Observational study of pre-operative intravenous iron given to anaemic patients before elective cardiac surgery.

Cardiac surgical patients with anaemia experience increased morbidity and mortality. Iron deficiency is the most common cause of pre-operative anaemia in this group. We designed and implemented the Cardiff Pathway, a pre-assessment and treatment pathway to identify cardiac surgical patients with anaemia and iron deficiency. Patients identified with anaemia and/or iron deficiency (Hb < 130 g.l-1 and ferritin < 100 µg.l-1 ) were offered intravenous iron infusion 20 mg.kg-1 pre-operatively. Treatment success was defined as Hb ≥ 130g.l-1 on the day of surgery. We analysed data from 447 patients: 300 (67%) were not anaemic; 75 (17%) were anaemic and treated with intravenous iron; and 72 (16%) were anaemic and not treated. Haemoglobin concentration increased in successfully treated anaemic patients by a mean (95%CI) of 17 (13-21) g.l-1 and they received a median (IQR [range]) of 0 (0-2 [0-15]) units of blood peri-operatively. Transfusion was avoided in 54% of the successfully treated anaemic patients, which was significantly more than the unsuccessfully treated anaemic (22%, p = 0.005) and untreated anaemic (28%, p = 0.018) patients and similar to non-anaemic patients who received a median (IQR [range] of 0 (0-1 [0-16])) units of blood and, 63% avoided transfusion). Mean (95%CI) Hb fell between pre-assessment and surgery in the untreated anaemic (-2 (0 to -4) g.l-1 ) and non-anaemic groups (-2 (-1 to -3) g.l-1 ). Twenty-one (7%) of the non-anaemic group became newly anaemic waiting for surgery. The Cardiff Pathway reliably identified patients with anaemia and iron deficiency. Anaemic patients who had their Hb restored to normal after treatment required less blood peri-operatively and over half of them required no transfusion at all.

An in vitro investigation of the survival and/or growth of Campylobacter jejuni in broiler digestate from different feed types.

Campylobacter spp. is the leading cause of bacterial gastroenteritis worldwide and poultry are the primary reservoir. The aim of this study was to investigate the survival and/or growth of Campylobacter jejuni NCTC 11168 in broiler digestate prepared from commercial starter, grower and finisher feed formulations. Bolton broth and digestates were prepared, inoculated with C. jejuni NCTC 11168 (approximately 3 log10 CFU per ml) and incubated under microaerobic conditions at 42°C for 24 h. Samples were taken at t = 0 (immediately after inoculation) and every 3 h thereafter, serially diluted and plated onto mCCDA. Campylobacter jejuni grew as expected in Bolton broth (control) reaching the early stationary phase after approximately 15 h. In contrast, although bacterial concentrations were maintained for at least 9 h, none of the feed digestates supported the growth of C. jejuni, which were not detected after 15 h. It is suggested that the nutrients available in the feed digestates are not enough to support C. jejuni growth and that additional factors may be at play in the avian gastrointestinal tract.

Imaging Fluorescence of He_{2}

We show unequivocal evidence for formation of He_{2}^{*} excimers in liquid He II created by ionizing radiation produced through neutron capture. Laser beams induce fluorescence of the excimers. The fluorescence is recorded at a rate of 55.6 Hz by a camera. The location of the fluorescence is determined with an uncertainty of 5 µm. The technique provides an opportunity to record the flow of He_{2}^{*} excimers in a medium with very small viscosity and enables measurement of turbulence around macroscopic liter size objects or vortex matter in three dimensions.

First Precision Measurement of the Parity Violating Asymmetry in Cold Neutron Capture on

We report the first precision measurement of the parity-violating asymmetry in the direction of proton momentum with respect to the neutron spin, in the reaction ^{3}He(n,p)^{3}H, using the capture of polarized cold neutrons in an unpolarized active ^{3}He target. The asymmetry is a result of the weak interaction between nucleons, which remains one of the least well-understood aspects of electroweak theory. The measurement provides an important benchmark for modern effective field theory and potential model calculations. Measurements like this are necessary to determine the spin-isospin structure of the hadronic weak interaction. Our asymmetry result is A_{PV}=[1.55±0.97(stat)±0.24(sys)]×10^{-8}, which has the smallest uncertainty of any hadronic parity-violating asymmetry measurement so far.

Effects of a novel bites, steps and eating rate-focused weight loss randomised controlled trial intervention on body weight and eating behaviours.

BACKGROUND: Eating rate (ER), comprising the amount of food consumed per unit of time, is associated with obesity and energy intake (EI). METHODS: The present study tested whether adding a self-monitoring wearable device to a multifaceted 8-week weight loss intervention increased weight loss. In addition, the device's effect on secondary change outcomes in EI, ER and estimated energy expenditure was explored. Tertiary outcomes included examining eating behaviours measured by the Weight-Related Eating Questionnaire (WREQ). Seventy-two adults who were overweight or obese [mean (SD) age, 37.7 (15.3) years; body mass index, 31.3 (3.2) kg m-2 ] were randomised into two groups: intervention workbook plus device (WD) or intervention workbook only (WO). Three 24-h dietary recalls were obtained before weeks 0 and 8. Participants were weighed, consumed a test meal and completed 7-day Physical Activity Recall and WREQ at weeks 0 and 8. RESULTS: There was no significant difference between WD and WO groups with respect to weight change [-0.46 (1.11) vs. 0.26 (0.82) kg, respectively], ER, EI, energy expenditure or WREQ scores, although there were significant changes over time, and within-group changes on all of these variables. At week 8, participants were dichotomised into weight loss or weight stable/gainers groups. A significant time by group change was seen in susceptibility to external cues scores, with significant time effects for susceptibility and restraint. CONCLUSIONS: An intervention focused on reducing ER, energy density and increasing steps was effective for weight loss, although the wearable device provided no additional benefit. Participants with higher susceptibility to external eating may be more responsive to this intervention.

First Observation of P-odd γ Asymmetry in Polarized Neutron Capture on Hydrogen.

We report the first observation of the parity-violating gamma-ray asymmetry A_{γ}^{np} in neutron-proton capture using polarized cold neutrons incident on a liquid parahydrogen target at the Spallation Neutron Source at Oak Ridge National Laboratory. A_{γ}^{np} isolates the ΔI=1, ^{3}S_{1}→^{3}P_{1} component of the weak nucleon-nucleon interaction, which is dominated by pion exchange and can be directly related to a single coupling constant in either the DDH meson exchange model or pionless effective field theory. We measured A_{γ}^{np}=[-3.0±1.4(stat)±0.2(syst)]×10^{-8}, which implies a DDH weak πNN coupling of h_{π}^{1}=[2.6±1.2(stat)±0.2(syst)]×10^{-7} and a pionless EFT constant of C^{^{3}S_{1}→^{3}P_{1}}/C_{0}=[-7.4±3.5(stat)±0.5(syst)]×10^{-11} MeV^{-1}. We describe the experiment, data analysis, systematic uncertainties, and implications of the result.

Precision determination of absolute neutron flux.

A technique for establishing the total neutron rate of a highly-collimated monochromatic cold neutron beam was demonstrated using an alpha-gamma counter. The method involves only the counting of measured rates and is independent of neutron cross sections, decay chain branching ratios, and neutron beam energy. For the measurement, a target of 10B-enriched boron carbide totally absorbed the neutrons in a monochromatic beam, and the rate of absorbed neutrons was determined by counting 478 keV gamma rays from neutron capture on 10B with calibrated high-purity germanium detectors. A second measurement based on Bragg diffraction from a perfect silicon crystal was performed to determine the mean de Broglie wavelength of the beam to a precision of 0.024%. With these measurements, the detection efficiency of a neutron monitor based on neutron absorption on 6Li was determined to an overall uncertainty of 0.058%. We discuss the principle of the alpha-gamma method and present details of how the measurement was performed including the systematic effects. We also describe how this method may be used for applications in neutron dosimetry and metrology, fundamental neutron physics, and neutron cross section measurements.

Understanding doctors' attitudes towards self-disclosure of mental ill health.

BACKGROUND: Understanding of doctors' attitudes towards disclosing their own mental illness has improved but assumptions are still made. AIMS: To investigate doctors' attitudes to disclosing mental illness and the obstacles and enablers to seeking support. METHODS: An anonymous, UK-wide online survey of doctors with and without a history of mental illness. The main outcome measure was likelihood of workplace disclosure of mental illness. RESULTS: In total, 1954 doctors responded and 60% had experienced mental illness. There was a discrepancy between how doctors think they might behave and how they actually behaved when experiencing mental illness. Younger doctors were least likely to disclose, as were trainees. There were multiple obstacles which varied across age and training grade. CONCLUSIONS: For all doctors, regardless of role, this study found that what they think they would do is different to what they actually do when they become unwell. Trainees, staff and associate speciality doctors and locums appeared most vulnerable, being reluctant to disclose mental ill health. Doctors continued to have concerns about disclosure and a lack of care pathways was evident. Concerns about being labelled, confidentiality and not understanding the support structures available were identified as key obstacles to disclosure. Addressing obstacles and enablers is imperative to shape future interventions.

Standards for 'Health for Health Professionals' services in the UK.

BACKGROUND: Doctors are more likely to suffer from work-related mental ill-health than other professions in the UK and internationally. Services to support doctors with health problems are emerging in the UK and have diverse models of delivery and funding. Services should be able to demonstrate agreed standards of practice for those who wish to commission, develop or access them. AIMS: To develop consensus about standards for 'Health for Health Professionals' (HHP) services in the UK through a modified Delphi study. METHODS: We conducted a two-stage Delphi study over 6 months. The questionnaire development took place during the UK Association of Physician Health (UKAPH) meeting in London in 2012, an invited meeting for clinicians with a specific interest in the area of physician health. The final questionnaire was disseminated via the UKAPH database. RESULTS: Forty-four people took part in round 1 and 40 in round 2. Participants were mainly GPs, occupational physicians and psychiatrists. Consensus was reached on major criteria for HHP services, with greatest consensus (45% agreement or greater) for four statements concerning the clarity and transparency of the services offered and one statement that anyone working within the service should have received suitable training in physician health. Consensus about some statements varied among the three specialities. CONCLUSIONS: This study will assist discussion about providing and improving consistent services across the UK, while recognizing the flexibility required in view of geographical differences.

Improved determination of the neutron lifetime.

The most precise determination of the neutron lifetime using the beam method was completed in 2005 and reported a result of τ(n)=(886.3±1.2[stat]±3.2[syst]) s. The dominant uncertainties were attributed to the absolute determination of the fluence of the neutron beam (2.7 s). The fluence was measured with a neutron monitor that counted the neutron-induced charged particles from absorption in a thin, well-characterized 6Li deposit. The detection efficiency of the monitor was calculated from the areal density of the deposit, the detector solid angle, and the evaluated nuclear data file, ENDF/B-VI 6Li(n,t)4He thermal neutron cross section. In the current work, we measure the detection efficiency of the same monitor used in the neutron lifetime measurement with a second, totally absorbing neutron detector. This direct approach does not rely on the 6Li(n,t)4He cross section or any other nuclear data. The detection efficiency is consistent with the value used in 2005 but is measured with a precision of 0.057%, which represents a fivefold improvement in the uncertainty. We verify the temporal stability of the neutron monitor through ancillary measurements, allowing us to apply the measured neutron monitor efficiency to the lifetime result from the 2005 experiment. The updated lifetime is τ(n)=(887.7±1.2[stat]±1.9[syst]) s.

Unconventional isoquinoline-based SERMs elicit fulvestrant-like transcriptional programs in ER+ breast cancer cells.

Estrogen receptor alpha (ERα) is a ligand-dependent master transcriptional regulator and key driver of breast cancer pathology. Small molecule hormones and competitive antagonists favor unique ERα conformational ensembles that elicit ligand-specific transcriptional programs in breast cancer and other hormone-responsive tissues. By affecting disparate ligand binding domain structural features, unconventional ligand scaffolds can redirect ERα genomic binding patterns to engage novel therapeutic transcriptional programs. To improve our understanding of these ERα structure-transcriptional relationships, we develop a series of chemically unconventional antagonists based on the antiestrogens elacestrant and lasofoxifene. High-resolution x-ray co-crystal structures show that these molecules affect both classical and unique structural motifs within the ERα ligand binding pocket. They show moderately reduced antagonistic potencies on ERα genomic activities but are effective anti-proliferative agents in luminal breast cancer cells. Interestingly, they favor a 4-hydroxytamoxifen-like accumulation of ERα in breast cancer cells but lack uterotrophic activities in an endometrial cell line. Importantly, RNA sequencing shows that the lead molecules engage transcriptional pathways similar to the selective estrogen receptor degrader fulvestrant. This advance shows that fulvestrant-like genomic activities can be achieved without affecting ERα accumulation in breast cancer cells.

A novel nuclear form of estradiol receptor in MCF-7 human breast cancer cells.

Nuclear estrogen receptor from MCF-7 cells undergoes a time-dependent, hormone-inducible transformation to a form that is less extractable from nuclei and less exchangeable with ligand. This receptor-modifying, intranuclear event is independent of receptor loss (processing) and appears associated with hormone responsiveness (progesterone-receptor induction) in these cells. The magnitude of receptor loss, however, is variable and apparently not a prerequisite for hormone action to induce progesterone receptor.

Sequence and expression of human estrogen receptor complementary DNA.

The mechanism by which the estrogen receptor and other steroid hormone receptors regulate gene expression in eukaryotic cells is not well understood. In this study, a complementary DNA clone containing the entire translated portion of the messenger RNA for the estrogen receptor from MCF-7 human breast cancer cells was sequenced and then expressed in Chinese hamster ovary (CHO-K1) cells to give a functional protein. An open reading frame of 1785 nucleotides in the complementary DNA corresponded to a polypeptide of 595 amino acids and a molecular weight of 66,200, which is in good agreement with published molecular weight values of 65,000 to 70,000 for the estrogen receptor. Homogenates of transformed Chinese hamster ovary cells containing a protein that bound [3H]estradiol and sedimented as a 4S complex in salt-containing sucrose gradients and as an 8 to 9S complex in the absence of salt. Interaction of this receptor-[3H]estradiol complex with a monoclonal antibody that is specific for primate ER confirms the identity of the expressed complementary DNA as human estrogen receptor. Amino acid sequence comparisons revealed significant regional homology among the human estrogen receptor, the human glucocorticoid receptor, and the putative v-erbA oncogene product. This suggests that steroid receptor genes and the avian erythroblastosis viral oncogene are derived from a common primordial gene. The homologous region, which is rich in cysteine, lysine, and arginine, may represent the DNA-binding domain of these proteins.

Hibernation and longevity in the Turkish hamster Mesocricetus brandti.

A positive correlation was found between the length of life of 288 Turkish hamsters and the amount of time spent in hibernation, suggesting that the process of aging is slowed during hibernation.

Molecular cloning of the chicken progesterone receptor.

To define the functional domains of the progesterone receptor required for gene regulation, complementary DNA (cDNA) clones encoding the chicken progesterone receptor have been isolated from a chicken oviduct lambda gt11 cDNA expression library. Positive clones expressed antigenic determinants that cross-reacted with six monospecific antibodies derived from two independent sources. A 36-amino acid peptide sequence obtained by microsequencing of purified progesterone receptor was encoded by nucleotide sequences in the longest cDNA clone. Analysis of the amino acid sequence of the progesterone receptor deduced from the cDNA clones revealed a cysteine-rich region that was homologous to a region found in the estrogen and glucocorticoid receptors and to the avian erythroblastosis virus gag-erb-A fusion protein. Northern blot analysis with chicken progesterone receptor cDNA's indicated the existence of at least three messenger RNA species. These messages were found only in oviduct and could be induced by estrogens.

Estrogen binding, receptor mRNA, and biologic response in osteoblast-like osteosarcoma cells.

High specific activity estradiol labeled with iodine-125 was used to detect approximately 200 saturable, high-affinity (dissociation constant approximately equal to 1.0 nM) nuclear binding sites in rat (ROS 17/2.8) and human (HOS TE85) clonal osteoblast-like osteosarcoma cells. Of the steroids tested, only testosterone exhibited significant cross-reactivity with estrogen binding. RNA blot analysis with a complementary DNA probe to the human estrogen receptor revealed putative receptor transcripts of 6 to 6.2 kilobases in both rat and human osteosarcoma cells. Type I procollagen and transforming growth factor-beta messenger RNA levels were enhanced in cultured human osteoblast-like cells treated with 1 nM estradiol. Thus, estrogen can act directly on osteoblasts by a receptor-mediated mechanism and thereby modulate the extracellular matrix and other proteins involved in the maintenance of skeletal mineralization and remodeling.

Preliminary meteorological results on Mars from the viking 1 lander.

The results from the meteorology instruments on the Viking 1 lander are presented for the first 4 sols of operation. The instruments are working satisfactorily. Temperatures fluctuated from a low of 188 degrees K to an estimated maximum of 244 degrees K. The mean pressure is 7.65 millibars with a diurnal variation of amplitude 0.1 millibar. Wind speeds averaged over several minutes have ranged from essentially calm to 9 meters per second. Wind directions have exhibited a remarkable regularity which may be associated with nocturnal downslope winds and gravitational oscillations, or to tidal effects of the diurnal pressure wave, or to both.

Mars climatology from viking 1 after 20 sols.

The results from the meteorology instruments on the Viking 1 lander are presented for the first 20 sols of operation. The daily patterns of temperature, wind, and pressure have been highly consistent during the period. Hence, these have been assembled into 20-sol composites and analyzed harmonically. Maximum temperature was 241.8 degrees K and minimum 187.2 degrees K. The composite wind vector has a mean diurnal magnitude of 2.4 meters per second with prevailing wind from the south and counterclockwise diurnal rotation. Pressure exhibits diurnal and semidiurnal oscillations. The diurnal is ascribed to a combination of effects, and the semidiurnal appears to be the solar semidiurnal tide. Similarities to Earth are discussed. A major finding is a continual secular decrease in diurnal mean pressure. This is ascribed to carbon dioxide deposition at the south polar cap.

The Association between Physical Activity and Metabolic Syndrome in Older Adults with Obesity.

BACKGROUND: Physical activity reduces the likelihood of developing metabolic syndrome (MetS). However, the association between different physical activity levels and MetS remains unclear in older adults with obesity. METHODS: This cross-sectional study used four waves of data (2007-2008, 2009-2010, 2011-2012, 2013-2014) from two datasets: The National Health and Nutrition Examination Survey and United Sates Department of Agriculture's Food Patterns Equivalents Database. The sample included adults 60+ years of age (n= 613) with obesity who had physical activity and MetS data. Physical activity was assessed using the Global Physical Activity Questionnaire and categorized into three physical activity levels (low, medium, and high); and medium or high physical activity levels are aligned with or exceed current physical activity recommendations. Participants were classified as having MetS using a commonly agreed upon definition. Multiple logistic regression models examined the association between the three physical activity levels and MetS risk factors and MetS. All analyses adjusted for potential confounding variables and accounted for complex sampling. RESULTS: Of 613 respondents, 72.1% (n=431) were classified as having MetS, and 44.3% (n = 263) had not met physical activity recommendations. Participants with high levels of physical activity had a lower risk of MetS (OR = 0.31, 95%CI: 0.13, 0.72) and more healthful levels of high-density lipoprotein cholesterol (OR = 0.39, 95%CI: 0.18, 0.84), blood pressure (OR = 0.39, 95%CI: 0.20, 0.77), fasting glucose (OR = 0.34, 95%CI: 0.15, 0.78) than participants categorized as having low physical activity. CONCLUSIONS: Physical activity is associated with lower risk of MetS only for participants with the highest level of physical activity, which suggests that physical activity dosage is important to reduce MetS risk in older adults with obesity.