Purpose
– The purpose of this paper is to present a new method to establish a kinematic model for a continuum manipulator, whose end can be controlled to move in a three-dimensional workspace. A ...continuum manipulator has significant advantages over traditional, rigid manipulators in many applications because of its ability to conform to the environment. Moreover, because of its excellent flexibility, light weight, low energy consumption, low production cost, it has a number of potential applications in areas of earthquake relief, agricultural harvesting, medical facilities and space exploration.
Design/methodology/approach
– This paper uses basic theory of material mechanics to deduct motion equations of the manipulator. Unlike other published papers, the manipulator is not based on segments tactics, but regarded as an integrated flexible system, which simplifies its kinematics modelling and motion controlling. The workspace of the manipulator is analysed by theoretical deducing and simulation modelling. For verification of the presented theory, simulation based on ADAMS software was implemented, while a prototype of the manipulator was developed. Both the software simulation and prototype experiment show that the theoretical analysis in this paper is reasonable. The manipulator can move accurately along the desired trajectories.
Findings
– This paper developed a novel and fully continuous manipulator driven by steel wires. A kinematic model of the manipulator was established. The physical manipulator developed for verifying the kinematic model can effectively track the prescribed trajectory. The presented kinematic model agrees with not only the simulation but also with the experiment.
Research limitations/implications
– The manipulator presented in this paper is constructed by steel wires. It possesses the advantages of structural continuity, high flexibility and low production cost. It can be extensively used in many fields, such as search and rescue robotic systems. The limitation of this research is that the dynamic model of the manipulator is not yet clear, which is one of the directions for future research.
Practical implications
– The manipulator breaks through the limitation of the joint-type or flexible-link-type manipulator, which can also be extensively used in many fields such as search and rescue robotic systems.
Social implications
– The manipulator developed in this paper, currently, is a prototype under the project of “Automatic Picking Manipulator Research”. It possesses a good market value.
Originality/value
– The value of this research is that the manipulator breaks through the limitation of the joint-type or flexible-link-type manipulator and establishes the kinematic model for a fully continuous manipulator by a simple strategy. This is the first study that uses such a strategy for establishing the motion equations of a monolithic continuum manipulator.
•Symptoms of irritable bowel syndrome (IBS) are common reasons for endoscopic procedures.•We examined the yield of colonoscopy and upper endoscopy in IBS in a large cohort.•Inflammatory bowel ...disease, precancerous polyps, colorectal cancer, and celiac disease were all less common in IBS compared to controls.•Microscopic colitis was more common in IBS patients.•The yield of upper endoscopy and colonoscopy for organic disease is low in patients with a first-time diagnosis of IBS.
: Symptoms of irritable bowel syndrome (IBS) are common reasons for endoscopic procedures. We examined the yield of colonoscopy and upper endoscopy in IBS for several organic diseases.
: Matched population-based prevalence study in Sweden. We identified 21,944 participants diagnosed with IBS from 1987 to 2016 undergoing colonoscopy with a biopsy from all of Sweden's 28 pathology departments within 6 months of diagnosis. We compared prevalence of histopathology-proven diagnoses of inflammatory bowel disease (IBD), colorectal cancer, precancerous polyps, and microscopic colitis between patients recently diagnosed with IBS and matched controls without IBS (n = 81,101) undergoing colonoscopy. We also compared prevalence of celiac disease between patients diagnosed with IBS (n = 9,965) and matched controls (n = 45,584) undergoing upper endoscopy with biopsy. IBS patients were also compared to their siblings. Conditioned logistic regression estimated adjusted odds ratios (aORs).
: Biopsy-proven IBD was seen in 1.6% of IBS and in 5.9% of controls (aOR=0.21; 95%CI=0.19–0.24). The prevalence of precancerous polyps was 4.1% vs. 13.0% (aOR=0.28; 95%CI=0.26–0.30), colorectal cancer 0.8% vs. 6.3% (aOR=0.17; 95%CI=0.14–0.20) and celiac disease 1.9% vs. 3.4% (aOR=0.54; 95%CI=0.47–0.63). Conversely, the prevalence of microscopic colitis was 2.9% vs. 1.7% (aOR=1.77; 95%CI=1.61–1.95), with higher prevalence in older patients and patients with IBS with diarrhea. Yield of colonoscopy for precancerous polyps, colorectal cancer, and microscopic colitis increased by age. Our findings were consistent using unaffected siblings as the comparator group.
: The diagnostic yield of upper endoscopy and colonoscopy for organic disease is low in patients with a first-time diagnosis of IBS, though increases with age.
Polygenic risk scores (PRS) which summarize individuals' genetic risk profile may enhance targeted colorectal cancer screening. A critical step towards clinical implementation is rigorous external ...validations in large community-based cohorts. This study externally validated a PRS-enhanced colorectal cancer risk model comprising 140 known colorectal cancer loci to provide a comprehensive assessment on prediction performance.
The model was developed using 20,338 individuals and externally validated in a community-based cohort (n = 85,221). We validated predicted 5-year absolute colorectal cancer risk, including calibration using expected-to-observed case ratios (E/O) and calibration plots, and discriminatory accuracy using time-dependent AUC. The PRS-related improvement in AUC, sensitivity and specificity were assessed in individuals of age 45 to 74 years (screening-eligible age group) and 40 to 49 years with no endoscopy history (younger-age group).
In European-ancestral individuals, the predicted 5-year risk calibrated well E/O = 1.01; 95% confidence interval (CI), 0.91-1.13 and had high discriminatory accuracy (AUC = 0.73; 95% CI, 0.71-0.76). Adding the PRS to a model with age, sex, family and endoscopy history improved the 5-year AUC by 0.06 (P < 0.001) and 0.14 (P = 0.05) in the screening-eligible age and younger-age groups, respectively. Using a risk-threshold of 5-year SEER colorectal cancer incidence rate at age 50 years, adding the PRS had a similar sensitivity but improved the specificity by 11% (P < 0.001) in the screening-eligible age group. In the younger-age group it improved the sensitivity by 27% (P = 0.04) with similar specificity.
The proposed PRS-enhanced model provides a well-calibrated 5-year colorectal cancer risk prediction and improves discriminatory accuracy in the external cohort.
The proposed model has potential utility in risk-stratified colorectal cancer prevention.
Background
A preventive potential of high calcium intake against colorectal cancer has been indicated for distal colon cancer, which is inversely associated with high-level CpG island methylator ...phenotype (CIMP), high-level microsatellite instability (MSI), and
BRAF
and
PIK3CA
mutations. In addition,
BRAF
mutation is strongly inversely correlated with
KRAS
mutation. We hypothesized that the association between calcium intake and colon cancer risk might vary by these molecular features.
Methods
We prospectively followed 88,506 women from the Nurses’ Health Study and 47,733 men from the Health Professionals Follow-up Study for up to 30 years. Duplication-method Cox proportional cause-specific hazards regression was used to estimate multivariable hazard ratios (HRs), and 95% confidence intervals (95% CIs) for the associations between calcium intake and the risk of colon cancer subtypes. By Bonferroni correction, the α-level was adjusted to 0.01.
Results
Based on 853 colon cancer cases, the inverse association between dietary calcium intake and colon cancer risk differed by CIMP status (
p
heterogeneity
= 0.01). Per each 300 mg/day increase in intake, multivariable HRs were 0.84 (95% CI 0.76–0.94) for CIMP-negative/low and 1.12 (95% CI 0.93–1.34) for CIMP-high. Similar differential associations were suggested for MSI subtypes (
p
heterogeneity
= 0.02), with the corresponding HR being 0.86 (95% CI 0.77–0.95) for non-MSI-high and 1.10 (95% CI 0.92–1.32) for MSI-high. No differential associations were observed by
BRAF, KRAS
, or
PIK3CA
mutations.
Conclusion
The inverse association between dietary calcium intake and colon cancer risk may be specific to CIMP-negative/low and possibly non-MSI-high subtypes.
The association between prediagnostic antibody responses to
(
) and subsequent risk of colorectal cancer is not established.
We conducted a nested case-control study of 8,126 participants in a ...consortium of 10 prospective cohorts in the United States.
Higher seroprevalence of any
antibody was observed among non-White participants (51.1%) compared with White participants (31.2%). We did not find any statistically significant association between seropositivity to any of the eight
proteins and colorectal cancer risk.
Prediagnostic antibody responses to
proteins were not associated with the risk of colorectal cancer.
Future studies may consider a more specific detection of the immunoglobulin isotypes or focus on examining
in stool or tissue samples.
Epidemiologic evidence for specific types and sources of dietary fat and individual fatty acid with colorectal cancer (CRC) risk remains inconclusive. We aimed to comprehensively examine the ...associations of intake of specific types (saturated-, monounsaturated-, polyunsaturated-, and trans-) and sources (animal-, dairy-, and vegetable-) of dietary fat and fatty acids with CRC risk.
We prospectively followed-up 65,550 women from the Nurses’ Health Study (1986–2014) and 45,684 men from the Health Professionals Follow-up Study (1986–2014). Dietary intake was assessed every 4 years using food frequency questionnaires. Self-reported CRC cases were confirmed through medical record review. Time-dependent Cox proportional hazards regression was used to estimate the HR for intakes of dietary fat and fatty acids and CRC risk.
During 2,705,560 person-years of follow-up, 2726 incident CRC cases were confirmed. Intake of monounsaturated fatty acid (MUFA) tended to be positively associated with the risk of CRC (HR comparing extreme quintiles 1.21; 95% CI 1.00, 1.47; P = 0.06 for trend) compared with total carbohydrates. This positive association was mainly driven by MUFA from animal sources (MUFA-As) (HR 1.25; 95% CI 1.02, 1.53; P = 0.02 for trend). The positive association between MUFA-As and CRC was attenuated after adjusting for red and processed meat consumption (HR 1.17; 95% CI 0.94, 1.46). Other types and sources of fat intake and individual fatty acid intake were not associated with CRC risk. Isocalorically replacing MUFA-As with equivalent energy (5%) from carbohydrates from whole grains was associated with a trend towards a lower risk of CRC (HR 0.88; 95% CI 0.77, 1.01).
Higher intake of MUFA-As was associated with higher CRC risk compared with total carbohydrates or carbohydrates from whole grains, possibly due to other components of animal-sourced foods. We did not find clear associations between other types and sources of dietary fat and CRC risk.
National Institutes of Health (UM1 CA186107, P01 CA87969, and U01 CA167552)
Incidence of early-onset colorectal cancer (EOCRC), defined by a diagnosed age under 50 years, is increasing, but its heterogeneous etiologies that differ from general CRC remain undetermined. We ...initially characterize the genome, epigenome, transcriptome, and proteome of tumors from 79 patients in a Chinese CRC cohort. Data for an additional 126 EOCRC subjects are obtained from the International Cancer Genome Consortium Chinese cohort and The Cancer Genome Atlas European cohort. We observe that early-onset tumors have a high tumor mutation burden; increased DNA repair features by mutational signature 3 and multi-layer pathway enrichments; strong perturbations at effects of DNA methylation and somatic copy-number alteration on gene expression; and upregulated immune infiltration as hot tumors underlying immunophenotypes. Notably, LMTK3 exhibits ancestral mutation disparity, potentially being a functional modulator and biomarker that drives molecular alterations in EOCRC development and immunotherapies. This integrative omics study provides valuable knowledge for precision oncology of CRC.
Display omitted
•An integrative omics study of early-onset colorectal cancer in a Chinese cohort•Omics architecture supports early-onset tumorigenesis and therapeutic development•Mutational landscape varies by ancestry, and LMTK3 mutation has Chinese specificity•LMTK3 works at DNA repair process, immunophenotype, and drug target
The molecular characterization of early-onset colorectal cancer remains undetermined. We report a multi-omics landscape of young colorectal tumors in a Chinese cohort. These profiles reveal distinct molecular alterations and immunophenotypes in early-onset tumorigenesis and provide an ancestry-specific LMTK3 as a modulator, biomarker, and therapeutic target for precision oncology.
Chronic inflammation may play a role in colorectal cancer (CRC) pathogenesis. The relationship between soluble tumour necrosis factor receptor type II (sTNF-RII) and survival among CRC patients is ...not well defined.
We prospectively evaluated the association between pre-diagnosis plasma levels of sTNF-RII and mortality in 544 CRC patients from the Nurses' Health Study and Health Professionals Follow-Up Study diagnosed from 1990 to 2010. Primary and secondary end points were overall and CRC-specific mortality, respectively. Cox proportional hazards models were used to calculate multivariate hazard ratios for mortality.
Higher sTNF-RII levels were significantly associated with increased overall mortality (multivariate HR=1.48, 95% CI 1.02-2.16, P-trend=0.006), but not with CRC-specific mortality (HR=1.23, 95% CI 0.72-2.08, P-trend=0.34). In subgroup analyses, among regular aspirin users, those with higher sTNF-RII levels had an adjusted HR of 0.52 (95% CI 0.20-1.33) for overall mortality compared with those with lower sTNF-RII levels, whereas among nonregular aspirin users the adjusted HR was 2.26 (95% CI 1.23-4.01, P for interaction=0.53).
Among CRC patients, higher sTNF-RII levels are associated with a significant increase in overall mortality, but not CRC-specific mortality. The role of inflammation and anti-inflammatory medications in survival of CRC patients warrants further exploration.
A positive association between circulating C-reactive protein (CRP) and colorectal cancer survival was reported in observational studies, which are susceptible to unmeasured confounding and reverse ...causality. We used a Mendelian randomization approach to evaluate the association between genetically predicted CRP concentrations and colorectal cancer-specific survival.
We used individual-level data for 16,918 eligible colorectal cancer cases of European ancestry from 15 studies within the International Survival Analysis of Colorectal Cancer Consortium. We calculated a genetic-risk score based on 52 CRP-associated genetic variants identified from genome-wide association studies. Because of the non-collapsibility of hazard ratios from Cox proportional hazards models, we used the additive hazards model to calculate hazard differences (HD) and 95% confidence intervals (CI) for the association between genetically predicted CRP concentrations and colorectal cancer-specific survival, overall and by stage at diagnosis and tumor location. Analyses were adjusted for age at diagnosis, sex, body mass index, genotyping platform, study, and principal components.
Of the 5,395 (32%) deaths accrued over up to 10 years of follow-up, 3,808 (23%) were due to colorectal cancer. Genetically predicted CRP concentration was not associated with colorectal cancer-specific survival (HD, -1.15; 95% CI, -2.76 to 0.47 per 100,000 person-years;
= 0.16). Similarly, no associations were observed in subgroup analyses by stage at diagnosis or tumor location.
Despite adequate power to detect moderate associations, our results did not support a causal effect of circulating CRP concentrations on colorectal cancer-specific survival.
Future research evaluating genetically determined levels of other circulating inflammatory biomarkers (i.e., IL6) with colorectal cancer survival outcomes is needed.
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