Single gene analysis in yeast suggests nonequilibrium regulatory dynamics for transcription.

Fluctuations in the initiation rate of transcription, the first step in gene expression, ensue from the stochastic behavior of the molecular process that controls transcription. In steady state, the regulatory process is often assumed to operate reversibly, i.e.

Radiation exposure and leukaemia risk among cohorts of persons exposed to low and moderate doses of external ionising radiation in childhood.

Background: Many high-dose groups demonstrate increased leukaemia risks, with risk greatest following childhood exposure; risks at low/moderate doses are less clear.

Methods: We conducted a pooled analysis of the major radiation-associated leukaemias (acute myeloid leukaemia (AML) with/without the inclusion of myelodysplastic syndrome (MDS), chronic myeloid leukaemia (CML), acute lymphoblastic leukaemia (ALL)) in ten childhood-exposed groups, including Japanese atomic bomb survivors, four therapeutically irradiated and five diagnostically exposed cohorts, a mixture of incidence and mortality data. Relative/absolute risk Poisson regression models were fitted.

Human lesions and animal studies link the claustrum to perception, salience, sleep and pain.

The claustrum is the most densely interconnected region in the human brain. Despite the accumulating data from clinical and experimental studies, the functional role of the claustrum remains unknown. Here, we systematically review claustrum lesion studies and discuss their functional implications.

Model-based learning retrospectively updates model-free values.

Reinforcement learning (RL) is widely regarded as divisible into two distinct computational strategies. Model-free learning is a simple RL process in which a value is associated with actions, whereas model-based learning relies on the formation of internal models of the environment to maximise reward. Recently, theoretical and animal work has suggested that such models might be used to train model-free behaviour, reducing the burden of costly forward planning.

The MuvB complex binds and stabilizes nucleosomes downstream of the transcription start site of cell-cycle dependent genes.

The chromatin architecture in promoters is thought to regulate gene expression, but it remains uncertain how most transcription factors (TFs) impact nucleosome position. The MuvB TF complex regulates cell-cycle dependent gene-expression and is critical for differentiation and proliferation during development and cancer. MuvB can both positively and negatively regulate expression, but the structure of MuvB and its biochemical function are poorly understood.

Lymphoma and multiple myeloma in cohorts of persons exposed to ionising radiation at a young age.

There is limited evidence that non-leukaemic lymphoid malignancies are radiogenic. As radiation-related cancer risks are generally higher after childhood exposure, we analysed pooled lymphoid neoplasm data in nine cohorts first exposed to external radiation aged <21 years using active bone marrow (ABM) and, where available, lymphoid system doses, and harmonised outcome classification. Relative and absolute risk models were fitted.

Occupational radiation and haematopoietic malignancy mortality in the retrospective cohort study of US radiologic technologists, 1983-2012.

Objectives: To evaluate cumulative occupational radiation dose response and haematopoietic malignancy mortality risks in the US radiologic technologist cohort.

Methods: Among 110 297 radiologic technologists (83 655 women, 26 642 men) who completed a baseline questionnaire sometime during 1983-1998, a retrospective cohort study was undertaken to assess cumulative, low-to-moderate occupational radiation dose and haematopoietic malignancy mortality risks during 1983-2012. Cumulative bone marrow dose (mean 8.

Lung cancer mortality associated with protracted low-dose occupational radiation exposures and smoking behaviors in U.S. radiologic technologists, 1983-2012.

In the Japanese atomic bomb survivors, risk of lung cancer has been shown to increase with greater acute exposure to ionizing radiation. Although similar findings have been observed in populations exposed to low-dose, protracted radiation, such studies lack information on cigarette smoking history, a potential confounder. In a cohort of 106 068 U.

Association of Radioactive Iodine Treatment With Cancer Mortality in Patients With Hyperthyroidism.

Importance: Radioactive iodine (RAI) has been used extensively to treat hyperthyroidism since the 1940s. Although widely considered a safe and effective therapy, RAI has been associated with elevated risks of total and site-specific cancer death among patients with hyperthyroidism.

Objective: To determine whether greater organ- or tissue-absorbed doses from RAI treatment are associated with overall and site-specific cancer mortality in patients with hyperthyroidism.

Occupational radiation exposure and risk of cataract incidence in a cohort of US radiologic technologists.

It has long been known that relatively high-dose ionising radiation exposure (> 1 Gy) can induce cataract, but there has been no evidence that this occurs at low doses (< 100 mGy). To assess low-dose risk, participants from the US Radiologic Technologists Study, a large, prospective cohort, were followed from date of mailed questionnaire survey completed during 1994-1998 to the earliest of self-reported diagnosis of cataract/cataract surgery, cancer other than non-melanoma skin, or date of last survey (up to end 2014). Cox proportional hazards models with age as timescale were used, adjusted for a priori selected cataract risk factors (diabetes, body mass index, smoking history, race, sex, birth year, cumulative UVB radiant exposure).

Leukaemia and myeloid malignancy among people exposed to low doses (<100 mSv) of ionising radiation during childhood: a pooled analysis of nine historical cohort studies.

Background: Substantial evidence links exposure to moderate or high doses of ionising radiation, particularly in childhood, with increased risk of leukaemia. The association of leukaemia with exposure to low-dose (<100 mSv) radiation is less certain, although this is the dose range most relevant to the general population. We aimed to estimate the risk of leukaemia associated with low-dose radiation exposure in childhood (age <21 years).

Work history and radioprotection practices in relation to cancer incidence and mortality in US radiologic technologists performing nuclear medicine procedures.

Introduction: Technologists working in nuclear medicine (NM) are exposed to higher radiation doses than most other occupationally exposed populations. The aim of this study was to estimate the risk of cancer in NM technologists in relation to work history, procedures performed and radioprotection practices.

Methods: From the US Radiologic Technologists cohort study, 72 755 radiologic technologists who completed a 2003-2005 questionnaire were followed for cancer mortality through 31 December 2012 and for cancer incidence through completion of a questionnaire in 2012-2013.

Tobacco, alcohol use and risk of hepatocellular carcinoma and intrahepatic cholangiocarcinoma: The Liver Cancer Pooling Project.

Background: While tobacco and alcohol are established risk factors for hepatocellular carcinoma (HCC), the most common type of primary liver cancer, it is unknown whether they also increase the risk of intrahepatic cholangiocarcinoma (ICC). Thus, we examined the association between tobacco and alcohol use by primary liver cancer type.

Methods: The Liver Cancer Pooling Project is a consortium of 14 US-based prospective cohort studies that includes data from 1,518,741 individuals (HCC n = 1423, ICC n = 410).

Occupational radiation exposure and thyroid cancer incidence in a cohort of U.S. radiologic technologists, 1983-2013.

Although childhood exposure to ionizing radiation is a well-established risk factor for thyroid cancer, the risk associated with adulthood exposure remains unclear. We prospectively examined the association between cumulative, low-to-moderate dose occupational radiation exposure to the thyroid and thyroid cancer incidence in the U.S.

Incidence, correlates and outcomes associated with falls in the intensive care unit: a retrospective cohort study.

Background: Falls among hospitalised patients contribute to avoidable morbidity and prolonged hospital stay. We aimed to describe the incidence, circumstances and outcomes associated with patient falls occurring in intensive care units.

Methods: Retrospective cohort study of adult admissions to an academic, tertiary ICU in Edmonton, Canada between 1 January 2013 and 30 April 2016.

Cataract Risk in a Cohort of U.S. Radiologic Technologists Performing Nuclear Medicine Procedures.

Purpose To estimate the risk of cataract in a cohort of nuclear medicine (NM) radiologic technologists on the basis of their work histories and radiation protection practices. Materials and Methods In the years 2003-2005 and 2012-2013, 42 545 radiologic technologists from a U.S.

The Premenopausal Breast Cancer Collaboration: A Pooling Project of Studies Participating in the National Cancer Institute Cohort Consortium.

Breast cancer is a leading cancer diagnosis among premenopausal women around the world. Unlike rates in postmenopausal women, incidence rates of advanced breast cancer have increased in recent decades for premenopausal women. Progress in identifying contributors to breast cancer risk among premenopausal women has been constrained by the limited numbers of premenopausal breast cancer cases in individual studies and resulting low statistical power to subcategorize exposures or to study specific subtypes.

Hyperthyroidism, Hypothyroidism, and Cause-Specific Mortality in a Large Cohort of Women.

Background: The prevalence of hyperthyroidism and hypothyroidism is 0.5-4% in iodine-replete communities, but it is 5-10 times higher in women than in men. Those conditions are associated with a broad range of metabolic disorders and cardiovascular diseases.

Occupational Radiation Exposure and Deaths From Malignant Intracranial Neoplasms of the Brain and CNS in U.S. Radiologic Technologists, 1983-2012.

Objective: Childhood exposure to acute, high-dose radiation has consistently been associated with risk of benign and malignant intracranial tumors of the brain and CNS, but data on risks of adulthood exposure to protracted, low-to-moderate doses of radiation are limited. In a large cohort of radiologic technologists, we quantified the association between protracted, low-to-moderate doses of radiation and malignant intracranial tumor mortality.

Materials And Methods: The study population included 83,655 female and 26,642 male U.

Breast cancer risk and protracted low-to-moderate dose occupational radiation exposure in the US Radiologic Technologists Cohort, 1983-2008.

Background: Although high-dose ionising radiation is associated with increased breast cancer risks, the association with protracted low-dose-rate exposures remains unclear. The US Radiologic Technologist study provides an opportunity to examine the association between low-to-moderate dose radiation and breast cancer incidence and mortality.

Methods: One thousand nine hundred and twenty-two self-reported first primary cancers were diagnosed during 1983-2005 among 66 915 female technologists, and 586 breast cancer deaths occurred during 1983-2008 among 83 538 female cohort members.

Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus.

Background: Multiple recent genome-wide association studies (GWAS) have identified a single nucleotide polymorphism (SNP), rs10771399, at 12p11 that is associated with breast cancer risk.

Method: We performed a fine-scale mapping study of a 700 kb region including 441 genotyped and more than 1300 imputed genetic variants in 48,155 cases and 43,612 controls of European descent, 6269 cases and 6624 controls of East Asian descent and 1116 cases and 932 controls of African descent in the Breast Cancer Association Consortium (BCAC; http://bcac.ccge.

Historical Patterns in the Types of Procedures Performed and Radiation Safety Practices Used in Nuclear Medicine From 1945-2009.

The authors evaluated historical patterns in the types of procedures performed in diagnostic and therapeutic nuclear medicine and the associated radiation safety practices used from 1945-2009 in a sample of U.S. radiologic technologists.

Cancer Risks in U.S. Radiologic Technologists Working With Fluoroscopically Guided Interventional Procedures, 1994-2008.

Objective: The purpose of this study was to examine risks of cancer incidence and mortality among U.S. radiation technologists performing or assisting with fluoroscopically guided interventional procedures.