Characterization of cold sensitivity and thermal preference using an operant orofacial assay

BACKGROUND: A hallmark of many orofacial pain disorders is cold sensitivity, but relative to heat-related pain, mechanisms of cold perception and the development of cold allodynia are not clearly understood. Molecular mediators of cold sensation such as TRPM8 have been recently identified and characterized using in vitro studies. In this study we characterized operant behavior with respect to individually presented cold stimuli (24, 10, 2, and -4°C) and in a thermal preference task where rats chose between -4 and 48°C stimulation. We also evaluated the effects of menthol, a TRPM8 agonist, on operant responses to cold stimulation (24, 10, and -4°C). Male and female rats were trained to drink sweetened milk while pressing their shaved faces against a thermode. This presents a conflict paradigm between milk reward and thermal stimulation. RESULTS: We demonstrated that the cold stimulus response function was modest compared to heat. There was a significant effect of temperature on facial (stimulus) contacts, the ratio of licking contacts to stimulus contacts, and the stimulus duration/contact ratio. Males and females differed only in their facial contacts at 10°C. In the preference task, males preferred 48°C to -4°C, despite the fact that 48°C and -4°C were equally painful as based on their reward/stimulus and duration/contact ratios. We were able to induce hypersensitivity to cold using menthol at 10°C, but not at 24 or -4°C. CONCLUSION: Our results indicate a strong role for an affective component in processing of cold stimuli, more so than for heat, which is in concordance with human psychophysical findings. The induction of allodynia with menthol provides a model for cold allodynia. This study provides the basis for future studies involving orofacial pain and analgesics, and is translatable to the human experience

Now the wars are over: The past, present and future of Scottish battlefields

Battlefield archaeology has provided a new way of appreciating historic battlefields. This paper provides a summary of the long history of warfare and conflict in Scotland which has given rise to a large number of battlefield sites. Recent moves to highlight the archaeological importance of these sites, in the form of Historic Scotland’s Battlefields Inventory are discussed, along with some of the problems associated with the preservation and management of these important cultural sites

Diabetes status and post-load plasma glucose concentration in relation to site-specific cancer mortality: findings from the original Whitehall study

ObjectiveWhile several studies have reported on the relation of diabetes status with pancreatic cancer risk, the predictive value of this disorder for other malignancies is unclear. Methods: The Whitehall study, a 25year follow-up for mortality experience of 18,006 men with data on post-challenge blood glucose and self-reported diabetes, allowed us to address these issues. Results: There were 2158 cancer deaths at follow-up. Of the 15 cancer outcomes, diabetes status was positively associated with mortality from carcinoma of the pancreas and liver, while the relationship with lung cancer was inverse, after controlling for a range of potential covariates and mediators which included obesity and socioeconomic position. After excluding deaths occurring in the first 10years of follow-up to examine the effect of reverse causality, the magnitude of the relationships for carcinoma of the pancreas and lung was little altered, while for liver cancer it was markedly attenuated. Conclusions: In the present study, diabetes status was related to pancreatic, liver, and lung cancer risk. Cohorts with serially collected data on blood glucose and covariates are required to further examine this area

Site-specific prolapse surgery. I. Reliability and durability of native tissue paravaginal repair

Introduction and hypothesis: This study aims to compare native tissue abdominal and vaginal paravaginal repair, and to investigate whether surgical outcome was independent of operative route. Methods: Retrospective comparison of 111 displacement cysto-urethrocoeles, repaired between 1997 and 2007. Treatment was by surgeon assignment, 52 women having abdominal (APVR) and 59 vaginal paravaginal repairs. Main outcome measures were same-site prolapse recurrence, time to failure and surgical complications. Initial reliability was evaluated by chi-square test, 10-year durability by Kaplan-Meier survival analysis and Cox proportional hazards model. Results: When examined in the Cox proportional hazards model, anatomic results of APVR were more durable than a mechanically analogous transvaginal operation done [95% CI=1.029-2.708 (p value=0.038)]. Kaplan-Meier curves plateaued within 38 months. Symptom resolution was broadly equivalent. Surgical complication rate was 3.6%. Conclusions: Site-specific re-suture of torn native tissue has genuine curative potential. Most of the long-term success was attributable to site-specific repair, rather than nonspecific scar formation.9 page(s

Lung Cancer Risk after Exposure to Polycyclic Aromatic Hydrocarbons: A Review and Meta-Analysis

Typical polycyclic aromatic hydrocarbon mixtures are established lung carcinogens, but the quantitative exposure–response relationship is less clear. To clarify this relationship we conducted a review and meta-analysis of published reports of occupational epidemiologic studies. Thirty-nine cohorts were included. The average estimated unit relative risk (URR) at 100 μg/m(3) years benzo[a]pyrene was 1.20 [95% confidence interval (CI), 1.11–1.29] and was not sensitive to particular studies or analytic methods. However, the URR varied by industry. The estimated means in coke ovens, gasworks, and aluminum production works were similar (1.15–1.17). Average URRs in other industries were higher but imprecisely estimated, with those for asphalt (17.5; CI, 4.21–72.78) and chimney sweeps (16.2; CI, 1.64–160.7) significantly higher than the three above. There was no statistically significant variation of URRs within industry or in relation to study design (including whether adjusted for smoking), or source of exposure information. Limited information on total dust exposure did not suggest that dust exposure was an important confounder or modified the effect. These results provide a more secure basis for risk assessment than was previously available

Blood pressure and site-specific cancer mortality: evidence from the original Whitehall study

Studies relating blood pressure to cancer risk have some shortcomings and have revealed inconsistent findings. In 17498 middle-aged London-based government employees we related systolic and diastolic blood pressure recorded at baseline examination (1967-1970) to the risk of cancer mortality risk at 13 anatomical sites 25 years later. Following adjustment for potential confounding and mediating factors, inverse associations between blood pressure and mortality due to leukaemia and cancer of the pancreas (diastolic only) were seen. Blood pressure was also positively related to cancer of the liver and rectum (diastolic only). The statistically significant blood pressure-cancer associations seen in this large-scale prospective investigation offering high power were scarce and of sufficiently small magnitude as to be attributable to chance or confounding

The R-Process Alliance: Fourth Data Release from the Search for R-process-enhanced Stars in the Galactic Halo

This compilation is the fourth data release from the R-Process Alliance (RPA) search for r-process-enhanced stars and the second release based on "snapshot" high-resolution (R ~ 30,000) spectra collected with the du Pont 2.5 m Telescope. In this data release, we propose a new delineation between the r-I and r-II stellar classes at $[\mathrm{Eu}/\mathrm{Fe}]=+0.7$, instead of the empirically chosen $[\mathrm{Eu}/\mathrm{Fe}]=+1.0$ level previously in use, based on statistical tests of the complete set of RPA data released to date. We also statistically justify the minimum level of [Eu/Fe] for definition of the r-I stars, [Eu/Fe] > +0.3. Redefining the separation between r-I and r-II stars will aid in the analysis of the possible progenitors of these two classes of stars and determine whether these signatures arise from separate astrophysical sources at all. Applying this redefinition to previous RPA data, the number of identified r-II and r-I stars changes to 51 and 121, respectively, from the initial set of data releases published thus far. In this data release, we identify 21 new r-II, 111 new r-I (plus 3 re-identified), and 7 new (plus 1 re-identified) limited-r stars out of a total of 232 target stars, resulting in a total sample of 72 new r-II stars, 232 new r-I stars, and 42 new limited-r stars identified by the RPA to date