To estimate risk of colorectal cancer (CRC) for first-degree relatives of CRC cases based on CRC molecular subtypes and tumour pathology features.
We studied a cohort of 33,496 first-degree relatives ...of 4853 incident invasive CRC cases (probands) who were recruited to the Colon Cancer Family Registry through population cancer registries in the USA, Canada and Australia. We categorised the first-degree relatives into four groups: 28,156 of 4095 mismatch repair (MMR)-proficient probands, 2302 of 301 MMR-deficient non-Lynch syndrome probands, 1799 of 271 suspected Lynch syndrome probands and 1239 of 186 Lynch syndrome probands. We compared CRC risk for first-degree relatives stratified by the absence or presence of specific tumour molecular pathology features in probands across each of these four groups and for all groups combined.
Compared with first-degree relatives of MMR-proficient CRC cases, a higher risk of CRC was estimated for first-degree relatives of CRC cases with suspected Lynch syndrome (HR 2.06, 95% CI 1.59 to 2.67) and with Lynch syndrome (HR 5.37, 95% CI 4.16 to 6.94), but not with MMR-deficient non-Lynch syndrome (HR 1.04, 95% CI 0.82 to 1.31). A greater risk of CRC was estimated for first-degree relatives if CRC cases were diagnosed before age 50 years, had proximal colon cancer or if their tumours had any of the following: expanding tumour margin, peritumoral lymphocytes, tumour-infiltrating lymphocytes or synchronous CRC.
Molecular pathology features are potentially useful to refine screening recommendations for first-degree relatives of CRC cases and to identify which cases are more likely to be caused by genetic or other familial factors.
Low vitamin D status is common globally and is associated with multiple disease outcomes. Understanding the correlates of vitamin D status will help guide clinical practice, research, and ...interpretation of studies. Correlates of circulating 25-hydroxyvitamin D (25(OH)D) concentrations measured in a single laboratory were examined in 4,723 cancer-free men and women from 10 cohorts participating in the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers, which covers a worldwide geographic area. Demographic and lifestyle characteristics were examined in relation to 25(OH)D using stepwise linear regression and polytomous logistic regression. The prevalence of 25(OH)D concentrations less than 25 nmol/L ranged from 3% to 36% across cohorts, and the prevalence of 25(OH)D concentrations less than 50 nmol/L ranged from 29% to 82%. Seasonal differences in circulating 25(OH)D were most marked among whites from northern latitudes. Statistically significant positive correlates of 25(OH)D included male sex, summer blood draw, vigorous physical activity, vitamin D intake, fish intake, multivitamin use, and calcium supplement use. Significant inverse correlates were body mass index, winter and spring blood draw, history of diabetes, sedentary behavior, smoking, and black race/ethnicity. Correlates varied somewhat within season, race/ethnicity, and sex. These findings help identify persons at risk for low vitamin D status for both clinical and research purposes.
Bioconversion of crude glycerol by fungi Nicol, R. W.; Marchand, K.; Lubitz, W. D.
Applied microbiology and biotechnology,
03/2012, Letnik:
93, Številka:
5
Journal Article
Recenzirano
The production of synthetic glycerol from petrochemical feedstocks has been decreasing in recent years. This is largely due to increasing supplies of crude glycerol derived as a co-product from the ...oleochemical industry, especially biodiesel production. The price of glycerol is at historic lows, and the supply of crude glycerol is projected to grow faster than its industrial uses. This oversupply is driving the transition from glycerol as a product to glycerol as a precursor for new industrial applications, including its use as a substrate for bioconversion. This article reviews the use of fungi for the bioconversion of crude glycerol to the value-added products 1,2-propanediol, ethanol, single cell oil, specialty polyunsaturated fatty acids, biosurfactants, and organic acids. Information on the impurities of crude glycerol from different industrial processes is also included.
To identify prediagnostic plasma metabolomic biomarkers associated with amyotrophic lateral sclerosis (ALS).
We conducted a global metabolomic study using a nested case-control study design within 5 ...prospective cohorts and identified 275 individuals who developed ALS during follow-up. We profiled plasma metabolites using liquid chromatography-mass spectrometry and identified 404 known metabolites. We used conditional logistic regression to evaluate the associations between metabolites and ALS risk. Further, we used machine learning analyses to determine whether the prediagnostic metabolomic profile could discriminate ALS cases from controls.
A total of 31 out of 404 identified metabolites were associated with ALS risk (
< 0.05). We observed inverse associations (n = 27) with plasma levels of diacylglycerides and triacylglycerides, urate, purine nucleosides, and some organic acids and derivatives, while we found positive associations for a cholesteryl ester, 2 phosphatidylcholines, and a sphingomyelin. The number of significant associations increased to 67 (63 inverse) in analyses restricted to cases with blood samples collected within 5 years of onset. None of these associations remained significant after multiple comparison adjustment. Further, we were not able to reliably distinguish individuals who became cases from controls based on their metabolomic profile using partial least squares discriminant analysis, elastic net regression, random forest, support vector machine, or weighted correlation network analyses.
Although the metabolomic profile in blood samples collected years before ALS diagnosis did not reliably separate presymptomatic ALS cases from controls, our results suggest that ALS is preceded by a broad, but poorly defined, metabolic dysregulation years before the disease onset.
The production of the
η
c
(
1
S
)
state in proton-proton collisions is probed via its decay to the
p
p
¯
final state with the LHCb detector, in the rapidity range
2.0
<
y
<
4.5
and in the meson ...transverse-momentum range
p
T
>
6.5
GeV
/
c
. The cross-section for prompt production of
η
c
(
1
S
)
mesons relative to the prompt
J
/
ψ
cross-section is measured, for the first time, to be
σ
η
c
(
1
S
)
/
σ
J
/
ψ
=
1.74
±
0.29
±
0.28
±
0
.
18
B
at a centre-of-mass energy
s
=
7
TeV
using data corresponding to an integrated luminosity of 0.7 fb
-
1
, and
σ
η
c
(
1
S
)
/
σ
J
/
ψ
=
1.60
±
0.29
±
0.25
±
0
.
17
B
at
s
=
8
TeV
using 2.0 fb
-
1
. The uncertainties quoted are, in order, statistical, systematic, and that on the ratio of branching fractions of the
η
c
(
1
S
)
and
J
/
ψ
decays to the
p
p
¯
final state. In addition, the inclusive branching fraction of
b
-hadron decays into
η
c
(
1
S
)
mesons is measured, for the first time, to be
B
(
b
→
η
c
X
)
=
(
4.88
±
0.64
±
0.29
±
0
.
67
B
)
×
10
-
3
, where the third uncertainty includes also the uncertainty on the
J
/
ψ
inclusive branching fraction from
b
-hadron decays. The difference between the
J
/
ψ
and
η
c
(
1
S
)
meson masses is determined to be
114.7
±
1.5
±
0.1
MeV
/
c
2
.
Objective
The relationship of diet quality assessed by established indices (HEI‐2010, AHEI‐2010, aMED, DASH) with adiposity measures was examined, especially visceral adipose tissue (VAT) and ...nonalcoholic fatty liver (NAFL).
Methods
Close to 2,000 participants of the Multiethnic Cohort completed validated food frequency questionnaires at cohort entry (1993‐1996) and clinic visit (2013‐2016) when they underwent whole‐body dual‐energy x‐ray absorptiometry and abdominal magnetic resonance imaging scans. Linear regression was used to estimate mean values of adiposity measures by dietary index tertiles at baseline and standardized regression coefficients (βs) after adjusting for total adiposity and other covariates. Logistic regression of VAT and NAFL on dietary indices was also performed.
Results
Higher dietary quality scores at cohort entry were inversely related to all adiposity measures, with the strongest associations for percent liver fat (βs = −0.14 to −0.08), followed by VAT (βs = −0.11 to −0.05), BMI (βs = −0.11 to −0.06), and total body fat (βs = −0.09 to −0.05). Odds ratios adjusted for total adiposity ranged between 0.57 and 0.77 for NAFL and between 0.41 and 0.65 for high VAT when comparing the highest versus lowest tertiles of diet quality.
Conclusions
These longitudinal findings indicate that maintaining a high‐quality diet during mid‐to‐late adulthood may prevent adverse metabolic consequences related to VAT and NAFL.
Is high vitamin B12 status a cause of lung cancer? Fanidi, Anouar; Carreras‐Torres, Robert; Larose, Tricia L. ...
International journal of cancer,
15 September 2019, Letnik:
145, Številka:
6
Journal Article
Recenzirano
Odprti dostop
Vitamin B supplementation can have side effects for human health, including cancer risk. We aimed to elucidate the role of vitamin B12 in lung cancer etiology via direct measurements of ...pre‐diagnostic circulating vitamin B12 concentrations in a nested case–control study, complemented with a Mendelian randomization (MR) approach in an independent case–control sample. We used pre‐diagnostic biomarker data from 5183 case–control pairs nested within 20 prospective cohorts, and genetic data from 29,266 cases and 56,450 controls. Exposures included directly measured circulating vitamin B12 in pre‐diagnostic blood samples from the nested case–control study, and 8 single nucleotide polymorphisms associated with vitamin B12 concentrations in the MR study. Our main outcome of interest was increased risk for lung cancer, overall and by histological subtype, per increase in circulating vitamin B12 concentrations. We found circulating vitamin B12 to be positively associated with overall lung cancer risk in a dose response fashion (odds ratio for a doubling in B12 ORlog2B12 = 1.15, 95% confidence interval (95%CI) = 1.06–1.25). The MR analysis based on 8 genetic variants also indicated that genetically determined higher vitamin B12 concentrations were positively associated with overall lung cancer risk (OR per 150 pmol/L standard deviation increase in B12 ORSD = 1.08, 95%CI = 1.00–1.16). Considering the consistency of these two independent and complementary analyses, these findings support the hypothesis that high vitamin B12 status increases the risk of lung cancer.
What's new?
Several B‐complex vitamins have been linked to cancer risk. In this study, high serum levels of vitamin B12 were associated with an increased risk of lung cancer. The authors first ran a nested case‐control study, then confirmed their findings using a Mendelian randomization approach based on genetic data from a much larger database including both lung‐cancer patients and controls. The authors conclude that these findings support the hypothesis that high circulating vitamin B12 concentrations increase the risk of lung cancer.
The literature on associations of circulating concentrations of minerals and vitamins with risk of colorectal cancer is limited and inconsistent. Evidence from randomized controlled trials (RCTs) to ...support the efficacy of dietary modification or nutrient supplementation for colorectal cancer prevention is also limited.
To complement observational and RCT findings, we investigated associations of genetically predicted concentrations of 11 micronutrients (β-carotene, calcium, copper, folate, iron, magnesium, phosphorus, selenium, vitamin B-6, vitamin B-12, and zinc) with colorectal cancer risk using Mendelian randomization (MR).
Two-sample MR was conducted using 58,221 individuals with colorectal cancer and 67,694 controls from the Genetics and Epidemiology of Colorectal Cancer Consortium, Colorectal Cancer Transdisciplinary Study, and Colon Cancer Family Registry. Inverse variance-weighted MR analyses were performed with sensitivity analyses to assess the impact of potential violations of MR assumptions.
Nominally significant associations were noted for genetically predicted iron concentration and higher risk of colon cancer ORs per SD (ORSD): 1.08; 95% CI: 1.00, 1.17; P value = 0.05 and similarly for proximal colon cancer, and for vitamin B-12 concentration and higher risk of colorectal cancer (ORSD: 1.12; 95% CI: 1.03, 1.21; P value = 0.01) and similarly for colon cancer. A nominally significant association was also noted for genetically predicted selenium concentration and lower risk of colon cancer (ORSD: 0.98; 95% CI: 0.96, 1.00; P value = 0.05) and similarly for distal colon cancer. These associations were robust to sensitivity analyses. Nominally significant inverse associations were observed for zinc and risk of colorectal and distal colon cancers, but sensitivity analyses could not be performed. None of these findings survived correction for multiple testing. Genetically predicted concentrations of β-carotene, calcium, copper, folate, magnesium, phosphorus, and vitamin B-6 were not associated with disease risk.
These results suggest possible causal associations of circulating iron and vitamin B-12 (positively) and selenium (inversely) with risk of colon cancer.
High-speed electric drive design is concerned with paying particular attention to thermal and mechanical design of the machine. Therefore, this paper proposes a multiphysic modeling of an interior ...permanent-magnet synchronous machine (IPMSM) dedicated to high speed, including magnetic, electric, thermal, and mechanical aspects. The proposed analytical models are verified using finite-element (FE) computations. These models are then subjected to a multiobjective optimization-based on genetic algorithm-to design an IPMSM for a high-speed compressor application that develops 30 kW at 20 000 r/min. The design is formulated as a constrained optimization problem consisting of maximizing the machine efficiency while minimizing its weight. The result of this process is a Pareto front between efficiency and weight of the machine allowing the designer to make a posteriori choice. A particular optimal machine is chosen and its performances are validated with FE analysis. This study carries out an optimal multiphysic and multiobjective design approach that allows rationalization of the design process in a realistic computation time thanks to the analytical models involved.
Estuaries of Southeast Asia are increasingly impacted by land-cover changes and pollution. Here, our research objectives were to (1) determine the origins of nutrient loads along the Can Gio estuary ...(Vietnam) and (2) identify the processes that affect the nutrient pools during the monsoon. We constructed four 24-h time-series along the salinity gradient measuring nutrient concentrations and stable isotopes values. In the upper estuary, urban effluents from Ho Chi Minh City were the main input of nutrients, leading to dissolved oxygen saturation <20%. In the lower estuary, ammonium and nitrite concentration peaks were explained by mangrove export. No contribution from aquaculture was detected, as it represents <0.01% of the total river discharge. Along the salinity gradient, nutrient inputs were rapidly consumed, potentially by phytoplankton while nitrate dual-stable isotopes indicated that nitrification occurred. Thus, even in a large and productive estuary, urban wastewater can affect nutrient dynamics with potentially important ecological risks.
•Nutrient dynamics during the wet season were studied along the Can Gio Estuary.•Nutrients in the upper estuary originated from urban wastewater•Mangrove-derived nutrients dominated the lower estuary•Nutrients from aquaculture seemed to be rapidly diluted.•Nitrification, phytoplankton and heterotrophic activity are key elements of nutrient cycling.
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