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Introduction: Increasing opioid prescribing has been linked to an epidemic of opioid misuse. Our objective was to synthesize available evidence about patient-, prescriber-, medication-, and system-level risk factors for developing opioid misuse from prescribed opioids among patients presenting with pain unrelated to cancer. Our hypothesis was that we would identify risk factors predisposing patients to developing opioid misuse. Methods: We developed a systematic search strategy and applied it to nine electronic reference databases and six clinical trial registries. We hand searched related journals and conference proceedings, the reference lists of included studies, and the top 100 hits on Google. We included studies where a medical professional exposed adults or children to an opioid through a prescription. We excluded studies with over 50% cancer patients, palliative patients, and those with illicit opioid initiation. Two reviewers independently reviewed titles, abstracts, and full texts, and extracted data using standardized forms. We assessed study quality using risk of bias. We synthesized effect sizes of dichotomous risk factors on opioid misuse using inverse variance random-effects meta-analysis, and the inverse variance-weighted mean difference between opioid misusers and non-misusers for continuously measured factors. We conducted an a priori defined subgroup analysis among opioid-naïve patients. Results: Among 9,629 studies, 67 met our inclusion criteria. Among those who had been prescribed outpatient opioids, the following factors were associated with the development of misuse: a prior history of illicit drug use (OR: 4.21, 95% CI: 2.31-7.65), recent benzodiazepine use (OR: 2.57, 95% CI: 1.23-5.38), any mental health diagnosis (OR: 2.45, 95% CI: 1.91-3.15), any short acting (IR) opioid prescription (OR: 2.40, 95% CI: 1.15-5.02), younger age (OR: 2.19, 95%CI: 1.81-2.64), and male sex (OR: 1.23, 95% CI: 1.10-1.36). Among studies limiting their population to opioid-naïve patients, younger age was the most significant risk factor for opioid misuse (OR: 5.42, 95% CI:1.51-19.43). Conclusion: Of the risk factors examined, non-cancer pain patients with a prior history of substance use or mental health diagnoses were at highest risk for prescription opioid misuse. Younger opioid-naïve patients were at highest risk of misuse. Clinicians should consider these risk factors when managing acute pain in the emergency department.
An insect trap constructed using three-dimensional (3D) printing technology was tested in potato (Solanum tuberosum Linnaeus; Solanaceae) fields to determine whether it could substitute for the standard yellow sticky card used to monitor Bactericera cockerelli (Šulc) (Hemiptera: Psylloidea: Triozidae). Sticky cards have shortcomings that prompted search for a replacement: cards are messy, require weekly replacement, are expensive to purchase, and accumulate large numbers of nontarget insects. Bactericera cockerelli on sticky cards also deteriorate enough that specimens cannot be tested reliably for the presence of vectored plant pathogens. A prototype trap constructed using 3D printing technology for monitoring Diaphorina citri Kuwayama (Hemiptera: Psylloidea: Liviidae) was tested for monitoring B. cockerelli. The trap was designed to attract B. cockerelli visually to the trap and then funnel specimens into preservative-filled vials at the trap bottom. Prototype traps were paired against yellow sticky cards at multiple fields to compare the captures of B. cockerelli between cards and traps. The prototype trap was competitive with sticky cards early in the growing season when B. cockerelli numbers were low. We estimated that two or three prototype traps would collect as many B. cockerelli as one sticky card under these conditions. Efficacy of the prototype declined as B. cockerelli numbers increased seasonally. The prototype trap accumulated nontarget taxa that are common on sticky cards (especially Thysanoptera and Diptera), and was also found to capture taxa of possible interest in integrated pest management research, including predatory insects, parasitic Hymenoptera, and winged Aphididae (Hemiptera), suggesting that the traps could be useful outside of the purpose targeted here. We believe that 3D printing technology has substantial promise for developing monitoring tools that exploit behavioural traits of the targeted insect. Ongoing work includes the use of this technology to modify the prototype, with a focus on making it more effective at capturing psyllids and less susceptible to capture of nontarget species.
Tissue engineering aims to grow artificial tissues in vitro to replace those in the body that have been damaged through age, trauma or disease. A recent approach to engineer artificial cartilage involves seeding cells within a scaffold consisting of an interconnected 3D-printed lattice of polymer fibres combined with a cast or printed hydrogel, and subjecting the construct (cell-seeded scaffold) to an applied load in a bioreactor. A key question is to understand how the applied load is distributed throughout the construct. To address this, we employ homogenisation theory to derive equations governing the effective macroscale material properties of a periodic, elastic–poroelastic composite. We treat the fibres as a linear elastic material and the hydrogel as a poroelastic material, and exploit the disparate length scales (small inter-fibre spacing compared with construct dimensions) to derive macroscale equations governing the response of the composite to an applied load. This homogenised description reflects the orthotropic nature of the composite. To validate the model, solutions from finite element simulations of the macroscale, homogenised equations are compared to experimental data describing the unconfined compression of the fibre-reinforced hydrogels. The model is used to derive the bulk mechanical properties of a cylindrical construct of the composite material for a range of fibre spacings and to determine the local mechanical environment experienced by cells embedded within the construct.
Improvements in feed efficiency of beef cattle have the potential to increase producer profitability and simultaneously lower the environmental footprint of beef production. Although there are many different approaches to measuring feed efficiency, residual feed intake (RFI) has increasingly become the measure of choice. Defined as the difference between an animal’s actual and predicted feed intake (based on weight and growth), RFI is conceptually independent of growth and body size. In addition, other measurable traits related to energy expenditure such as estimates of body composition can be included in the calculation of RFI to also force independence from these traits. Feed efficiency is a multifactorial and complex trait in beef cattle and inter-animal variation stems from the interaction of many biological processes influenced, in turn, by physiological status and management regimen. Thus, the purpose of this review was to summarise and interpret current published knowledge and provide insight into research areas worthy of further investigation. Indeed, where sufficient suitable reports exist, meta-analyses were conducted in order to mitigate ambiguity between studies in particular. We have identified a paucity of information on the contribution of key biological processes, including appetite regulation, post-ruminal nutrient absorption, and cellular energetics and metabolism to the efficiency of feed utilisation in cattle. In addition, insufficient information exists on the relationship between RFI status and productivity-related traits at pasture, a concept critical to the overall lifecycle of beef production systems. Overall, published data on the effect of RFI status on both terminal and maternal traits, coupled with the moderate repeatability and heritability of the trait, suggest that breeding for improved RFI, as part of a multi-trait selection index, is both possible and cumulative, with benefits evident throughout the production cycle. Although the advent of genomic selection, with associated improved prediction accuracy, will expedite the introgression of elite genetics for feed efficiency within beef cattle populations, there are challenges associated with this approach which may, in the long-term, be overcome by increased international collaborative effort but, in the short term, will not obviate the on-going requirement for accurate measurement of the primary phenotype.
One method to grow artificial body tissue is to place a porous scaffold seeded with cells, known as a tissue construct, into a rotating bioreactor filled with a nutrient-rich fluid. The flow within the bioreactor is affected by the movement of the construct relative to the bioreactor which, in turn, is affected by the hydrodynamical and gravitational forces the construct experiences. The construct motion is thus coupled to the flow within the bioreactor. Over the time scale of a few hours, the construct appears to move in a periodic orbit but, over tens of hours, the construct drifts from periodicity. In the biological literature, this effect is often attributed to the change in density of the construct that occurs via tissue growth. In this paper, we show that weak inertia can cause the construct to drift from its periodic orbit over the same time scale as tissue growth. We consider the coupled flow and construct motion problem within a rotating high-aspect-ratio vessel bioreactor. Using an asymptotic analysis, we investigate the case where the Reynolds number is large but the geometry of the bioreactor yields a small reduced Reynolds number, resulting in a weak inertial effect. In particular, to accurately couple the bioreactor and porous flow regions, we extend the nested boundary layer analysis of Dalwadi et al. (J. Fluid Mech., vol. 798, 2016, pp. 88–139) to include moving walls and the thin region between the porous construct and the bioreactor wall. This allows us to derive a closed system of nonlinear ordinary differential equations for the construct trajectory, from which we show that neglecting inertia results in periodic orbits; we solve the inertia-free problem analytically, calculating the periodic orbits in terms of the system parameters. Using a multiple-scale analysis, we then systematically derive a simpler system of nonlinear ordinary differential equations that describe the long-time drift of the construct due to the effect of weak inertia. We investigate the bifurcations of the construct trajectory behaviour, and the limit cycles that appear when the construct is less dense than the surrounding fluid and the rotation rate is large enough. Thus, we are able to predict when the tissue construct will drift towards a stable limit cycle within the bioreactor and when it will drift out until it hits the bioreactor edge.
An ambition of depression biomarker research is to augment psychometric and cognitive assessment of clinically relevant phenomena with neural measures. Although such applications have been slow to arrive, we observe a steady evolution of the idea and anticipate emerging technologies with some optimism. To highlight critical themes and innovations in depression biomarker research, we take as our point of reference a specific research narrative. We begin with an early model of frontal-limbic dysfunction, which represents a conceptual shift from localized pathology to understanding symptoms as an emergent property of distributed networks. Over the decades, this model accommodates perspectives from neurology, psychiatry, clinical, and cognitive neuroscience, and preserves past insight as more complex methods become available. We also track the expanding mission of brain biomarker research: from the development of diagnostic tools to treatment selection algorithms, measures of neurocognitive functioning and novel targets for neuromodulation. To conclude, we draw from this particular research narrative future directions for biomarker research. We emphasize integration of measurement modalities to describe dynamic change in domain-general networks, and we speculate that a brain-based framework for psychiatric problems may dissolve classical diagnostic and disciplinary boundaries. (JINS, 2017, 23, 870–880)
Lower and middle income countries (LMICs) are home to >80% of the global population, but mental health researchers and LMIC investigator led publications are concentrated in 10% of LMICs. Increasing research and research outputs, such as in the form of peer reviewed publications, require increased capacity building (CB) opportunities in LMICs. The National Institute of Mental Health (NIMH) initiative, Collaborative Hubs for International Research on Mental Health reaches across five regional ‘hubs’ established in LMICs, to provide training and support for emerging researchers through hub-specific CB activities. This paper describes the range of CB activities, the process of monitoring, and the early outcomes of CB activities conducted by the five research hubs.
The indicators used to describe the nature, the monitoring, and the early outcomes of CB activities were developed collectively by the members of an inter-hub CB workgroup representing all five hubs. These indicators included but were not limited to courses, publications, and grants.
Results for all indicators demonstrate a wide range of feasible CB activities. The five hubs were successful in providing at least one and the majority several courses; 13 CB recipient-led articles were accepted for publication; and nine grant applications were successful.
The hubs were successful in providing CB recipients with a wide range of CB activities. The challenge remains to ensure ongoing CB of mental health researchers in LMICs, and in particular, to sustain the CB efforts of the five hubs after the termination of NIMH funding.
The method of matched asymptotic expansions is used to study the canonical problem of steady laminar flow through a narrow two-dimensional channel blocked by a tight-fitting finite-length highly permeable porous obstacle. We investigate the behaviour of the local flow close to the interface between the single-phase and porous regions (governed by the incompressible Navier–Stokes and Darcy flow equations, respectively). We solve for the flow in these inner regions in the limits of low and high Reynolds number, facilitating an understanding of the nature of the transition from Poiseuille to plug to Poiseuille flow in each of these limits. Significant analytical progress is made in the high Reynolds number limit, and we explore in detail the rich boundary layer structure that occurs. We derive general results for the interfacial stress and for the conditions that couple the flow in the outer regions away from the interface. We consider the three-dimensional generalization to unsteady laminar flow through and around a tight-fitting highly permeable cylindrical porous obstacle within a Hele-Shaw cell. For the high Reynolds number limit, we give the coupling conditions and interfacial stress in terms of the outer flow variables, allowing information from a nonlinear three-dimensional problem to be obtained by solving a linear two-dimensional problem. Finally, we illustrate the utility of our analysis by considering the specific example of time-dependent forced far-field flow in a Hele-Shaw cell containing a porous cylinder with a circular cross-section. We determine the internal stress within the porous obstacle, which is key for tissue engineering applications, and the interfacial stress on the boundary of the porous obstacle, which has applications to biofilm erosion. In the high Reynolds number limit, we demonstrate that the fluid inertia can result in the cylinder experiencing a time-independent net force, even when the far-field forcing is periodic with zero mean.
The late stages of stellar evolution of stars with low or intermediate mass (1 M⊙ to 8 M⊙) are characterized by extensive mass loss, which can be traced in their circumstellar environment. Here we consider the case of IRAS 16342-3814, a bipolar proto planetary nebula which shows very high velocity (~ 50 km s-1) OH maser emission (Sahai et al. 1999). We present the complete Infrared Space Observatory (ISO) spectrum and an infrared TIMMI2 Q-band image of this source. Based on these data we discuss the composition and geometry of the circumstellar dust in IRAS 16342-3814.
GK Per, a classical nova system that erupted in 1901, is one of the more unusual examples of its type. It has the longest known orbital period for a classical nova (1.997d; Crampton, Cowley & Fisher 1986); and it contains a white dwarf primary with an evolved K2 sub-giant secondary. Most remarkably, the IRAS Sky Survey (1991) reveals that GK Per exhibits far-IR dust emission extending ~ 17′ to the NW and SE of the nova (Bode et al. 1987; Seaquist et al. 1989). We have re-analysed the IRAS data using maximum entropy reconstruction (Bontekoe et al. 1991; Bontekoe, Koper & Kester 1994) to resolve structures at a spatial resolution approaching the diffraction limit of IRAS, which is 1′ at 60 μm and 1.7′ at 100/μm.
The reasons for the unprecedented mortality during the 1918 influenza pandemic remain poorly understood. We examined morbidity records from three military cohorts from years prior to and during the 1918 pandemic period to assess the effects of previous respiratory illnesses on experiences during the pandemic. Clinical registers and morbidity lists were examined to identify all medical encounters for acute respiratory illnesses in students at two U.S. military officer training academies and Australian soldiers deployed in Europe. Influenza-like illness prior to the major pandemic wave of 1918 predisposed Australian soldiers [relative risk (RR) 1·37, 95% confidence interval (CI) 1·18–1·60, P < 0·0001] and US officer trainees at West Point (RR 3·10, 95% CI 2·13–4·52, P < 0·0001) and Annapolis (RR 2·03, 95% CI 1·65–2·50, P < 0·0001) to increased risks of medically treated illnesses in late 1918. The findings suggest that susceptibility to and/or clinical expressions of the 1918 pandemic influenza virus depended on previous experiences with respiratory infectious agents. The findings are consistent with observations during the 2009 pandemic in Canada and may reflect antibody-dependent enhancement of influenza infection.
Haematological profiles indicate the health status of an animal and can be used to identify sub-clinical stress responses. The objectives of the study were to examine (i) the effect of breed and plane of nutrition, on haematological profiles of artificially reared Holstein-Friesian and Jersey bull calves in response to gradual weaning, and (ii) the effect of breed on immune response genes in bovine whole blood using real-time quantitative PCR. Holstein-Friesian and Jersey bull calves were group housed indoors and individually fed using an automatic feeder. They were allocated to a high, medium or low plane of nutrition, based on milk replacer (MR) and concentrate. The nutrition treatments were calculated using National Research Council guidelines in order to achieve a high, medium or low growth rate for each respective breed. During the weaning phase MR was gradually reduced over a 14-day (d) period (d −13 to d 0). Calves were blood sampled on d −14, −6, −3, 0, 1, 3, 8 and 14 relative to weaning (d 0) for subsequent haematological analysis. On d −14, 1 and 8, a subset of eight Holstein-Friesian calves randomly selected from the medium nutrition treatment and eight Jersey calves randomly selected from the high nutrition treatment, were blood sampled for gene expression profiling, targeting biomarkers of weaning stress. These two treatment groups were chosen to examine the effect of breed on expression of the genes of interest, as energy intake and animal performance were similar. There was no effect of breed×plane of nutrition interaction nor effect of plane of nutrition on any variable measured (P>0.05). Gradual weaning produced differential biological responses in the two breeds evidenced by breed×time interactions for lymphocyte, monocyte and red blood cell number, plasma haemoglobin and haptoglobin concentrations (P<0.05). The typical stress response consisting of neutrophilia and lymphopaenia was not observed for any treatment. An immune response to gradual weaning was observed as the relative gene expression level of the pro-apoptotic gene, Fas, increased on d 1 relative to d −14 (P<0.05). Relative gene expression levels were greater in Jersey calves compared with Holstein-Friesian for the pro-inflammatory cytokine CXCL8 (P=0.05) and the glucocorticoid receptor, GRα (P<0.05). The increased levels of these transcripts suggest that Jersey calves may have a more sensitive immune system compared with Holstein-Friesian.
Over the past decade, a growing number of deep imaging surveys have started to provide meaningful constraints on the population of extrasolar giant planets at large orbital separation. Primary targets for these surveys have been carefully selected based on their age, distance and spectral type, and often on their membership to young nearby associations where all stars share common kinematics, photometric and spectroscopic properties. The next step is a wider statistical analysis of the frequency and properties of low mass companions as a function of stellar mass and orbital separation. In late 2009, we initiated a coordinated European Large Program using angular differential imaging in the H band (1.66 μm) with NaCo at the VLT. Our aim is to provide a comprehensive and statistically significant study of the occurrence of extrasolar giant planets and brown dwarfs at large (5-500 AU) orbital separation around ~150 young, nearby stars, a large fraction of which have never been observed at very deep contrast. The survey has now been completed and we present the data analysis and detection limits for the observed sample, for which we reach the planetary-mass domain at separations of ≳50 AU on average. We also present the results of the statistical analysis that has been performed over the 75 targets newly observed at high-contrast. We discuss the details of the statistical analysis and the physical constraints that our survey provides for the frequency and formation scenario of planetary mass companions at large separation.
To review the aetiology, investigation, diagnosis, treatment and clinical outcome of children with recurrent croup.
Retrospective case note review of all children with recurrent croup referred to the otolaryngology service at our hospital from November 2002 to March 2011.
Ninety children with recurrent croup were identified. Twenty-five children (28 per cent) had anatomical airway abnormalities, of which 16 (18 per cent) demonstrated degrees of subglottic stenosis. Twenty-three children (26 per cent) had positive microlaryngobronchoscopy findings suggestive of reflux. Eleven children were treated for gastroesophageal reflux disease, 10 (91 per cent) of whom responded well to anti-reflux medication (p = 0.006). No cause was identified for 41 (45 per cent) of the children; this was the group most likely to continue having episodes of croup at follow up. One death occurred in this group.
Airway anomalies are common in children that present with recurrent croup. Laryngobronchoscopy allows identification of the cause of croup and enables a more accurate prognosis. In the current study, laryngobronchoscopy findings that indicated reflux were predictive of benefit from anti-reflux medications, whereas the clinical presentation of reflux was not. Routine measurement of immunoglobulin E and complement proteins did not appear to be helpful.
In this study, we examine a steady two-dimensional slow flow past a rigid cylinder coated with a thin layer of immiscible fluid. The Reynolds number for the external bulk flow is assumed small and flow within the film is driven by the action of the bulk fluid’s tangential viscous stress acting at the interface. Using double asymptotic expansions based on the bulk fluid’s Reynolds number and the aspect ratio of the film thickness to the cylinder’s radius, we derive the leading- and first-order equations governing the steady-state film dynamics, and obtain analytical solutions, in terms of the film thickness, for the bulk flow. We solve the governing film equations, finding that solutions feature a drained region. We briefly discuss the influence of the Capillary number and fluid viscosities, and conclude by showing how the presence of the film affects the drag on the film-coated cylinder.
The use of thiourea/ammonia pre-treatments on (100) InP, followed by chemical bath deposition (CBD) of CdS thin films (∼ 30 Å), with low-temperature, low-pressure chemical vapor deposited SiO2 has been shown to produce metal-insulator-semiconductor (MIS) samples with near-ideal capacitance-voltage (C-V) response. Here, we report on x-ray photoelectron spectroscopy (XPS) analysis of the near-surface of InP following pre-treatment and CdS deposition. The pre-treatment was shown by XPS to form an indium sulfide layer and effectively remove native oxides from the InP surface. The subsequent deposition of CdS on a sulfur-passivated surface forms a stable layer which protects the substrate from oxidation during SiO2 chemical vapor deposition. MIS samples prepared using the pre-treatment without CdS deposition showed improved C- V response, while samples prepared with both the pre-treatment and CdS deposition showed a dramatic reduction in the density of interface states.
Maternal experience of childhood maltreatment and maternal antenatal depression
are both associated with offspring childhood maltreatment and offspring adjustment
problems. We have investigated the relative impact of maternal childhood
maltreatment and exposure to depression in utero on offspring
maltreatment and psychopathology.
The sample included 125 families from the South London Child Development Study. A
prospective longitudinal design was used. Data on maternal childhood maltreatment,
maternal antenatal depression (36 weeks of pregnancy), offspring childhood
maltreatment (age 11 years) and offspring adolescent antisocial behaviour and
depression (ages 11 and 16 years) were obtained from parents and offspring through
Mothers who experienced childhood maltreatment were significantly more likely to
be depressed during pregnancy [odds ratio (OR) 10.00]. Offspring of mothers who
experienced only childhood maltreatment or only antenatal depression were no more
at risk of being maltreated or having psychopathology; however, offspring of
mothers who experienced both maternal childhood maltreatment and antenatal
depression were exposed to significantly greater levels of childhood maltreatment
and exhibited significantly higher levels of adolescent antisocial behaviour
compared with offspring not so exposed. Furthermore, maternal childhood
maltreatment accounted for a significant proportion of the variance in offspring
childhood maltreatment in only those offspring exposed to depression in
Maternal childhood maltreatment and maternal antenatal depression are highly
associated. The co-occurrence of both insults significantly increases the risk of
offspring adversity. The antenatal period is an optimum period to identify
vulnerable women and to provide interventions.
Antenatal depression and childhood maltreatment have each been associated
with offspring psychopathology, but have never been examined in the same
To determine whether childhood maltreatment influences the association
between antenatal depression and offspring psychopathology.
Prospectively collected data on antenatal depression, offspring
maltreatment (age 11) and offspring psychopathology (age 11 and 16) were
analysed in 120 mother–offspring dyads from the community-based South
London Child Development Study.
Antenatal depression increased the risk of maltreatment in the offspring
by almost four times. Children exposed only to antenatal depression or
only to childhood maltreatment were no more at risk of developing
psychopathology; however, children exposed to both antenatal depression
and childhood maltreatment were at almost 12 times greater risk of
developing psychopathology than offspring not so exposed.
Research investigating exposure to adverse events in
utero and offspring psychopathology should take account of
postnatal adverse events such as maltreatment.
Intergranular glass phases can have a significant influence on the fracture resistance (R-curve behavior) of silicon nitride ceramics and appears to be related to the debonding of the β-Si3N4/oxynitride-glass interfaces. Applying the results from β-Si3N4-whisker/oxynitride-glass model systems, self-reinforced silicon nitrides with different sintering additive ratios were investigated. Silicon nitrides sintered with a lower Al2O3:Y2O3 additive ratio exhibited higher steady-state fracture toughness together with a steeply-rising R-curve. Analytical electron microscopy studies suggested that the different fracture behavior is related to the Al content in the SiAlON growth band on the elongated grains, which could result in differences in interfacial bonding structures between the grains and the intergranular glass.
Boron nitride thin films on sapphire substrates were investigated for their tribological and optoelectronic applications. A gridless end Hall gun source and an electron cyclotron resonance (ECR) source were used for nitrogen species delivery while pure boron was evaporated at a rate of 0.2 Å/s. The surface stability of these thin films was investigated by high temperature annealing. Atomic force microscopy (AFM), friction force microscopy (FFM), and Knoop microhardness measurements were performed on the materials in order to assess their merits as tribological coatings. Finally, BN thin films were subjected to laser transient photoconductivity (TPC) experiments to determine both their optical laser damage threshold as well as their photoconductivity characteristics. For both single-pulse shot and multiple-pulse irradiation regimes, preliminary tests showed the higher the ion beam current used during growth (70–150 mA), the higher the optical damage threshold. The lower damage threshold was typical of BN films grown using an ECR plasma source and was measured to be in the range of ∼50 MW/cm2. Optical damage of films grown at ion beam currents above 100 mA was not observed at laser intensities up to few hundreds MW/cm2. A multiphoton excitation technique was utilized to obtain PC signals from this wide band gap material and preliminary results show that unusual PC voltage amplitudes as high as 0.5 V were observed.