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Smoking prevalence is higher amongst individuals with schizophrenia and depression compared with the general population. Mendelian randomisation (MR) can examine whether this association is causal using genetic variants identified in genome-wide association studies (GWAS).
We conducted two-sample MR to explore the bi-directional effects of smoking on schizophrenia and depression. For smoking behaviour, we used (1) smoking initiation GWAS from the GSCAN consortium and (2) we conducted our own GWAS of lifetime smoking behaviour (which captures smoking duration, heaviness and cessation) in a sample of 462690 individuals from the UK Biobank. We validated this instrument using positive control outcomes (e.g. lung cancer). For schizophrenia and depression we used GWAS from the PGC consortium.
There was strong evidence to suggest smoking is a risk factor for both schizophrenia (odds ratio (OR) 2.27, 95% confidence interval (CI) 1.67–3.08, p < 0.001) and depression (OR 1.99, 95% CI 1.71–2.32, p < 0.001). Results were consistent across both lifetime smoking and smoking initiation. We found some evidence that genetic liability to depression increases smoking (β = 0.091, 95% CI 0.027–0.155, p = 0.005) but evidence was mixed for schizophrenia (β = 0.022, 95% CI 0.005–0.038, p = 0.009) with very weak evidence for an effect on smoking initiation.
These findings suggest that the association between smoking, schizophrenia and depression is due, at least in part, to a causal effect of smoking, providing further evidence for the detrimental consequences of smoking on mental health.
X-ray microscopy is a field that has developed rapidly in recent years. Two different approaches have been used. Zone plates have been employed to produce focussed beams with sizes as low as 0.07 pm for x-ray energies below 1 keV. Images of biological materials and elemental maps for major and minor low Z have been produced using above and below absorption edge differences. At higher energies collimators and focussing mirrors have been used to make small diameter beams for excitation of characteristic K— or L-x rays of all elements in the periodic
The hypothalamic–pituitary–adrenal axis (HPAA) plays a critical role in the functioning of all other biological systems. Thus, studying how the environment may influence its ontogeny is paramount to understanding developmental origins of health and disease. The early post-conceptional (EPC) period could be particularly important for the HPAA as the effects of exposures on organisms’ first cells can be transmitted through all cell lineages. We evaluate putative relationships between EPC maternal cortisol levels, a marker of physiologic stress, and their children’s pre-pubertal HPAA activity (n=22 dyads). Maternal first-morning urinary (FMU) cortisol, collected every-other-day during the first 8 weeks post-conception, was associated with children’s FMU cortisol collected daily around the start of the school year, a non-experimental challenge, as well as salivary cortisol responses to an experimental challenge (all Ps<0.05), with some sex-related differences. We investigated whether epigenetic mechanisms statistically mediated these links and, therefore, could provide cues as to possible biological pathways involved. EPC cortisol was associated with >5% change in children’s buccal epithelial cells’ DNA methylation for 867 sites, while children’s HPAA activity was associated with five CpG sites. Yet, no CpG sites were related to both, EPC cortisol and children’s HPAA activity. Thus, these epigenetic modifications did not statistically mediate the observed physiological links. Larger, prospective peri-conceptional cohort studies including frequent bio-specimen collection from mothers and children will be required to replicate our analyses and, if our results are confirmed, identify biological mechanisms mediating the statistical links observed between maternal EPC cortisol and children’s HPAA activity.
The aim of the current research is to analyse potential changes in the phenology of Cabernet Sauvignon under future climate change scenarios. The study compares results from two areas with different climatic conditions in Spain: Ribera del Duero and Penedès. Phenology data for budbreak (BB), bloom (BL), veraison (V) and maturity (M) were analysed for the period 2004–2015 in Ribera del Duero and for 1996–2012 in Penedès. Thermal requirements to initiate the growing cycle and to reach each phenological event were evaluated. Simulated data of changes in climate from eight models provided by Agencia Estatal de Meteorología (AEMET) of Spain, and for two Representative Concentration Pathways (RCP) (greenhouse gas concentration trajectories) – RCP4.5 and RCP8.5 by 2030, 2050 and 2070 were used. Differences of approximately 6 days for BL and about 12 days, on average, for V existed between the two areas. Based on the predicted changes of temperature and the accumulated degree days needed to reach each stage, future changes in phenology were modelled. The results indicate potentially greater changes in the warmer region (Penedès), particularly for the later growth stages, which is in agreement with greater temperature increases in Penedès. The advance of BB, BL, V and M by 2070 could be up to 5, 11, 17 and 24 days, respectively, under the RCP4.5 emission trajectory, and up to 50% higher in some stages under the RCP8.5 emission trajectory.
Important Bird and Biodiversity Areas (IBAs) are sites identified as being globally important for the conservation of bird populations on the basis of an internationally agreed set of criteria. We present the first review of the development and spread of the IBA concept since it was launched by BirdLife International (then ICBP) in 1979 and examine some of the characteristics of the resulting inventory. Over 13,000 global and regional IBAs have so far been identified and documented in terrestrial, freshwater and marine ecosystems in almost all of the world’s countries and territories, making this the largest global network of sites of significance for biodiversity. IBAs have been identified using standardised, data-driven criteria that have been developed and applied at global and regional levels. These criteria capture multiple dimensions of a site’s significance for avian biodiversity and relate to populations of globally threatened species (68.6% of the 10,746 IBAs that meet global criteria), restricted-range species (25.4%), biome-restricted species (27.5%) and congregatory species (50.3%); many global IBAs (52.7%) trigger two or more of these criteria. IBAs range in size from < 1 km2 to over 300,000 km2 and have an approximately log-normal size distribution (median = 125.0 km2, mean = 1,202.6 km2). They cover approximately 6.7% of the terrestrial, 1.6% of the marine and 3.1% of the total surface area of the Earth. The launch in 2016 of the KBA Global Standard, which aims to identify, document and conserve sites that contribute to the global persistence of wider biodiversity, and whose criteria for site identification build on those developed for IBAs, is a logical evolution of the IBA concept. The role of IBAs in conservation planning, policy and practice is reviewed elsewhere. Future technical priorities for the IBA initiative include completion of the global inventory, particularly in the marine environment, keeping the dataset up to date, and improving the systematic monitoring of these sites.
Ischemic stroke treatment is time-sensitive, and barriers to providing prehospital care encountered by Emergency Medical Services (EMS) providers have been under-studied.
This study described barriers to providing prehospital care, identified predictors of these barriers, and assessed the impact of these barriers on EMS on-scene time and administration of tissue plasminogen activator (tPA) in the emergency department (ED).
A retrospective cohort study was performed using the Get With The Guidelines-Stroke (GWTG-S; American Heart Association [AHA]; Dallas, Texas USA) registry at two hospitals to identify ischemic stroke patients arriving by EMS. Variables were abstracted from prehospital and hospital medical records and merged with registry data. Barriers to care were grouped into themes. Logistic regression was used to identify predictors of barriers to care, and bi-variate tests were used to assess differences in EMS on-scene time and the proportion of patients receiving tPA between patients with and without barriers.
Barriers to providing prehospital care were documented for 15.5% of patients: 29.6% related to access, 26.7% communication, 23.0% extrication and transportation, 20.0% refusal, and 14.1% assessment/management. Non-white and non-black race (OR: 3.69; 95% CI, 1.63-8.36) and living alone (OR: 1.53; 95% CI, 1.05-2.23) were associated with greater odds of barriers to providing care. The EMS on-scene time was ≥15 minutes for 70.4% of patients who had a barrier to care, compared with 49.0% of patients who did not (P<.001). There was no significant difference in the proportion of patients who were administered tPA between those with and without barriers to care (14.1% vs 19.2%; P=.159).
Barriers to providing prehospital care were documented for a sizable proportion of ischemic stroke patients, with the majority related to patient access and communication, and occurred more frequently among non-white and non-black patients and those living alone. Although EMS on-scene time was longer for patients with barriers to care, the proportion of patients receiving tPA in the ED did not differ.
LiT, CushmanJT, ShahMN, KellyAG, RichDQ, JonesCMC. Barriers to Providing Prehospital Care to Ischemic Stroke Patients: Predictors and Impact on Care. Prehosp Disaster Med.2018;33(5):501–507.
Globally, the prevalence of tuberculosis (TB) disease is higher in males. This study examined the effect of sex and age on Mycobacterium tuberculosis (Mtb) infection. Demographic and exposure data were collected on household contacts of sputum smear-positive pulmonary TB patients in Brazil. Contacts with tuberculin skin test induration ⩾10 mm at baseline or 12 weeks were considered Mtb infected. The study enrolled 917 household contacts from 160 households; 508 (55.4%) were female, median age was 21.0 years (range 0.30–87.0) and 609 (66.4%) had Mtb infection. The proportion infected increased with age from 63.3% in girls <5 years to 75.4% in women ⩾40 years and from 44.9% in boys <5 years to 73.6% in men ⩾40 years. Multivariable modelling showed the odds of infection increased between age 5 and 14 years among female contacts (OR 1.5 per 5-year age increase; 95% CI 1.1–2.2; P = 0.02) and between ages 0–4 and 15–39 years among male contacts (OR 2.7, 95% CI 0.83–8.9 and 1.1, 95% CI 0.99–1.3 per 5-year age increase; P = 0.10, 0.07, respectively). The study suggests that the age at which Mtb infection increases most is different in females compared with males. Studies are needed to explore whether these findings are due to differences in host susceptibility, exposure outside the household or other factors.
Giant electromagnetic pulses (EMP) generated during the interaction of high-power lasers with solid targets can seriously degrade electrical measurements and equipment. EMP emission is caused by the acceleration of hot electrons inside the target, which produce radiation across a wide band from DC to terahertz frequencies. Improved understanding and control of EMP is vital as we enter a new era of high repetition rate, high intensity lasers (e.g. the Extreme Light Infrastructure). We present recent data from the VULCAN laser facility that demonstrates how EMP can be readily and effectively reduced. Characterization of the EMP was achieved using B-dot and D-dot probes that took measurements for a range of different target and laser parameters. We demonstrate that target stalk geometry, material composition, geodesic path length and foil surface area can all play a significant role in the reduction of EMP. A combination of electromagnetic wave and 3D particle-in-cell simulations is used to inform our conclusions about the effects of stalk geometry on EMP, providing an opportunity for comparison with existing charge separation models.
At the QEII Health Sciences Centre Emergency Department (ED) in Halifax, Nova Scotia, advanced care paramedics (ACPs) perform procedural sedation and analgesia (PSA) for many indications, including orthopedic procedures. We have begun using ACPs as sedationists for emergent upper gastrointestinal (UGI) endoscopy. This study compares ACP-performed ED PSA for UGI endoscopy and orthopedic procedures in terms of adverse events, airway intervention, vasopressor requirement, and PSA medication use.
A data set was built from an ED PSA quality control database matching 61 UGI endoscopy PSAs to 183 orthopedic PSAs by propensity scores calculated using age, gender, and the American Society of Anesthesiologists (ASA) classification. Outcomes assessed were hypotension (systolic BP<100 mm Hg or a 15% decrease from baseline), hypoxia (SaO2<90%), apnea (>30 sec), vomiting, arrhythmias, death, airway intervention, vasopressor requirement, and PSA medication use.
UGI endoscopy patients experienced hypotension more frequently than orthopedic patients (OR=4.11, CI: 2.05-8.22) and required airway repositioning less often (OR=0.24, CI: 0.10-0.59). They received ketamine more frequently (OR=15.7, CI: 4.75-67.7) and fentanyl less often (OR=0.30, CI: 0.15-0.63) than orthopedic patients. Four endoscopy patients received phenylephrine, and one required intubation. No patient died in either group.
In ACP-led sedation for UGI endoscopy and orthopedic procedures, adverse events were rare with the notable exception of hypotension, which was more frequent in the endoscopy group. Only endoscopy patients required vasopressor treatment and intubation. We provide preliminary evidence that ACPs can manage ED PSA for emergent UGI endoscopy, although priorities must shift from pain control to hemodynamic optimization.
To understand increasing rates of hepatitis C virus (HCV) infection in Tennessee, we conducted testing, risk factor analysis and a nested case–control study among persons who use drugs. During June–October 2016, HCV testing with risk factor assessment was conducted in sexually transmitted disease clinics, family planning clinics and an addiction treatment facility in eastern Tennessee; data were analysed by using multivariable logistic regression. A nested case–control study was conducted to assess drug-using risks and behaviours among persons who reported intranasal or injection drug use (IDU). Of 4753 persons tested, 397 (8.4%) were HCV-antibody positive. HCV infection was significantly associated with a history of both intranasal and IDU (adjusted odds ratio (aOR) 35.4, 95% confidence interval (CI) 24.1–51.9), IDU alone (aOR 52.7, CI 25.3–109.9), intranasal drug use alone (aOR 2.6, CI 1.8–3.9) and incarceration (aOR 2.7, CI 2.0–3.8). By 4 October 2016, 574 persons with a reported history of drug use; 63 (11%) were interviewed further. Of 31 persons who used both intranasal and injection drugs, 26 (84%) reported previous intranasal drug use, occurring 1–18 years (median 5.5 years) before their first IDU. Our findings provide evidence that reported IDU, intranasal drug use and incarceration are independent indicators of risk for past or present HCV infection in the study population.
The longstanding association between the major histocompatibility complex (MHC) locus and schizophrenia (SZ) risk has recently been accounted for, partially, by structural variation at the complement component 4 (C4) gene. This structural variation generates varying levels of C4 RNA expression, and genetic information from the MHC region can now be used to predict C4 RNA expression in the brain. Increased predicted C4A RNA expression is associated with the risk of SZ, and C4 is reported to influence synaptic pruning in animal models.
Based on our previous studies associating MHC SZ risk variants with poorer memory performance, we tested whether increased predicted C4A RNA expression was associated with reduced memory function in a large (n = 1238) dataset of psychosis cases and healthy participants, and with altered task-dependent cortical activation in a subset of these samples.
We observed that increased predicted C4A RNA expression predicted poorer performance on measures of memory recall (p = 0.016, corrected). Furthermore, in healthy participants, we found that increased predicted C4A RNA expression was associated with a pattern of reduced cortical activity in middle temporal cortex during a measure of visual processing (p < 0.05, corrected).
These data suggest that the effects of C4 on cognition were observable at both a cortical and behavioural level, and may represent one mechanism by which illness risk is mediated. As such, deficits in learning and memory may represent a therapeutic target for new molecular developments aimed at altering C4’s developmental role.
The mainstay of management of epistaxis refractory to first aid and cautery is intranasal packing. This review aimed to identify evidence surrounding nasal pack use.
A systematic review of the literature was performed using standardised methodology.
Twenty-seven eligible articles were identified relating to non-dissolvable packs and nine to dissolvable packs. Nasal packing appears to be more effective when applied by trained professionals. For non-dissolvable packs, the re-bleed rates for Rapid Rhino and Merocel were similar, but were higher with bismuth iodoform paraffin paste packing. Rapid Rhino packs were the most tolerated non-dissolvable packs. Evidence indicates that 96 per cent of re-bleeding occurs within the first 4 hours after nasal pack removal. Limited evidence suggests that dissolvable packs are effective and well tolerated by patients. There was a lack of evidence relating to: the duration of pack use, the economic effects of pack choice and the appropriate care setting for non-dissolvable packs.
Rapid Rhino packs are the best tolerated, with efficacy equivalent to nasal tampons. FloSeal is easy to use, causes less discomfort and may be superior to Merocel in anterior epistaxis cases. There is no strong evidence to support prophylactic antibiotic use.
The application of digital monitoring biomarkers in health, wellness and disease management is reviewed. Harnessing the near limitless capacity of these approaches in the managed healthcare continuum will benefit from a systems-based architecture which presents data quality, quantity, and ease of capture within a decision-making dashboard.
A framework was developed which stratifies key components and advances the concept of contextualized biomarkers. The framework codifies how direct, indirect, composite, and contextualized composite data can drive innovation for the application of digital biomarkers in healthcare.
The de novo framework implies consideration of physiological, behavioral, and environmental factors in the context of biomarker capture and analysis. Application in disease and wellness is highlighted, and incorporation in clinical feedback loops and closed-loop systems is illustrated.
The study of contextualized biomarkers has the potential to offer rich and insightful data for clinical decision making. Moreover, advancement of the field will benefit from innovation at the intersection of medicine, engineering, and science. Technological developments in this dynamic field will thus fuel its logical evolution guided by inputs from patients, physicians, healthcare providers, end-payors, actuarists, medical device manufacturers, and drug companies.
Housed pigs are exposed chronically to aerial pollutants, principally dust and ammonia, at concentrations that may affect performance, possibly by raising the incidence and prevalence of multi-factorial respiratory diseases. Tolerable limits for aerial pollutants are unknown. The aim of this experiment was to test the hypothesis that chronic exposure of weaner pigs to controlled concentrations of aerial dust and ammonia lead to slower growth and lower feed intake compared with controls kept in ‘fresh air’.
The Taipan galaxy survey (hereafter simply ‘Taipan’) is a multi-object spectroscopic survey starting in 2017 that will cover 2π steradians over the southern sky (δ ≲ 10°, |b| ≳ 10°), and obtain optical spectra for about two million galaxies out to z < 0.4. Taipan will use the newly refurbished 1.2-m UK Schmidt Telescope at Siding Spring Observatory with the new TAIPAN instrument, which includes an innovative ‘Starbugs’ positioning system capable of rapidly and simultaneously deploying up to 150 spectroscopic fibres (and up to 300 with a proposed upgrade) over the 6° diameter focal plane, and a purpose-built spectrograph operating in the range from 370 to 870 nm with resolving power R ≳ 2000. The main scientific goals of Taipan are (i) to measure the distance scale of the Universe (primarily governed by the local expansion rate, H0) to 1% precision, and the growth rate of structure to 5%; (ii) to make the most extensive map yet constructed of the total mass distribution and motions in the local Universe, using peculiar velocities based on improved Fundamental Plane distances, which will enable sensitive tests of gravitational physics; and (iii) to deliver a legacy sample of low-redshift galaxies as a unique laboratory for studying galaxy evolution as a function of dark matter halo and stellar mass and environment. The final survey, which will be completed within 5 yrs, will consist of a complete magnitude-limited sample (i ⩽ 17) of about 1.2 × 106 galaxies supplemented by an extension to higher redshifts and fainter magnitudes (i ⩽ 18.1) of a luminous red galaxy sample of about 0.8 × 106 galaxies. Observations and data processing will be carried out remotely and in a fully automated way, using a purpose-built automated ‘virtual observer’ software and an automated data reduction pipeline. The Taipan survey is deliberately designed to maximise its legacy value by complementing and enhancing current and planned surveys of the southern sky at wavelengths from the optical to the radio; it will become the primary redshift and optical spectroscopic reference catalogue for the local extragalactic Universe in the southern sky for the coming decade.
The immune system not only provides protection against infectious disease but also contributes to the etiology of neoplastic, atopic, and cardiovascular and metabolic diseases. Prenatal and postnatal nutritional and microbial environments have lasting effects on multiple aspects of immunity, indicating that immune processes may play important roles in the developmental origins of disease. The objective of this study is to evaluate the association between birth weight and the distribution of leukocyte (white blood cell) subsets in peripheral blood in young adulthood. Postnatal microbial exposures were also considered as predictors of leukocyte distribution. Participants (n=486; mean age=20.9 years) were drawn from a prospective birth cohort study in the Philippines, and analyses focused on the following cell types: CD4 T lymphocytes, CD8 T lymphocytes, B lymphocytes, natural killer cells, monocytes, granulocytes. Higher birth weight was a strong predictor of higher proportion of CD4 T lymphocytes (B=0.12, s.e.=0.041, P=0.003), lower proportion of CD8 T lymphocytes (B=−0.874, s.e.=0.364, P=0.016), higher CD4:CD8 ratio (B=1.964, s.e.=0.658, P=0.003), and higher B lymphocytes (B=0.062, s.e.=0.031, P=0.047). Measures of microbial exposure in infancy were negatively associated with proportions of B lymphocytes and granulocytes, and lower CD4:CD8 ratio. Leukocytes are the key regulators and effectors of innate and specific immunity, but the origins of variation in the distribution of cell type across individuals are not known. Our findings point toward nutritional and microbial exposures in infancy as potentially important determinants of immune-phenotypes in adulthood, and they suggest that leukocyte distribution is a plausible mechanism through which developmental environments have lasting effects on disease risk in adulthood.