Body size and the risk of biliary tract cancer: a population-based study in China

Though obesity is an established risk factor for gall bladder cancer, its role in cancers of the extrahepatic bile ducts and ampulla of Vater is less clear, as also is the role of abdominal obesity. In a population-based case–control study of biliary tract cancer in Shanghai, China, odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for biliary tract cancer in relation to anthropometric measures, including body mass index (BMI) at various ages and waist-to-hip ratio (WHR), adjusting for age, sex, and education. The study included 627 patients with biliary tract cancer (368 gall bladder, 191 bile duct, 68 ampulla of Vater) and 959 healthy subjects randomly selected from the population. A higher BMI at all ages, including early adulthood (ages 20–29 years), and a greater WHR were associated with an increased risk of gall bladder cancer. A high usual adult BMI (⩾25) was associated with a 1.6-fold risk of gall bladder cancer (95% CI 1.2–2.1, P for trend <0.001). Among subjects without gallstones, BMI was also positively associated with gall bladder cancer risk. Regardless of BMI levels, increasing WHR was associated with an excess risk of gall bladder cancer risk, with those having a high BMI (⩾25) and a high WHR (>0.90) having the highest risk of gall bladder cancer (OR=12.6, 95% CI 4.8–33.2), relative to those with a low BMI and WHR. We found no clear risk patterns for cancers of the bile duct and ampulla of Vater. These results suggest that both overall and abdominal obesity, including obesity in early adulthood, are associated with an increased risk of gall bladder cancer. The increasing prevalence of obesity and cholesterol stones in Shanghai seems at least partly responsible for the rising incidence of gall bladder cancer in Shanghai

Learning Moore Machines from Input-Output Traces

The problem of learning automata from example traces (but no equivalence or membership queries) is fundamental in automata learning theory and practice. In this paper we study this problem for finite state machines with inputs and outputs, and in particular for Moore machines. We develop three algorithms for solving this problem: (1) the PTAP algorithm, which transforms a set of input-output traces into an incomplete Moore machine and then completes the machine with self-loops; (2) the PRPNI algorithm, which uses the well-known RPNI algorithm for automata learning to learn a product of automata encoding a Moore machine; and (3) the MooreMI algorithm, which directly learns a Moore machine using PTAP extended with state merging. We prove that MooreMI has the fundamental identification in the limit property. We also compare the algorithms experimentally in terms of the size of the learned machine and several notions of accuracy, introduced in this paper. Finally, we compare with OSTIA, an algorithm that learns a more general class of transducers, and find that OSTIA generally does not learn a Moore machine, even when fed with a characteristic sample

A nurse-led implantable loop recorder service is safe and cost effective

Introduction: Implantable loop recorders (ILR) are predominantly implanted by cardiologists in the catheter laboratory. We developed a nurse‐delivered service for the implantation of LINQ (Medtronic; Minnesota) ILRs in the outpatient setting. This study compared the safety and cost‐effectiveness of the introduction of this nurse‐delivered ILR service with contemporaneous physician‐led procedures. / Methods: Consecutive patients undergoing an ILR at our institution between 1st July 2016 and 4th June 2018 were included. Data were prospectively entered into a computerized database, which was retrospectively analyzed. / Results: A total of 475 patients underwent ILR implantation, 271 (57%) of these were implanted by physicians in the catheter laboratory and 204 (43%) by nurses in the outpatient setting. Six complications occurred in physician‐implants and two in nurse‐implants (P = .3). Procedural time for physician‐implants (13.4 ± 8.0 minutes) and nurse‐implants (14.2 ± 10.1 minutes) were comparable (P = .98). The procedural cost was estimated as £576.02 for physician‐implants against £279.95 with nurse‐implants, equating to a 57.3% cost reduction. In our center, the total cost of ILR implantation in the catheter laboratory by physicians was £10 513.13 p.a. vs £6661.55 p.a. with a nurse‐delivered model. When overheads for running, cleaning, and maintaining were accounted for, we estimated a saving of £68 685.75 was performed by moving to a nurse‐delivered model for ILR implants. Over 133 catheter laboratory and implanting physician hours were saved and utilized for other more complex procedures. / Conclusion: ILR implantation in the outpatient setting by suitably trained nurses is safe and leads to significant financial savings

Ordering phenomena in quasi one-dimensional organic conductors

Low-dimensional organic conductors could establish themselves as model systems for the investigation of the physics in reduced dimensions. In the metallic state of a one-dimensional solid, Fermi-liquid theory breaks down and spin and charge degrees of freedom become separated. But the metallic phase is not stable in one dimension: as the temperature is reduced, the electronic charge and spin tend to arrange themselves in an ordered fashion due to strong correlations. The competition of the different interactions is responsible for which broken-symmetry ground state is eventually realized in a specific compound and which drives the system towards an insulating state. Here we review the various ordering phenomena and how they can be identified by optic and magnetic measurements. While the final results might look very similar in the case of a charge density wave and a charge-ordered metal, for instance, the physical cause is completely different. When density waves form, a gap opens in the density of states at the Fermi energy due to nesting of the one-dimension Fermi surface sheets. When a one-dimensional metal becomes a charge-ordered Mott insulator, on the other hand, the short-range Coulomb repulsion localizes the charge on the lattice sites and even causes certain charge patterns. We try to point out the similarities and conceptional differences of these phenomena and give an example for each of them. Particular emphasis will be put on collective phenomena which are inherently present as soon as ordering breaks the symmetry of the system.Comment: Review article Naturwissenschaften 200

SMARTphone-based, early cardiac REHABilitation in patients with acute coronary syndromes [SMART-REHAB Trial]: A randomized controlled trial protocol

© 2016 The Author(s). Background: There are well-documented treatment gaps in secondary prevention of coronary heart disease and no clear guidelines to assist early physical activity after acute coronary syndromes (ACS). Smartphone technology may provide an innovative platform to close these gaps. This paper describes the study design of a randomized controlled trial assessing whether a smartphone-based secondary prevention program can facilitate early physical activity and improve cardiovascular health in patients with ACS. Methods: We have developed a multi-faceted, patient-centred smartphone-based secondary prevention program emphasizing early physical activity with a graduated walking program initiated on discharge from ACS admission. The program incorporates; physical activity tracking through the smartphone's accelerometer with interactive feedback and goal setting; a dynamic dashboard to review and optimize cardiovascular risk factors; educational messages delivered twice weekly; a photographic food diary; pharmacotherapy review; and support through a short message service. The primary endpoint of the trial is change in exercise capacity, as measured by the change in six-minute walk test distance at 8-weeks when compared to baseline. Secondary endpoints include improvements in cardiovascular risk factor status, psychological well-being and quality of life, medication adherence, uptake of cardiac rehabilitation and re-hospitalizations. Discussion: This randomized controlled trial will use a smartphone-phone based secondary prevention program to emphasize early physical activity post-ACS. It will provide evidence regarding the feasibility and utility of this innovative platform in closing the treatment gaps in secondary prevention. Trial registration: The trial was retrospectively registered in the Australian New Zealand Clinical Trials Registry (ANZCTR) on April 4, 2016. The registration number is ACTRN12616000426482

Long-Term Impact of Body Mass Index on Survival of Patients Undergoing Cardiac Resynchronization Therapy: A Multi-Centre Study

Obesity is a risk factor for heart failure (HF), but its presence among HF patients may be associated with favorable outcomes. We investigated the long-term outcomes across different body mass index (BMI) groups, after cardiac resynchronization therapy (CRT), and whether defibrillator back-up (CRT-D) confers survival benefit. One thousand two-hundred seventy-seven (1,277) consecutive patients (mean age: 67.0 ± 12.7 years, 44.1% women, and mean BMI: 28.3 ± 5.6 Kg/m2) who underwent CRT implantation in 5 centers between 2000-2014 were followed-up for a median period of 4.9 years (IQR 2.4 to 7.5). More than 10% of patients had follow-up for ≥10 years. Patients were classified according to BMI as normal: 75% of patients, but were used less frequently in obese individuals. The composite endpoint of all-cause mortality or cardiac transplant/left ventricular assist device (LVAD) occurred in 50.9% of patients. At 10-year follow-up, less than a quarter of patients in the lowest and highest BMI categories were still alive and free from heart transplant/LVAD. After adjustment BMI of 25 to 29.9 Kg/m2 (HR = 0.73 [95%CI 0.56 to 0.96], p = 0.023) and use of CRT-D (HR = 0.74 [95% CI 0.55 to 0.98], p = 0.039) were independent predictors of survival free from LVAD/heart transplant. BMI of 25 to 29.9 Kg/m2 at the time of implant was independently associated with favourable long-term 10-year survival. Use of CRT-D was associated with improved survival irrespective of BMI class

Estimating required information size by quantifying diversity in random-effects model meta-analyses

<p>Abstract</p> <p>Background</p> <p>There is increasing awareness that meta-analyses require a sufficiently large information size to detect or reject an anticipated intervention effect. The required information size in a meta-analysis may be calculated from an anticipated <it>a priori </it>intervention effect or from an intervention effect suggested by trials with low-risk of bias.</p> <p>Methods</p> <p>Information size calculations need to consider the total model variance in a meta-analysis to control type I and type II errors. Here, we derive an adjusting factor for the required information size under any random-effects model meta-analysis.</p> <p>Results</p> <p>We devise a measure of diversity (<it>D</it>²) in a meta-analysis, which is the relative variance reduction when the meta-analysis model is changed from a random-effects into a fixed-effect model. <it>D</it>²is the percentage that the between-trial variability constitutes of the sum of the between-trial variability and a sampling error estimate considering the required information size. <it>D</it>²is different from the intuitively obvious adjusting factor based on the common quantification of heterogeneity, the inconsistency (<it>I</it>²), which may underestimate the required information size. Thus, <it>D</it>²and <it>I</it>²are compared and interpreted using several simulations and clinical examples. In addition we show mathematically that diversity is equal to or greater than inconsistency, that is <it>D</it>²≥ <it>I</it>², for all meta-analyses.</p> <p>Conclusion</p> <p>We conclude that <it>D</it>²seems a better alternative than <it>I</it>²to consider model variation in any random-effects meta-analysis despite the choice of the between trial variance estimator that constitutes the model. Furthermore, <it>D</it>²can readily adjust the required information size in any random-effects model meta-analysis.</p

Risk of second primary cancer in men with breast cancer

INTRODUCTION: A retrospective registry-based cohort study was conducted to examine the risk of second primary cancer following the occurrence of breast cancer in males. METHODS: Data obtained from the California Cancer Registry in the period 1988 to 2003 included 1,926 men aged 85 years and younger diagnosed with a first primary breast cancer. Person-year analysis was applied to determine the risk of second primary cancers after the occurrence of a first primary breast cancer. The effects of age, race, and time since the first breast cancer diagnosis were assessed. RESULTS: Of the 1,926 male breast cancer cases, 221 (11.5%) developed a second primary cancer. Men with first incidence of breast cancer have a significantly higher risk of second cancer (standardized incidence ratio (SIR) = 1.16, 95% confidence interval (CI) = 1.01–1.32). The risk of a second site-specific cancer is elevated for breast cancer (SIR = 52.12, 95% CI = 31.83–80.49), cutaneous melanoma (SIR = 2.98, 95% CI = 1.63–5.00) and stomach cancer (SIR = 2.11, 95% CI = 1.01–3.88). There is a general tendency towards higher risks of second malignancies among younger men compared to older men and the risk increased with the passage of time. CONCLUSION: Male breast cancer patients should be monitored carefully for the occurrence of second primary cancers, especially a second primary breast cancer

Increased Incidence of Choroid Plexus Carcinoma Due to the Germline TP53 R337H Mutation in Southern Brazil

International audienceBACKGROUND: Choroid plexus carcinomas (CPC) are rare tumors predominantly found in children. Given the high frequency of the germline R337H mutation in the TP53 gene in southern Brazil, we have evaluated the frequency of the R337H mutation in families with CPC in children. METHODOLOGY/PRINCIPAL FINDINGS: The present series included 29 patients that were admitted to the same institution from 1992 to 2010, including 22 children with CPC (0.08-13.6 years of age at diagnosis) and 7 children with papilloma of the choroid plexus (Pp; 0.5-9.8 years of age). Surgical resection was possible in 28 children. Blood and/or tumor DNA was extracted and analyzed using PCR-RFLP and results were confirmed by sequencing 240 bp of the TP53 exon 10. The patients, all parents, and some relatives submitted samples for blood DNA analysis. In addition, we have also examined the presence of the mutation in DNA from paraffin-embedded tumor samples to evaluate loss of heterozygosity. We found 63.3% (14/22) of the CPC patients positive for the germline R337H mutation; CPC samples were either heterozygous (n = 7), lost only the wild-type (n = 4), or only the R337H copy (n = 2). One CPC sample was not available. All Pp cases (7/7, 100%) were negative for R337H. Cure (>5 years survival free of disease) was observed in 18.1% of the CPC cases with the R337H mutation (2/11), 71.4% of the Pp (5/7), and 25% of CPC cases negative for the R337H mutation (2/8). Family history of cancer (with 2 or more cancer cases) was exclusively identified on the parental side segregating the R337H mutation, and 50% (7/14) of them were compatible with Li-Fraumeni-like syndrome. SIGNIFICANCE: Our results show for the first time that the R337H TP53 mutation is responsible for 63% of the CPC cases in children, suggesting a higher incidence of CPC in southern Brazil