bluuebunny/crossref_metadata_2025 huggingface dataset:
Reacquisition of E-cadherin expression in metastatic deposits of signet-ring cell carcinoma of the upper gastrointestinal system: a potential anchor for metastatic deposition
Authors: Ma Yihong R , Siegal Gene P , Wei Shi
Published: November 2016

Aims

To examine the expression of E-cadherin in paired primary and metastatic signet-ring cell carcinomas (SRCC) of various organ systems in order to explore the potential role of the molecule in metastatic dissemination of this unique tumour type.

Methods

Thirty-seven consecutive cases of SRCC from various organs with paired primary and metastatic tumorous tissue available were retrieved. The intensity of membranous E-cadherin expression was semiquantitatively scored on a scale of 0–3+.

Results

Reduced E-cadherin expression was a distinct feature of primary SRCC and was observed in 78% of primary tumours. Interestingly, the E-cadherin reduction was less frequently seen in metastatic SRCC when compared with their primary counterparts, and was only found in 57% of tumours in lymph node metastases or at distant sites of relapse. Furthermore, the mean score of E-cadherin expression of primary SRCC was significantly lower than that of their metastatic counterparts (2.3 vs 1.8; p=0.008). When divided by organ systems, the reacquisition of E-cadherin expression in the metastatic deposits was most remarkable in the SRCC of upper gastrointestinal tract origin (2.3 vs 1.4; p=0.003), whereas no significant difference was observed in other organ systems.

Conclusions

While the reduction of E-cadherin in primary SRCC supports its pivotal role in epithelial-mesenchymal transition, a process crucial in tumour progression and metastatic dissemination, the re-expression of this molecule in metastatic SRCC cells implies a reversal to their epithelial phenotype (thus mesenchymal-epithelial transition) which, in turn, theoretically helps tumour cells to anchor and form cohesive metastatic deposits.
What are the critical steps in processing blood cultures? A prospective audit evaluating current practice of reporting blood cultures in a centralised laboratory serving secondary care hospitals
Authors: Meda Manjula , Clayton James , Varghese Reela , Rangaiah Jayakeerthi , Grundy Clive , Dashti Farnaz , Garner David , Groves Katherine , Fitzmaurice Karen , Hutley E
Published: November 2016

Aims

To assess current procedures of processing positive blood cultures against national standards with an aim to evaluate its clinical impact and to determine the utility of currently available rapid identification and susceptibility tests in processing of blood cultures.

Methods

Blood cultures from three secondary care hospitals, processed at a centralised laboratory, were prospectively audited. Data regarding processing times, communication with prescribers, changes to patient management and mortality within 30 days of a significant blood culture were collected in a preplanned pro forma for a 4-week period.

Results

Of 2206 blood cultures, 211 positive blood cultures flagged positive. Sixty-nine (3.1%) of all cultures were considered to be contaminated. Fifty per cent of blood cultures that flagged positive had a Gram stain reported within 2 hours. Two (0.99%) patients with a significant bacteraemia had escalation of antimicrobial treatment at the point of reporting the Gram stain that was subsequently deemed necessary once sensitivity results were known. Most common intervention was de-escalation of therapy for Gram-positive organisms at the point of availability of pathogen identification (25.6% in Gram positive vs 10% in Gram negative; p=0.012). For Gram-negative organisms, the most common intervention was de-escalation of therapy at the point of availability of sensitivity results (43% in Gram negatives vs 17.9% in Gram positive; p=0.0097). Overall mortality within 30 days of a positive blood culture was 10.9% (23/211). Antibiotic resistance may have contributed to mortality in four of these patients (three Gram negative and one Gram positive).

Conclusion

Gram stain result had the least impact on antibiotic treatment interventions (escalation or de-escalation). Tests that improve identification time for Gram-positive pathogens and sensitivity time for Gram-negative pathogens had the greatest impact in making significant changes to antimicrobial treatment.
Evaluation of a rapid antigen test for detection ofStreptococcus pneumoniaein cerebrospinal fluid
Authors: Boulos Angel , Fairley Derek , McKenna James , Coyle Peter
Published: November 2016

Detection ofStreptococcus pneumoniaeantigen in cerebrospinal fluid (CSF) using lateral flow immunochromatography tests (ICTs) is an effective, rapid and low-cost method to diagnose pneumococcal meningitis. This study evaluated the diagnostic accuracy of the Uni-Gold ICT to detect pneumococcal antigen in CSF specimens, compared with gold standard bacteriology and quantitative real-time PCR (qPCR) testing. CSF specimens (n=69) from patients with suspected bacterial meningitis were included in the study. 13/69 (19%) were positive and 56/69 (81%) were negative for pneumococcus by the gold standard tests. The ICT had sensitivity of 85% (55%–98%), specificity of 96% (88%–100%), positive likelihood ratio of 23.7 (6–94) and negative likelihood ratio of 0.16 (0.04–0.57). Overall, a strong correlation between the ICT and qPCR results was seen (κ=0.81). In contrast, CSF microscopy and culture were exceptionally insensitive. The ICT method is sufficiently robust and accurate for use in algorithms to diagnose bacterial meningitis.
What is policy and where do we look for it when we want to research it?
Authors: Crammond Brad , Carey Gemma
Published: November 2016

Public health researchers are increasingly concerned with achieving ‘upstream’ change to achieve reductions in the global burden of disease and health inequalities. Consequently, understanding policy and how to change it has become a central goal of public health. Yet conceptualisation of what constitutes policy and where it can be found is very limited within this field. Our glossary demonstrates that policy is many headed. It is located in a vast array of documents, discussions dialogues and actions which can be captured variously by formal and informal forms of documentation and observation. Effectively understanding policy and its relevance for public health requires an awareness of the full range of places and contexts in which policy work happens and policy documents are produced.
Grit and burnout in UK doctors: a cross-sectional study across specialties and stages of training
Authors: Halliday Laura , Walker Abigail , Vig Stella , Hines John , Brecknell John
Published: November 2016

Purpose of the study

Grit is characterised by the ability to persevere during difficulties and maintain a sustained effort over an extended period of time. Throughout their careers, doctors will experience many periods of stress and difficulty. This may result in burnout, defined by the presence of exhaustion and disengagement from work. This study aims to characterise the relationship between grit and burnout in doctors and to establish whether there are differences between specialties and levels of training.

Study design

A multicentre cross-sectional survey by questionnaire was used. Participants were recruited from training days and an online medical forum. The survey consisted of the Short Grit Scale and the Oldenburg Burnout Inventory, which examine levels of grit and burnout, respectively.

Results

548 responses were collected. We found a weak negative correlation between grit and burnout in UK doctors (r=−0.243, p<0.001). Hospital consultants had significantly higher grit scores than trainees. The highest level of burnout was found among general practitioners (GPs). When GPs were analysed separately, the correlation between grit and resilience was not seen.

Conclusions

An understanding of an individual’s level of grit may be used to identify doctors at a greater risk of burnout. As a high level of grit is associated with less burnout, interventions to improve grit through resilience training should be examined. Further research is needed to understand how grit levels change during a doctor’s career and why GPs experience higher levels of burnout.
L5-LDL from ST-elevation myocardial infarction patients induces IL-1β production via LOX-1 and NLRP3 inflammasome activation in macrophages
Authors: Yang Tzu-Ching , Chang Po-Yuan , Lu Shao-Chun
Published: November 2016

L5-LDL, the most electronegative LDL associated with major cardiovascular risks, significantly rises in patients with ST-segment elevation myocardial infarction (STEMI). The inflammatory nature of atherosclerotic vascular diseases has prompted us to investigate whether L5-LDL induces the production of inflammatory cytokines, especially vascular ischemia-related interleukin (IL)-1β, in the pathogenesis of STEMI. Clinical data showed that plasma levels of L5-LDL and IL-1β were higher in the STEMI patients than in the controls ( P < 0.05). In THP-1-derived human macrophages, L5-LDL significantly increased the levels of both IL-1β and cleaved caspase-1, indicating the activation of NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasomes by L5-LDL. Knockdown of NLRP3 and its adaptor protein apoptosis-associated speck-like protein containing a CARD (ASC) resulted in decreased L5-LDL-induced IL-1β. Furthermore, knock down of the lectin-type oxidized LDL receptor (LOX-1) in THP-1 cells attenuated L5-LDL-induced activation of NF-κB and caspase-1, leading to subsequent inhibition of IL-1β in macrophages. Furthermore, blockade LOX-1 with neutralizing antibody also inhibited L5-LDL-induced IL-1β in human peripheral blood mononuclear cell-derived macrophages. In conclusion, L5-LDL induces IL-1β production in macrophages by activation of NF-κB and caspase-1 through the LOX-1-dependent pathway. This study represents the evidence linking L5-LDL and the inflammatory cytokine IL-1β in STEMI, and identifies L5-LDL as a novel therapeutic target in acute myocardial infarction.

NEW & NOTEWORTHY This study represents the evidence linking L5-LDL and the inflammatory cytokine IL-1β in ST-segment elevation myocardial infarction (STEMI). We elucidate the molecular mechanism underlying L5-LDL-induced production of IL-1β in macrophages. The results showed that L5-LDL induced activation of caspase-1 and NF-κB through the lectin-type oxidized LDL receptor (LOX-1)-dependent pathway, leading to the production of IL-1β.
Transforming growth factor-β plays divergent roles in modulating vascular remodeling, inflammation, and pulmonary fibrosis in a murine model of scleroderma
Authors: Tsujino Kazuyuki , Reed Nilgun Isik , Atakilit Amha , Ren Xin , Sheppard Dean
Published: November 2016

The efficacy and feasibility of targeting transforming growth factor-β (TGFβ) in pulmonary fibrosis and lung vascular remodeling in systemic sclerosis (SSc) have not been well elucidated. In this study we analyzed how blocking TGFβ signaling affects pulmonary abnormalities in Fos-related antigen 2 (Fra-2) transgenic (Tg) mice, a murine model that manifests three important lung pathological features of SSc: fibrosis, inflammation, and vascular remodeling. To interrupt TGFβ signaling in the Fra-2 Tg mice, we used a pan-TGFβ-blocking antibody, 1D11, and Tg mice in which TGFβ receptor type 2 ( Tgfbr2) is deleted from smooth muscle cells and myofibroblasts (α-SMA-CreER; Tgfbr2flox/flox). Global inhibition of TGFβ by 1D11 did not ameliorate lung fibrosis histologically or biochemically, whereas it resulted in a significant increase in the number of immune cells infiltrating the lungs. In contrast, 1D11 treatment ameliorated the severity of pulmonary vascular remodeling in Fra-2 Tg mice. Similarly, genetic deletion of Tgfbr2 from smooth muscle cells resulted in improvement of pulmonary vascular remodeling in the Fra-2 Tg mice, as well as a decrease in the number of Ki67-positive vascular smooth muscle cells, suggesting that TGFβ signaling contributes to development of pulmonary vascular remodeling by promoting the proliferation of vascular smooth muscle cells. Deletion of Tgfbr2 from α-smooth muscle actin-expressing cells had no effect on fibrosis or inflammation in this model. These results suggest that efforts to target TGFβ in SSc will likely require more precision than simply global inhibition of TGFβ function.
Double-hit mouse model of cigarette smoke priming for acute lung injury
Authors: Sakhatskyy Pavlo , Wang Zhengke , Borgas Diana , Lomas-Neira Joanne , Chen Yaping , Ayala Alfred , Rounds Sharon , Lu Qing
Published: November 2016

Epidemiological studies indicate that cigarette smoking (CS) increases the risk and severity of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). The mechanism is not understood, at least in part because of lack of animal models that reproduce the key features of the CS priming process. In this study, using two strains of mice, we characterized a double-hit mouse model of ALI induced by CS priming of injury caused by lipopolysaccharide (LPS). C57BL/6 and AKR mice were preexposed to CS briefly (3 h) or subacutely (3 wk) before intratracheal instillation of LPS and ALI was assessed 18 h after LPS administration by measuring lung static compliance, lung edema, vascular permeability, inflammation, and alveolar apoptosis. We found that as little as 3 h of exposure to CS enhanced LPS-induced ALI in both strains of mice. Similar exacerbating effects were observed after 3 wk of preexposure to CS. However, there was a strain difference in susceptibility to CS priming for ALI, with a greater effect in AKR mice. The key features we observed suggest that 3 wk of CS preexposure of AKR mice is a reproducible, clinically relevant animal model that is useful for studying mechanisms and treatment of CS priming for a second-hit-induced ALI. Our data also support the concept that increased susceptibility to ALI/ARDS is an important adverse health consequence of CS exposure that needs to be taken into consideration when treating critically ill individuals.
PAX3-FOXO1A Expression in Rhabdomyosarcoma Is Driven by the Targetable Nuclear Receptor NR4A1
Authors: Lacey Alexandra , Rodrigues-Hoffman Aline , Safe Stephen
Published: November 2016

Alveolar rhabdomyosarcoma (ARMS) is a devastating pediatric disease driven by expression of the oncogenic fusion gene PAX3-FOXO1A. In this study, we report overexpression of the nuclear receptor NR4A1 in rhabdomyosarcomas that is sufficient to drive high expression of PAX3-FOXO1A there. RNAi-mediated silencing of NR4A1 decreased expression of PAX3-FOXO1A and its downstream effector genes. Similarly, cell treatment with the NR4A1 small-molecule antagonists 1,1-bis(3-indolyl)-1-(p-hydroxy or p-carbomethoxyphenyl)methane (C-DIM) decreased PAX3-FOXO1A. Mechanistic investigations revealed a requirement for the NR4A1/Sp4 complex to bind GC-rich promoter regions to elevate transcription of the PAX3-FOXO1A gene. In parallel, NR4A1 also regulated expression of β1-integrin, which with PAX3-FOXO1A, contributed to tumor cell migration that was blocked by C-DIM/NR4A1 antagonists. Taken together, our results provide a preclinical rationale for the use of NR4A1 small-molecule antagonists to treat ARMS and other rhabdomyosarcomas driven by PAX3-FOXO1A. Cancer Res; 77(3); 732–41. ©2016 AACR.
Systems Approaches to Cancer Biology
Authors: Archer Tenley C. , Fertig Elana J. , Gosline Sara J.C. , Hafner Marc , Hughes Shannon K. , Joughin Brian A. , Meyer Aaron S. , Piccolo Stephen R. , Shajahan-Haq Ayesha N.
Published: November 2016

Cancer systems biology aims to understand cancer as an integrated system of genes, proteins, networks, and interactions rather than an entity of isolated molecular and cellular components. The inaugural Systems Approaches to Cancer Biology Conference, cosponsored by the Association of Early Career Cancer Systems Biologists and the National Cancer Institute of the NIH, focused on the interdisciplinary field of cancer systems biology and the challenging cancer questions that are best addressed through the combination of experimental and computational analyses. Attendees found that elucidating the many molecular features of cancer inevitably reveals new forms of complexity and concluded that ensuring the reproducibility and impact of cancer systems biology studies will require widespread method and data sharing and, ultimately, the translation of important findings to the clinic. Cancer Res; 76(23); 6774–7. ©2016 AACR.
Systemic Levels of Estrogens and PGE2 Synthesis in Relation to Postmenopausal Breast Cancer Risk
Authors: Kim Sangmi , Campbell Jeff , Yoo Wonsuk , Taylor Jack A. , Sandler Dale P.
Published: November 2016

Background:

Prostaglandin E2 (PGE2) induces aromatase expression in adipose tissue, leading to increased estrogen production that may promote the development and progression of breast cancer. However, few studies have simultaneously investigated systemic levels of PGE2 and estrogen in relation to postmenopausal breast cancer risk.

Methods:

Here, we determined urinary estrogen metabolites (EM) using mass spectrometry in a case–cohort study (295 incident breast cancer cases and 294 subcohort members), and using linear regression estimated the effect of urinary levels of a major PGE2 metabolite (PGE-M) on EMs. HRs for the risk of developing breast cancer in relation to PGE-M and EMs were compared between Cox regression models with and without mutual adjustment.

Results:

PGE-M was a significant predictor of estrone (E1), but not estradiol (E2) levels in multivariable analysis. Elevated E2 levels were associated with an increased risk of developing breast cancer [HRQ5vs.Q1, 1.54; 95% confidence interval (CI), 1.01–2.35], and this association remained unchanged after adjustment for PGE-M (HRQ5vs.Q1, 1.52; 95% CI, 0.99–2.33). Similarly, elevated levels of PGE-M were associated with increased risk of developing breast cancer (HRQ4vs.Q1, 2.01; 95% CI, 1.01–4.29), and this association was only nominally changed after consideration of E1 or E2 levels.

Conclusions:

Urinary levels of PGE-M and estrogens were independently associated with future risk of developing breast cancer among these postmenopausal women.

Impact:

Increased breast cancer risk associated with PGE-M might not be fully explained by the estrogens–breast cancer association alone but also by additional effects related to inflammation. Cancer Epidemiol Biomarkers Prev; 26(3); 383–8. ©2016 AACR.
How Subclonal Modeling Is Changing the Metastatic Paradigm
Authors: Macintyre Geoff , Van Loo Peter , Corcoran Niall M. , Wedge David C. , Markowetz Florian , Hovens Christopher M.
Published: November 2016

A concerted effort to sequence matched primary and metastatic tumors is vastly improving our ability to understand metastasis in humans. Compelling evidence has emerged that supports the existence of diverse and surprising metastatic patterns. Enhancing these efforts is a new class of algorithms that facilitate high-resolution subclonal modeling of metastatic spread. Here we summarize how subclonal models of metastasis are influencing the metastatic paradigm. Clin Cancer Res; 23(3); 630–5. ©2016 AACR.
The Landscape of Viral Expression Reveals Clinically Relevant Viruses with Potential Capability of Promoting Malignancy in Lower-Grade Glioma
Authors: Wang Zheng , Hao Yajing , Zhang Chuanbao , Wang Zhiliang , Liu Xing , Li Guanzhang , Sun Lihua , Liang Jingshan , Luo Jianjun , Zhou Dabiao , Chen Runsheng , Jiang Tao
Published: November 2016

Purpose: RNA sequencing (RNA-seq) has recently proved to be effective for revealing novel virus–tumor associations. To get a thorough investigation of virus–glioma associations, we screened viruses in gliomas with RNA-seq data from the Chinese Glioma Genome Atlas project.

Experimental Design: In total, 325 samples were enrolled into this study. Reads that failed to map to the human genome were aligned to viral genomes and screened for potential virus-derived transcripts. For quantification, VPKM was calculated according to mapped reads weighted by genome sizes and sequencing depth.

Results: We observed that viruses tended to concertedly express in a certain subgroup of patients. Survival analysis revealed that individuals who were infected with Simian virus 40 (SV40) or woolly monkey sarcoma virus (WMSV) had a significantly shorter overall survival than those uninfected. A multivariate Cox proportional hazards model, taking clinical and molecular factors into account, was applied to assess the prognostic value of SV40 and WMSV. Both SV40 and WMSV were independent prognostic factors for predicting patient's survival in lower-grade gliomas. Subsequent gene analysis demonstrated that SV40 was correlated with regulation of transcription, whereas WMSV was correlated with cell-cycle phase, which indicated frequent proliferation of tumor cells.

Conclusions: RNA-seq was sufficient to identify virus infection in glioma samples. SV40 and WMSV were identified to be prognostic markers for patients with lower-grade gliomas and showed potential values for targeting therapy. Clin Cancer Res; 23(9); 2177–85. ©2016 AACR.
AMPK–ULK1-Mediated Autophagy Confers Resistance to BET Inhibitor JQ1 in Acute Myeloid Leukemia Stem Cells
Authors: Jang Ji Eun , Eom Ju-In , Jeung Hoi-Kyung , Cheong June-Won , Lee Jung Yeon , Kim Jin Seok , Min Yoo Hong
Published: November 2016

Purpose: Bromodomain and extraterminal domain (BET) inhibitors are promising epigenetic agents for the treatment of various subsets of acute myeloid leukemia (AML). However, the resistance of leukemia stem cells (LSC) to BET inhibitors remains a major challenge. In this study, we evaluated the mechanisms underlying LSC resistance to the BET inhibitor JQ1.

Experimental Design: We evaluated the levels of apoptosis and autophagy induced by JQ1 in LSC-like leukemia cell lines and primary CD34+CD38− leukemic blasts obtained from AML cases with normal karyotype without recurrent mutations.

Results: JQ1 effectively induced apoptosis in a concentration-dependent manner in JQ1-sensitive AML cells. However, in JQ1-resistant AML LSCs, JQ1 induced little apoptosis and led to upregulation of beclin-1, increased LC3-II lipidation, formation of autophagosomes, and downregulation of p62/SQSTM1. Inhibition of autophagy by pharmacologic inhibitors or knockdown of beclin-1 using specific siRNA enhanced JQ1-induced apoptosis in resistant cells, indicating that prosurvival autophagy occurred in these cells. Independent of mTOR signaling, activation of the AMPK (pThr172)/ULK1 (pSer555) pathway was found to be associated with JQ1-induced autophagy in resistant cells. AMPK inhibition using the pharmacologic inhibitor compound C or by knockdown of AMPKα suppressed autophagy and promoted JQ1-induced apoptosis in AML LSCs.

Conclusions: These findings revealed that prosurvival autophagy was one of the mechanisms involved in the resistance AML LSCs to JQ1. Targeting the AMPK/ULK1 pathway or inhibition of autophagy could be an effective therapeutic strategy for combating resistance to BET inhibitors in AML and other types of cancer. Clin Cancer Res; 23(11); 2781–94. ©2016 AACR.
Tumor Thickness and Mitotic Rate Robustly Predict Melanoma-Specific Survival in Patients with Primary Vulvar Melanoma: A Retrospective Review of 100 Cases
Authors: Nagarajan Priyadharsini , Curry Jonathan L. , Ning Jing , Piao Jin , Torres-Cabala Carlos A. , Aung Phyu P. , Ivan Doina , Ross Merrick I. , Levenback Charles F. , Frumovitz Michael , Gershenwald Jeffrey E. , Davies Michael A. , Malpica Anais , Prieto Victor G. , Tetzlaff Michael T.
Published: November 2016

Purpose: Primary vulvar melanoma (PVM) is the second most common vulvar malignancy. Despite their distinct anatomic site and unique molecular–genetic alterations, PVMs are staged according to the American Joint Committee on Cancer (AJCC) guidelines for primary cutaneous melanomas (PCM). However, whether parameters derived for PCM also apply to PVM remain a critical yet largely unexplored clinical question. The objective of this study was to determine the parameters predictive of survival in PVM.

Experimental Design: We retrospectively reviewed 100 patients with PVM and determined associations between clinical and histopathologic parameters and disease-specific survival (DSS) and overall survival (OS).

Results: Univariate Cox regression analysis demonstrated older age (>56 years), greater tumor thickness, higher dermal mitotic rate, ulceration, lymphovascular invasion, perineural invasion, microscopic satellitosis, and absence of precursor nevus associated with decreased OS. Furthermore, age, midline, and/or multifocal involvement, greater tumor thickness, higher dermal mitotic rate, ulceration, lack of regression, lymphovascular invasion, perineural invasion, and microscopic satellitosis associated with decreased DSS. Multivariate analysis demonstrated tumor thickness, dermal mitotic rate, lymphovascular invasion, microscopic satellitosis, and absence of precursor nevus independently predicted shorter OS. Only tumor thickness and increased dermal mitotic rate (≥2/mm2) independently predicted reduced DSS. In comparison with the AJCC T-category, a novel, bivariate T-category based only on tumor thickness and dermal mitotic rate robustly predicted OS and DSS in our patient cohort.

Conclusions: In the largest single institutional study of PVM, we demonstrate a combination of tumor thickness and mitotic rate comprise a simple but robust T-category to direct staging and prognosis. Clin Cancer Res; 23(8); 2093–104. ©2016 AACR.
Deubiquitinase OTUD6B Isoforms Are Important Regulators of Growth and Proliferation
Authors: Sobol Anna , Askonas Caroline , Alani Sara , Weber Megan J. , Ananthanarayanan Vijayalakshmi , Osipo Clodia , Bocchetta Maurizio
Published: November 2016

Deubiquitinases (DUB) are increasingly linked to the regulation of fundamental processes in normal and cancer cells, including DNA replication and repair, programmed cell death, and oncogenes and tumor suppressor signaling. Here, evidence is presented that the deubiquitinase OTUD6B regulates protein synthesis in non–small cell lung cancer (NSCLC) cells, operating downstream from mTORC1. OTUD6B associates with the protein synthesis initiation complex and modifies components of the 48S preinitiation complex. The two main OTUD6B splicing isoforms seem to regulate protein synthesis in opposing fashions: the long OTUD6B-1 isoform is inhibitory, while the short OTUD6B-2 isoform stimulates protein synthesis. These properties affect NSCLC cell proliferation, because OTUD6B-1 represses DNA synthesis while OTUD6B-2 promotes it. Mutational analysis and downstream mediators suggest that the two OTUD6B isoforms modify different cellular targets. OTUD6B-2 influences the expression of cyclin D1 by promoting its translation while regulating (directly or indirectly) c-Myc protein stability. This phenomenon appears to have clinical relevance as NSCLC cells and human tumor specimens have a reduced OTUD6B-1/OTUD6B-2 mRNA ratio compared with normal samples. The global OTUD6B expression level does not change significantly between nonneoplastic and malignant tissues, suggesting that modifications of splicing factors during the process of transformation are responsible for this isoform switch.

Implications: Because protein synthesis inhibition is a viable treatment strategy for NSCLC, these data indicate that OTUD6B isoform 2, being specifically linked to NSCLC growth, represents an attractive, novel therapeutic target and potential biomarker for early diagnosis of malignant NSCLC. Mol Cancer Res; 15(2); 117–27. ©2016 AACR.
Endoscopic Management of Idiopathic Subglottic Stenosis
Authors: Shabani Sepehr , Hoffman Matthew R. , Brand William T. , Dailey Seth H.
Published: November 2016

Objective:

To describe a homogeneous idiopathic subglottic stenosis (ISS) population undergoing endoscopic balloon dilation and evaluate factors affecting inter-dilation interval (IDI).

Methods:

Retrospective review of 37 patients. Co-morbidity prevalence versus normal population was evaluated using chi-square tests. Correlations were evaluated using Pearson product moment tests. Independent samples t tests/rank sum tests assessed differences between groups of interest.

Results:

All patients were female aged 45.9 ± 15.4 years at diagnosis. Four required a tracheotomy during management. Most prevalent co-morbidity was gastroesophageal reflux disease (GERD) (64.9%; P = .036). Body mass indices (BMI) at first and most recent dilation were 29.8 and 30.8 ( P = .564). Degree of stenosis before first dilation was 53 ± 14%. Patients underwent 3.8 ± 1.8 dilations (range, 1-11). Average IDI was 635 ± 615 days (range, 49-3130 days), including 556 ± 397 days for patients receiving concomitant steroid injection and 283 ± 36 for those who did not ( P = .079). Inter-dilation interval was not correlated with BMI ( r = 0.0486; P = .802) or number of co-morbidities ( r = −0.225, P = .223).

Conclusions:

Most patients with ISS can be managed endoscopically, and IDI may be increased with steroid injection. Gastroesophageal reflux disease is a common co-morbidity. Body mass index did not change over time despite potential effects on exercise tolerance; BMI did not affect IDI. Methods to determine optimal timing for next intervention are warranted.
Simultaneous Imaging and Spectroscopy of Detonation Interaction in Reactive and Energetic Materials
Authors: Johnson Stephanie , Clemenson Michael , Glumac Nick
Published: November 2016

A dual framing camera system was coupled with custom-designed ultrafast imaging spectrometer optics to yield simultaneous imaging and imaging spectroscopy of extremely short detonation interaction events in reactive materials. For short exposures of 100 ns or less, spectral resolutions of 2.4 Å are achievable, allowing for time-resolved identification of key intermediate species evolving from prompt reaction. Under some circumstances, emission can be fit to a local emission temperature, assuming the optically thin limit. Applications to reactive metal systems involving aluminum, magnesium, titanium, boron, and silicon are demonstrated.
Comparison of Fiber Optic and Conduit Attenuated Total Reflection (ATR) Fourier Transform Infrared (FT-IR) Setup for In-Line Fermentation Monitoring
Authors: Koch Cosima , Posch Andreas E. , Herwig Christoph , Lendl Bernhard
Published: November 2016

The performance of a fiber optic and an optical conduit in-line attenuated total reflection mid-infrared (IR) probe during in situ monitoring of Penicillium chrysogenum fermentation were compared. The fiber optic probe was connected to a sealed, portable, Fourier transform infrared (FT-IR) process spectrometer via a plug-and-play interface. The optical conduit, on the other hand, was connected to a FT-IR process spectrometer via a knuckled probe with mirrors that had to be adjusted prior to each fermentation, which were purged with dry air. Penicillin V (PenV) and its precursor phenoxyacetic acid (POX) concentrations were determined by online high-performance liquid chromatography and the obtained concentrations were used as reference to build partial least squares regression models. Cross-validated root-mean-square errors of prediction were found to be 0.2 g L−1 (POX) and 0.19 g L−1 (PenV) for the fiber optic setup and 0.17 g L−1 (both POX and PenV) for the conduit setup. Higher noise-levels and spectrum-to-spectrum variations of the fiber optic setup lead to higher noise of estimated (i.e., unknown) POX and PenV concentrations than was found for the conduit setup. It seems that trade-off has to be made between ease of handling (fiber optic setup) and measurement accuracy (optical conduit setup) when choosing one of these systems for bioprocess monitoring.
Analysis of the Thermo-Reflectivity Coefficient Influence Using Photothermal Pump–Probe Techniques
Authors: Zanuto Vitor S. , Capeloto Otávio A. , Sandrini Marcelo , Malacarne Luis C. , Astrath Nelson G.C. , Bialkowski Stephen E.
Published: November 2016

Recent improvements in the modeling of photo-induced thermo–optical–mechanical effects have broadened the application of photothermal techniques to a large class of solids and fluids. During laser excitation, changes in optical reflectivity due to temperature variation may affect the photothermal signal. In this study, the influence of the reflectivity change due to heating is analyzed for two pump–probe photothermal techniques, thermal lens and thermal mirror. A linear equation for the temperature dependence of the reflectivity is derived, and the solution is tested using optical properties of semi-transparent and opaque materials. For semi-transparent materials, the influence of the reflectivity change in photothermal signals is less than 0.01%, while for opaque materials it is lower than 3%.
Simultaneous Burst Imaging of Dual Species Using Planar Laser-Induced Fluorescence at 50 kHz in Turbulent Premixed Flames
Authors: Li Zheming , Rosell Joakim , Aldén Marcus , Richter Mattias
Published: November 2016

Spatially and temporally resolved measurements are of great importance in turbulent premixed flame studies, especially when investigating rapid processes such as when flame local extinction, re-ignition, or flashback occur in a reacting flow. Here, an experimental approach for simultaneously probing two different species at high frame rates (50 kHz) is presented by employing a multi-YAG laser system. The laser radiation at 355 nm generated by a multi-YAG laser system was split into two beam paths: one beam for exciting formaldehyde and the other for pumping an optical parametric oscillator (OPO). To be able to capture the resulting fluorescence at such a high frame rate without significant loss in spatial resolution, two framing cameras, containing a total of 16 intensified charge-coupled devices (CCDs), were employed. In principle, the proposed setup provides the possibility of probing formaldehyde and simultaneously accessing the distribution of one other relevant species at this high frame rate. In this demonstration, the laser wavelength was tuned to 283 nm and, in conjunction with the 355 nm beam path, simultaneously high speed two-dimensional (2D) visualization of OH-radicals and formaldehyde was achieved. A modified flat flame, McKenna-type burner was used to provide a turbulent premixed jet-flame supported by a surrounding pilot flame. Local flame extinction and re-ignition processes were recorded for fuel/air jet speeds of 120 m/s.
Creating Community-Inclusive Organizations: Managerial Accountability Framework
Authors: Fujimoto Yuka , Azmat Fara , Subramaniam Nava
Published: November 2016

Based on a community psychology perspective, this qualitative study explores the community-inclusion effort of one of the largest pulp and paper companies in the world. Extending the literature on workforce diversity/inclusion, we present the community-inclusive organizational framework, which signifies the dynamics of community inclusiveness of organizations highlighting key managerial accountabilities (i.e., cultural, collective, relational, and structural accountabilities) based on the community psychology perspective. Theoretical and practical implications are presented for promoting community-inclusive organizations, along with avenues for further research.
The Sacred, the Occult and the Distinctiveness of Religion
Authors: Dawes Gregory W.
Published: November 2016

Is there a distinctively religious attitude? Durkheim suggested there was: it was that of regarding certain beliefs, persons, institutions, practices, or places as sacred. The idea of the sacred also featured prominently in the work of historians and phenomenologists of religion, where it referred to the transcendent (“other-worldly”) object of devotion. While the phenomenologists’ idea of the sacred has fallen out of favor, Durkheim’s idea is undergoing a revival, to which the present paper is a contribution. To regard something as sacred, it argues, is to see it as having a particular kind of normative significance, which arises from its connection with an “occult” or hidden realm. While phenomenologists regarded this attitude as irreducible, this assumption is unwarranted. While serving to explain human behavior, this distinctively religious attitude also requires an explanation, one that will acknowledge both its human origins and its political role.
La haine de la vie et l’œuvre mauvaise de Dieu. Analyse de Qohélet 2,17
Authors: Lavoie Jean-Jacques
Published: November 2016

Qo 2,17 est un texte choquant, aussi bien du point de vue anthropologique que du point de vue théologique, et c’est sans doute pourquoi il a été tantôt escamoté, tantôt édulcoré. Pourtant, une analyse textuelle, structurelle et littéraire montre que ce texte a une connotation éthique : Qohélet hait la vie, car elle n’est aucunement l’aboutissement de la sagesse (Qo 2,14b–16) ; l’œuvre de Dieu est « mauvaise sur Qohélet », car elle est injuste : en effet, le sage comme le fou va mourir et il n’y aura aucun souvenir d’eux (Qo 2,14b–16).
Exploring tensions in knowledge networks: Convergences and divergences from social capital, actor-network theory and sociologies of the south
Authors: Suarez Estrada Marcela
Published: November 2016

Knowledge networks have been discussed as mechanisms that facilitate access to resources and information. They are noted as organizations that promote the generation of new contacts and interactions between actors in order to produce knowledge that increases the speed and reliability of communication. They are also understood as platforms that encourage learning and knowledge coordination in order to advance technoscientific innovation processes. Despite these benefits, knowledge networks can engender areas of tension. The article examines the tensions in knowledge networks by analysing the theoretical convergences and divergences between social capital insights, actor-network theory and several contributions from the sociologies of the south. The following four categories are discussed: (1) hierarchy production; (2) blockages to the access to resources; (3) the spatialization of networks; and (4) the different ways of understanding power. The latter offer opportunities to make the tensions in knowledge networks visible. The article proposes initiating a discussion focused on the dynamic movement of asymmetries to analyse knowledge networks between the global North and the global South as entities that are in a process of constant negotiation.
Authentic leadership in context: An analysis of banking CEO narratives during the global financial crisis
Authors: Liu Helena , Cutcher Leanne , Grant David
Published: November 2016

The concept of authentic leadership rose to prominence through its idealization as an inherently moral and universally desirable trait. We problematize this romantic notion by exploring how the ‘authenticity’ of the CEOs of four major Australian banks was discursively constructed before and during the global financial crisis (GFC). Using multimodal discourse analysis of media texts, we show how what it meant to be an ‘authentic leader’ was co-constructed differently by the CEOs and the media. We also highlight the dynamic nature of context, where the GFC was variously framed by and for each of the CEOs. Our study challenges the acontextual notion of authentic leadership by showing how a discursively constructed context can reinforce or undermine leaders’ narratives of authenticity.
Who is dominant? Occupational Health and Safety management in Chinese shipping
Authors: Xue Conghua , Tang Lijun , Walters David
Published: November 2016

This article investigates the implementation of the International Safety Management Code in the Chinese chemical shipping industry. In particular, it examines the tension between management focus on speedy production and seafarers’ participation in safety-related decision-making and analyses how this tension is managed. It shows that while on paper companies have policies stating safety commitment in compliance with the International Safety Management Code, in practice shore management tends to prioritise efficient production. When Occupational Health and Safety and ship’s sailing schedules are in conflict, managers implicitly request shipmasters to prioritise the ‘core interest’ of the company. Although the International Safety Management Code endows shipmasters with overriding authority in relation to shipboard safety management, they tend to read between the lines and tacitly follow managers’ intentions. The study suggests that if the implementation of the International Safety Management Code makes a difference, it is the practice that managers become more subtle in giving orders to exert their dominance. The study further reveals that the management’s practice is not only irresponsive to seafarers’ safety concerns, but also makes rather limited contributions to promote Occupational Health and Safety management.
Building Identity in Collegiate Midlevel Choral Ensembles
Authors: Major Marci L.
Published: November 2016

This study was designed to explore the director’s perspective on the role organizational images play in social identity development in midlevel choral ensembles. Using a phenomenological methodology, I interviewed 10 current or former directors of midlevel choral ensembles from eight midwestern U.S. colleges and universities. Directors cited different choral configurations, high performance standards, unique group identity, strong personal connections, and good faculty relationships as the primary tools used to build identity. Directors also revealed their perceived challenges with regard to midlevel choirs: director continuity, discrepancy in student musical ability and dedication, negative perceptions, and the need for director flexibility. No director mentioned preparing students to sing in the top ensemble as a purpose or priority of the midlevel ensemble; however, many stated that a good midlevel choir achieved this result and also raised the quality of the entire choral program. Implications of these findings reveal the importance of recognizing and addressing a midlevel identity phenomenon and the impact identity building efforts can make to facilitate stronger midlevel ensembles.
The Relationship Between Coach and Player Training Load Perceptions in Professional Soccer
Authors: Redkva Paulo Eduardo , Gregorio da Silva Sergio , Paes Mauro Ricetti , Dos-Santos Julio Wilson
Published: November 2016

The training load imposed and perceived by coaches and soccer players, respectively, was compared for three weeks of the basic preparatory period of a professional soccer team through session ratings of perceived exertion (S-RPE). Participants were 24 professional Brazilian soccer players (all males, age: 24.1 ± 3.4 years) and their coaches. Athletes responded to the scale of perceived exertion (scores from 0 to10) after the training, while the coaches completed the scale prior to the training session, based on prior planning. The t-test for independent samples was used to compare S-RPE responses, and the Pearson correlation test was used to examine possible correlations between the parameters analyzed. There were no statistical differences between perceptions of prescribed (coaches) and experienced (players) S-RPE, and moderate correlations were found between these parameters ( r = .60; p = .003). No statistically significant group differences were found in the perceived exertion during any of three types of training: physical, technical, or tactical. The results suggest that the S-RPE prescribed during the preseason period (by coaches) was not different from that perceived by professional soccer players.
Police officer disability sensitivity training
Authors: Viljoen Erna , Bornman Juan , Wiles Louise , Tönsing Kerstin M
Published: November 2016

This paper presents a systematic research review regarding disability sensitivity training programmes provided to police officers. Thirteen databases between 1980 and 2015 were searched. After records were screened, 19 full-text studies were assessed. Three studies met the eligibility criteria. Quality appraisal was undertaken using the McMaster tool. Data were synthesised qualitatively using narrative summaries. Limited evidence for the effectiveness of training programmes in improving knowledge and skills of police officers towards people with disabilities exists. This review highlights the need for custom-designed training with a demonstrated evidence base. Further research should be conducted to develop, implement and evaluate such programmes.
‘Walking on egg shells’
Authors: Javaid Aliraza
Published: November 2016

The aim of this present work is to explore police officers’ experiences and views in respect of male rape. I critically examine the role of the police, and their experiences and perceptions of handling male rape cases. This study presents detailed, in-depth, and rich data from the police in England. The findings are generated from the police, male rape counsellors, male rape therapists and voluntary agency workers. The participants were interviewed and filled out qualitative questionnaires, which were kept anonymous. I ensured that those who were interviewed did not also fill out a questionnaire, as each method addresses issues in a different form. To inform the development of the semi-structured interview schedule and the qualitative questionnaires, I drew on Abdullah-Khan (2008) in order to shape the types of questions that I asked. Overall, this study gained a sample size of 70 participants. In this paper, I solely focus on state agencies’ responses and attitudes toward male rape. From the findings, five distinct themes emerged: (1) level of communications between officers and victims; (2) perpetuation of male rape myths and stereotypes by judges and juries; (3) lack of evidence in male rape cases; (4) attrition in male rape cases; and (5) issues of consent in male rape cases. There are serious concerns in terms of how the criminal justice system deals with male rape victims, resulting not only in poor treatment of the victims, but also increasing the attrition rate and decreasing the conviction rate in male rape cases. I attempt to tackle poor police practice herein.
Understanding Prison Management in the Philippines
Authors: Narag Raymund E. , Jones Clarke R.
Published: November 2016

Current prison management models strictly prohibit inmates from assisting with prison administration or governance. This is feasible in developed countries where governments can provide adequate resources, security, and personnel. It is not, however, realistic in developing countries like the Philippines, which is characterized by poverty, corruption, and underresourcing of correctional facilities. In such circumstances, inmate leaders tend to share governance with prison administrators. Despite occurring out of necessity, not by design, this system normalizes social conditions within a prison. This article examines the ramifications of such a shared governance model for correctional management by means of ethnographic research.
In Search of Generativity in Prison Officer Work
Authors: Halsey Mark , Deegan Simone
Published: November 2016

Generativity, defined as the actions of an individual or group that enable others to care in meaningful ways for themselves and their significant others, has become an important concept for thinking about desistance from crime. In this article, we explore opportunities for prison officers in metropolitan and regional South Australia to model and/or engage in generative conduct. We find the emergence of generativity to be idiosyncratic—linked to individual officer’s capacities to resist the dominant “us” versus “them” culture—and to be often thwarted by a fatalistic outlook. Correctional policy implications are discussed.