Evidence for two-electron processes in the mutual neutralization of O- with O+ and N+ at Subthermal Collision Energies

We have measured total absolute cross sections for the Mutual Neutralization (MN) of O- with O+/N+. A fine resolution (of about 50 meV) in the kinetic energy spectra of the product neutral atoms allows unique identification of the atomic states participating in the mutual neutralization process. Cross sections and branching ratios have also been calculated down to 1 meV center-of-mass collision energy for these two systems with a multi-channel Landau-Zener model and an asymptotic method for the ionic-covalent coupling matrix elements. The importance of two-electron processes in one-electron transfer is demonstrated by the dominant contribution of a core-excited configuration of the nitrogen atom in N+ + O- collisions. This effect is partially accounted for by introducing configuration mixing in the evaluation of coupling matrix elements.Comment: 5 pages, 4 figure

TP53 mutations, amplification of P63 and expression of cell cycle proteins in squamous cell carcinoma of the oesophagus from a low incidence area in Western Europe

In Europe, high incidence rates of oesophageal squamous cell carcinoma (SCCE) are observed in western France (Normandy and Brittany) and in north-eastern Italy. Analysis of TP53 mutations in tumours from these regions has shown a high prevalence of mutations at A:T basepairs that may result from DNA damage caused by specific mutagens. However, the spectrum of TP53 mutations in regions of low incidence is unknown. We report here TP53 mutation analysis in 33 SCCE collected in Lyon, an area of low incidence. These tumours were also examined for MDM2 and P63 amplification, and for expression of p16INK4a/CDKN2a, cyclin E, p27Kipland Cox2. TP53 mutations were detected in 36% of the cases (12/33). In contrast with regions of high incidence, the mutation spectrum did not show a high prevalence of mutations at A:T base pairs. P63 was amplified in 5/32 cases tested (15.5%). No amplification of MDM2 was found. Expression studies revealed frequent loss of p16INK4a/CDKN2a(46%) and p27Kipl(25%) expression, and frequent overexpression of Cyclin E (70%) and Cox2 (42%). Overall, these results indicate that in Europe, SCCE from areas of high and low incidence present a similar pattern of molecular alterations but differ by the type of TP53 mutations. © 2001 Cancer Research Campaign http://www.bjcancer.co

Circulating adrenomedullin estimates survival and reversibility of organ failure in sepsis: the prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock-1 (AdrenOSS-1) study

Background: Adrenomedullin (ADM) regulates vascular tone and endothelial permeability during sepsis. Levels of circulating biologically active ADM (bio-ADM) show an inverse relationship with blood pressure and a direct relationship with vasopressor requirement. In the present prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock 1 (, AdrenOSS-1) study, we assessed relationships between circulating bio-ADM during the initial intensive care unit (ICU) stay and short-term outcome in order to eventually design a biomarker-guided randomized controlled trial. Methods: AdrenOSS-1 was a prospective observational multinational study. The primary outcome was 28-day mortality. Secondary outcomes included organ failure as defined by Sequential Organ Failure Assessment (SOFA) score, organ support with focus on vasopressor/inotropic use, and need for renal replacement therapy. AdrenOSS-1 included 583 patients admitted to the ICU with sepsis or septic shock. Results: Circulating bio-ADM levels were measured upon admission and at day 2. Median bio-ADM concentration upon admission was 80.5 pg/ml [IQR 41.5-148.1 pg/ml]. Initial SOFA score was 7 [IQR 5-10], and 28-day mortality was 22%. We found marked associations between bio-ADM upon admission and 28-day mortality (unadjusted standardized HR 2.3 [CI 1.9-2.9]; adjusted HR 1.6 [CI 1.1-2.5]) and between bio-ADM levels and SOFA score (p < 0.0001). Need of vasopressor/inotrope, renal replacement therapy, and positive fluid balance were more prevalent in patients with a bio-ADM > 70 pg/ml upon admission than in those with bio-ADM ≤ 70 pg/ml. In patients with bio-ADM > 70 pg/ml upon admission, decrease in bio-ADM below 70 pg/ml at day 2 was associated with recovery of organ function at day 7 and better 28-day outcome (9.5% mortality). By contrast, persistently elevated bio-ADM at day 2 was associated with prolonged organ dysfunction and high 28-day mortality (38.1% mortality, HR 4.9, 95% CI 2.5-9.8). Conclusions: AdrenOSS-1 shows that early levels and rapid changes in bio-ADM estimate short-term outcome in sepsis and septic shock. These data are the backbone of the design of the biomarker-guided AdrenOSS-2 trial. Trial registration: ClinicalTrials.gov, NCT02393781. Registered on March 19, 2015

Factors influencing time from presentation to treatment of colorectal and breast cancer in urban and rural areas

Stage at diagnosis and survival from cancer vary according to where people live, suggesting some may have delays in diagnosis. The aim of this study was to determine if time from presentation to treatment was longer for colorectal and breast cancer patients living further from cancer centres, and identify other important factors in delay. Data were collected on 1097 patients with breast and 1223 with colorectal cancer in north and northeast Scotland. Women with breast cancer who lived further from cancer centres were treated more quickly than those living closer to cancer centres (P = 0.011). Multilevel modelling found that this was largely due to them receiving earlier treatment at hospitals other than cancer centres. Breast lump, change in skin contour, lymphadenopathy, more symptoms and signs, and increasing age predicted faster treatment. Screen detected cancers and private referrals were treated more quickly. For colorectal cancer, time to treatment was similar for people in rural and urban areas. Quicker treatment was associated with palpable rectal or abdominal masses, tenesmus, abdominal pain, frequent GP consultations, age between 50 and 74 years, tumours of the transverse colon, and iron medication at presentation. Delay was associated with past anxiety or depression. There was variation between general practices and treatment appeared quicker at practices with more female general practitioners

Esophageal cancer risk by type of alcohol drinking and smoking: a case-control study in Spain

<p>Abstract</p> <p>Background</p> <p>The effect of tobacco smoking and alcohol drinking on esophageal cancer (EC) has never been explored in Spain where black tobacco and wine consumptions are quite prevalent. We estimated the independent effect of different alcoholic beverages and type of tobacco smoking on the risk of EC and its main histological cell type (squamous cell carcinoma) in a hospital-based case-control study in a Mediterranean area of Spain.</p> <p>Methods</p> <p>We only included incident cases with histologically confirmed EC (n = 202). Controls were frequency-matched to cases by age, sex and province (n = 455). Information on risk factors was elicited by trained interviewers using structured questionnaires. Multiple logistic regression was used to estimate adjusted odds ratios and 95% confidence intervals (CI).</p> <p>Results</p> <p>Alcohol drinking and tobacco smoking were strong and independent risk factors for esophageal cancer. Alcohol was a potent risk factor with a clear dose-response relationship, particularly for esophageal squamous-cell cancer. Compared to never-drinkers, the risk for heaviest drinkers (≥ 75 g/day of pure ethanol) was 7.65 (95%CI, 3.16–18.49); and compared with never-smokers, the risk for heaviest smokers (≥ 30 cigarettes/day) was 5.07 (95%CI, 2.06–12.47). A low consumption of only wine and/or beer (1–24 g/d) did not increase the risk whereas a strong positive trend was observed for all types of alcoholic beverages that included any combination of hard liquors with beer and/or wine (p-trend<0.00001). A significant increase in EC risk was only observed for black-tobacco smoking (2.5-fold increase), not for blond tobacco. The effects for alcohol drinking were much stronger when the analysis was limited to the esophageal squamous cell carcinoma (n = 160), whereas a lack of effect for adenocarcinoma was evidenced. Smoking cessation showed a beneficial effect within ten years whereas drinking cessation did not.</p> <p>Conclusion</p> <p>Our study shows that the risk of EC, and particularly the squamous cell type, is strongly associated with alcohol drinking. The consumption of any combination of hard liquors seems to be harmful whereas a low consumption of only wine may not. This may relates to the presence of certain antioxidant compounds found in wine but practically lacking in liquors. Tobacco smoking is also a clear risk factor, black more than blond.</p

Colorectal cancer screening awareness among physicians in Greece

BACKGROUND: Data comparison between SEER and EUROCARE database provided evidence that colorectal cancer survival in USA is higher than in European countries. Since adjustment for stage at diagnosis markedly reduces the survival differences, a screening bias was hypothesized. Considering the important role of primary care in screening activities, the purpose of the study was to investigate the colorectal cancer screening awareness among Hellenic physicians. METHODS: 211 primary care physicians were surveyed by mean of a self-reported prescription-habits questionnaire. Both physicians' colorectal cancer screening behaviors and colorectal cancer screening recommendations during usual check-up visits were analyzed. RESULTS: Only 50% of physicians were found to recommend screening for colorectal cancer during usual check-up visits, and only 25% prescribed cost-effective procedures. The percentage of physicians recommending stool occult blood test and sigmoidoscopy was 24% and 4% respectively. Only 48% and 23% of physicians recognized a cancer screening value for stool occult blood test and sigmoidoscopy. Colorectal screening recommendations were statistically lower among physicians aged 30 or less (p = 0.012). No differences were found when gender, level and type of specialization were analyzed, even though specialists in general practice showed a trend for better prescription (p = 0.054). CONCLUSION: Contemporary recommendations for colorectal cancer screening are not followed by implementation in primary care setting. Education on presymptomatic control and screening practice monitoring are required if primary care is to make a major impact on colorectal cancer mortality

Evaluating risk factor assumptions: a simulation-based approach

<p>Abstract</p> <p>Background</p> <p>Microsimulation models are an important tool for estimating the comparative effectiveness of interventions through prediction of individual-level disease outcomes for a hypothetical population. To estimate the effectiveness of interventions targeted toward high risk groups, the mechanism by which risk factors influence the natural history of disease must be specified. We propose a method for evaluating these risk factor assumptions as part of model-building.</p> <p>Methods</p> <p>We used simulation studies to examine the impact of risk factor assumptions on the relative rate (RR) of colorectal cancer (CRC) incidence and mortality for a cohort with a risk factor compared to a cohort without the risk factor using an extension of the CRC-SPIN model for colorectal cancer. We also compared the impact of changing age at initiation of screening colonoscopy for different risk mechanisms.</p> <p>Results</p> <p>Across CRC-specific risk factor mechanisms, the RR of CRC incidence and mortality decreased (towards one) with increasing age. The rate of change in RRs across age groups depended on both the risk factor mechanism and the strength of the risk factor effect. Increased non-CRC mortality attenuated the effect of CRC-specific risk factors on the RR of CRC when both were present. For each risk factor mechanism, earlier initiation of screening resulted in more life years gained, though the magnitude of life years gained varied across risk mechanisms.</p> <p>Conclusions</p> <p>Simulation studies can provide insight into both the effect of risk factor assumptions on model predictions and the type of data needed to calibrate risk factor models.</p

Food groups, oils and butter, and cancer of the oral cavity and pharynx

To elucidate the role of dietary habits, a study was carried out in 1992-1997 in the province of Pordenone in Northeastern Italy, and those of Rome and Latina in central Italy. Cases were 512 men and 86 women with cancer of the oral cavity and pharynx (lip, salivary glands and nasopharynx excluded) and controls were 1008 men and 483 women who had been admitted to local hospitals for a broad range of acute non-neoplastic conditions. The validated dietary section of the questionnaire included 78 foods or recipes and ten questions on fat intake patterns. After allowance for education, smoking, alcohol and total energy intake, significant trends of increasing risk with increasing intake emerged for soups, eggs, processed meats, cakes and desserts, and butter. Risk was approximately halved in the highest compared to the lowest intake quintile for coffee and tea, white bread, poultry, fish, raw and cooked vegetables, citrus fruit, and olive oil. The inverse association with oils, especially olive oil, was only slightly attenuated by allowance for vegetable intake. Thus, frequent consumption of vegetables, citrus fruit, fish and vegetable oils were the major features of a low-risk diet for cancer of the oral cavity and pharynx

Circulating 25-Hydroxyvitamin D and Risk of Esophageal and Gastric Cancer: Cohort Consortium Vitamin D Pooling Project of Rarer Cancers

Upper gastrointestinal (GI) cancers of the stomach and esophagus have high incidence and mortality worldwide, but they are uncommon in Western countries. Little information exists on the association between vitamin D and risk of upper GI cancers. This study examined the association between circulating 25-hydroxyvitamin D (25(OH)D) and upper GI cancer risk in the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers. Concentrations of 25(OH)D were measured from 1,065 upper GI cancer cases and 1,066 age-, sex-, race-, and season-of blood draw–matched controls from 8 prospective cohort studies. In multivariate-adjusted models, circulating 25(OH)D concentration was not significantly associated with upper GI cancer risk. Subgroup analysis by race showed that among Asians, but not Caucasians, lower concentrations of 25(OH)D (<25 nmol/L) were associated with a statistically significant decreased risk of upper GI cancer (reference: 50–<75 nmol/L) (odds ratio = 0.53, 95% confidence interval: 0.31, 0.91; P trend = 0.003). Never smokers with concentrations of <25 nmol/L showed a lower risk of upper GI cancers (odds ratio = 0.55, 95% confidence interval: 0.31, 0.96). Subgroup analyses by alcohol consumption produced opposing trends. Results do not support the hypothesis that interventions aimed at increasing vitamin D status would lead to a lower risk of these highly fatal cancers

Prospective study of serum 25(OH)-vitamin D concentration and risk of oesophageal and gastric cancers

We prospectively examined the relation between pretrial serum vitamin D status and risk of oesophageal and gastric cancers among subjects who developed cancer over 5.25 years of follow-up, including 545 oesophageal squamous cell carcinomas (ESCC), 353 gastric cardia adenocarcinomas, 81 gastric noncardia adenocarcinomas, and an age- and sex-stratified random sample of 1105 subjects. The distribution of serum 25(OH)D was calculated using the known sampling weights. For the cohort as a whole, the 25th, 50th, and 75th percentile concentrations of 25(OH)-vitamin D were 19.6, 31.9, and 48.7 nmol l−1, respectively, and we found that higher serum 25(OH)D concentrations were associated with monotonically increasing risk of ESCC in men, but not in women. Comparing men in the fourth quartile of serum 25(OH)D concentrations to those in the first, we found a hazard ratio (HR) (95% confidence interval (CI)) of 1.77 (1.16–2.70), P trend=0.0033. The same comparison in women had a HR (95% CI) of 1.06 (0.71–1.59), P trend=0.70. We found no associations for gastric cardia or noncardia adenocarcinoma. Among subjects with low vitamin D status, higher serum 25(OH)D concentrations were associated with significantly increased risk of ESCC in men, but not in women. Further refinements of the analysis did not suggest any factors, which could explain this unexpected result