Assessing the consequences of cyberbullying on mental health

Advances in technology and the advent of social media have led to the emergence of a new phenomenon — cyberbullying. Although there are some similarities, approaches to tackling traditional bullying are largely ineffective in combating cyberbullying, which has been linked to adverse mental health and, in extreme cases, suicide

Protecting against researcher bias in secondary data analysis: challenges and potential solutions

Analysis of secondary data sources (such as cohort studies, survey data, and administrative records) has the potential to provide answers to science and society’s most pressing questions. However, researcher biases can lead to questionable research practices in secondary data analysis, which can distort the evidence base. While pre-registration can help to protect against researcher biases, it presents challenges for secondary data analysis. In this article, we describe these challenges and propose novel solutions and alternative approaches. Proposed solutions include approaches to (1) address bias linked to prior knowledge of the data, (2) enable pre-registration of non-hypothesis-driven research, (3) help ensure that pre-registered analyses will be appropriate for the data, and (4) address difficulties arising from reduced analytic flexibility in pre-registration. For each solution, we provide guidance on implementation for researchers and data guardians. The adoption of these practices can help to protect against researcher bias in secondary data analysis, to improve the robustness of research based on existing data

Continuity of cannabis use and violent offending over the life course

Although the association between cannabis use and violence has been reported in the literature, the precise nature of this relationship, especially the directionality of the association, is unclear. Young males from the Cambridge Study of Delinquent Development (n = 411) were followed up between the ages of 8 and 56 years to prospectively investigate the association between cannabis use and violence. A multi-wave (eight assessments, T1–T8) follow-up design was employed that allowed temporal sequencing of the variables of interest and the analysis of violent outcome measures obtained from two sources: (i) criminal records (violent conviction); and (ii) self-reports. A combination of analytic approaches allowing inferences as to the directionality of associations was employed, including multivariate logistic regression analysis, fixed-effects analysis and cross-lagged modelling. Multivariable logistic regression revealed that compared with never-users, continued exposure to cannabis (use at age 18, 32 and 48 years) was associated with a higher risk of subsequent violent behaviour, as indexed by convictions [odds ratio (OR) 7.1, 95% confidence interval (CI) 2.19–23.59] or self-reports (OR 8.9, 95% CI 2.37–46.21). This effect persisted after controlling for other putative risk factors for violence. In predicting violence, fixed-effects analysis and cross-lagged modelling further indicated that this effect could not be explained by other unobserved time-invariant factors. Furthermore, these analyses uncovered a bi-directional relationship between cannabis use and violence. Together, these results provide strong indication that cannabis use predicts subsequent violent offending, suggesting a possible causal effect, and provide empirical evidence that may have implications for public policy

Systematic Review and Meta-analysis of Genetically Informed Research: Associations between Parent Anxiety and Offspring Internalizing Problems

OBJECTIVE: Parent anxiety is associated with offspring internalizing problems (emotional problems related to anxiety and depression). This may reflect causal processes, whereby exposure to parent anxiety directly influences offspring internalizing (and/or vice versa). However, parent-offspring associations could also be attributable to their genetic relatedness. We present a systematic review and meta-analysis to investigate whether exposure to parent anxiety is associated with offspring internalizing after controlling for genetic relatedness. METHOD: A literature search in five databases identified 429 records. Publications were retained if they used a quasi-experimental design in a general population sample to control for participant relatedness in associations between parent anxiety and offspring internalizing outcomes. Publications were excluded if they involved an experimental exposure or intervention. Studies of pre- and post-natal anxiety exposure were meta-analysed separately. Pearson's correlation coefficient estimates (r) were pooled using multilevel random effects models. RESULTS: Eight publications were retained. Data were drawn from four population cohorts, each unique to a quasi-experimental design: adoption, sibling-comparison, children-of-twins or in-vitro-fertilisation. Cohorts were located in northern Europe or America. Families were predominantly of European ancestry. Three publications (Nfamilies>11,700; offspring aged 0.5-10 years) showed no association between prenatal anxiety exposure and offspring internalizing outcomes after accounting for participant relatedness (r=.04, CI -.07,.14). Six publications (Nfamilies>12,700; offspring aged 0.75-22 years) showed a small but significant association between concurrent symptoms in parents and offspring, after accounting for participant relatedness (r=.13, CI .04,.21). CONCLUSION: Initial literature, derived from homogenous populations, suggests that prenatal anxiety exposure does not cause offspring internalizing outcomes. However, postnatal anxiety exposure may be causally associated with concurrent offspring internalizing, via non-genetic pathways. Longitudinal stability, child-to-parent effects, and the role of moderators and methodological biases require attention

Combining multivariate genomic approaches to elucidate the comorbidity between autism spectrum disorder and attention deficit hyperactivity disorder

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are two highly heritable neurodevelopmental disorders. Several lines of evidence point towards the presence of shared genetic factors underlying ASD and ADHD. We conducted genomic analyses of common risk variants (i.e. single nucleotide polymorphisms, SNPs) shared by ASD and ADHD, and those specific to each disorder. METHODS: With the summary data from two GWAS, one on ASD (N = 46,350) and another on ADHD (N = 55,374) individuals, we used genomic structural equation modelling and colocalization analysis to identify SNPs shared by ASD and ADHD and SNPs specific to each disorder. Functional genomic analyses were then conducted on shared and specific common genetic variants. Finally, we performed a bidirectional Mendelian randomization analysis to test whether the shared genetic risk between ASD and ADHD was interpretable in terms of reciprocal relationships between ASD and ADHD. RESULTS: We found that 37.5% of the SNPs associated with ASD (at p < 1e-6) colocalized with ADHD SNPs and that 19.6% of the SNPs associated with ADHD colocalized with ASD SNPs. We identified genes mapped to SNPs that are specific to ASD or ADHD and that are shared by ASD and ADHD, including two novel genes INSM1 and PAX1. Our bidirectional Mendelian randomization analyses indicated that the risk of ASD was associated with an increased risk of ADHD and vice versa. CONCLUSIONS: Using multivariate genomic analyses, the present study uncovers shared and specific genetic variants associated with ASD and ADHD. Further functional investigation of genes mapped to those shared variants may help identify pathophysiological pathways and new targets for treatment

Resting heart rate and antisocial behaviour: a Mendelian randomisation study

Observational studies frequently report phenotypic associations between low resting heart rate (RHR) and higher levels of antisocial behaviour (ASB), although it remains unclear whether this relationship reflects causality. To triangulate evidence, we conducted two-sample univariable Mendelian randomisation (MR), multivariable MR and linkage disequilibrium score regression (LDSC) analyses. Genetic data were accessed from published genome-wide association studies (GWAS) for RHR (n = 458,835) and ASB (n = 85,359) for the univariable analyses, along with a third GWAS for heart rate variability (HRV; n = 53,174) for all other analyses. Genome-wide significant (p < 5 × 10-8) single-nucleotide polymorphisms associated with RHR (n = 278) were selected as instrumental variables and the outcome was a composite measure of ASB. No causal association was observed between RHR and ASB (BIVW =  - 0.0004, p = 0.841). The multivariable MR analyses including RHR and HRV also suggested no causal associations (BIVW = 0.016, p = 0.914) and no genetic correlations between the heart rate measures and ASB were observed using LDSC (rg = 0.057, p = 0.169). Sensitivity analyses suggested that our results are not likely to be affected by heterogeneity, pleiotropic effects, or reverse causation. These findings suggest that individual differences in autonomic nervous system functioning indexed by RHR are not likely to directly contribute to the development of ASB. Therefore, previously observed associations between RHR and ASB may arise from confounding, reverse causation, and/or additional study characteristics. Further causally informative longitudinal research is required to confirm our findings, and caution should be applied when using measures of RHR in interventions targeting ASB

Keto-on-the-Clock: A Survey of Dietetic Care Contact Time Taken to Provide Ketogenic Diets for Drug-Resistant Epilepsy in the UK

From MDPI via Jisc Publications RouterHistory: accepted 2021-07-16, pub-electronic 2021-07-21Publication status: PublishedMedical ketogenic diets (KDs) are effective yet resource-intensive treatment options for drug-resistant epilepsy (DRE). We investigated dietetic care contact time, as no recent data exist. An online survey was circulated to ketogenic dietitians in the UK and Ireland. Data were collected considering feeding route, KD variant and type of ketogenic enteral feed (KEF), and the estimated number of hours spent on patient-related activities during the patient journey. Fifteen dietitians representing nine KD centres responded. Of 335 patients, 267 (80%) were 18 years old or under. Dietitians spent a median of 162 h (IQR 54) of care contact time per patient of which a median of 48% (IQR 6) was direct contact. Most time was required for the classical KD taken orally (median 193 h; IQR 213) as a combined tube and oral intake (median 211 h; IQR 172) or a blended food KEF (median 189 h; IQR 148). Care contact time per month was higher for all KDs during the three-month initial trial compared to the two-year follow-up stage. Patients and caregivers with characteristics such as learning or language difficulties were identified as taking longer. Twelve out of fifteen (80%) respondents managed patients following the KD for more than two years, requiring an estimated median contact care time of 2 h (IQR 2) per patient per month. Ten out of fifteen (67%) reported insufficient official hours for dietetic activities. Our small survey gives insight into estimated dietetic care contact time, with potential application for KD provision and service deliver

Human Spotted Fever Rickettsial Infections

Serum specimens from patients at 4 sites in Peru were tested for evidence of spotted fever group rickettsial infection. Results showed that 30 (18%) of 170 patients had spotted fever group rickettsial infections, which likely caused their illnesses. These findings document laboratory-confirmed spotted fever from diverse areas of Peru

Acquired resistance to DZNep-mediated apoptosis is associated with copy number gains of AHCY in a B-cell lymphoma model

BackgroundEnhancer of zeste homolog 2 (EZH2) is considered an important driver of tumor development and progression by its histone modifying capabilities. Inhibition of EZH2 activity is thought to be a potent treatment option for eligible cancer patients with an aberrant EZH2 expression profile, thus the indirect EZH2 inhibitor 3-Deazaneplanocin A (DZNep) is currently under evaluation for its clinical utility. Although DZNep blocks proliferation and induces apoptosis in different tumor types including lymphomas, acquired resistance to DZNep may limit its clinical application.MethodsTo investigate possible mechanisms of acquired DZNep resistance in B-cell lymphomas, we generated a DZNep-resistant clone from a previously DZNep-sensitive B-cell lymphoma cell line by long-term treatment with increasing concentrations of DZNep (ranging from 200 to 2000nM) and compared the molecular profiles of resistant and wild-type clones. This comparison was done using molecular techniques such as flow cytometry, copy number variation assay (OncoScan and TaqMan assays), fluorescence in situ hybridization, Western blot, immunohistochemistry and metabolomics analysis.ResultsWhole exome sequencing did not indicate the acquisition of biologically meaningful single nucleotide variants. Analysis of copy number alterations, however, demonstrated among other acquired imbalances an amplification (about 30 times) of the S-adenosyl-L-homocysteine hydrolase (AHCY) gene in the resistant clone. AHCY is a direct target of DZNep and is critically involved in the biological methylation process, where it catalyzes the reversible hydrolysis of S-adenosyl-L-homocysteine to L-homocysteine and adenosine. The amplification of the AHCY gene is paralleled by strong overexpression of AHCY at both the transcriptional and protein level, and persists upon culturing the resistant clone in a DZNep-free medium.ConclusionsThis study reveals one possible molecular mechanism how B-cell lymphomas can acquire resistance to DZNep, and proposes AHCY as a potential biomarker for investigation during the administration of EZH2-targeted therapy with DZNep

Coulomb-blockade transport in single-crystal organic thin-film transistors

Coulomb-blockade transport—whereby the Coulomb interaction between electrons can prohibit their transport around a circuit—occurs in systems in which both the tunnel resistance, RT, between neighbouring sites is large (»h/e2) and the charging energy, EC (EC = e2/2C, where C is the capacitance of the site), of an excess electron on a site is large compared to kT. (Here e is the charge of an electron, k is Boltzmann's constant, and h is Planck's constant.) The nature of the individual sites—metallic, superconducting, semiconducting or quantum dot—is to first order irrelevant for this phenomenon to be observed. Coulomb blockade has also been observed in two-dimensional arrays of normal-metal tunnel junctions, but the relatively large capacitances of these micrometre-sized metal islands results in a small charging energy, and so the effect can be seen only at extremely low temperatures. Here we demonstrate that organic thin-film transistors based on highly ordered molecular materials can, to first order, also be considered as an array of sites separated by tunnel resistances. And as a result of the sub-nanometre sizes of the sites (the individual molecules), and hence their small capacitances, the charging energy dominates at room temperature. Conductivity measurements as a function of both gate bias and temperature reveal the presence of thermally activated transport, consistent with the conventional model of Coulomb blockade.