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Combined smoking and heavy drinking is a significant health burden. Varenicline, an efficacious tobacco pharmacotherapy that also shows promise for drinking, has yielded mixed results among heavy-drinking smokers. This pilot study investigated integrated tobacco and alcohol counselling plus varenicline for this vulnerable group.
Twelve-week parallel, randomized controlled pilot trial of two behavioural interventions in combination with open-label varenicline. Participants were randomized using computer-generated tables, stratified by sex.
Outpatient academic medical centre research clinic.
Volunteers who reported smoking and heavy drinking and sought tobacco or alcohol treatment (N = 26).
(1) Integrated tobacco + alcohol counselling (INT; n = 13) or (2) counselling focused on their presenting concern (i.e., tobacco or alcohol) (SINGLE; n = 13), plus varenicline (2 mg) for 12 weeks.
Feasibility/acceptability, smoking quit rates and heavy drinking.
INT feasibility/acceptability was high among men but not women. More participants quit smoking in INT than SINGLE. This outcome was only in men, not significant, but had a medium effect size. Both conditions yielded significant drinking reductions.
Integrated tobacco and alcohol behavioural counselling plus varenicline may be feasible and promote smoking cessation among men who smoke and drink heavily, but a larger sample is needed to replicate this finding.
Flax seed meal (FSM) is rich in various nutrients, especially CP and energy, and can be used as animal protein feed. In animal husbandry production, it is a long-term goal to replace soybean meal (SBM) in animal feed with other plant protein feed. However, studies on the effects of replacing SBM with FSM in fattening sheep are limited. The aim of this experiment was to study the effects of replacing a portion of SBM with FSM on nutrient digestibility, rumen microbial protein synthesis and growth performance in sheep. Thirty-six Dorper × Small Thin-Tailed crossbred rams (BW = 40.4 ± 1.73 kg, mean ± SD) were randomly assigned into four groups. The dietary treatments (forage/concentrate, 45 : 55) were isocaloric according to the nutrient requirements of rams. Soybean meal was replaced with FSM at different levels (DM basis): (1) 18% SBM (18SBM), (2) 12% SBM and 6% FSM (6FSM), (3) 6% SBM and 12% FSM (12FSM) and (4) 18% FSM (18FSM). The rams were fed in individual pens for 60 days, with the first 10 days for adaptation to diets, and then the digestibility of nutrients was determined. There was no significant difference in DM intake, but quadratic (P < 0.001) effects on the average daily gain and feed efficiency were detected, with the highest values in the 6FSM and 12FSM groups. For DM and NDF digestibility, quadratic effects were observed with the higher values in the 6FSM and 12FSM groups, but the digestibility of CP linearly decreased with the increase in FSM in the diet (P = 0.043). There was a quadratic (P < 0.001) effect of FSM inclusion rate on the estimated microbial CP yield. However, the values of intestinally absorbable dietary protein decreased linearly (P < 0.001). For the supply of metabolisable protein, both the linear (P = 0.001) and quadratic (P = 0.044) effects were observed with the lowest value in the 18FSM group. Overall, the results indicated that SBM can be effectively replaced by FSM in the diets of fattening sheep and the optimal proportion was 12.0% under the conditions of this experiment.
Household food insecurity (HFI) is a major concern in South Asia. The pathways by which HFI may reduce child growth remain inadequately understood. In a cohort study of 12 693 maternal–infant dyads in rural Bangladesh, we examined association and likely explanatory pathways linking HFI, assessed using a validated nine-item perception-based index, to infant size at 6 months. Mothers were assessed early in pregnancy for anthropometric status, dietary diversity and socio-economic status. Infants were assessed for weight, length, and arm, chest and head circumferences and breast and complementary feeding status at birth and 6 months of age. Extent of HFI shared a negative, dose–response association with all measures of infant size at 6 months and odds of wasting and stunting; 57–89 % of variances in the unadjusted models were explained by prenatal factors (maternal nutritional status and dietary diversity), and birth size adjusted for gestational age. Postnatal infant breast and complementary feeding and morbidity exposures explained the remaining fraction of the significant association between HFI and differences in infant arm and chest circumferences and odds of underweight. Contextual (i.e. socio-economic) factors finally brought remaining non-significant fractions of the food insecurity-related mid-infancy growth deficit to practically zero. Improving food security prior to pregnancy and during gestation would likely improve infant growth the most in rural Bangladesh.
Tuberculosis (TB) is generally considered a disease that principally afflicts the low-income segments of a population. In the Nanshan District of Shenzhen, China, with the economic transformation and a new Headquarters Economy (HE) emerging, there are now more cases in office workers than in manufacturing workers. To illustrate this trend, we describe a small TB outbreak in an office building located in the centre of the rapidly growing HE district. Two active pulmonary tuberculosis cases were found in workers who shared an office, and whole genome sequencing showed that the genetic distance between the strains of the two cases was just one single nucleotide polymorphism, consistent with intra-office transmission. Investigation of 30 other workers in the same or adjacent offices with interviews, interferon-gamma release assays (IGRAs) and chest X-rays, identified one new TB case and latent tuberculosis infection (LTBI) in 40.0% (12/30) of the contacts. The offices were under-ventilated. None of the IGRA positive, asymptomatic contacts agreed to receive treatment for LTBI, presumably due to TB stigma, and over the next 2 years 69.0% (20/29) of the contacts were lost to follow-up. Treatment for LTBI and stigma of TB remain challenges here. Office workers in the HE of rapidly economic developing areas should be targeted with increased vigilance by TB control programmes.
This study evaluated the effects of rumen-protected folic acid (RPFA) and betaine (BT) on growth performance, nutrient digestion and blood metabolites in bulls. Forty-eight Angus bulls were blocked by body weight and randomly assigned to four treatments in a 2 × 2 factorial design. BT of 0 or 0·6 g/kg DM was supplemented to diet without or with the addition of 6 mg/kg DM of folic acid from RPFA, respectively. Average daily gain increased by 25·2 and 6·29 % for addition of BT without RPFA and with RPFA, respectively. Digestibility and ruminal total volatile fatty acids of neutral-detergent fibre and acid-detergent fibre increased, feed conversion ratio and blood folate decreased with the addition of BT without RPFA, but these parameters were unchanged with BT addition in diet with RPFA. Digestibility of DM, organic matter and crude protein as well as acetate:propionate ratio increased with RPFA or BT addition. Ruminal ammonia-N decreased with RPFA addition. Activity of carboxymethyl cellulase, cellobiase, xylanase, pectinase and protease as well as population of total bacteria, protozoa, Fibrobacter succinogenes and Ruminobacter amylophilus increased with RPFA or BT addition. Laccase activity and total fungi, Ruminococcus flavefaciens and Prevotella ruminicola population increased with RPFA addition, whereas Ruminococcus albus population increased with BT addition. Blood glucose, total protein, albumin, growth hormone and insulin-like growth factor-1 increased with RPFA addition. Addition of RPFA or BT decreased blood homocysteine. The results indicated that addition of BT stimulated growth and nutrient digestion in bulls only when RPFA was not supplemented.
Tuberculosis (TB) is the leading cause of death among infectious diseases. China has a high burden of TB and accounted for almost 13% of the world's cases of multi-drug resistant (MDR) TB. Spinal TB is one reason for the resurgence of TB in China. Few large case studies of MDR spinal TB in China have been conducted. The aim of this research was to observe the epidemiological characteristics of inpatients with MDR spinal TB in six provinces and cities of China from 1999–2015. This is a multicentre retrospective observational study. Patients' information was collected from the control disease centre and infectious disease database of hospitals in six provinces and cities in China. A total of 3137 patients with spinal TB and 272 patients with MDR spinal TB were analysed. The result showed that MDR spinal TB remains a public health concern and commonly affects patients 15–30 years of age (34.19%). The most common lesions involved the thoracolumbar spine (35.66%). Local pain was the most common symptom (98.53%). Logistic analysis showed that for spinal TB patients, reside in rural district (OR 1.79), advanced in years (OR 1.92) and high education degree (OR 2.22) were independent risk factors for the development of MDR spinal TB. Women were associated with a lower risk of MDR spinal TB (OR 0.48). The most common first-line and second-line resistant drug was isoniazid (68.75%) and levofloxacin (29.04%), respectively. The use of molecular diagnosis resulted in noteworthy clinical advances, including earlier initiation of MDR spinal TB treatment, improved infection control and better clinical outcome. Chemotherapy and surgery can yield satisfactory outcomes with timely diagnosis and long-term treatment. These results enable a better understanding of the MDR spinal TB in China among the general public.
Several studies suggested that depression might worsen the clinical outcome of diabetes mellitus; however, such association was confounded by duration of illness and baseline complications. This study aimed to assess whether depression increases the risk of diabetes complications and mortality among incident patients with diabetes.
This was a population-based matched cohort study using Taiwan's National Health Insurance Research Database. A total of 38 537 incident patients with diabetes who had depressive disorders and 154 148 incident diabetes patients without depression who were matched by age, sex and cohort entry year were randomly selected. The study endpoint was the development of macrovascular and microvascular complications, all-cause mortality and cause-specific mortality.
Among participants, the mean (±SD) age was 52.61 (±12.45) years, and 39.63% were male. The average duration of follow-up for mortality was 5.5 years, ranging from 0 to 14 years. The adjusted hazard ratios were 1.35 (95% confidence interval [CI], 1.32–1.37) for macrovascular complications and 1.08 (95% CI, 1.04–1.12) for all-cause mortality. However, there was no association of depression with microvascular complications, mortality due to cardiovascular diseases or mortality due to diabetes mellitus. The effect of depression on diabetes complications and mortality was more prominent among young adults than among middle-aged and older adults.
Depression was associated with macrovascular complications and all-cause mortality in our patient cohort. However, the magnitude of association was less than that in previous studies. Further research should focus on the benefits and risks of treatment for depression on diabetes outcome.
The combined addition of branched-chain volatile fatty acids (BCVFAs) and folic acid (FA) could improve growth performance and nutrient utilization by stimulating ruminal microbial growth and enzyme activity. This study was conducted to evaluate the effects of BCVFA and FA addition on growth performance, ruminal fermentation, nutrient digestibility, microbial enzyme activity, microflora and excretion of urinary purine derivatives (PDs) in calves. Thirty-six Chinese Holstein weaned calves (60 ± 5.4 days of age and 107 ± 4.7 kg of BW) were assigned to one of four groups in a randomized block design. Treatments were control (without additives), FA (with 10 mg FA/kg dietary DM), BCVFA (with 5 g BCVFA/kg dietary DM) and the combined addition of FA and BCVFA (10 mg/kg DM of FA and 5 g/kg DM of BCVFA). Supplements were hand-mixed into the top one-third of total mixed ration. Dietary concentrate to maize silage ratio was 50 : 50 on a DM basis. Dietary BCVFA or FA addition did not affect dry matter intake but increased average daily gain (ADG) and feed conversion efficiency. Ruminal pH and ammonia N were lower, and total volatile fatty acids (VFAs) concentration was higher for BCVFA or FA addition than for control. Dietary BCVFA or FA addition did not affect acetate proportion but decreased propionate proportion and increased acetate to propionate ratio. Total tract digestibility of DM, organic matter, CP and NDF was higher for BCVFA or FA addition than for control. Dietary BCVFA or FA addition increased activity of carboxymethyl cellulase and cellobiase, population of total bacteria, fungi, Ruminococcus albus, R. flavefaciens, Fibrobacter succinogenes and Prevotella ruminicola as well as total PD excretion. Ruminal xylanase, pectinase and protease activity and Butyrivibrio fibrisolvens population were increased by BCVFA addition, whereas population of protozoa and methanogens was increased by FA addition. The BCVFA × FA interaction was significant for acetate to propionate ratio, cellobiase activity and total PD excretion, and these variables increased more with FA addition in diet without BCVFA than in diet with BCVFA. The data indicated that supplementation with BCVFA or FA increased ADG, nutrient digestibility, ruminal total VFA concentration and microbial protein synthesis by stimulating ruminal microbial growth and enzyme activity in calves.
The Murchison Widefield Array (MWA) is an open access telescope dedicated to studying the low-frequency (80–300 MHz) southern sky. Since beginning operations in mid-2013, the MWA has opened a new observational window in the southern hemisphere enabling many science areas. The driving science objectives of the original design were to observe 21 cm radiation from the Epoch of Reionisation (EoR), explore the radio time domain, perform Galactic and extragalactic surveys, and monitor solar, heliospheric, and ionospheric phenomena. All together
programs recorded 20 000 h producing 146 papers to date. In 2016, the telescope underwent a major upgrade resulting in alternating compact and extended configurations. Other upgrades, including digital back-ends and a rapid-response triggering system, have been developed since the original array was commissioned. In this paper, we review the major results from the prior operation of the MWA and then discuss the new science paths enabled by the improved capabilities. We group these science opportunities by the four original science themes but also include ideas for directions outside these categories.
The Murchison Widefield Array (MWA) is an electronically steered low-frequency (<300 MHz) radio interferometer, with a ‘slew’ time less than 8 s. Low-frequency (∼100 MHz) radio telescopes are ideally suited for rapid response follow-up of transients due to their large field of view, the inverted spectrum of coherent emission, and the fact that the dispersion delay between a 1 GHz and 100 MHz pulse is on the order of 1–10 min for dispersion measures of 100–2000 pc/cm3. The MWA has previously been used to provide fast follow-up for transient events including gamma-ray bursts (GRBs), fast radio bursts (FRBs), and gravitational waves, using systems that respond to gamma-ray coordinates network packet-based notifications. We describe a system for automatically triggering MWA observations of such events, based on Virtual Observatory Event standard triggers, which is more flexible, capable, and accurate than previous systems. The system can respond to external multi-messenger triggers, which makes it well-suited to searching for prompt coherent radio emission from GRBs, the study of FRBs and gravitational waves, single pulse studies of pulsars, and rapid follow-up of high-energy superflares from flare stars. The new triggering system has the capability to trigger observations in both the regular correlator mode (limited to ≥0.5 s integrations) and using the Voltage Capture System (VCS, 0.1 ms integration) of the MWA and represents a new mode of operation for the MWA. The upgraded standard correlator triggering capability has been in use since MWA observing semester 2018B (July–Dec 2018), and the VCS and buffered mode triggers will become available for observing in a future semester.
There is an overabundance of microswimmers in nature, including bacteria, algae, mammalian cells and so on. They use flagellum, cilia or global shape changes (amoeboid motion) to move forward. In the presence of confining channels, these swimmers exhibit often non-trivial behaviours, such as accumulation at the wall, navigation and so on, and their swimming speed may be strongly influenced by the geometric confinement. Several numerical studies have reported that the presence of walls either enhances or reduces the swimming speed depending on the nature of the swimmer, and also on the confinement. The purpose of this paper is to provide an analytical explanation of several previously obtained numerical results. We treat the case of amoeboid swimmers and the case of squirmers having either a tangential (the classical situation) or normal velocity prescribed at the swimmer surface (pumper). For amoeboid motion we consider a quasi-circular swimmer which allows us to tackle the problem analytically and to extract the equations of the motion of the swimmer, with several explicit analytical or semi-analytical solutions. It is found that the deformation of the amoeboid swimmer as well as a high enough order effect due to confinement are necessary in order to account for previous numerical results. The analytical theory accounts for several features obtained numerically also for non-deformable swimmers.
This study proposed the application of a novel immersed boundary method (IBM) for the treatment of irregular geometries using Cartesian computational grids for high speed compressible gas flows modelled using the unsteady Euler equations. Furthermore, the method is accelerated through the use of multiple Graphics Processing Units – specifically using Nvidia’s CUDA together with MPI - due to the computationally intensive nature associated with the numerical solution to multi-dimensional continuity equations. Due to the high degree of locality required for efficient multiple GPU computation, the Split Harten-Lax-van-Leer (SHLL) scheme is employed for vector splitting of fluxes across cell interfaces. NVIDIA visual profiler shows that our proposed method having a computational speed of 98.6 GFLOPS and 61% efficiency based on the Roofline analysis that provides the theoretical computing speed of reaching 160 GLOPS with an average 2.225 operations/byte. To demonstrate the validity of the method, results from several benchmark problems covering both subsonic and supersonic flow regimes are presented. Performance testing using 96 GPU devices demonstrates a speed up of 89 times that of a single GPU (i.e. 92% efficiency) for a benchmark problem employing 48 million cells. Discussions regarding communication overhead and parallel efficiency for varying problem sizes are also presented.
Bipolar disorder (BD) is a highly heritable mood disorder with complex genetic architecture and poorly understood etiology. Previous transcriptomic BD studies have had inconsistent findings due to issues such as small sample sizes and difficulty in adequately accounting for confounders like medication use.
We performed a differential expression analysis in a well-characterized BD case-control sample (Nsubjects = 480) by RNA sequencing of whole blood. We further performed co-expression network analysis, functional enrichment, and cell type decomposition, and integrated differentially expressed genes with genetic risk.
While we observed widespread differential gene expression patterns between affected and unaffected individuals, these effects were largely linked to lithium treatment at the time of blood draw (FDR < 0.05, Ngenes = 976) rather than BD diagnosis itself (FDR < 0.05, Ngenes = 6). These lithium-associated genes were enriched for cell signaling and immune response functional annotations, among others, and were associated with neutrophil cell-type proportions, which were elevated in lithium users. Neither genes with altered expression in cases nor in lithium users were enriched for BD, schizophrenia, and depression genetic risk based on information from genome-wide association studies, nor was gene expression associated with polygenic risk scores for BD.
These findings suggest that BD is associated with minimal changes in whole blood gene expression independent of medication use but emphasize the importance of accounting for medication use and cell type heterogeneity in psychiatric transcriptomic studies. The results of this study add to mounting evidence of lithium's cell signaling and immune-related mechanisms.
Temperature resulting from the joule heating power and the turn-on and turn-off dissipation of high-power, high-frequency applications is the root cause of their thermal instability, electrical performance degradation, and even thermal-fatigue failure. Thus, the study presents thermal and electrical characterizations of the power MOSFET module packaged in SOT-227 under natural convection and forced convection through three-dimensional (3D) thermal-electric (TE) coupled field analysis. In addition, the influences of some key parameters like electric loads, ambient conditions, thermal management considerations (heat sink, heat spreader) and operation conditions (duty cycle and switching frequency) on the power loss and thermal performance of the power module are addressed. The study starts from a suitable estimation of the power losses, where the conduction losses are calculated using the temperature- and gate-voltage-dependent on-state resistance and drain current through the device, and the switching losses are predicted based on the ideal switching waveforms of the power MOSFETs applied. The effectiveness of the theoretical predictions in terms of device’s power losses and temperatures is demonstrated through comparison with the results of circuit simulation and thermal experiment.
Origami, the ancient paper folding art has inspired the engineering equipment and design for decades. The basic concept of origami is very general, which leads to applications ranging from small scale to large scale. Recently, researchers are interested in being able to create self-folding structures. Such a structure enables kinematic manipulation by external forces or moments without folding and/or unfolding operations. This is a beneficial application for many fields including aerospace systems, robots, small devices and self-assembly systems. In this paper, the investigation and analyses of the previous literatures on the key driving force of the actuation structure, including the heat, light, electricity, gas and other actuation methods. The aims are to provide researchers and practitioners with the support to systematically understand the latest technologies in this important and evolving field, with inspiration and direction for follow-up.
This paper presents a comprehensive analytical approach to the modelling of wall-pressure fluctuations under a turbulent boundary layer, unifying and expanding the analytical models that have been proposed over many decades. The Poisson equation governing pressure fluctuations is Fourier transformed in the wavenumber domain to obtain a modified Helmholtz equation, which is solved with a Green’s function technique. The source term of the differential equations is composed of turbulence–mean shear and turbulence–turbulence interaction terms, which are modelled separately within the hypothesis of a joint normal probability distribution of the turbulent field. The functional expression of the turbulence statistics is shown to be the most critical point for a correct representation of the wall-pressure spectrum. The effect of various assumptions on the shape of the longitudinal correlation function of turbulence is assessed in the first place with purely analytical considerations using an idealised flow model. Then, the effect of the hypothesis on the spectral distribution of boundary-layer turbulence on the resulting wall-pressure spectrum is compared with the results of direct numerical simulation computations and pressure measurements on a controlled-diffusion aerofoil. The boundary layer developing over the suction side of this aerofoil in test conditions is characterised by an adverse pressure gradient. The final part of the paper discusses the numerical aspect of wall-pressure spectrum computation. A Monte Carlo technique is used for a fast evaluation of the multi-dimensional integral formulation developed in the theoretical part.
This paper presents a comparative study on three types of slim coil structures used as a three-dimensional (3-D) receiver in a wireless power transfer system with a planar transmitter coil. The mutual coupling values and their variations between the receiver structures and the transmitter coil are compared under different distances and angular orientations with respect to the transmitter coil. The merits of performance are related to the consistency of the mutual coupling values under different orientations in a range of distances from the transmitter coil. The practical results show that slim 3-D receiver coil structures can be compatible with a planar transmitter coil with reasonably high-mutual coupling.
Maternal systemic inflammation during pregnancy may restrict embryo−fetal growth, but the extent of this effect remains poorly established in undernourished populations. In a cohort of 653 maternal−newborn dyads participating in a multi-armed, micronutrient supplementation trial in southern Nepal, we investigated associations between maternal inflammation, assessed by serum α1-acid glycoprotein and C-reactive protein, in the first and third trimesters of pregnancy, and newborn weight, length and head and chest circumferences. Median (IQR) maternal concentrations in α1-acid glycoprotein and C-reactive protein in the first and third trimesters were 0.65 (0.53–0.76) and 0.40 (0.33–0.50) g/l, and 0.56 (0.25–1.54) and 1.07 (0.43–2.32) mg/l, respectively. α1-acid glycoprotein was inversely associated with birth size: weight, length, head circumference and chest circumference were lower by 116 g (P = 2.3 × 10−6), and 0.45 (P = 3.1 × 10−5), 0.18 (P = 0.0191) and 0.48 (P = 1.7 × 10−7) cm, respectively, per 50% increase in α1-acid glycoprotein averaged across both trimesters. Adjustment for maternal age, parity, gestational age, nutritional and socio-economic status and daily micronutrient supplementation failed to alter any association. Serum C-reactive protein concentration was largely unassociated with newborn size. In rural Nepal, birth size was inversely associated with low-grade, chronic inflammation during pregnancy as indicated by serum α1-acid glycoprotein.