Pancreatitis is a known risk factor for pancreatic cancer; however, an unknown fraction of the disease is thought to be a consequence of tumor-related duct obstruction.
A pooled analysis of a history ...of pancreatitis and risk of pancreatic cancer was carried out considering the time interval between diagnoses and potential modification by covariates. Adjusted pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated from 10 case–control studies (5048 cases of ductal pancreatic adenocarcinoma and 10 947 controls) taking part in the International Pancreatic Cancer Case-Control Consortium (PanC4).
The association between pancreatitis and pancreatic cancer was nearly three-fold at intervals of >2 years between diagnoses (OR: 2.71, 95% CI: 1.96–3.74) and much stronger at intervals of ≤2 years (OR: 13.56, 95% CI: 8.72–21.90) probably reflecting a combination of reverse causation and antecedent misdiagnosis of pancreas cancer as pancreatitis. The younger (<65 years) pancreatic cancer cases showed stronger associations with previous (>2 years) pancreatitis (OR: 3.91, 95% CI: 2.53–6.04) than the older (≥65 years) cases (OR: 1.68, 95% CI: 1.02–2.76; P value for interaction: 0.006).
Despite a moderately strong association between pancreatitis (diagnosed before >2 years) and pancreatic cancer, the population attributable fraction was estimated at 1.34% (95% CI: 0.612–2.07%), suggesting that a relatively small proportion of pancreatic cancer might be avoided if pancreatitis could be prevented.
Gut microbiota has been suggested to affect lipid metabolism. The objective of this study was to characterize the faecal microbiota signature and both short chain fatty acids (SCFAs) and bile acids ...(BA) profile of hypercholesterolemic subjects. Microbiota composition, SCFAs, BA and blood lipid profile from male volunteers with hypercholesterolemia (HC) and normocholesterolemia (NC) were determined by 16S rDNA sequencing, HPLC, GC and NMR, respectively. HC subjects were characterized by having lower relative abundance of Anaeroplasma (0.002% vs 0.219%, p-value = 0.026) and Haemophilus (0.041% vs 0.078%, p-value = 0.049), and higher of Odoribacter (0.51% vs 0.16%; p-value = 0.044). Correlation analysis revealed that Anaeroplasma and Haemophilus were associated to an unfavourable lipid profile: they correlated negatively to cholesterol and triglycerides related biomarkers and the ratio total to high density lipoprotein (HDL) cholesterol, and positively to HDL size. Odoribacter displayed an opposite behaviour. Faecal SCFAs profile revealed higher abundance of isobutyric (2.76% vs 0.82%, p-value = 0.049) and isovaleric acid (1.32% vs 0.06%, p-value = 0.016) in HC. Isobutyric acid correlated positively with Odoribacter and lipid parameters indicative of an unfavourable profile. BA profile did not show differences between groups. It was concluded that HC subjects showed a particular faecal bacterial signature and SCFAs profile associated with their lipid profile.
Abstract
Massive stars (∼8–25
M
⊙
) stripped of their hydrogen-rich envelopes via binary interaction are thought to be the main progenitors for merging neutron stars and stripped-envelope supernovae. ...We recently presented the discovery of the first set of such stripped stars in a companion paper. Here, we fit the spectra of 10 stars with new atmosphere models in order to constrain their stellar properties precisely. We find that the stellar properties align well with the theoretical expectations from binary evolution models for helium-core burning envelope-stripped stars. The fits confirm that the stars have high effective temperatures (
T
eff
∼ 50–100 kK), high surface gravities (
log
g
∼
5), and hydrogen-poor/helium-rich surfaces (
X
H,surf
∼ 0–0.4) while showing for the first time a range of bolometric luminosities (10
3
–10
5
L
⊙
), small radii (∼0.5–1
R
⊙
), and low Eddington factors (Γ
e
∼ 0.006–0.4). Using these properties, we derive intermediate current masses (∼1–8
M
⊙
), which suggest that their progenitors were massive stars (∼5–25
M
⊙
) and that a subset will reach core-collapse, leaving behind neutron stars or black holes. Using the model fits, we also estimate the emission rates of ionizing photons for these stars, which agree well with previous model expectations. Further, by computing models for a range of mass-loss rates, we find that the stellar winds are weaker than predicted by any existing scheme (
M
̇
wind
≲
10
−
9
M
⊙
yr
−1
). The properties of this first sample of intermediate-mass helium stars suggest they both contain progenitors of type Ib and IIb supernovae, and provide important benchmarks for binary evolution and population synthesis models.
The hydrogen-rich outer layers of massive stars can be removed by interactions with a binary companion. Theoretical models predict that this stripping produces a population of hot helium stars of ~2 ...to 8 solar masses (
), however, only one such system has been identified thus far. We used ultraviolet photometry to identify potential stripped helium stars then investigated 25 of them using optical spectroscopy. We identified stars with high temperatures (~60,000 to 100,000 kelvin), high surface gravities, and hydrogen-depleted surfaces; 16 stars also showed binary motion. These properties match expectations for stars with initial masses of 8 to 25
that were stripped by binary interaction. Their masses fall in the gap between subdwarf helium stars and Wolf-Rayet stars. We propose that these stars could be progenitors of stripped-envelope supernovae.
In this work, we study in detail the sensitivity of the Antarctic Impulsive Transient Antenna (ANITA) to possible ντ point source fluxes detected via τ-lepton-induced air showers. This investigation ...is framed around the observation of four upward-going extensive air shower events very close to the horizon seen in ANITA-IV. We find that these four upgoing events are not observationally inconsistent with τ-induced EASs from Earth-skimming ντ both in their spectral properties as well as in their observed locations on the sky. These four events as well as the overall diffuse and point source exposure to Earth-skimming ντ are also compared against published ultrahigh-energy neutrino limits from the Pierre Auger Observatory. While none of these four events occurred at sky locations simultaneously visible by Auger, the implied fluence necessary for ANITA to observe these events is in strong tension with limits set by Auger across a wide range of energies and is additionally in tension with ANITA’s Askaryan in-ice neutrino channel above 1019 eV. We conclude by discussing some of the technical challenges with simulating and analyzing these near horizon events and the potential for future observatories to observe similar events.
Purpose The surgical margin is the main prognostic factor over which the surgeon has control during resection of oral squamous cell carcinoma (OSCC). This study examined the association between ...surgical excision margins of patients with OSCC and outcomes of disease-free and overall survival. Materials and Methods The authors implemented a retrospective cohort study. The sample was composed of patients with OSCC having resection as their initial treatment. The predictor variable was the pathologic surgical margin, defined as clear (>5 mm), close (1 to 5 mm), or involved (<1 mm). The outcome variables were disease-free (absence of locoregional recurrence) and overall survival. Data were analyzed using Kaplan-Meier survival curves and Cox regression hazard model. Results The sample was composed of 54 patients with a mean age of 60.5 years (range, 19 to 85 yr) and 26% were women. The 2- and 5-year overall survival rates were 59 and 50%, respectively. The clear surgical margin group showed higher disease-free survival rates than patients with close and involved margins (5-yr probability, 0.78 vs 0.43 and 0.29; P = .014) and a trend toward increased overall survival at 2 and 5 years ( P = .093). Conclusion The results suggest that the presence of a close surgical margin (1 to 5 mm) is an adverse risk feature comparable to an involved margin and therefore is associated with decreased disease-free and overall survival. Future studies are needed to replicate these findings before they can be used as a basis for clinical recommendations.
During the last century, afforestation and intensification of sheep grazing in the British uplands have led to widespread declines in globally rare heather moorland. We quantified changes in heather ...cover over 70 years in relation to changes in sheep grazing on Langholm Moor, and examined the impact on red grouse, a gamebird inhabiting heather moorland. Between 1948 and 2009, when grazed heavily by sheep, heather-dominated vegetation declined from 53 to 14% cover. Large-scale sheep reductions from 2011 then allowed increase of heather-dominated vegetation cover to 18% by 2015. However, changes in heather cover were associated with changes in grouse abundance only where heather-dominated cover was reduced below thresholds of 27% (95% CL 18–36%; pre-breeding) and 17% (95% CL 13–20%; post-breeding). The number of grouse shot between 1951 and 1992 remained high where 37–65% of dominant heather cover was retained, but then declined between 1992 and 1996 following increased predation by raptors, leading to the cessation of shooting. Subsequently, grouse densities fluctuated in relation to periodic management by gamekeepers (1992–1999 and 2008–2016), but heather loss continued possibly until 2011, and predation in this context prevented sustained increases sufficient for ‘driven’ shooting. Grouse shooting provides an economic incentive to maintain and restore heather moorland. On Langholm Moor, however, afforestation in the surrounding landscape and isolation from other heather moors may have led to a grouse population less well buffered against growing predation pressure, especially outside keepered periods. As grouse shooting could not be restored, the future management of the moor remains uncertain.
Summary Background Preclinical studies have shown synergistic antitumour activity by inhibition of insulin-like growth factor-1 receptor (IGF-1R) and mTOR. The expression of IGF-1R seems to be ...crucial for this effect. We investigated the safety and efficacy of the combination of the IGF-1R antibody cixutumumab and the mTOR inhibitor temsirolimus in patients with chemotherapy-refractory bone and soft-tissue sarcomas according to IGF-1R expression by immunohistochemistry. Methods We undertook a multicentre, open-label, phase 2 study in 19 cancer centres in the USA. Patients aged at least 16 years with a histologically confirmed diagnosis of bone or soft-tissue sarcoma were allocated on the basis of IGF-1R expression by immunohistochemistry to one of three treatment groups: IGF-1R-positive soft-tissue sarcoma (group A), IGF-1R-positive bone sarcomas (group B), or IGF-1R-negative bone and soft-tissue sarcoma (group C). Patients received weekly treatment with cixutumumab (6 mg/kg, intravenous) and temsirolimus (25 mg, intravenous flat dose) in 6-week cycles. A Simon optimal two-stage design was used for every arm. The primary endpoint was progression-free survival (PFS) at 12 weeks by intention-to-treat analysis in the first 54 patients assigned to every treatment arm. Although patients still remain on treatment, this trial has completed enrolment and this represents the final analysis. This study is registered with ClinicalTrials.gov , number NCT01016015. Findings Between Nov 18, 2009, and April 11, 2012, 388 patients were screened for IGF-1R expression and 54 were assigned to each arm. 17 of 54 patients in the IGF-1R-positive soft-tissue sarcoma group (31%; one-sided 95% CI lower bound 21%; two-sided 90% CI 21–43), 19 of 54 in IGF-1R-positive bone sarcoma group (35%; one-sided 95% CI lower bound 24%; two-sided 90% CI 24–47), and 21 of 54 in the IGF-1R-negative group (39%, one-sided 95% CI lower bound 28%; two-sided 90% CI 28–51) were progression free at 12 weeks. On April 6, 2011, the protocol was amended to include three additional patients in the IGF-1R-positive soft-tissue sarcoma group (total of 57 patients) and nine more in the IGF-1R-negative group (total of 63 patients). There were 2546 adverse events reported during the study, 214 (8%) of which were grade 3–4. The most common grade 3–4 toxicities in the 174 treated patients were anaemia in 16 (9%) patients, hyperglycaemia in 18 (10%), hypophosphataemia in 16 (9%), lymphopenia in 25 (14%), oral mucositis in 19 (11%), and thrombocytopenia in 19 (11%). Interpretation The combination of cixutumumab and temsirolimus shows clinical activity in patients with sarcoma and forms a basis for future trials. However, IGF-1R expression by immunohistochemistry is not predictive of clinical outcome after treatment with this combination. Funding National Cancer Institute and CycleforSurvival Fund, Memorial Sloan-Kettering Cancer Center.
The evaluation of abiotic and biotic variables can provide information for understanding the structure and function of lotic systems. To obtain this information, measurements of 15 chemical and ...physical variables and of phytoplankton were conducted at two sampling stations. The present study aims to evaluate the temporal and spatial variation of planktonic diatoms in terms of abiotic variables and the trophic level of the river water and to select diatom species as descriptors of the physical and chemical conditions of the water upstream (S1) and downstream (S2) of the Iguassu River over an annual cycle. Sampling station S1 was classified as oligotrophic to mesotrophic, and S2 was classified as ultra-oligotrophic to oligotrophic. A total of 98 diatom species distributed among 39 genera was recorded, showing no dominant species but 36 abundant species. Although the differences of chemical and physical variables between S1 and S2 were limited to greater turbulence and turbidity, processes triggered by heavy rainfall exerted a significant influence on community structure, and a temporal change in composition was observed. At the end of the dry period, due to the recovery of nutrients and high transparency, there was an abundance of Cocconeis placentula var. lineata. In the rainy period, with increased turbulence and turbidity processes resulting from higher rainfall, there was an abundance of Aulacoseira granulata var. granulata.
Background
Over the past 30 years, the prevalence of diabetes has steadily increased among Canadians, and is particularly evident among First Nations (FN) women. The interplay between FN ancestry, ...gestational diabetes and the development of subsequent diabetes among mothers remains unclear.
Methods
After excluding known pre‐existing diabetes, we explored whether FN ancestry may modify the association between gestational diabetes and post‐partum diabetes among women in Manitoba (1981–2011) via a historical prospective cohort database study. We analysed administrative data in the Population Health Research Data Repository using Kaplan–Meier survival analysis and Cox proportional hazards regression.
Results
Gestational diabetes was diagnosed in 11 906 of 404 736 deliveries (2.9%), 6.7% of FN and 2.2% of non‐FN pregnant women (P < 0.0001). Post‐partum diabetes during ≤ 30 years follow‐up was more than three times higher among FN women than among non‐FN women (P < 0.0001). Diabetes developed in 76.0% of FN and 56.2% of non‐FN women with gestational diabetes within the follow‐up period. The hazard ratio of gestational diabetes for post‐partum diabetes was 10.6 among non‐FN women and 5.4 among FN women. Other factors associated with a higher risk of diabetes included lower family income among FN and non‐FN women and rural/remote residences among FN women. Among non‐FN women, urban residence was associated with a higher risk of diabetes.
Conclusion
Gestational diabetes increases post‐partum diabetes in FN and non‐FN women. FN women had substantially more gestational diabetes or post‐partum diabetes than non‐FN women, partially due to socio‐economic and environmental barriers. Reductions in gestational diabetes and socio‐economic inequalities are required to prevent diabetes in women, particularly in FN population.
What's new?
This historical cohort study examined the impact of gestational diabetes after excluding pre‐existing diabetes in mothers who delivered between 1981 and 2011 in Manitoba, Canada.
First Nations (FN) women had two times more gestational diabetes and were three times more likely to develop post‐partum diabetes than non‐FN women.
Post‐partum diabetes in both FN and non‐FN mothers was affected by gestational diabetes, lower family income and rural residence.
The relative risk of developing post‐partum diabetes in non‐FN women was higher than in FN women.
The findings suggest that reductions in gestational diabetes and socio‐economic inequities are required to prevent post‐partum diabetes in FN and non‐FN women.
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