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Studies suggest that alcohol consumption and alcohol use disorders have distinct genetic backgrounds.
We examined whether polygenic risk scores (PRS) for consumption and problem subscales of the Alcohol Use Disorders Identification Test (AUDIT-C, AUDIT-P) in the UK Biobank (UKB; N = 121 630) correlate with alcohol outcomes in four independent samples: an ascertained cohort, the Collaborative Study on the Genetics of Alcoholism (COGA; N = 6850), and population-based cohorts: Avon Longitudinal Study of Parents and Children (ALSPAC; N = 5911), Generation Scotland (GS; N = 17 461), and an independent subset of UKB (N = 245 947). Regression models and survival analyses tested whether the PRS were associated with the alcohol-related outcomes.
In COGA, AUDIT-P PRS was associated with alcohol dependence, AUD symptom count, maximum drinks (R2 = 0.47–0.68%, p = 2.0 × 10−8–1.0 × 10−10), and increased likelihood of onset of alcohol dependence (hazard ratio = 1.15, p = 4.7 × 10−8); AUDIT-C PRS was not an independent predictor of any phenotype. In ALSPAC, the AUDIT-C PRS was associated with alcohol dependence (R2 = 0.96%, p = 4.8 × 10−6). In GS, AUDIT-C PRS was a better predictor of weekly alcohol use (R2 = 0.27%, p = 5.5 × 10−11), while AUDIT-P PRS was more associated with problem drinking (R2 = 0.40%, p = 9.0 × 10−7). Lastly, AUDIT-P PRS was associated with ICD-based alcohol-related disorders in the UKB subset (R2 = 0.18%, p < 2.0 × 10−16).
AUDIT-P PRS was associated with a range of alcohol-related phenotypes across population-based and ascertained cohorts, while AUDIT-C PRS showed less utility in the ascertained cohort. We show that AUDIT-P is genetically correlated with both use and misuse and demonstrate the influence of ascertainment schemes on PRS analyses.
Mental disorders in children are a significant and growing cause of morbidity worldwide. Although interventions to help overcome barriers along the pathway to accessing health care for children with mental disorders exist, there is no overview of randomised controlled trials (RCTs) on these interventions as yet. This study aimed to systematically identify RCTs of interventions to improve access to mental health care for children and synthesise them using a conceptual framework of access to health care.
This systematic review was performed following a predefined protocol registered with PROSPERO (ID: CRD42018081714). We searched the databases MEDLINE, EMBASE, PsycINFO and CENTRAL for RCTs up to 15 May 2019 using terms related to the concepts ‘young people,’ ‘mental disorders’ and ‘help-seeking interventions’ and scanned reference lists from relevant studies. Two reviewers independently screened all identified articles in a two-stage process, extracted results on outcomes of interest (knowledge, attitudes, intentions, help-seeking, accessing care, mental health outcomes and satisfaction), assessed the risk of bias and conducted meta-analyses where deemed appropriate.
After screening 5641 identified articles, 34 RCTs were eligible for inclusion. Eighty per cent of universal school-based interventions measuring knowledge (n = 5) and 67% measuring attitudes (n = 6) reported significantly better results compared with controls on those outcomes, whereas 20% measuring access to care (n = 5) and none measuring mental health outcomes (n = 7) did. In contrast, 71% of interventions targeting at-risk individuals (n = 21) reported better access to care compared with controls, while just 33% (n = 6) did for mental health outcomes. For satisfaction with care, this proportion was 80% (n = 5). Meta-analyses of interventions measuring initial appointment attendance yielded combined odds ratios of 3.11 (2.07–4.67) for appointment reminder interventions and 3.51 (2.02–6.11) for treatment engagement interventions. The outcomes for universal school-based interventions were heterogeneous and could not be summarised quantitatively through meta-analysis.
To have a population-level effect on improving children's access to mental health care, two-stage interventions that identify those in need and then engage them in the health-care system may be necessary. We need more evidence on interventions to target contextual factors such as affordability and infrastructural barriers.
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.
Autism Spectrum Disorder (ASD) and schizophrenia are neurodevelopmental disorders which share substantial overlap in cognitive deficits during adulthood. However, treatment evaluation in ASD and treatment comparisons across ASD and schizophrenia are limited by a dearth of empirical work establishing the validity of a standard cognitive battery across ASD and schizophrenia. Promisingly, the MATRICS Consensus Cognitive Battery (MCCB) has been validated in schizophrenia and encompasses cognitive domains that are impacted in ASD. Thus, this study aimed to establish MCCB's generalizability from schizophrenia to ASD.
Community-residing adults with schizophrenia (N = 100) and ASD (N = 113) underwent MCCB assessment. Using multigroup confirmatory factor analysis, MCCB's transdiagnostic validity was evaluated by examining whether schizophrenia and ASD demonstrate the same configuration, magnitude, and directionality of relationships within and among measures and their underlying cognitive domains.
Across schizophrenia and ASD, the same subsets of MCCB measures inform three cognitive domains: processing speed, attention/working memory, and learning. Except for group means in category fluency, continuous performance, and spatial span, both groups show vastly comparable factor structures and characteristics.
To our knowledge, this study is the first to establish the validity of a standard cognitive battery in adults with ASD and furthermore the first to establish a cognitive battery's comparability across ASD and schizophrenia. Cognitive domain scores can be compared across new samples using weighted sums of MCCB scores resulting from this study. These findings highlight MCCB's applicability to ASD and support its utility for standardizing treatment evaluation of cognitive outcomes across the autism-schizophrenia spectrum.
Many seed quality tests are conducted by first randomly assigning seeds into replicates of a given size. The replicate results are then used to check whether or not any problems occur in the realization of the test. The two main tools developed for this verification are the ratio of the observed variance of the replicate results to a theoretical variance and the tolerance for the range of the results. In this paper, we derive the theoretical distribution and its related properties of the sequence of numbers of seeds with a given quality attribute present in the replicates. From these theoretical results, we revisit the two quality checking tools widely used for the germination test. We show a precaution to be taken when relying on the variance ratio to check for under- or over-dispersion of the replicate results. This has led to the development of tables providing credible intervals of the variance ratio. The International Seed Testing Association tolerance tables for the range of the results are also compared with tolerances computed from the exact theoretical distribution of the range, leading us to recommend a revision of these tables.
Numerous studies have demonstrated that genetic and environmental factors interact to influence alcohol problems. Yet prior research has primarily focused on samples of European descent and little is known about gene–environment interactions in relation to alcohol problems in non-European populations. In this study, we examined whether and how genetic risk for alcohol problems and peer deviance and interpersonal traumatic events independently and interactively influence trajectories of alcohol use disorder symptoms in a sample of African American students across the college years (N = 1,119; Mage = 18.44 years). Data were drawn from the Spit for Science study where participants completed multiple online surveys throughout college and provided a saliva sample for genotyping. Multilevel growth curve analyses indicated that alcohol dependence genome-wide polygenic risk scores did not predict trajectory of alcohol use disorder symptoms, while family history of alcohol problems was associated with alcohol use disorder symptoms at the start of college but not with the rate of change in symptoms over time. Peer deviance and interpersonal traumatic events were associated with more alcohol use disorder symptoms across college years. Neither alcohol dependence genome-wide polygenic risk scores nor family history of alcohol problems moderated the effects of these environmental risk factors on alcohol use disorder symptoms. Our findings indicated that peer deviance and experience of interpersonal traumatic events are salient risk factors that elevate risk for alcohol problems among African American college students. Family history of alcohol problems could be a useful indicator of genetic risk for alcohol problems. Gene identification efforts with much larger samples of African descent are needed to better characterize genetic risk for alcohol use disorders, in order to better understand gene–environment interaction processes in this understudied population.
Genetic predispositions play an important role in the development of internalizing and externalizing behaviors. Understanding the mechanisms through which genetic risk unfolds to influence these developmental outcomes is critical for developing prevention and intervention efforts, capturing key elements of Irv's research agenda and scientific legacy. In this study, we examined the role of parenting and personality in mediating the effect of genetic risk on adolescents’ major depressive disorder and conduct disorder symptoms. Longitudinal data were drawn from a sample of 709 European American adolescents and their mothers from the Collaborative Studies on Genetics of Alcoholism. Results from multivariate path analysis indicated that adolescents’ depressive symptoms genome-wide polygenic scores (DS_GPS) predicted lower parental knowledge, which in turn was associated with more subsequent major depressive disorder and conduct disorder symptoms. Adolescents’ DS_GPS also had indirect effects on these outcomes via personality, with a mediating effect via agreeableness but not via other dimensions of personality. Findings revealed that the pattern of associations was similar across adolescent gender. Our findings emphasize the important role of evocative gene–environment correlation processes and intermediate phenotypes in the pathways of risk from genetic predispositions to complex adolescent outcomes.
Using a large and nationally representative sample, we examined how adolescents’ 5-HTTLPR genotype and perceived parenting quality independently and interactively associated with trajectories of alcohol use from early adolescence to young adulthood and whether/how gender may moderate these associations. The sample for this study included 13,749 adolescents (53.3% female; 56.3% non-Hispanic White, 21.5% Black, 16.0% Hispanic, and 6.1% Asian) followed prospectively from adolescence to young adulthood. Using growth mixture modeling, we identified four distinct trajectories of alcohol use (i.e., persistent heavy alcohol use, developmentally limited alcohol use, late-onset heavy alcohol use, and non/light alcohol use). Results indicated that the short allele of 5-HTTLPR was associated with higher risk of membership in the persistent and the late-onset heavy alcohol use trajectories. Parenting quality was associated with lower likelihoods of following the persistent heavy and the developmentally limited alcohol use trajectories but was not associated with risk of membership for the late-onset heavy drinking trajectory. 5-HTTLPR interacted with parenting quality to predict membership in the persistent heavy alcohol use trajectory for males but not for females. Findings highlighted the importance of considering the heterogeneity in trajectories of alcohol use across development and gender in the study of Gene Environment interactions in alcohol use.
In our attempt to investigate the basic active galactic nucleus (AGN) paradigm requiring a centrally located supermassive black hole (SMBH), a close to Keplerian accretion disk and a jet perpendicular to its plane, we have searched for radio continuum in galaxies with H2O megamasers in their disks. We observed 18 such galaxies with the Very Large Baseline Array in C band (5 GHz, ~2 mas resolution) and we detected 5 galaxies at 8 σ or higher levels. For those sources for which the maser data is available, the positions of masers and those of the 5 GHz radio continuum sources coincide within the uncertainties, and the radio continuum is perpendicular to the maser disk’s orientation within the position angle uncertainties.
Introduction: In 2015, there were 476 apparent illicit drug overdose deaths, prompting BC’s Provincial Health Officer to declare a public health emergency on 14 Apr 2016. Paramedics of BC’s Ambulance Service (BCAS) are on the front lines in this crisis. Here we examine recent trends in the number of suspected overdose events attended by the BCAS and the use of naloxone, an opioid antagonist, by BCAS paramedics. Methods: The BC Centre for Disease Control receives a weekly data feed from BC Emergency Health Services that includes all records from the BCAS Patient Care Record where: naloxone was administered by paramedics; the primary impression code indicates poisoning or overdose; or, the originating call is associated with ingestion poisoning (‘card 23’). Here, we report a descriptive analysis of these data for suspected drug overdose events during the period January 1, 2010 to September 30, 2016. Results: Between January 2010 and September 2016 BCAS paramedics attended 164,227 suspected overdose events; 12% of these events (n=16,944) included naloxone administration by BCAS paramedics. Paralleling the rise in illicit drug overdose deaths in BC, naloxone administration by paramedics has been increasing rapidly, doubling from approximately 180/month in 2014, to 370/month in 2016. When naloxone was administered by paramedics, 90% of these patients were transported, whereas 77% were transported when naloxone was not administered. Administrations occurred most frequently on Friday and Saturday evenings. Almost half (46%) of all naloxone administrations by paramedics were recorded as being in a home or residence; 18% were recorded as occurring on a street or highway. The proportion of naloxone administrations among males has increased yearly. In 2010, 58% of naloxone administrations were in males compared to 69% in 2016. Conclusion: The number of overdose deaths in BC has risen drastically in recent years and the proportion of ambulance calls requiring administration of naloxone by BCAS has climbed correspondingly. The vast majority of overdose cases-especially those requiring naloxone-are transported to the emergency department. With the overdose crisis showing little sign of abating, the administration of naloxone by BC paramedics will continue to be a critical element of the provincial response.
Previous research failed to uncover a replicable dimensional structure underlying the symptoms of depression. We aimed to examine two neglected methodological issues in this research: (a) adjusting symptom correlations for overall depression severity; and (b) analysing general population samples v. subsamples of currently depressed individuals.
Using population-based cross-sectional and longitudinal data from two nations (Switzerland, 5883 young men; USA, 2174 young men and 2244 young women) we assessed the dimensions of the nine DSM-IV depression symptoms in young adults. In each general-population sample and each subsample of currently depressed participants, we conducted a standardised process of three analytical steps, based on exploratory and confirmatory factor and bifactor analysis, to reveal any replicable dimensional structure underlying symptom correlations while controlling for overall depression severity.
We found no evidence of a replicable dimensional structure across samples when adjusting symptom correlations for overall depression severity. In the general-population samples, symptoms correlated strongly and a single dimension of depression severity was revealed. Among depressed participants, symptom correlations were surprisingly weak and no replicable dimensions were identified, regardless of severity-adjustment.
First, caution is warranted when considering studies assessing dimensions of depression because general population-based studies and studies of depressed individuals generate different data that can lead to different conclusions. This problem likely generalises to other models based on the symptoms’ inter-relationships such as network models. Second, whereas the overall severity aligns individuals on a continuum of disorder intensity that allows non-affected individuals to be distinguished from affected individuals, the clinical evaluation and treatment of depressed individuals should focus directly on each individual's symptom profile.
Exposure to trauma was found to increase later violent behaviours in youth but the underlying psychopathological mechanisms are unclear. This study aimed to test whether posttraumatic stress disorder (PTSD) is related to violent behaviours and whether PTSD symptoms mediate the relationship between the number of trauma experiences and violent behaviours in adolescents.
The present study is based on a nationally representative sample of 9th grade students with 3434 boys (mean age = 15.5 years) and 3194 girls (mean age = 15.5 years) in Switzerland. Lifetime exposure to traumatic events and current PTSD were assessed by the use of the University of California at Los Angeles Posttraumatic Stress Disorder Reaction Index (UCLA-RI). Logistic regression was used to assess associations between PTSD and violent behaviours, and structural equation modelling (SEM) was used to examine the meditation effects of PTSD.
PTSD (boys: OR = 7.9; girls: OR = 5.5) was strongly related to violent behaviours. PTSD symptoms partially mediated the association between trauma exposure and violent behaviours in boys but not in girls. PTSD symptoms of dysphoric arousal were positively related to violent behaviours in both genders. Anxious arousal symptoms were negatively related to violent behaviours in boys but not in girls.
In addition to trauma, posttraumatic stress is related to violent outcomes. However, specific symptom clusters of PTSD seem differently related to violent behaviours and they do not fully explain a trauma-violence link. Specific interventions to improve emotion regulation skills may be useful particularly in boys with elevated PTSD dysphoric arousal in order to break up the cycle of violence.
Eating disorders (EDs) have long-term physical and mental impacts on those affected. However, few population-based studies have estimated the prevalence of EDs. We aimed to estimate the lifetime and 12-month prevalence rates of EDs using DSM-IV criteria, and to examine differences against the DSM-5 criteria for anorexia.
A nationally representative sample of 10 038 residents in Switzerland was interviewed, and prevalence rates for anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED) were assessed using WHO Composite International Diagnostic Interviews (WHO-CIDI).
The lifetime prevalence rate for any ED was found to be 3.5%. Lifetime prevalence estimates for AN, BN, and/or BED were 1.2%, 2.4%, and 2.4%, respectively, among women and 0.2%, 0.9%, and 0.7%, respectively, among men. Utilizing the DSM-5 criteria, the prevalence of AN in women increased by more than 50%, from 1.2% to 1.9%. Among those meeting the criteria for any ED, only 49.4% of men and 67.9% of women had ever sought professional help about their problems with eating or weight.
The higher prevalence of BN we detected relative to other studies should prompt further monitoring for a possible increasing trend. The female v. male ratios, especially for bulimia and BED, are decreasing. Given that more than half of those affected have never consulted any professional about their problems with eating or weight, routine inquiries about eating and weight by clinicians, school teachers/psychologists, and family members may help those who are at risk, especially among men.
Functional and mental health impairments that adults with attention-deficit/hyperactivity disorder (ADHD) experience may be exacerbated by regular substance use and co-morbidity with substance use disorders (SUD). This may be especially true during young adulthood, which represents a critical stage of life associated with increased substance use and associated problems. However, previous studies investigating the association between ADHD and substance use and SUD have demonstrated inconsistent results, probably due to methodological limitations (e.g., small and non-representative samples). Thus, the relationship of ADHD with substance use and related disorders remains unclear. The aim of the present study was to examine the association between ADHD and both the use of licit and illicit substances and the presence of SUD in a large, representative sample of young men.
The sample included 5677 Swiss men (mean age 20 ± 1.23 years) who participated in the Cohort Study on Substance Use Risk Factors (C-SURF). ADHD was assessed using the adult ADHD Self Report Screener (ASRS). The association between ADHD and substance use and SUD was assessed for alcohol, nicotine, cannabis and other illicit drugs, while controlling for socio-demographic variables and co-morbid psychiatric disorders (i.e., major depression (MD) and anti-social personality disorder (ASPD)).
Men with ADHD were more likely to report having used nicotine, cannabis and other illicit drugs at some time in their life, but not alcohol. ADHD was positively associated with early initiation of alcohol, nicotine and cannabis use, the risky use of these substances, and the presence of alcohol use disorders, and nicotine and cannabis dependence. Additionally, our analyses revealed that these patterns are also highly associated with ASPD. After adjusting for this disorder, the association between ADHD and licit and illicit substance use and the presence of SUDs was reduced, but remained significant.
Our findings suggest that adult ADHD is significantly associated with a propensity to experiment with licit and illicit substances, especially at earlier ages, to exhibit risky substance use patterns, and to subsequently develop SUDs. Preventive strategies that include early intervention and addressing co-morbidity with ASPD may be crucial to reducing substance use and the development of pathological substance use patterns in young men affected by ADHD and, thus, helping to prevent further illness burden later in life.
We made dynamical black hole mass measurements from nineteen Seyfert 2 galaxies which host sub-parsec H2O maser disks using the H2O megamaser technique. The nearly perfect Keplerian rotation curves in many of these maser systems guarantee the high accuracy and precision of the black hole mass measurements. With the stellar velocity dispersion (σ∗) of the galaxy bulges measured with the Dupont 2.5 m telescope at Las Campanas Observatory in the South and the Apache Point Observatory (APO) 3.5m telescope in the North, we found that H2O maser galaxies, most of which host pseudo bulges rather than classical bulges, do not all follow the MBH–σ∗ relation shown in the literature. This result is well consistent with the latest findings by Kormendy & Ho (2013) that only early type galaxies and galaxies with classical bulges follow a tight MBH–σ∗ relation. Such a tight correlation may not exist in pseudo bulge galaxies.
We studied the association between drinking water, agriculture and sporadic human campylobacteriosis in one region of British Columbia (BC), Canada. We compared 2992 cases of campylobacteriosis to 4816 cases of other reportable enteric diseases in 2005–2009 using multivariate regression. Cases were geocoded and assigned drinking water source, rural/urban environment and socioeconomic status (SES) according to the location of their residence using geographical information systems analysis methods. The odds of campylobacteriosis compared to enteric disease controls were higher for individuals serviced by private wells than municipal surface water systems (odds ratio 1·4, 95% confidence interval 1·1–1·8). In rural settings, the odds of campylobacteriosis were higher in November (P = 0·014). The odds of campylobacteriosis were higher in individuals aged ⩾15 years, especially in those with higher SES. In this region of BC, campylobacteriosis risk, compared to other enteric diseases, seems to be mediated by vulnerable drinking water sources and rural factors. Consideration should be given to further support well-water users and to further study the microbiological impact of agriculture on water.
Transcritical flow of a stratified fluid past a broad localised topographic obstacle is studied analytically in the framework of the forced extended Korteweg–de Vries, or Gardner, equation. We consider both possible signs for the cubic nonlinear term in the Gardner equation corresponding to different fluid density stratification profiles. We identify the range of the input parameters: the oncoming flow speed (the Froude number) and the topographic amplitude, for which the obstacle supports a stationary localised hydraulic transition from the subcritical flow upstream to the supercritical flow downstream. Such a localised transcritical flow is resolved back into the equilibrium flow state away from the obstacle with the aid of unsteady coherent nonlinear wave structures propagating upstream and downstream. Along with the regular, cnoidal undular bores occurring in the analogous problem for the single-layer flow modelled by the forced Korteweg–de Vries equation, the transcritical internal wave flows support a diverse family of upstream and downstream wave structures, including kinks, rarefaction waves, classical undular bores, reversed and trigonometric undular bores, which we describe using the recent development of the nonlinear modulation theory for the (unforced) Gardner equation. The predictions of the developed analytic construction are confirmed by direct numerical simulations of the forced Gardner equation for a broad range of input parameters.
Retinal ganglion cells (RGCs), the output neurons of the retina, have axons that project via the optic nerve to diverse targets in the brain. Typically, RGC axons do not branch before exiting the retina and thus do not provide it with synaptic feedback. Although a small subset of RGCs with intraretinal axon collaterals has been previously observed in human, monkey, cat, and turtle, their function remains unknown. A small, more recently identified population of RGCs expresses the photopigment melanopsin. These intrinsically photosensitive retinal ganglion cells (ipRGCs) transmit an irradiance-coding signal to visual nuclei in the brain, contributing both to image-forming vision and to several nonimage-forming functions, including circadian photoentrainment and the pupillary light reflex. In this study, using melanopsin immunolabeling in monkey and a genetic method to sparsely label the melanopsin cells in mouse, we show that a subgroup of ipRGCs have axons that branch en route to the optic disc, forming intraretinal axon collaterals that terminate in the inner plexiform layer of the retina. The previously described collateral-bearing population identified by intracellular dye injection is anatomically indistinguishable from the collateral-bearing melanopsin cells identified here, suggesting they are a subset of the melanopsin-expressing RGC type and may therefore share its functional properties. Identification of an anatomically distinct subpopulation in mouse, monkey, and human suggests this pathway may be conserved in these and other species (turtle and cat) with intraretinal axon collaterals. We speculate that ipRGC axon collaterals constitute a likely synaptic pathway for feedback of an irradiance signal to modulate retinal light responses.
The crystal structure of a-plane GaN/ZnO heterostructures on r-plane sapphire was investigated by using the XRD and TEM measurment. It was found the formation of (220) ZnGa2O4 and crystal orientation of semipolar (10
3) GaN at GaN/ZnO interface. The epitaxial relation of normal surface direction are the sapphire (1
02) // a-GaN (11
0) and ZnGa2O4 (220) // semi-polar GaN (10
). Beside, the emission peak energy of ZnO appears shift about 60 meV in the GaN/ZnO/GaN heterostructures due to the re-crystallization of ZnO layer with Ga or N atom and the formation of the localized state.
The problem of acoustic noise is becoming increasingly serious with the growing use of industrial and medical equipment, appliances, and consumer electronics. Active noise control (ANC), based on the principle of superposition, was developed in the early 20th century to help reduce noise. However, ANC is still not widely used owing to the effectiveness of control algorithms, and to the physical and economical constraints of practical applications. In this paper, we briefly introduce some fundamental ANC algorithms and theoretical analyses, and focus on recent advances on signal processing algorithms, implementation techniques, challenges for innovative applications, and open issues for further research and development of ANC systems.