Risk factors and biomarkers of life-threatening cancers

There is growing evidence that risk factors for cancer occurrence and for cancer death are not necessarily the same. Knowledge of cancer aggressiveness risk factors (CARF) may help in identifying subjects at high risk of developing a potentially deadly cancer (and not just any cancer). The availability of CARFs may have positive consequences for health policies, medical practice, and the search for biomarkers. For instance, cancer chemoprevention and cancer screening of subjects with CARFs would probably be more ethical and cost-effective than recommending chemoprevention and screening to entire segments of the population. Also, the harmful consequences of chemoprevention and of screening would be reduced while effectiveness would be optimised. We present examples of CARF already in use (e.g. mutations of the breast cancer (BRCA) gene), of promising avenues for the discovery of biomarkers thanks to the investigation of CARFs (e.g. breast radiological density and systemic inflammation), and of biomarkers commonly used that are not real CARFs (e.g. certain mammography images, prostate-specific antigen (PSA) concentration, nevus number)

Predicting contaminant transport pathways in the Caribou-Poker Creek Research Watershed

Thesis (M.S.) University of Alaska Fairbanks, 2002In order to evaluate the impact of natural organic matter (NOM) on drinking water, the hydrology of the Caribou-Poker Creeks Research Watershed (CPCRW) was considered. The CPCRW provided an excellent opportunity to investigate contaminant transport as it relates to hydrology in a well studied, discontinuous permafrost environment. The seasonal variation of organic chemistry of three different water sources (i.e. ground water, artesian spring and stream) was studied during the course of the year 2001. This thesis comprises three chapters, each of which seeks to gain a better understanding of the contaminant transport pathways in a boreal watershed, Caribou Poker Creeks Research Watershed. The hypothesis of Chapter One was that the heavy metal Cadmium (Cd) is strongly correlated to NOM. The objective was to establish the likely sources of cadmium mobility in organic rich soils. Cadmium was selected because of its tendency to be more mobile in soils than other heavy metals. The hypothesis of Chapter Two was as follows; the chemical nature of dissolved organic matter (DOM) changes during the course of a year in a boreal watershed. The objective of this study was to evaluate the seasonal character of DOM in the CPCRW. DOM was characterized using pyrolysis-gas chromatograph/mass spectrometry (Py-GC/MS), as well as ultraviolet absorbance at 254 nanometers (UV254) and dissolved organic carbon (DOC). Finally, Chapter Three had for central hypothesis that water could be traced to its origin through a correlation of NOM fingerprints. NOM was used as a natural tracer. One hypothesis was that the water appearing on the discharge areas (north-facing slopes) was derived from infiltration at higher elevation on recharging area (south-facing slopes). It was also expected to find that surface water in downstream segments could be correlated with an upstream source, and that this relationship would change during the course of the year. The main objective of this thesis was to establish the relationship of NOM type (chemical/physical characteristic) to Cd mobilization.Factors affecting cadmium mobility in a boreal soil -- Seasonal variation in organic matter chemistry in a boreal watershed -- Hydrology of the boreal watershed, Caribou-Poker Creeks Research Watershed

Strain superlattices and macroscale suspension of Graphene induced by corrugated substrates

We investigate the organized formation of strain, ripples and suspended features in macroscopic CVD-prepared graphene sheets transferred onto a corrugated substrate made of an ordered arrays of silica pillars of variable geometries. Depending on the aspect ratio and sharpness of the corrugated array, graphene can conformally coat the surface, partially collapse, or lay, fakir-like, fully suspended between pillars over tens of micrometers. Upon increase of pillar density, ripples in collapsed films display a transition from random oriented pleats emerging from pillars to ripples linking nearest neighboring pillars organized in domains of given orientation. Spatially-resolved Raman spectroscopy, atomic force microscopy and electronic microscopy reveal uniaxial strain domains in the transferred graphene, which are induced and controlled by the geometry. We propose a simple theoretical model to explain the transition between suspended and collapsed graphene. For the arrays with high aspect ratio pillars, graphene membranes stays suspended over macroscopic distances with minimal interaction with pillars tip apex. It offers a platform to tailor stress in graphene layers and open perspectives for electron transport and nanomechanical applications

Stable incidence of advanced breast cancer argues against screening effectiveness

Swedish trials on mammography screening of women aged 40-74 years indicated that two to four rounds of screening could significantly reduce the risk of being diagnosed with and dying from advanced breast cancer.1 Because stage at diagnosis is independent of treatment efficacy, the trials concluded that the introduction of screening in general populations would be reflected by a reduced incidence of advanced breast cancer and mortality from breast cancer

Melanoma mortality following skin cancer screening in Germany

In 2003, a skin cancer screening campaign based on total body skin examination was launched in the federal state of Schleswig-Holstein, Germany. 20% of adults aged 20 and over were screened. In 2008, a 48% decline in melanoma mortality was reported. In the same year, skin screening was extended to the rest of Germany. We evaluated whether melanoma mortality trends decreased in Germany as compared with surrounding countries where skin screening is uncommon. We also evaluated whether the initial decreasing mortality trend observed in Schleswig-Holstein was maintained with a longer follow-up.  Regional and national melanoma mortality data from 1995 to 2013 were extracted from the GEKID database and the Federal Statistical Office. Mortality data for Germany and surrounding countries from 1980 to 2012 were extracted from the WHO mortality database.  Age-adjusted (European Standard Population) mortality rates were computed and joinpoint analysis performed for Schleswig-Holstein, Germany and surrounding countries.  In Schleswig-Holstein, melanoma mortality rates declined by 48% from 2003 to 2008, and from 2009 to 2013 returned to levels observed before screening initiation. During the 5 years of the national programme (2008-2012), melanoma mortality rates increased by 2.6% (95% CI -0.1 to 5.2) in men and 0.02% (95% CI -1.8 to 1.8) in women. No inflexion point in trends was identified after 2008 that could have suggested a decreasing melanoma mortality. Trends of cutaneous melanoma mortality in Germany from 1980 to 2012 did not differ from those observed in surrounding countries.  The transient decrease mortality in Schleswig-Holstein followed by return to pre-screening levels could reflect a temporal modification in the reporting of death causes. An in-depth evaluation of the screening programme is required

Study on potato consumption will increase confusion regarding food and the risk of gestational diabetes

Using data from the Nurses’ Health Study II, Bao and colleagues found a higher prevalence of gestational diabetes mellitus (GDM) with increasing potato consumption.1 The authors stated that the high glycaemic index of potatoes, which causes a sharp postprandial rise in blood glucose concentrations and a risk of associated pancreatic β cells exhaustion, could explain this association

The forthcoming inexorable decline of cutaneous melanoma mortality in light-skinned populations

Reasons underlying time changes in cutaneous melanoma mortality in light-skinned populations are not well understood. An analysis of long-term time trends in melanoma mortality was carried out after regrouping countries in homogeneous regions.  Using the World Health Organisation (WHO) mortality database, age-period-cohort models were fitted for seven regions where the majority of population is light-skinned. Cohort effects are denoted as changes in rates occurring at different times in steadily older age groups. Period effects are denoted as changes in rates occurring simultaneously in several age groups.  Cohort effects better explained changes in melanoma mortality over time than period effects. Lifetime risk to die from melanoma increased in successive generations from 1875 until a peak year. Peak years were for subjects born in 1936-1940 in Oceania, 1937-1943 in North America, 1941-1942 in Northern Europe, 1945-1953 in the United Kingdom (UK) and Ireland, 1948 in Western Europe and 1957 in Central Europe. After peak years, lifetime risk of melanoma death gradually decreased in successive generations and risks of subjects born in 1990-1995 were back to risk levels observed for subjects born before 1900-1905. In Southern Europe, birth years with highest lifetime risk of melanoma death have not yet been attained. As time passes, melanoma deaths will steadily rarefy in younger age groups and concentrate in older age groups, for ultimately fade away after 2040-2050.  Independently from screening or treatment, over next decades, death from melanoma is likely to become an increasingly rare event. The temporary epidemic of fatal melanoma was most probably due to excessive UV-exposure of children that prevailed in 1900-1960, and mortality decreases would be due to progressive reductions in UV-exposure of children over the last decades

Strain induced pressure effect in pulsed laser deposited thin films of the strongly correlated oxide V2O3

V2O3 thin films about 10 nm thick were grown on Al2O3 (0001) by pulsed laser deposition. The XRD analysis is in agreement with R-3c space group. Some of them exhibit the metal / insulator transition characteristic of V2O3 bulk material and others samples exhibit a metallic behavior. For the latter, the XPS analysis indicates an oxidation state of +III for vanadium. There is no metal / insulator transition around 150 K in this sample and a strongly correlated Fermi liquid rho = AT2 behavior of the resistivity at low temperature is observed, with a value of A of 1.2 10-4 ohm cm, 3 times larger than the bulk value at 25 kbar

Variation of prostate-specific antigen value in men and risk of high-grade prostate vancer : analysis of the prostate, lung, colorectal, and ovarian cancer screening trial study

To investigate variations in prostate-specific antigen (PSA) levels among men with an initial normal PSA level in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial study. Data were extracted from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial study data set on all men in the interventional arm, with 2 tests performed in a period of < 2 years and with an initial result of the first test <4 ng/mL. The range of variation between first and second tests was computed. Risks of cancer stratified on Gleason score were computed using logistic regression. A total of 31,286 men had 2 PSA tests within 2 years and with an initial value < 4 ng/mL. From the first to the second test, the median variation of PSA levels was 3.4% (interquartile range, -15% to +26%). The variation in PSA value was not associated with the delay between the first and the second test (P = .36), age (P = .16), body mass index (P = .41), and race (P = .12). A total of 2,781 prostate cancers were diagnosed during follow-up. Adjusting for age and initial PSA level, the risk of prostate cancer increased linearly with increasing PSA level at the second test, with an odds ratio of 1.079 (95% confidence interval, 1.058-1.101) for each percent increase in PSA level. However, the variation in PSA was not associated with a higher Gleason score (P = .95 for level variations in cancer of Gleason score < 7 vs ≥ 7). Although an increase in PSA level over time is associated with increased risk of prostate cancer, this association is not related to more aggressive tumors