Unveiling unconventional magnetism at the surface of Sr2RuO4.

Materials with strongly correlated electrons often exhibit interesting physical properties. An example of these materials is the layered oxide perovskite Sr2RuO4, which has been intensively investigated due to its unusual properties. Whilst the debate on the symmetry of the superconducting state in Sr2RuO4 is still ongoing, a deeper understanding of the Sr2RuO4 normal state appears crucial as this is the background in which electron pairing occurs. Here, by using low-energy muon spin spectroscopy we discover the existence of surface magnetism in Sr2RuO4 in its normal state. We detect static weak dipolar fields yet manifesting at an onset temperature higher than 50 K. We ascribe this unconventional magnetism to orbital loop currents forming at the reconstructed Sr2RuO4 surface. Our observations set a reference for the discovery of the same magnetic phase in other materials and unveil an electronic ordering mechanism that can influence electron pairing with broken time reversal symmetry.

Glomerular hyperfiltration with hyperglycemia in the spontaneously diabetic Torii (SDT) fatty rat, an obese type 2 diabetic model.

Glomerular hyperfiltration is observed in an early stage of kidney diseases including diabetic nephropathy. A better understanding of pathophysiological changes in glomerular hyperfiltration is essential for development of new therapies to prevent kidney disease progression. In this study, we investigated glomerular changes including glomerular filtration rate (GFR) and glomerular size in the Spontaneously Diabetic Torii (SDT) fatty rat, an obese type 2 diabetic model, and we also evaluated pharmacological effects of the sodium glucose cotransporter 2 inhibitor dapagliflozin on the renal lesions. Dapagliflozin was administered to SDT fatty rats from 5 to 17 weeks of age. Blood and urinary biochemical parameters were periodically measured. GFR was determined by transdermal GFR monitor at 16 weeks of age and histopathological analysis was performed at 17 weeks of age. SDT fatty rat developed severe hyperglycemia and exhibited pathophysiological abnormalities in the kidney, such as an increased GFR, glomerular hypertrophy and tissue lesions. Dapagliflozin achieved good glycemic control during the experimental period, inhibited the increase in GFR, and improved histopathological abnormalities in tubules. These results suggest that the SDT fatty rat is a useful model for analyzing the pathogenesis of diabetic nephropathy during its early stage and dapagliflozin improves not only hyperglycemia but also glomerular hyperfiltration and tubule lesions in SDT fatty rat.

Messenger RNA expression and localization of xenin in the gastrointestinal tract in sheep.

The present study aimed to determine the primary sequence of ovine xenin and clarify the mRNA expression and peptide localization of xenin in the gastrointestinal tract in sheep. The colocalization of xenin and glucose-dependent insulinotropic polypeptide was also compared in the antrum and duodenum. Analysis of the nucleotide sequence of ovine xenin revealed a high degree (97.9%) of sequence homology of the sequence between sheep and cattle, and the amino acids sequence determined for ovine xenin coincided (100%) with that of other mammalian species. Real-time quantitative PCR for ovine xenin did not show regional difference in the mRNA expression ratio of xenin. In contrast to the real-time quantitative PCR results, anti-xenin positive cells were abundantly localized in the abomasal antrum (P < 0.01) and at a lesser amount in the duodenum, but no antixenin positive cells were observed in the other regions. Anti-xenin single-positive cells were in a majority in the abomasal antrum, whereas anti-xenin single-positive cells, and anti-GIP single-positive cells, and double-positive cells were even colocalized in the duodenum. These results suggest that abomasal antrum is a major source of xenin in the ovine gastrointestinal tract.

Higher levels of social and material deprivation are associated with higher rates of influenza-like illness-related emergency department visits: Edmonton, Alberta, 2004-2014.

OBJECTIVES: Neighbourhood-level deprivation is associated with hospitalization related to respiratory infections; however, hospitalizations exclude many who seek care with less severe respiratory illnesses. Another major seasonal contributor to respiratory illness-associated healthcare burdens are influenza-like illness (ILI)-related emergency department (ED) visits. We investigated associations between area-level social and material deprivation and ILI-related ED use. STUDY DESIGN: This is a retrospective ecological study. METHODS: We linked ILI-related ED visit data (2004-2014) for Edmonton, Alberta to a Canadian area-level material and social deprivation index, categorizing deprivation into quintiles. Using a multivariable Poisson model with log population as the offset, we modelled the relationship between visit rates and material and social deprivation adjusting for week and season, age, sex and the interaction between age and sex. RESULTS: We included 67,585 ILI-related ED visits, representing 1075.5 (95% confidence interval (CI) = 1067.4-1083.6) visits per 100,000 person-years. ILI-related visit rates increased as each of material and social deprivation increased; increases were slightly greater for material deprivation. Comparing the most deprived quintile to the least deprived quintile: for material deprivation, ILI-related ED visit rates were two times higher (rate ratio (RR) = 2.00, 95% CI = 1.96-2.05); and, for social deprivation, one-and-a-half times higher (RR = 1.47, 95% CI = 1.44-1.51). CONCLUSIONS: Higher area-level material and social deprivation were associated with higher ILI-related ED visit rates. These findings can be used to identify areas that may need additional public health and healthcare resources and to improve targeting of prevention strategies. Understanding differentials in healthcare use such as this may be especially relevant to ensuring equity of outcomes for pandemic preparedness planning.

Predicting influenza-like illness-related emergency department visits by modelling spatio-temporal syndromic surveillance data.

Predicting the magnitude of the annual seasonal peak in influenza-like illness (ILI)-related emergency department (ED) visit volumes can inform the decision to open influenza care clinics (ICCs), which can mitigate pressure at the ED. Using ILI-related ED visit data from the Alberta Real Time Syndromic Surveillance Net for Edmonton, Alberta, Canada, we developed (training data, 1 August 2004-31 July 2008) and tested (testing data, 1 August 2008-19 February 2014) spatio-temporal statistical prediction models of daily ILI-related ED visits to estimate high visit volumes 3 days in advance. Our Main Model, based on a generalised linear mixed model with random intercept, incorporated prediction residuals over 14 days and captured increases in observed volume ahead of peaks. During seasonal influenza periods, our Main Model predicted volumes within ±30% of observed volumes for 67%-82% of high-volume days and within 0.3%-21% of observed seasonal peak volumes. Model predictions were not as successful during the 2009 H1N1 pandemic. Our model can provide early warning of increases in ILI-related ED visit volumes during seasonal influenza periods of differing intensities. These predictions may be used to support public health decisions, such as if and when to open ICCs, during seasonal influenza epidemics.

Long-term crude probabilities of death among breast cancer patients by age and stage: a population-based survival study in Northeastern Spain (Girona-Tarragona 1985-2004)

Background: We provide population-based long-term survival indicators of breast cancer patients by quantifying the observed survival, and the probabilities of death due to breast cancer and to other causes by age and tumor stage at diagnosis. Methods; We included a total of 10,195 female patients diagnosed before 85 years with invasive primary breast cancer in Girona and Tarragona during the periods 1985-1994 and 1995-2004 and followed-up until December 31st 2014. The survival indicators were estimated at 5, 10, 15 and 20 years of follow-up comparing diagnostic periods. Results: Comparing diagnostic periods: I) the probability of death due to other causes did not change; II) the 20-year survival for women diagnosed ≤ 49 years increased 13% (1995-2004 = 68%; 1985-1994:55%), whereas their probability of death due to breast cancer decreased at the same pace (1995-2004 = 29%; 1985-1994 = 42%); III) at 10 years of follow-up, decreases in the probabilities of death due to breast cancer across age groups switched from 11 to 17% resulting in a risk of death reduction of 19% after adjusting by stage. During 1995-2004, the stage-specific 10-year probabilities of death due to breast cancer switched from: 3-6% in stage I, 18-20% in stage II, 34-46% in stage III and surpassed 70% in stage IV beyond 5 years after diagnosis. Conclusions: In our study, women diagnosed with breast cancer had higher long-term probability to die from breast cancer than from other causes. The improvements in treatment and the lead-time bias in detecting cancer in an early stage resulted in a reduction of 19% in the risk of death between diagnostic periods

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Long-term crude probabilities of death among breast cancer patients by age and stage: a population-based survival study in Northeastern Spain (Girona-Tarragona 1985-2004).

BACKGROUND: We provide population-based long-term survival indicators of breast cancer patients by quantifying the observed survival, and the probabilities of death due to breast cancer and to other causes by age and tumor stage at diagnosis. METHODS: We included a total of 10,195 female patients diagnosed before 85 years with invasive primary breast cancer in Girona and Tarragona during the periods 1985-1994 and 1995-2004 and followed-up until December 31st 2014. The survival indicators were estimated at 5, 10, 15 and 20 years of follow-up comparing diagnostic periods. RESULTS: Comparing diagnostic periods: I) the probability of death due to other causes did not change; II) the 20-year survival for women diagnosed ≤ 49 years increased 13% (1995-2004 = 68%; 1985-1994:55%), whereas their probability of death due to breast cancer decreased at the same pace (1995-2004 = 29%; 1985-1994 = 42%); III) at 10 years of follow-up, decreases in the probabilities of death due to breast cancer across age groups switched from 11 to 17% resulting in a risk of death reduction of 19% after adjusting by stage. During 1995-2004, the stage-specific 10-year probabilities of death due to breast cancer switched from: 3-6% in stage I, 18-20% in stage II, 34-46% in stage III and surpassed 70% in stage IV beyond 5 years after diagnosis. CONCLUSIONS: In our study, women diagnosed with breast cancer had higher long-term probability to die from breast cancer than from other causes. The improvements in treatment and the lead-time bias in detecting cancer in an early stage resulted in a reduction of 19% in the risk of death between diagnostic periods.

Anatomy of the inferior extensor retinaculum and its role in lateral ankle ligament reconstruction: a pictorial essay.

The inferior extensor retinaculum (IER) is an aponeurotic structure, which is in continuation with the anterior part of the sural fascia. The IER has often been used to augment the reconstruction of the lateral ankle ligaments, for instance in the Broström-Gould procedure, with good outcomes reported. However, its anatomy has not been described in detail and only a few studies are available on this structure. The presence of a non-constant oblique supero-lateral band appears to be important. This structure defines whether the augmentation of the lateral ankle ligaments reconstruction is performed using true IER or only the anterior part of the sural fascia. It is concluded that the use of this structure will have an impact on the resulting ankle stability.

Synovial mesenchymal stem cells from osteo- or rheumatoid arthritis joints exhibit good potential for cartilage repair using a scaffold-free tissue engineering approach.

OBJECTIVE: To assess whether synovial mesenchymal stem cells (SMSCs) from patients with osteoarthritis (OA) or rheumatoid arthritis (RA) can be used as an alternative cell source for cartilage repair using allogenic tissue engineered construct (TEC). METHODS: Twenty-five patients (17 female, average age 61.8 years) were divided according to their pathology (control trauma group; N = 6, OA group; N = 6) and RA patients were subdivided into two groups to evaluate the impact of biologics in accordance with whether treated with biologics [Bio(+)RA; N = 7] or not [Bio(-)RA; N = 6]. We compared the following characteristics among these groups: (1) The cell proliferation capacity of SMSCs; (2) The influence of passage number on features of SMSCs; (3) The weight and volume of TEC from the same number of SMSCs; (4) Inflammatory cytokine gene expressions levels of TEC; (5) The chondrogenic potential of TEC; and (6) Osteochondral repair using TEC in athymic nude rats. RESULTS: SMSCs from the four groups exhibited equivalent features in the above evaluation items. In in vivo studies, the TEC-treated repair tissues for all groups exhibited significantly better outcomes than those for the untreated group and no significant differences among the four TEC groups. CONCLUSION: SMSCs from OA or RA patients are no less appropriate for repairing cartilage than those from trauma patients and thus, may be an effective source for allogenic cell-based cartilage repair.

Possible observation of highly itinerant quantum magnetic monopoles in the frustrated pyrochlore Yb2Ti2O7.

The low-energy elementary excitations in frustrated quantum magnets have fascinated researchers for decades. In frustrated Ising magnets on a pyrochlore lattice possessing macroscopically degenerate spin-ice ground states, the excitations have been discussed in terms of classical magnetic monopoles, which do not contain quantum fluctuations. Here we report unusual behaviours of magneto-thermal conductivity in the disordered spin-liquid regime of pyrochlore Yb2Ti2O7, which hosts frustrated spin-ice correlations with large quantum fluctuations owing to pseudospin-1/2 of Yb ions. The analysis of the temperature and magnetic field dependencies shows the presence of gapped elementary excitations. We find that the gap energy is largely suppressed from that expected in classical monopoles. Moreover, these excitations propagate a long distance without being scattered, in contrast to the diffusive nature of classical monopoles. These results suggests the emergence of highly itinerant quantum magnetic monopole, which is a heavy quasiparticle that propagates coherently in three-dimensional spin liquids.

Google Flu Trends in Canada: a comparison of digital disease surveillance data with physician consultations and respiratory virus surveillance data, 2010-2014.

The value of Google Flu Trends (GFT) remains unclear after it overestimated the proportion of physician visits related to influenza-like illness (ILI) in the United States in 2012-2013. However, GFT estimates (%GFT) have not been examined nationally in Canada nor compared with positivity for respiratory viruses other than influenza. For 2010-2014, we compared %GFT for Canada to Public Health Agency of Canada ILI consultation rates (%PHAC) and to positivity for influenza A and B, respiratory syncytial virus (RSV), human metapneumovirus (hMPV), and rhinoviruses. %GFT correlated well with %PHAC (ρ = 0·77-0·90) and influenza A positivity (ρ = 0·64-0·96) and overestimated the 2012-2013 %PHAC peak by 0·99 percentage points. %GFT peaks corresponded temporally with peaks in positivity for influenza A and rhinoviruses (all seasons) and RSV and hMPV when their peaks preceded influenza peaks. In Canada, %GFT represented traditional surveillance data and corresponded temporally with patterns in circulating respiratory viruses.

Survival in stage I-III breast cancer patients by surgical treatment in a publicly funded health care system.

BACKGROUND: Recent investigations of breast cancer survival in the United States suggest that patients who receive mastectomy have poorer survival than those who receive breast-conserving surgery (BCS) plus radiotherapy, despite clinically established equivalence. This study investigates breast cancer survival in the publicly funded health care system present in Alberta, Canada. PATIENTS AND METHODS: Surgically treated stage I-III breast cancer cases diagnosed in Alberta from 2002 to 2010 were included. Demographic, treatment and mortality information were collected from the Alberta Cancer Registry. Unadjusted overall and breast cancer-specific mortality was assessed using Kaplan-Meier and cumulative incidence curves, respectively. Cox proportional hazards models were used to calculate stage-specific mortality hazard estimates associated with surgical treatment received. RESULTS: A total of 14 939 cases of breast cancer (14 633 patients) were included in this study. The unadjusted 5-year all-cause survival probabilities for patients treated with BCS plus radiotherapy, mastectomy, and BCS alone were 94% (95% CI 93% to 95%), 83% (95% CI 82% to 84%) and 74% (95% CI 70% to 78%), respectively. Stage II and III patients who received mastectomy had a higher all-cause (stage II HR = 1.36, 95% CI 1.13-1.48; stage III HR = 1.74, 95% CI 1.24-2.45) and breast cancer-specific (stage II HR = 1.39, 95% CI 1.09-1.76; stage III HR = 1.79, 95% CI 1.21-2.65) mortality hazard compared with those who received BCS plus radiotherapy, adjusting for patient and clinical characteristics. BCS alone was consistently associated with poor survival. CONCLUSIONS: Stage II and III breast cancer patients diagnosed in Alberta, Canada, who received mastectomy had a significantly higher all-cause and breast cancer-specific mortality hazard compared with those who received BCS plus radiotherapy. We suggest greater efforts toward educating and encouraging patients to receive BCS plus radiotherapy rather than mastectomy when it is medically feasible and appropriate.

Subgroup effects in a randomised trial of different types and doses of exercise during breast cancer chemotherapy.

BACKGROUND: The Combined Aerobic and Resistance Exercise Trial tested different types and doses of exercise in breast cancer patients receiving chemotherapy. Here, we explore potential moderators of the exercise training responses. METHODS: Breast cancer patients initiating chemotherapy (N=301) were randomly assigned to three times a week, supervised exercise of a standard dose of 25-30 min of aerobic exercise, a higher dose of 50-60 min of aerobic exercise, or a higher dose of 50-60 min of combined aerobic and resistance exercise. Outcomes were patient-reported symptoms and health-related fitness. Moderators were baseline demographic, exercise/fitness, and cancer variables. RESULTS: Body mass index moderated the effects of the exercise interventions on bodily pain (P for interaction=0.038), endocrine symptoms (P for interaction=0.029), taxane/neuropathy symptoms (P for interaction=0.013), aerobic fitness (P for interaction=0.041), muscular strength (P for interaction=0.007), and fat mass (P for interaction=0.005). In general, healthy weight patients responded better to the higher-dose exercise interventions than overweight/obese patients. Menopausal status, age, and baseline fitness moderated the effects on patient-reported symptoms. Premenopausal, younger, and fitter patients achieved greater benefits from the higher-dose exercise interventions. CONCLUSIONS: Healthy weight, fitter, and premenopausal/younger breast cancer patients receiving chemotherapy are more likely to benefit from higher-dose exercise interventions.

Anatomical and functional pathways of rhythmogenic inspiratory premotor information flow originating in the pre-Bötzinger complex in the rat medulla.

The pre-Bötzinger complex (preBötC) of the ventrolateral medulla is the kernel for inspiratory rhythm generation. However, it is not fully understood how inspiratory neural activity is generated in the preBötC and propagates to other medullary regions. We analyzed the detailed anatomical connectivity to and from the preBötC and functional aspects of the inspiratory information propagation from the preBötC on the transverse plane of the medulla oblongata. Tract-tracing with immunohistochemistry in young adult rats demonstrated that neurokinin-1 receptor- and somatostatin-immunoreactive neurons in the preBötC, which could be involved in respiratory rhythmogenesis, are embedded in the plexus of axons originating in the contralateral preBötC. By voltage-imaging in rhythmically active slices of neonatal rats, we analyzed origination and propagation of inspiratory neural activity as depolarizing wave dynamics on the entire transverse plane as well as within the preBötC. Novel combination of pharmacological blockade of glutamatergic transmission and mathematical subtraction of the video images under blockade from the control images enabled to extract glutamatergic signal propagations. By ultra-high-speed voltage-imaging we first demonstrated the inter-preBötC conduction process of inspiratory action potentials. Intra-preBötC imaging with high spatiotemporal resolution during a single spontaneous inspiratory cycle unveiled deterministic nonlinearities, i.e., chaos, in the population recruitment. Collectively, we comprehensively elucidated the anatomical pathways to and from the preBötC and dynamics of inspiratory neural information propagation: (1) From the preBötC in one side to the contralateral preBötC, which would synchronize the bilateral rhythmogenic kernels, (2) from the preBötC directly to the bilateral hypoglossal premotor and motor areas as well as to the nuclei tractus solitarius, and (3) from the hypoglossal premotor areas toward the hypoglossal motor nuclei. The coincidence of identified anatomical and functional connectivity between the preBötC and other regions in adult and neonatal rats, respectively, indicates that this fundamental connectivity is already well developed at the time of birth.

Breast cancer: trends in international incidence in men and women.

BACKGROUND: The age-standardised incidence of breast cancer varies geographically, with rates in the highest-risk countries more than five times those in the lowest-risk countries. METHODS: We investigated the correlation between male (MBC) and female breast cancer (FBC) incidence stratified by female age-group (<50 years, and ≥50 years) and used Poisson regression to examine male incidence rate ratios according to female incidence rates. RESULTS: Age-adjusted breast cancer incidence rates for males and females share a similar geographic distribution (Spearman's correlation=0.51; P<0.0001). A correlation with male incidence rates was found for the entire female population and for women aged 50 years and over. Breast cancer incidence rates in males aged <50 years were not associated with FBC incidence, whereas those in males aged 50 years were. MBC incidence displays a small 'hook' similar to the Clemmesen's hook for FBC, but at a later age than the female hook. INTERPRETATION: Further investigation of possible explanations for these patterns is warranted. Although the incidence of breast cancer is much lower in men than in women, it may be possible to identify a cause common to both men and women.

socs7, a target gene of microRNA-145, regulates interferon-ß induction through STAT3 nuclear translocation in bladder cancer cells.

We recently reported that microRNA (miR)-145 is downregulated and induces apoptosis in human bladder cancer cells. Also, it is suggested that the ectopic expression of miR-145 induces apoptosis with the induction of TRAIL expression in several cancer cells. Here, we demonstrated a novel mechanism of apoptosis induction by miR-145 in bladder cancer cells. Exogenous miR-145 in T24 and NKB1 cells markedly increased the expression levels of interferon (IFN)-ß, 2'-5'-oligoadenylate synthetase 1, which lies upstream of 2'-5' oligoadenylates/RNase L system, and TRAIL, and induced apparent caspase-dependent apoptosis that was suppressed by cotreatment with a pan-caspase inhibitor; moreover, these expression levels were reduced by cotreatment with an miR-145 inhibitor. The apoptosis did not depend on Toll-like receptor 3 (TLR3) expression, because TLR3-silencing failed to inhibit IFN-ß induction by miR-145. Then, we focused on the suppressor of cytokine signaling 7 (socs7), whose expression level was upregulated in bladder cancer cells compared with its level in normal human urothelial cells, as a putative target gene involved in IFN-ß induction by miR-145. Expectedly, exogenous miR-145 decreased the expression level of SOCS7, and socs7-silencing enhanced IFN-ß induction by transfection with a TLR3 ligand, polyinosinic acid-polycytidylic acid (PIC). The results of a luciferase reporter assay revealed that miR-145 targeted socs7. In addition, socs7-silencing significantly decreased the level of p-Akt and suppressed the growth of T24 cells. Furthermore, exogenous miR-145 or socs7-silencing promoted nuclear translocation of STAT3. In conclusion, the machinery of IFN-ß induction through the regulation of SOCS7 by miR-145 was closely associated with the induction of apoptosis. Moreover, exogenous miR-145 promoted IFN-ß induction by targeting socs7, which resulted in the nuclear translocation of STAT3. Additionally, our data indicate that SOCS7 functioned as an oncogene, the finding that revealed a novel mechanism of carcinogenesis in bladder cancer cells.

Noninvasive estimation of fibrosis progression overtime using the FIB-4 index in chronic hepatitis C.

The FIB-4 index is a simple formula to predict liver fibrosis based on the standard biochemical values (AST, ALT and platelet count) and age. We here investigated the utility of the index for noninvasive prediction of progression in liver fibrosis. The time-course alteration in the liver fibrosis stage between paired liver biopsies and the FIB-4 index was examined in 314 patients with chronic hepatitis C. The average interval between liver biopsies was 4.9 years. The cases that showed a time-course improvement in the fibrosis stage exhibited a decrease in the FIB-4 index, and those that showed deterioration in the fibrosis stage exhibited an increase in the FIB-4 index with a significant correlation (P < 0.001). Increase in the ΔFIB-4 index per year was an independent predictive factor for the progression in liver fibrosis with an odds ratio of 3.90 (P = 0.03). The area under the receiver operating characteristic curve of the ΔFIB-4 index/year for the prediction of advancement to cirrhosis was 0.910. Using a cut-off value of the ΔFIB-4 index/year <0.4 or ≥ 0.4, the cumulative incidence of fibrosis progression to cirrhosis at 5 and 10 years was 34% and 59%, respectively in patients with the ΔFIB-4 index/year ≥0.4, whereas it was 0% and 3% in those with the ΔFIB-4 index/year <0.4 (P < 0.001). In conclusion, measurement of the time-course changes in the FIB-4 index is useful for the noninvasive and real-time estimation of the progression in liver fibrosis.

Referral rate to oncologists and its variation by hospital for colorectal cancer patients.

BACKGROUND: Recent population-based studies in Alberta, Canada, found that approximately 50% of patients with stage III colon or stages II/III rectal adenocarcinoma did not receive guideline-recommended treatment (surgery plus chemotherapy or chemoradiation); a primary reason was not having an oncologist consult. We assessed the relationship between the hospital where the surgery was performed and the probability of a patient not having an oncologist consult. METHODS: All patients diagnosed with stage III colon or stage II/III rectal adenocarcinoma between 2002 and 2005 in Alberta who had surgery were identified from the Alberta Cancer Registry and included in the study. Multivariable logistic regression modeling with hospitals as random effects was used to estimate cancer-type-specific odds ratios of not having an oncologist consult for each hospital, adjusted for age, sex, and comorbidities, relative to the overall nonconsultation rate. RESULTS: Overall, 21% of stage III colon, 25% of stage II rectal, and 13% of stage III rectal adenocarcinoma patients did not have an oncologist consult. Rates varied appreciably across hospitals and between cancer types within hospitals, even after the case-mix adjustment (adjusted odds ratios of nonconsultation ranged from 0.4 to 8.1). Small hospitals that performed 12 or fewer surgeries had nearly 100% consultation rates. CONCLUSIONS: The variation in oncologist-consult rates, particularly for stage II rectal cancer patients, is concerning. We are presenting the findings to the surgical community and discussing interventions to improve oncologist-consult rates.

Early-stage formation of an epigenetic field defect in a mouse colitis model, and non-essential roles of T- and B-cells in DNA methylation induction.

Epigenetic fields for cancerization are involved in development of human cancers, especially those associated with inflammation and multiple occurrences. However, it is still unclear when such field defects are formed and what component of inflammation is involved in induction of aberrant DNA methylation. Here, in a mouse colitis model induced by dextran sulfate sodium (DSS), we identified three CpG islands specifically methylated in colonic epithelial cells exposed to colitis. Their methylation levels started to increase as early as 8 weeks after DSS treatment and continued to increase until colon cancers developed at 15 weeks. In contrast to the temporal profile of DNA methylation levels, infiltration of inflammatory cells spiked immediately after the DSS treatment and then gradually decreased. Exposure of cultured colonic epithelial cells to DSS did not induce DNA methylation and it was indicated that inflammation triggered by the DSS treatment was responsible for methylation induction. To clarify components of inflammation involved, severe combined immunodeficiency (SCID) mice that lack functional T- and B-cells were similarly treated. Even in SCID mice, DNA methylation, along with colon tumors, were induced at the same levels as in their background strain of mice (C.B17). Comparative analysis of inflammation-related genes showed that Ifng, Il1b and Nos2 had expression concordant with methylation induction whereas Il2, Il6, Il10, Tnf did not. These results showed that an epigenetic field defect is formed at early stages of colitis-associated carcinogenesis and that functional T and B cells are non-essential for the formation.

Adherence to treatment guidelines in stage II/III rectal cancer in Alberta, Canada.

AIMS: Evidence suggests that pre- and/or postoperative treatment benefits patients with stage II/III rectal cancer. This study aimed to quantify treatment patterns and adherence to treatment guidelines, and to identify barriers to having a consultation with an oncologist and barriers to receiving treatment in stage II/III rectal cancer, in a publicly funded medical care system. MATERIALS AND METHODS: Patients with surgically treated stage II/III rectal adenocarcinoma, diagnosed from 2002 to 2005 in Alberta, a Canadian province with a population of 3 million, were included. Demographic and treatment information from the Alberta Cancer Registry were linked to data from electronic medical records, hospital discharge data and the 2001 Canadian Census. The study outcomes were 'not having an oncologist consultation' and 'not receiving guideline-based treatment'. The relative risks of the two outcomes in association with patient characteristics were estimated using multivariable log-binomial regression. RESULTS: Of a total of 910 surgically treated stage II/III rectal adenocarcinoma patients, 748 (82%) had a consultation with an oncologist and 414 (45.5%) received treatment. Pre-/post-surgical treatment modalities and timing varied; 96 (10.5%) received neoadjuvant treatment only, 389 (42.7%) received adjuvant treatment only, 119 (13.1%) received both, and 306 (33.6%) had surgery alone. Factors related to not having a consultation with an oncologist included older age, co-morbidities, cancer stage II and region of residence. Older age was the most significantly associated factor with not receiving treatment (relative risk=2.23; 95% confidence interval: 1.89, 2.64). CONCLUSIONS: Disparities exist in the receipt of treatment in stage II/III rectal cancer. Factors such as age, region of residence and stage should not be barriers to consulting an oncologist to discuss or receive treatment. The reasons for these disparities need to be identified and addressed.