HLA-E expression in cervical adenocarcinomas: association with improved long-term survival

<p>Abstract</p> <p>Background</p> <p>Cervical cancer is the third most common cancer in women worldwide. The most common histopathological subtype is cervical squamous cell carcinoma (SCC, 75-80%), followed by adenocarcinoma (AC) and adenosquamous carcinoma (ASC; together 15-20%). Rising incidence rates of AC have been observed relative and absolute to SCC and evidence is accumulating that cervical AC is a distinct clinical entity. Cervical SCC, ASC, and AC are caused by a persistent infection with high-risk human papillomavirus (HPV) and failed control of the immune system plays a pivotal role in the carcinogenesis of all three histopathological subtypes. Human leukocyte antigen E (HLA-E), a non-classical HLA class Ib molecule, plays an important role in immune surveillance and immune escape of virally infected cells. In this study we investigated HLA-E expression in three well-defined cohorts of cervical AC, ASC, and SCC patients, and determined whether HLA-E expression was associated with histopathological parameters and patient survival.</p> <p>Methods and results</p> <p>HLA-E expression was assessed by immunohistochemistry on formalin-fixed, paraffin-embedded tissue sections of 79 SCC, 38 ASC, and 75 AC patients. All patients included were International Federation of Gynaecology and Obstetrics stage I-II and underwent radical hysterectomy with lymphadenectomy as primary treatment. Significant differences between the histopathological subgroups were detected for age distribution, HPV positivity, HPV type distribution, tumour size, tumour infiltration depth, lymph-vascular space invasion, and adjuvant radiotherapy. High expression of HLA-E was found in 107/192 (56%) cervical carcinomas, with significantly more overexpression in cervical AC compared to SCC and ASC (37/79 SCC, 18/38 ASC, and 52/75 AC; <it>P</it> = 0.010). High HLA-E expression in cervical AC was associated with favourable long term disease-specific and recurrence-free survival (<it>P</it> = 0.005 and <it>P</it> = 0.001, respectively).</p> <p>Conclusion</p> <p>High expression of HLA-E occurred in the majority of all histopathological subtypes of cervical cancer; especially in cervical AC. High HLA-E expression in cervical AC was associated with improved patient survival. This study also highlights the importance of careful evaluation of cervical carcinomas to distinguish histopathological subtypes. In the future, insight into the biological behaviour and distinct molecular carcinogenetic processes of the AC, ASC, and SCC subtypes may contribute to the development of more tumour-specific treatment strategies.</p

The Interaction of High-Speed Turbulence with Flames: Global Properties and Internal Flame Structure

We study the dynamics and properties of a turbulent flame, formed in the presence of subsonic, high-speed, homogeneous, isotropic Kolmogorov-type turbulence in an unconfined system. Direct numerical simulations are performed with Athena-RFX, a massively parallel, fully compressible, high-order, dimensionally unsplit, reactive-flow code. A simplified reaction-diffusion model represents a stoichiometric H2-air mixture. The system being modeled represents turbulent combustion with the Damkohler number Da = 0.05 and with the turbulent velocity at the energy injection scale 30 times larger than the laminar flame speed. The simulations show that flame interaction with high-speed turbulence forms a steadily propagating turbulent flame with a flame brush width approximately twice the energy injection scale and a speed four times the laminar flame speed. A method for reconstructing the internal flame structure is described and used to show that the turbulent flame consists of tightly folded flamelets. The reaction zone structure of these is virtually identical to that of the planar laminar flame, while the preheat zone is broadened by approximately a factor of two. Consequently, the system evolution represents turbulent combustion in the thin-reaction zone regime. The turbulent cascade fails to penetrate the internal flame structure, and thus the action of small-scale turbulence is suppressed throughout most of the flame. Finally, our results suggest that for stoichiometric H2-air mixtures, any substantial flame broadening by the action of turbulence cannot be expected in all subsonic regimes.Comment: 30 pages, 9 figures; published in Combustion and Flam

Gravitational waves from inspiralling compact binaries: Parameter estimation using second-post-Newtonian waveforms

The parameters of inspiralling compact binaries can be estimated using matched filtering of gravitational-waveform templates against the output of laser-interferometric gravitational-wave detectors. Using a recently calculated formula, accurate to second post-Newtonian (2PN) order [order $(v/c)^4$, where $v$ is the orbital velocity], for the frequency sweep ($dF/dt$) induced by gravitational radiation damping, we study the statistical errors in the determination of such source parameters as the ``chirp mass'' $\cal M$, reduced mass $\mu$, and spin parameters $\beta$ and $\sigma$ (related to spin-orbit and spin-spin effects, respectively). We find that previous results using template phasing accurate to 1.5PN order actually underestimated the errors in $\cal M$, $\mu$, and $\beta$. For two inspiralling neutron stars, the measurement errors increase by less than 16 percent.Comment: 14 pages, ReVTe

Using Total Worker Health® implementation guidelines to design an organizational intervention for low-wage food service workers : the Workplace Organizational Health Study

Total Worker Health® (TWH) interventions that utilize integrated approaches to advance worker safety, health, and well-being can be challenging to design and implement in practice. This may be especially true for the food service industry, characterized by high levels of injury and turnover. This paper illustrates how we used TWH Implementation Guidelines to develop and implement an organizational intervention to improve pain, injury, and well-being among low-wage food service workers. We used the Guidelines to develop the intervention in two main ways: first, we used the six key characteristics of an integrated approach (leadership commitment; participation; positive working conditions; collaborative strategies; adherence; data-driven change) to create the foundation of the intervention; second, we used the four stages to guide integrated intervention planning. For each stage (engaging collaborators; planning; implementing; evaluating for improvement), the Guidelines provided a flexible and iterative process to plan the intervention to improve safety and ergonomics, work intensity, and job enrichment. This paper provides a real-world example of how the Guidelines can be used to develop a complex TWH intervention for food service workers that is responsive to organizational context and addresses targeted working conditions. Application of the Guidelines is likely transferable to other industries

The landscape of somatic mutations in Indonesian cervical cancer is predominated by the PI3K pathway

Molecular tumour pathology - and tumour genetic

The Interaction of High-Speed Turbulence with Flames: Turbulent Flame Speed

(Abridged) Direct numerical simulations of the interaction of a premixed flame with driven, subsonic, homogeneous, isotropic, Kolmogorov-type turbulence in an unconfined system are used to study the mechanisms determining the turbulent flame speed, S_T, in the thin reaction zone regime. High intensity turbulence is considered with the r.m.s. velocity 35 times the laminar flame speed, S_L, resulting in the Damkohler number Da = 0.05. Here we show that: (1) The flame brush has a complex internal structure, in which the isosurfaces of higher fuel mass fractions are folded on progressively smaller scales. (2) Global properties of the turbulent flame are best represented by the structure of the region of peak reaction rate, which defines the flame surface. (3) In the thin reaction zone regime, S_T is predominantly determined by the increase of the flame surface area, A_T, caused by turbulence. (4) The observed increase of S_T relative to S_L exceeds the corresponding increase of A_T relative to the surface area of the planar laminar flame, on average, by ~14%, varying from only a few percent to ~30%. (5) This exaggerated response is the result of tight flame packing by turbulence, which causes frequent flame collisions and formation of regions of high flame curvature, or "cusps." (6) The local flame speed in the cusps substantially exceeds its laminar value, which results in a disproportionately large contribution of cusps to S_T compared with the flame surface area in them. (7) A criterion is established for transition to the regime significantly influenced by cusp formation. In particular, at Karlovitz numbers Ka > 20, flame collisions provide an important mechanism controlling S_T, in addition to the increase of A_T by large-scale motions and the potential enhancement of diffusive transport by small-scale turbulence.Comment: 44 pages, 20 figures; published in Combustion and Flam

Neighborhood deprivation and risk of mortality among men with prostate cancer: Findings from a long-term follow-up study

Background: The overall survival rate of prostate cancer (PCa) has improved over the past decades. However, huge socioeconomic and racial disparities in overall and prostate cancer-specific mortality exist. The neighborhood-level factors including socioeconomic disadvantage and lack of access to care may contribute to disparities in cancer mortality. This study examines the impact of neighborhood deprivation on mortality among PCa survivors. Methods: North Carolina–Louisiana Prostate Cancer Project (PCaP) data were used. A total of 2113 men, 1046 AA and 1067 EA, with PCa were included in the analysis. Neighborhood deprivation was measured by the Area Deprivation Index (ADI) at the census block group level using data from the US Census Bureau. Quintiles of ADI were created. Cox proportional hazards and competing risk models with mixed effects were performed to estimate the effect of neighborhood deprivation on all-cause and PCa-specific mortality adjusted for age, race, study site, insurance status, and comorbidities. Results: Participants living in the most deprived neighborhoods had an increased risk for all-cause mortality (quintiles 4 + 5: adjusted hazard ratio [aHR] = 1.51, 95% confidence interval [CI] = 1.16–1.96) compared to those in the least deprived (quintile 1) neighborhoods. The risk of prostate cancer-specific mortality was also higher among those living in the deprived neighborhoods (quintiles 4 + 5: aHR = 1.90, 95% CI = 1.10–3.50) than those in the least deprived neighborhood. Conclusions: The findings suggest neighborhood-level resources or health interventions are essential to improve survival among men with PCa. Additional research should focus on the mechanisms of how the neighborhood environment affects mortality

Multi-lingual and multi-cultural information literacy; perspectives, models and good practice

Purpose This paper reviews current approaches to, and good practice, in information literacy development in multi-lingual and multi-cultural settings, with particular emphasis on provision for international students. Design/methodology/approach A selective and critical review of published literature is extended by evaluation of examples of multi-lingual information literacy tutorials and MOOCs. Findings Multi-lingual and multi-cultural information literacy are umbrella terms covering a variety of situations and issues. This provision is of increasing importance in an increasingly mobile and multi-cultural world. This article evaluates current approaches and good practice, focusing on issues of culture vis a vis language, the balance between individual and group needs, specific and generic information literacy instruction, and models for information literacy, pedagogy and culture. Recommendations for good practice and for further research are given, Originality/value This is one of very few articles critically reviewing how information literacy development is affected by linguistic and cultural factors

Specific mesenchymal/epithelial induction of olfactory receptor, vomeronasal, and gonadotropin-releasing hormone (GnRH) neurons

We asked whether specific mesenchymal/epithelial (M/E) induction generates olfactory receptor neurons (ORNs), vomeronasal neurons (VRNs) and gonadotropin releasing hormone (GnRH) neurons—the major neuron classes associated with the olfactory epithelium (OE). To assess specificity of M/E-mediated neurogenesis, we compared the influence of frontonasal mesenchyme on frontonasal epithelium, which becomes the OE, with that of the forelimb bud. Despite differences in position, morphogenetic and cytogenic capacity, both mesenchymal tissues support neurogenesis, expression of several signaling molecules and neurogenic transcription factors in the frontonasal epithelium. Only frontonasal mesenchyme, however, supports OE-specific patterning and activity of a subset of signals and factors associated with OE differentiation. Moreover, only appropriate pairing of frontonasal epithelial and mesenchymal partners yields ORNs, VRNs, and GnRH neurons. Accordingly, the position and molecular identity of specialized frontonasal epithelia and mesenchyme early in gestation and subsequent inductive interactions, specifies the genesis and differentiation of peripheral chemosensory and neuroendocrine neurons