Who Should Decide? Decision-Making Preferences for Primary HPV Testing for Cervical Cancer Screening Among U.S. Women

Revised U.S. guidelines for cervical cancer screening provide the option of primary human papillomavirus (HPV) testing, Pap testing, or co-testing. Primary HPV testing has not yet been an option for American women, and women may be reluctant to change screening methods. The purpose of this study was to assess correlates of women’s preferences for primary HPV testing decision-making (self, provider, or shared) for cervical cancer screening. Women, aged 30-65, completed an online survey in June of 2018 (n = 812). The outcome variable was preference for decision-making for an HPV test instead of a Pap test on a scale of, healthcare provider, me, or shared. Predictor variables included testing attitudes, social norms, information seeking, previous screening, and socio-demographics. Women who disagreed that people important to them think that they should get the HPV test instead of a Pap test, who were not willing to receive an HPV test instead of a Pap test, and who did not receive HPV vaccinations were less likely to include a provider in their decision-making. In contrast, women who were not up-to-date with their cervical cancer screenings, who had some college or technical level education, or who were over 50 years of age were more likely to prefer to have a healthcare provider included in their decision-making process. While some variation was discovered, women mostly preferred a shared decision or personal decision for HPV testing. Resources to facilitate the decision-making process about this new option for cervical cancer screening are needed

Exact Thermodynamics of the Double sinh-Gordon Theory in 1+1-Dimensions

We study the classical thermodynamics of a 1+1-dimensional double-well sinh-Gordon theory. Remarkably, the Schrodinger-like equation resulting from the transfer integral method is quasi-exactly solvable at several temperatures. This allows exact calculation of the partition function and some correlation functions above and below the short-range order (``kink'') transition, in striking agreement with high resolution Langevin simulations. Interesting connections with the Landau-Ginzburg and double sine-Gordon models are also established.Comment: 4 pages, 3 figures (embedded using epsf), uses RevTeX plus macro (included). Minor revision to match journal version, Phys. Rev. Lett. (in press

Noise-Induced Phase Space Transport in Two-Dimensional Hamiltonian Systems

First passage time experiments were used to explore the effects of low amplitude noise as a source of accelerated phase space diffusion in two-dimensional Hamiltonian systems, and these effects were then compared with the effects of periodic driving. The objective was to quantify and understand the manner in which ``sticky'' chaotic orbits that, in the absence of perturbations, are confined near regular islands for very long times, can become ``unstuck'' much more quickly when subjected to even very weak perturbations. For both noise and periodic driving, the typical escape time scales logarithmically with the amplitude of the perturbation. For white noise, the details seem unimportant: Additive and multiplicative noise typically have very similar effects, and the presence or absence of a friction related to the noise by a Fluctuation-Dissipation Theorem is also largely irrelevant. Allowing for colored noise can significantly decrease the efficacy of the perturbation, but only when the autocorrelation time becomes so large that there is little power at frequencies comparable to the natural frequencies of the unperturbed orbit. Similarly, periodic driving is relatively inefficient when the driving frequency is not comparable to these natural frequencies. This suggests strongly that noise-induced extrinsic diffusion, like modulational diffusion associated with periodic driving, is a resonance phenomenon. The logarithmic dependence of the escape time on amplitude reflects the fact that the time required for perturbed and unperturbed orbits to diverge a given distance scales logarithmically in the amplitude of the perturbation.Comment: 15 pages, including 13 Figures and 1 Table, uses Phys. Rev. macro

Chaos and the continuum limit in the gravitational N-body problem II. Nonintegrable potentials

This paper continues a numerical investigation of orbits evolved in `frozen,' time-independent N-body realisations of smooth time-independent density distributions corresponding to both integrable and nonintegrable potentials, allowing for N as large as 300,000. The principal focus is on distinguishing between, and quantifying, the effects of graininess on initial conditions corresponding, in the continuum limit, to regular and chaotic orbits. Ordinary Lyapunov exponents X do not provide a useful diagnostic for distinguishing between regular and chaotic behaviour. Frozen-N orbits corresponding in the continuum limit to both regular and chaotic characteristics have large positive X even though, for large N, the `regular' frozen-N orbits closely resemble regular characteristics in the smooth potential. Viewed macroscopically both `regular' and `chaotic' frozen-N orbits diverge as a power law in time from smooth orbits with the same initial condition. There is, however, an important difference between `regular' and `chaotic' frozen-N orbits: For regular orbits, the time scale associated with this divergence t_G ~ N^{1/2}t_D, with t_D a characteristic dynamical time; for chaotic orbits t_G ~ (ln N) t_D. At least for N>1000 or so, clear distinctions exist between phase mixing of initially localised orbit ensembles which, in the continuum limit, exhibit regular versus chaotic behaviour. For both regular and chaotic ensembles, finite-N effects are well mimicked, both qualitatively and quantitatively, by energy-conserving white noise with amplitude ~ 1/N. This suggests strongly that earlier investigations of the effects of low amplitude noise on phase space transport in smooth potentials are directly relevant to real physical systems.Comment: 20 pages, including 21 FIGURES, uses RevTeX macro

Regulation of cell survival by sphingosine-1-phosphate receptor S1P1 via reciprocal ERK-dependent suppression of bim and PI-3-kinase/protein kinase C-mediated upregulation of Mcl-1

Although the ability of bioactive lipid sphingosine-1-phosphate (S1P) to positively regulate anti-apoptotic/pro-survival responses by binding to S1P1 is well known, the molecular mechanisms remain unclear. Here we demonstrate that expression of S1P1 renders CCL39 lung fibroblasts resistant to apoptosis following growth factor withdrawal. Resistance to apoptosis was associated with attenuated accumulation of pro-apoptotic BH3-only protein Bim. However, although blockade of extracellular signal-regulated kinase (ERK) activation could reverse S1P1-mediated suppression of Bim accumulation, inhibition of caspase-3 cleavage was unaffected. Instead S1P1-mediated inhibition of caspase-3 cleavage was reversed by inhibition of phosphatidylinositol-3-kinase (PI3K) and protein kinase C (PKC), which had no effect on S1P1 regulation of Bim. However, S1P1 suppression of caspase-3 was associated with increased expression of anti-apoptotic protein Mcl-1, the expression of which was also reduced by inhibition of PI3K and PKC. A role for the induction of Mcl-1 in regulating endogenous S1P receptor-dependent pro-survival responses in human umbilical vein endothelial cells was confirmed using S1P receptor agonist FTY720-phosphate (FTY720P). FTY720P induced a transient accumulation of Mcl-1 that was associated with a delayed onset of caspase-3 cleavage following growth factor withdrawal, whereas Mcl-1 knockdown was sufficient to enhance caspase-3 cleavage even in the presence of FTY720P. Consistent with a pro-survival role of S1P1 in disease, analysis of tissue microarrays from ER+ breast cancer patients revealed a significant correlation between S1P1 expression and tumour cell survival. In these tumours, S1P1 expression and cancer cell survival were correlated with increased activation of ERK, but not the PI3K/PKB pathway. In summary, pro-survival/anti-apoptotic signalling from S1P1 is intimately linked to its ability to promote the accumulation of pro-survival protein Mcl-1 and downregulation of pro-apoptotic BH3-only protein Bim via distinct signalling pathways. However, the functional importance of each pathway is dependent on the specific cellular context

Chaos and Noise in Galactic Potentials

ABBREVIATED ABSTRACT: This paper summarises an investigation of the effects of weak friction and noise in time-independent, nonintegrable potentials which admit both regular and stochastic orbits. The aim is to understand the qualitative effects of internal and external irregularities associated, e.g., with discreteness effects or couplings to an external environment, which stars in any real galaxy must experience. The two principal conclusions are: (1) These irregularities can be important on time scales much shorter than the natural relaxation time scale t_R associated with the friction and noise. For stochastic orbits friction and noise induce an average exponential divergence from the unperturbed Hamiltonian trajectory at a rate set by the value of the local Lyapunov exponent. Even weak noise can make a pointwise interpretation of orbits suspect already on time scales much shorter than t_R. (2) The friction and noise can also have significant effects on the statistical properties of ensembles of stochastic orbits, these also occurring on time scales much shorter than t_R. Potential implications for galactic dynamics are discussed, including the problem of shadowing.Comment: 45 pages, uuencoded PostScript (figures included), LA-UR-94-282

Protein kinase Cδ expression in breast cancer as measured by real-time PCR, western blotting and ELISA

The protein kinase C (PKC) family of genes encode serine/threonine kinases that regulate proliferation, apoptosis, cell survival and migration. Multiple isoforms of PKC have been described, one of which is PKCδ. Currently, it is unclear whether PKCδ is involved in promoting or inhibiting cancer formation/progression. The aim of this study was therefore to investigate the expression of PKCδ in human breast cancer and relate its levels to multiple parameters of tumour progression. Protein kinase Cδ expression at the mRNA level was measured using real-time PCR (n=208) and at protein level by both immunoblotting (n=94) and ELISA (n=98). Following immunoblotting, two proteins were identified, migrating with molecular masses of 78 and 160 kDa. The 78 kDa protein is likely to be the mature form of PKCδ but the identity of the 160 kDa form is unknown. Levels of both these proteins correlated weakly but significantly with PKCδ concentrations determined by ELISA (for the 78 kDa form, r=0.444, P<0.005, n=91 and for the 160 kDa form, r=0.237, P=0.023, n=91) and with PKCδ mRNA levels (for the 78 kDa form, r=0.351, P=0.001, n=94 and for the 160 kDa form, r=0.216, P=0.037, n=94). Protein kinase Cδ mRNA expression was significantly higher in oestrogen receptor (ER)-positive compared with ER-negative tumours (P=0.007, Mann–Whitney U-test). Increasing concentrations of PKCδ mRNA were associated with reduced overall patient survival (P=0.004). Our results are consistent with a role for PKCδ in breast cancer progression

Antiproliferative activity of PEP005, a novel ingenol angelate that modulates PKC functions, alone and in combination with cytotoxic agents in human colon cancer cells

PEP005 is a novel ingenol angelate that modulates protein kinases C (PKC) functions by activating PKCδ and inhibiting PKCα. This study assessed the antiproliferative effects of PEP005 alone and in combination with several other anticancer agents in a panel of 10 human cancer cell lines characterised for expression of several PKC isoforms. PEP005 displayed antiproliferative effects at clinically relevant concentrations with a unique cytotoxicity profile that differs from that of most other investigated cytotoxic agents, including staurosporine. In a subset of colon cancer cells, the IC50 of PEP005 ranged from 0.01–140 μM. The antiproliferative effects of PEP005 were shown to be concentration- and time-dependent. In Colo205 cells, apoptosis induction was observed at concentrations ranging from 0.03 to 3 μM. Exposure to PEP005 also induced accumulation of cells in the G1 phase of the cell cycle. In addition, PEP005 increased the phosphorylation of PKCδ and p38. In Colo205 cells, combinations of PEP005 with several cytotoxic agents including oxaliplatin, SN38, 5FU, gemcitabine, doxorubicin, vinorelbine, and docetaxel yielded sequence-dependent antiproliferative effects. Cell cycle blockage induced by PEP005 in late G1 lasted for up to 24 h and therefore a 24 h lag-time between PEP005 and subsequent exposure to cytotoxics was required to optimise PEP005 combinations with several anticancer agents. These data support further evaluation of PEP005 as an anticancer agent and may help to optimise clinical trials with PEP005-based combinations in patients with solid tumours

Electric toothbrush application is a reliable and valid test for differentiating temporomandibular disorders pain patients from controls

<p>Abstract</p> <p>Background</p> <p>Current methods for identifying patients with pain hypersensitivity are sufficiently complex to limit their widespread application in clinical settings. We assessed the reliability and validity of a simple multi-modal vibrotactile stimulus, applied using an electric toothbrush, to evaluate its potential as a screening tool for central sensitization.</p> <p>Methods</p> <p>Fourteen female temporomandibular disorders (TMD) subjects with myofascial pain (RDC/TMD Ia or Ib) and arthralgia (RDC/TMD IIIa) were compared to 13 pain-free controls of matched age and gender. Vibrotactile stimulus was performed with an electric toothbrush, applied with 1 pound pressure for 30 seconds in four locations: over the lateral pole of the temporomandibular joint, masseter, temporalis, and mid-ventral surface of forearm. Pain intensity (0–10) was recorded following the stimulus at 0, 15, 30, and 60 seconds. Test-retest reliability was assessed with measurements from 8 participants, taken 2–12 hours apart. Case versus control differentiation involved comparison of area under the curve (AUC). A receiver operating characteristic (ROC) curve was used to determine cutoff AUC scores for maximum sensitivity and specificity for this multi-modal vibrotactile stimulus.</p> <p>Results</p> <p>Test-retest reliability resulted in an ICC of 0.87 for all 4 pooled sites. ROC-determined AUC cutoff scores resulted in a sensitivity of 57% and specificity of 92% for all 4 pooled sites.</p> <p>Conclusion</p> <p>The electric toothbrush stimulus had excellent test-retest reliability. Validity of the scores was demonstrated with modest sensitivity and good specificity for differentiating TMD pain patients from controls, which are acceptable properties for a screening test.</p