Post-consent assessment of dental subjects' understanding of informed consent in oral health research in Nigeria

Abstract Background Research participants may not adequately understand the research in which they agree to enroll. This could be due to a myriad of factors. Such a missing link in the informed consent process contravenes the requirement for an "informed" consent prior to the commencement of research. This study assessed the post consent understanding of Nigerian study participants of the oral health research they were invited to join. Methods A descriptive cross sectional study with research participants who had just consented to one of three ongoing research studies on oral health. Study sites included two centers, one in the northern and one in the southern part of Nigeria. Data were collected using a combination of quantitative and qualitative methods. Results A total of 113 research participants were interviewed. The southern part of the country had 58 respondents with the north having 55. The age range was 21 – 80 years. Mean age was 46.1 (SD16.3). The sample was predominantly male (69.9%) and married (64.6%). There was poor understanding of some key elements of the informed consent process such as involvement in research, benefits, contacts, confidentiality and voluntariness. Some identified factors potentially compromising understanding were poverty, illiteracy, therapeutic misconception and confusion about the dual roles of the Dentist and the researcher. Conclusion The participants recruited into the oral health research in Nigeria did not adequately understand the studies they were invited to join nor do they understand their rights as research participants. Measures should be taken to include research bioethics into the curricula of Dental schools and to train oral health researchers in the country on research ethics.</p

Sciatic Neuroma Presenting Forty Years After Above-Knee Amputation

We report a case of a sciatic neuroma presenting forty years after above knee amputation. Patients developing neuroma following a limb amputation can present with stump pain which is commonly resistant to medical intervention. The length of interval from the initial injury to presentation is widely variable. Diagnosis relies on clinical suspicion and accurate assessment, radiological imaging and, if indicated, surgical exploration. MRI provides a better soft tissue definition than CT and is more accurate in identifying small lesions than ultrasound. The aim of treatment for symptomatic neuroma is pain relief and improvement of function. This is often achieved by surgical excision

Entomological Surveillance of Behavioural Resilience and Resistance in Residual Malaria Vector Populations.

The most potent malaria vectors rely heavily upon human blood so they are vulnerable to attack with insecticide-treated nets (ITNs) and indoor residual spraying (IRS) within houses. Mosquito taxa that can avoid feeding or resting indoors, or by obtaining blood from animals, mediate a growing proportion of the dwindling transmission that persists as ITNs and IRS are scaled up. Increasing frequency of behavioural evasion traits within persisting residual vector systems usually reflect the successful suppression of the most potent and vulnerable vector taxa by IRS or ITNs, rather than their failure. Many of the commonly observed changes in mosquito behavioural patterns following intervention scale-up may well be explained by modified taxonomic composition and expression of phenotypically plastic behavioural preferences, rather than altered innate preferences of individuals or populations. Detailed review of the contemporary evidence base does not yet provide any clear-cut example of true behavioural resistance and is, therefore, consistent with the hypothesis presented. Caution should be exercised before over-interpreting most existing reports of increased frequency of behavioural traits which enable mosquitoes to evade fatal contact with insecticides: this may simply be the result of suppressing the most behaviourally vulnerable of the vector taxa that constituted the original transmission system. Mosquito taxa which have always exhibited such evasive traits may be more accurately described as behaviourally resilient, rather than resistant. Ongoing national or regional entomological monitoring surveys of physiological susceptibility to insecticides should be supplemented with biologically and epidemiologically meaningfully estimates of malaria vector population dynamics and the behavioural phenotypes that determine intervention impact, in order to design, select, evaluate and optimize the implementation of vector control measures

Callous-unemotional traits, low cortisol reactivity and physical aggression in children: findings from the Wirral Child Health and Development Study

Callous-unemotional (CU) traits are thought to confer risk for aggression via reduced amygdala responsivity to distress cues in others. Low cortisol reactivity is thought to confer risk for aggression via reduced arousal and this effect may be confined to boys. We tested the hypothesis that the association between childhood CU traits and aggression would be greatest in the absence of the inhibitory effects of cortisol reactivity, and that this effect would be sex dependent. Participants were 283 members of a stratified subsample within an epidemiological longitudinal cohort (WCHADS). Cortisol reactivity to a social stressor was assessed at 5 years. CU traits were reported by mothers at 5 years, and physical aggression by mothers and teachers at age 7. Results showed that CU traits were associated with elevated aggression at 7 years controlling for earlier aggression. There was no main effect of cortisol reactivity on regression. The association between CU traits and aggression was moderated by cortisol reactivity (p = .011) with a strong association between CU traits and aggression in the presence of low reactivity, and a small and non-significant association in the presence of high reactivity. This association was further moderated by child sex (p = .041) with the joint effect of high CU traits and low cortisol reactivity seen only in boys (p = .016). We report first evidence that a combined deficit in inhibitory processes associated with CU traits and low cortisol reactivity increases risk for childhood aggression, in a sex-dependent manner

Histological validation of a type 1 diabetes clinical diagnostic model for classification of diabetes

This is the final version. Available on open access from Wiley via the DOI in this recordAims: Misclassification of diabetes is common due to an overlap in the clinical features of type 1 and type 2 diabetes. Combined diagnostic models incorporating clinical and biomarker information have recently been developed that can aid classification, but they have not been validated using pancreatic pathology. We evaluated a clinical diagnostic model against histologically defined type 1 diabetes. Methods: We classified cases from the Network for Pancreatic Organ donors with Diabetes (nPOD) biobank as type 1 (n = 111) or non-type 1 (n = 42) diabetes using histopathology. Type 1 diabetes was defined by lobular loss of insulin-containing islets along with multiple insulin-deficient islets. We assessed the discriminative performance of previously described type 1 diabetes diagnostic models, based on clinical features (age at diagnosis, BMI) and biomarker data [autoantibodies, type 1 diabetes genetic risk score (T1D-GRS)], and singular features for identifying type 1 diabetes by the area under the curve of the receiver operator characteristic (AUC-ROC). Results: Diagnostic models validated well against histologically defined type 1 diabetes. The model combining clinical features, islet autoantibodies and T1D-GRS was strongly discriminative of type 1 diabetes, and performed better than clinical features alone (AUC-ROC 0.97 vs. 0.95; P = 0.03). Histological classification of type 1 diabetes was concordant with serum C-peptide [median < 17 pmol/l (limit of detection) vs. 1037 pmol/l in non-type 1 diabetes; P < 0.0001]. Conclusions: Our study provides robust histological evidence that a clinical diagnostic model, combining clinical features and biomarkers, could improve diabetes classification. Our study also provides reassurance that a C-peptide-based definition of type 1 diabetes is an appropriate surrogate outcome that can be used in large clinical studies where histological definition is impossible. Parts of this study were presented in abstract form at the Network for Pancreatic Organ Donors Conference, Florida, USA, 19–22 February 2019 and Diabetes UK Professional Conference, Liverpool, UK, 6–8 March 2019.Diabetes UKNational Institutes of Health (NIH)National Institute for Health Research (NIHR)JDRFHelmsley Charitable Trus

Has education lost sight of children?

The reflections presented in this chapter are informed by clinical and personal experiences of school education in the UK. There are many challenges for children and young people in the modern education system and for the professionals who support them. In the UK, there are significant gaps between the highly selective education provided to those who pay privately for it and to the majority of those educated in the state-funded system. Though literacy rates have improved around the world, many children, particularly boys, do not finish their education for reasons such as boredom, behavioural difficulties or because education does not ‘pay’. Violence, bullying, and sexual harassment are issues faced by many children in schools and there are disturbing trends of excluding children who present with behavioural problems at school whose origins are not explored. Excluded children are then educated with other children who may also have multiple problems which often just make the situation worse. The experience of clinicians suggests that school-related mental health problems are increasing in severity. Are mental health services dealing with the consequences of an education system that is not meeting children’s needs? An education system that is testing- and performance-based may not be serving many children well if it is driving important decisions about them at increasingly younger ages. Labelling of children and setting them on educational career paths can occur well before they reach secondary schools, limiting potential very early on in their developmental trajectory. Furthermore, the emphasis at school on testing may come at the expense of creativity and other forms of intelligence, which are also valuable and important. Meanwhile the employment marketplace requires people with widely different skills, with an emphasis on innovation, creativity, and problem solving. Is education losing sight of the children it is educating

Type 1 diabetes genetic risk score is discriminative of diabetes in non-Europeans: evidence from a study in India

Type 1 diabetes (T1D) is a significant problem in Indians and misclassification of T1D and type 2 diabetes (T2D) is a particular problem in young adults in this population due to the high prevalence of early onset T2D at lower BMI. We have previously shown a genetic risk score (GRS) can be used to discriminate T1D from T2D in Europeans. We aimed to test the ability of a T1D GRS to discriminate T1D from T2D and controls in Indians. We studied subjects from Pune, India of Indo-European ancestry; T1D (n = 262 clinically defined, 200 autoantibody positive), T2D (n = 345) and controls (n = 324). We used the 9 SNP T1D GRS generated in Europeans and assessed its ability to discriminate T1D from T2D and controls in Indians. We compared Indians with Europeans from the Wellcome Trust Case Control Consortium study; T1D (n = 1963), T2D (n = 1924) and controls (n = 2938). The T1D GRS was discriminative of T1D from T2D in Indians but slightly less than in Europeans (ROC AUC 0.84 v 0.87, p < 0.0001). HLA SNPs contributed the majority of the discriminative power in Indians. A T1D GRS using SNPs defined in Europeans is discriminative of T1D from T2D and controls in Indians. As with Europeans, the T1D GRS may be useful for classifying diabetes in Indians.This article is freely available via Open Access. Click on the Publisher URL to access it via the publisher's site.R.A.O. and M.N.W. hold a U.K. Medical Research Council Institutional Confidence in Concept grant to develop a 10-SNP biochip T1D genetic test in collaboration with Randox.published version, accepted version, submitted versio

Alcohol affects neuronal substrates of response inhibition but not of perceptual processing of stimuli signalling a stop response

Alcohol impairs inhibitory control, including the ability to terminate an initiated action. While there is increasing knowledge about neural mechanisms involved in response inhibition, the level at which alcohol impairs such mechanisms remains poorly understood. Thirty-nine healthy social drinkers received either 0.4g/kg or 0.8g/kg of alcohol, or placebo, and performed two variants of a Visual Stop-signal task during acquisition of functional magnetic resonance imaging (fMRI) data. The two task variants differed only in their instructions: in the classic variant (VSST), participants inhibited their response to a “Go-stimulus” when it was followed by a “Stop-stimulus”. In the control variant (VSST_C), participants responded to the “Go-stimulus” even if it was followed by a “Stop-stimulus”. Comparison of successful Stop-trials (Sstop)>Go, and unsuccessful Stop-trials (Ustop)>Sstop between the three beverage groups enabled the identification of alcohol effects on functional neural circuits supporting inhibitory behaviour and error processing. Alcohol impaired inhibitory control as measured by the Stop-signal reaction time, but did not affect other aspects of VSST performance, nor performance on the VSST_C. The low alcohol dose evoked changes in neural activity within prefrontal, temporal, occipital and motor cortices. The high alcohol dose evoked changes in activity in areas affected by the low dose but importantly induced changes in activity within subcortical centres including the globus pallidus and thalamus. Alcohol did not affect neural correlates of perceptual processing of infrequent cues, as revealed by conjunction analyses of VSST and VSST_C tasks. Alcohol ingestion compromises the inhibitory control of action by modulating cortical regions supporting attentional, sensorimotor and action-planning processes. At higher doses the impact of alcohol also extends to affect subcortical nodes of fronto-basal ganglia- thalamo-cortical motor circuits. In contrast, alcohol appears to have little impact on the early visual processing of infrequent perceptual cues. These observations clarify clinically-important effects of alcohol on behaviour

Interpersonal and affective dimensions of psychopathic traits in adolescents : development and validation of a self-report instrument

We report the development and psychometric evaluations of a self-report instrument designed to screen for psychopathic traits among mainstream community adolescents. Tests of item functioning were initially conducted with 26 adolescents. In a second study the new instrument was administered to 150 high school adolescents, 73 of who had school records of suspension for antisocial behavior. Exploratory factor analysis yielded a 4-factor structure (Impulsivity α = .73, Self-Centredness α = .70, Callous-Unemotional α = .69, and Manipulativeness α = .83). In a third study involving 328 high school adolescents, 130 with records of suspension for antisocial behaviour, competing measurement models were evaluated using confirmatory factor analysis. The superiority of a first-order model represented by four correlated factors that was invariant across gender and age was confirmed. The findings provide researchers and clinicians with a psychometrically strong, self-report instrument and a greater understanding of psychopathic traits in mainstream adolescents

Large introns in relation to alternative splicing and gene evolution: a case study of Drosophila bruno-3

Background: Alternative splicing (AS) of maturing mRNA can generate structurally and functionally distinct transcripts from the same gene. Recent bioinformatic analyses of available genome databases inferred a positive correlation between intron length and AS. To study the interplay between intron length and AS empirically and in more detail, we analyzed the diversity of alternatively spliced transcripts (ASTs) in the Drosophila RNA-binding Bruno-3 (Bru-3) gene. This gene was known to encode thirteen exons separated by introns of diverse sizes, ranging from 71 to 41,973 nucleotides in D. melanogaster. Although Bru-3's structure is expected to be conducive to AS, only two ASTs of this gene were previously described. Results: Cloning of RT-PCR products of the entire ORF from four species representing three diverged Drosophila lineages provided an evolutionary perspective, high sensitivity, and long-range contiguity of splice choices currently unattainable by high-throughput methods. Consequently, we identified three new exons, a new exon fragment and thirty-three previously unknown ASTs of Bru-3. All exon-skipping events in the gene were mapped to the exons surrounded by introns of at least 800 nucleotides, whereas exons split by introns of less than 250 nucleotides were always spliced contiguously in mRNA. Cases of exon loss and creation during Bru-3 evolution in Drosophila were also localized within large introns. Notably, we identified a true de novo exon gain: exon 8 was created along the lineage of the obscura group from intronic sequence between cryptic splice sites conserved among all Drosophila species surveyed. Exon 8 was included in mature mRNA by the species representing all the major branches of the obscura group. To our knowledge, the origin of exon 8 is the first documented case of exonization of intronic sequence outside vertebrates. Conclusion: We found that large introns can promote AS via exon-skipping and exon turnover during evolution likely due to frequent errors in their removal from maturing mRNA. Large introns could be a reservoir of genetic diversity, because they have a greater number of mutable sites than short introns. Taken together, gene structure can constrain and/or promote gene evolution