk between muscularis macrophages and enteric neurons that controls gastrointestinal motility.
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•Muscularis macrophages produce BMP2 that activates BMPR on enteric neurons•Enteric neurons produce CSF1 that promotes homeostasis of muscularis macrophages•Macrophage-neuronal crosstalk regulates constitutive gastrointestinal motility•Macrophage-neuronal crosstalk is driven by gut microbiota
A unique population of macrophages residing in the smooth muscle of the gut regulates gastrointestinal motility by communicating with enteric neurons. This macrophage-neuronal dialog is plastic and is affected by intestinal microbiota, a discovery that offers mechanistic insights into gastrointestinal motility disorders.
To update the recommendations for the use of tumor marker tests in the prevention, screening, treatment, and surveillance of gastrointestinal cancers.
For the 2006 update, an update committee ...composed of members from the full Panel was formed to complete the review and analysis of data published since 1999. Computerized literature searches of Medline and the Cochrane Collaboration Library were performed. The Update Committee's literature review focused attention on available systematic reviews and meta-analyses of published tumor marker studies.
For colorectal cancer, it is recommended that carcinoembryonic antigen (CEA) be ordered preoperatively, if it would assist in staging and surgical planning. Postoperative CEA levels should be performed every 3 months for stage II and III disease for at least 3 years if the patient is a potential candidate for surgery or chemotherapy of metastatic disease. CEA is the marker of choice for monitoring the response of metastatic disease to systemic therapy. Data are insufficient to recommend the routine use of p53, ras, thymidine synthase, dihydropyrimidine dehydrogenase, thymidine phosphorylase, microsatellite instability, 18q loss of heterozygosity, or deleted in colon cancer (DCC) protein in the management of patients with colorectal cancer. For pancreatic cancer, CA 19-9 can be measured every 1 to 3 months for patients with locally advanced or metastatic disease receiving active therapy. Elevations in serial CA 19-9 determinations suggest progressive disease but confirmation with other studies should be sought. New markers and new evidence to support the use of the currently reviewed markers will be evaluated in future updates of these guidelines.
Enterochromaffin cell-derived serotonin (5-HT) promotes intestinal inflammation. We tested hypotheses that peripheral tryptophan hydroxylase (TPH) inhibitors, administered orally, block 5-HT ...biosynthesis and deplete 5-HT from enterochromaffin cells sufficiently to ameliorate intestinal inflammation; moreover, peripheral TPH inhibitors fail to enter the murine enteric nervous system (ENS) or central nervous systems and thus do not affect constitutive gastrointestinal motility.
Two peripheral TPH inhibitors, LP-920540 and telotristat etiprate (LX1032; LX1606) were given orally to mice. Effects were measured on 5-HT levels in the gut, blood and brain, 5-HT immunoreactivity in the ENS, gastrointestinal motility and severity of trinitrobenzene sulfonic acid (TNBS)-induced colitis. Quantitation of clinical scores, histological damage and intestinal expression of inflammation-associated cytokines and chemokines with focused microarrays and real-time reverse transcriptase PCR were employed to evaluate the severity of intestinal inflammation.
LP-920540 and LX1032 reduced 5-HT significantly in the gut and blood but not in the brain. Neither LP-920540 nor LX1032 decreased 5-HT immunoreactive neurons or fibres in the myenteric plexus and neither altered total gastrointestinal transit time, colonic motility or gastric emptying in mice. In contrast, oral LP-920540 and LX1032 reduced the severity of TNBS-induced colitis; the expression of 24% of 84 genes encoding inflammation-related cytokines and chemokines was lowered at least fourfold and the reduced expression of 17% was statistically significant.
Observations suggest that that peripheral TPH inhibitors uncouple the positive linkage of enterochromaffin cell-derived 5-HT to intestinal inflammation. Because peripheral TPH inhibitors evidently do not enter the murine ENS, they lack deleterious effects on constitutive intestinal motility in mice.
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