A Pan-European Review of Good Practices in Early Intervention Safeguarding Practice with Children, Young People and Families: Evidence Gathering to Inform a Multi-disciplinary Training Programme (the ERICA Project) in Preventing Child Abuse and Neglect in Seven European Countries.

Child maltreatment has detrimental social and health effects for individuals, families and communities. The ERICA project is a pan-European training programme that equips non-specialist threshold practitioners with knowledge and skills to prevent and detect child maltreatment. This paper describes and presents the findings of a rapid review of good practice examples across seven participating countries including local services, programmes and risk assessment tools used in the detection and prevention of child maltreatment in the family. Learning was applied to the development of the generic training project. A template for mapping the good practice examples was collaboratively developed by the seven participating partner countries. A descriptive data analysis was undertaken organised by an a priori analysis framework. Examples were organised into three areas: programmes tackling child abuse and neglect, local practices in assessment and referral, risk assessment tools. Key findings were identified using a thematic approach. Seventy-two good practice examples were identified and categorised according to area, subcategory and number. A typology was developed as follows: legislative frameworks, child health promotion programmes, national guidance on child maltreatment, local practice guidance, risk assessment tools, local support services, early intervention programmes, telephone or internet-based support services, COVID-19 related good practices. Improved integration of guidance into practice and professional training in child development were highlighted as overarching needs. The impact of COVID-19 on safeguarding issues was apparent. The ERICA training programme formally responded to the learning identified in this international good practice review.

Understanding multimorbidity trajectories in Scotland using sequence analysis.

Understanding how multiple conditions develop over time is of growing interest, but there is currently limited methodological development on the topic, especially in understanding how multimorbidity (the co-existence of at least two chronic conditions) develops longitudinally and in which order diseases occur. We aim to describe how a longitudinal method, sequence analysis, can be used to understand the sequencing of common chronic diseases that lead to multimorbidity and the socio-demographic factors and health outcomes associated with typical disease trajectories. We use the Scottish Longitudinal Study (SLS) linking the Scottish census 2001 to disease registries, hospitalisation and mortality records. SLS participants aged 40-74 years at baseline were followed over a 10-year period (2001-2011) for the onset of three commonly occurring diseases: diabetes, cardiovascular disease (CVD), and cancer. We focused on participants who transitioned to at least two of these conditions over the follow-up period (N = 6300). We use sequence analysis with optimal matching and hierarchical cluster analysis to understand the process of disease sequencing and to distinguish typical multimorbidity trajectories. Socio-demographic differences between specific disease trajectories were evaluated using multinomial logistic regression. Poisson and Cox regressions were used to assess differences in hospitalisation and mortality outcomes between typical trajectories. Individuals who transitioned to multimorbidity over 10 years were more likely to be older and living in more deprived areas than the rest of the population. We found seven typical trajectories: later fast transition to multimorbidity, CVD start with slow transition to multimorbidity, cancer start with slow transition to multimorbidity, diabetes start with slow transition to multimorbidity, fast transition to both diabetes and CVD, fast transition to multimorbidity and death, fast transition to both cancer and CVD. Those who quickly transitioned to multimorbidity and death were the most vulnerable, typically older, less educated, and more likely to live in more deprived areas. They also experienced higher number of hospitalisations and overnight stays while still alive. Sequence analysis can strengthen our understanding of typical disease trajectories when considering a few key diseases. This may have implications for more active clinical review of patients beginning quick transition trajectories.

Recent Administration of Iodinated Contrast Renders Core Infarct Estimation Inaccurate Using RAPID Software.

BACKGROUND AND PURPOSE: Automated CTP software is increasingly used for extended window emergent large-vessel occlusion to quantify core infarct. We aimed to assess whether RAPID software underestimates core infarct in patients with an extended window recently receiving IV iodinated contrast. MATERIALS AND METHODS: We reviewed a prospective, single-center data base of 271 consecutive patients who underwent CTA ± CTP for acute ischemic stroke from May 2018 through January 2019. Patients with emergent large-vessel occlusion confirmed by CTA in the extended window (>6 hours since last known well) and CTP with RAPID postprocessing were included. Two blinded raters independently assessed CT ASPECTS on NCCT performed at the time of CTP. RAPID software used relative cerebral blood flow of <30% as a surrogate for irreversible core infarct. Patients were dichotomized on the basis of receiving recent IV iodinated contrast (<8 hours before CTP) for a separate imaging study. RESULTS: The recent IV contrast and contrast-naïve cohorts comprised 23 and 15 patients, respectively. Multivariate linear regression analysis demonstrated that recent IV contrast administration was independently associated with a decrease in the RAPID core infarct estimate (proportional increase = 0.34; 95% CI, 0.12-0.96; P = .04). CONCLUSIONS: Patients who received IV iodinated contrast in proximity (<8 hours) to CTA/CTP as part of a separate imaging study had a much higher likelihood of core infarct underestimation with RAPID compared with contrast-naïve patients. Over-reliance on RAPID postprocessing for treatment disposition of patients with extended window emergent large-vessel occlusion should be avoided, particularly with recent IV contrast administration.

Characterization of 3-Dimensional Printing and Casting Materials for use in Magnetic Resonance Imaging Phantoms at 3 T.

Imaging phantoms are used to calibrate and validate the performance of magnetic resonance imaging (MRI) systems. Many new materials have been developed for additive manufacturing (three-dimensional [3D] printing) processes that may be useful in the direct printing or casting of dimensionally accurate, anatomically accurate, patient-specific, and/or biomimetic MRI phantoms. The T1, T2, and T2* spin relaxation times of polymer samples were tested to discover materials for use as tissue mimics and structures in MRI phantoms. This study included a cohort of polymer compounds that was tested in cured form. The cohort consisted of 101 standardized polymer samples fabricated from: two-part silicones and polyurethanes used in commercial casting processes; one-part optically cured polyurethanes used in 3D printing; and fused deposition thermoplastics used in 3D printing. The testing was performed at 3 T using inversion recovery, spin echo, and gradient echo sequences for T1, T2, and T2*, respectively. T1, T2, and T2* values were plotted with error bars to allow the reader to assess how well a polymer matches a tissue for a specific application. A correlation was performed between T1, T2, T2* values and material density, elongation, tensile strength, and hardness. Two silicones, SI_XP-643 and SI_P-45, may be usable mimics for reported liver values; one silicone, SI_XP-643, may be a useful mimic for muscle; one silicone, SI_XP-738, may be a useful mimic for white matter; and four silicones, SI_P-15, SI_GI-1000, SI_GI-1040, and SI_GI-1110, may be usable mimics for spinal cord. Elongation correlated to T2 (p = 0.0007), tensile strength correlated to T1 (p = 0.002), T2 (p = 0.0003), and T2* (p = 0.003). The 80 samples not providing measurable signal with T1, T2, T2* relaxation values too short to measure with the standard sequences, may be useful for MRI-invisible fixturing and medical devices at 3 T.

Help or hindrance: young people's experiences of predictive testing for Huntington's disease.

A growing number of young people (YP) are requesting predictive testing (PT) for Huntington's disease (HD), yet there is little research in this area. The aim of this study was to explore YP's experiences of PT for HD, the impact of their result and any gaps in information or support. In-depth interviews were conducted with YP who sought PT for HD from nationally funded Genetics Services. Participants were recruited through the Grampian Genetics Service or Scottish Huntington's Association. Twelve female participants aged 17-26 years were recruited (seven below 20 years). Pre- and post-test interviews were conducted where possible. A qualitative thematic analysis suggests three main testing experiences, regardless of test result. Testing may be: (i) a journey of empowerment, (ii) an ambivalent process or (iii) a poor experience. In pre-test counselling, gaps in emotional support were highlighted. The post-test period was particularly difficult if there were unanticipated changes in family dynamics or an individual's result contradicted what they expected 'deep down'. YP's experiences of PT for HD are generally similar to those of adults, but testing may help or interfere with key issues related to this age and stage. Implications for clinical practice are outlined.

Validation of a portable EMG device to assess muscle activity during free-living situations.

Portable amplifiers that record electromyograms (EMGs) for longer than four hours are commonly priced over $20,000 USD. This cost, and the technical challenges associated with recording EMGs during free-living situations, typically restrict EMG use to laboratory settings. A low-cost system (µEMG; OT Bioelecttronica, 100€), using specialized concentric bipolar electrodes, has been developed specifically for free-living situations. The purpose of this study was to validate the µEMG system by comparing EMGs from µEMG with a laboratory-based alternative (Telemyo 900; Noraxon USA, Inc.). Surface EMGs from biceps brachii (BB) and tibialis anterior (TA) of ten subjects were recorded simultaneously with both systems as subjects performed maximal voluntary contractions (MVCs), submaximal contractions at 25%, 50%, and 75% MVC, seven simulated activities of daily living (ADLs), and >60min of simulated free-living inside the laboratory. In general, EMG parameters (e.g., average full-wave rectified EMG amplitude) derived from both systems were not significantly different for all outcome variables, except there were small differences across systems in baseline noise and absolute EMG amplitudes during MVCs. These results suggest that µEMG is a valid approach to the long-term recording of EMG.

Beaufort trout MicroPlex: a high-throughput multiplex platform comprising 38 informative microsatellite loci for use in resident and anadromous (sea trout) brown trout Salmo trutta genetic studies.

A flexible panel consisting of 38 informative microsatellite markers for Salmo trutta is described. These markers were selected from a pool of over 150 candidate loci that can be readily amplified in four multiplex PCR groups but other permutations are also possible. The basic properties of each markers were assessed in six population samples from both the Burrishoole catchment, in the west of Ireland, and Lough Neagh, in Northern Ireland. A method to assess the relative utility of individual markers for the detection of population genetic structuring is also described. Given its flexibility, technical reliability and high degree of informativeness, the use of this panel of markers is advocated as a standard for S. trutta genetic studies.

Examining links between sexual risk behaviors and dating violence involvement as a function of sexual orientation.

STUDY OBJECTIVE: To examine the association between dating violence perpetration and victimization and sexually risky behaviors among sexual minority and heterosexual adolescent girls. DESIGN: Adolescent girls reported on sexual orientation, sexual behaviors, and risk-taking, and their use of, and experience with, dating violence in the past year. Data were analyzed using multinomial regression adjusted for race, poverty, living in a single parent household, and gender of current partner to examine (1) whether sexual minority status was associated with sexual risk behaviors after sociodemographic correlates of sexual risk were controlled; and (2) whether dating violence context accounted for elevated risk. SETTING: Urban, population-based sample of girls interviewed in the home. PARTICIPANTS: 1,647 adolescent girls (38% European American, 57% African American, and 5% other) aged 17 years. Over one-third of the sample lived in poverty. INTERVENTIONS: None. MAIN OUTCOME MEASURE: Sexual risk-taking. RESULTS: Sexual minority status differentiated girls engaging in high sexual risk-taking from those reporting none, after controlling for sociodemographic and relationship characteristics. Dating violence perpetration and victimization made unique additional contributions to this model and did not account for the elevated risk conferred by sexual minority status. CONCLUSIONS: Sexual minority girls (SMGs) were more likely than heterosexual girls to report high sexual risk-taking and teen dating violence victimization. As with heterosexual girls, sexual risk-taking among SMGs was compounded by dating violence, which was not explained by partner gender. Adolescent girls' risky sexual behavior may be reduced by interventions for teen dating violence regardless of sexual minority status.

Pediatric intracranial nongalenic pial arteriovenous fistulas: clinical features, angioarchitecture, and outcomes.

BACKGROUND AND PURPOSE: NGAVFs are rare vascular malformations usually presenting in infancy or childhood. We sought to identify clinical and angiographic predictors of clinical outcome for these lesions. MATERIALS AND METHODS: Retrospective review of a neurointerventional data base identified 386 pediatric patients with intracranial AVFs and AVMs, from which a cohort of 25 patients with NGAVF were selected for medical record and imaging analysis. RESULTS: NGAVFs constituted 7.3% of pediatric intracranial vascular lesions with a nondural arteriovenous shunt. Seven of 8 patients who presented in the first month of life had CHF and harbored large, complex fistulas with multiple sites of arteriovenous shunting. Single-hole fistulas predominated later in childhood and more frequently presented with seizures, hemorrhage, or focal neurologic deficits. More treatment procedures were performed in subjects presenting at ≤ 2 years of age compared with older children (median = 3 versus 2, P = .041), and in those harboring a multi-hole fistula versus those with a single-hole fistula (median = 3 versus 2, P = .003). Eighteen patients (72%) had complete posttreatment elimination of NGAVF shunting. Compared with patients presenting at >2 years of age, patients presenting in the first 2 years of life were more likely to have a multi-hole fistula (100% versus 25%, P = .0001) and to have a poor clinical outcome (54% versus 0%, P = .0052), defined as a pediatric mRS of ≥ 3. CONCLUSIONS: The morbidity of NGAVF appears higher than previously reported despite a somewhat higher rate of angiographic cure. Poor clinical outcome occurred primarily in patients with multi-hole NGAVFs presenting at ≤ 2 years of age.

Prediction of glycosaminoglycan content in human cartilage by age, T1ρ and T2 MRI.

OBJECTIVE: A relationship between T1ρ relaxation time and glycosaminoglycan (GAG) content has been demonstrated in chemically degraded bovine cartilage, but has not been demonstrated with quantitative biochemistry in human cartilage. A relationship has also been established between T2 relaxation time in cartilage and osteoarthritis (OA) severity. We hypothesized that T1ρ relaxation time would be associated with GAG content in human cartilage with normal T2 relaxation times. METHODS: T2 relaxation time, T1ρ relaxation time, and glycosaminoglycan as a percentage of wet weight (sGAG) were measured for top and bottom regions at 7 anatomical locations in 21 human cadaver patellae. For our analysis, T2 relaxation time was classified as normal or elevated based on a threshold defined by the mean plus one standard deviation of the T2 relaxation time for all samples. RESULTS: In the normal T2 relaxation time subset, T1ρ relaxation time correlated with sGAG content in the full-thickness and bottom regions, but only marginally in the top region alone. sGAG content decreased significantly with age in all regions. CONCLUSION: In the subset of cartilage specimens with normal T2 relaxation time, T1ρ relaxation time was inversely associated with sGAG content, as hypothesized. A predictive model, which accounts for T2 relaxation time and the effects of age, might be able to determine longitudinal trends in GAG content in the same person based on T1ρ relaxation time maps.

Do common in silico tools predict the clinical consequences of amino-acid substitutions in the CFTR gene?

Computational methods are used to predict the molecular consequences of amino-acid substitutions on the basis of evolutionary conservation or protein structure, but their utility in clinical diagnosis or prediction of disease outcome has not been well validated. We evaluated three popular computer programs, namely, PANTHER, SIFT and PolyPhen, by comparing the predicted clinical outcomes for a group of known CFTR missense mutations against the diagnosis of cystic fibrosis (CF) and clinical manifestations in cohorts of subjects with CF-disease and CFTR-related disorders carrying these mutations. Owing to poor specificity, none of tools reliably distinguished between individual mutations that confer CF disease from mutations found in subjects with a CFTR-related disorder or no disease. Prediction scores for CFTR mutations derived from PANTHER showed a significant overall statistical correlation with the spectrum of disease severity associated with mutations in the CFTR gene. In contrast, PolyPhen- and SIFT-derived scores only showed significant differences between CF-causing and non-CF variants. Current computational methods are not recommended for establishing or excluding a CF diagnosis, notably as a newborn screening strategy or in patients with equivocal test results.

Association of maternal dopamine transporter genotype with negative parenting: evidence for gene x environment interaction with child disruptive behavior.

Although maternal parenting is central to child development, little is known about the interplay between molecular genetic and environmental factors that influence parenting. We tested the association of the 40-bp variable number tandem repeat polymorphism of the dopamine transporter (DAT1; SLC6A3) gene with three dimensions of observed maternal parenting behavior (positive parenting, negative parenting and total maternal commands). A significant nonadditive association was found between maternal DAT1 genotype and both negative parenting and total commands during a structured mother-child interaction task, even after controlling demographic factors, maternal psychopathology and disruptive child behavior during the task. Furthermore, the association between maternal DAT1 genotype and negative parenting was significantly stronger among mothers whose children were highly disruptive during the mother-child interaction task, suggesting a gene-environment interaction.

Young people's experiences of growing up in a family affected by Huntington's disease.

Previous research and clinical experience suggest that Huntington's disease (HD) can considerably affect family life, particularly for young people (YP) at risk. The goal of this study was to describe the experiences of YP from families affected by HD. YP were identified through the regional genetics clinic and the Scottish Huntington's Association. In-depth interviews were used to explore YP's experiences of finding out about HD in the family; perceptions of their own risk; caring activities; protective or risk factors; and the impact of HD on relationships with siblings, parents, extended family members, and the wider community. Thirty-three YP between the ages of 9 and 28 years were interviewed. A qualitative thematic analysis was undertaken. The analysis revealed four main themes: YP as carers, the worried well, those who cope, and those at risk/in need. These themes highlight the varied experience of growing up in a family affected by HD. Whilst some YP successfully coped, others experienced considerable problems and were at risk of physical and/or emotional harm. In understanding why some cope better than others, our findings suggest protective and risk factors within these themes. In particular, participants who grew up knowing about HD from an early age seemed to cope better.

Assessing biofilm formation by Listeria monocytogenes strains.

When a microtitre plate assay was used to quantify biofilm production by Listeria monocytogenes strains following growth in Tryptone Soy Broth (TSB) for 48 h at 20 degrees C, 127 of 138 strains (92.0%) were classified as weak, 9 of 138 strains (6.5%) as moderate and only 2 of 138 strains (1.5%) as strong biofilm formers. The strains included environmental, animal, food (persistent and sporadic strains) and clinical isolates previously typed using esterase electrophoresis (ESE) and multi-locus enzyme electrophoresis (MEE). Strains from different sources produced similar quantities of biofilm, whereas biofilm production by ESE type II strains, irrespective of source, was greater than that observed for other ESE types. No correlation between MEE type and biofilm production was observed. A Petri dish assay which allowed parallel quantification and microscopic examination of biofilms was used to examine biofilm formation by selected L. monocytogenes strains during growth in TSB for 14 days at 20 degrees C. Results from these assays showed that following prolonged incubation, some L. monocytogenes strains categorized as weak biofilm formers by the 48 h microtitre assay, were able to form biofilms similar in terms of quantity and structure to those produced by strains classified as strong or medium biofilm formers. Results from 14-day Petri dish assays confirmed 48 h microtitre assays regarding greater biofilm production by ESE type II strains compared to other ESE types of L. monocytogenes. Biofilm production was similar for ESE type II persistent and sporadic food isolates but reduced for ESE type II clinical strains.

The effects of ad libitum overfeeding and moderate and marked dietary restriction on age-related spontaneous pancreatic islet pathology in Sprague-Dawley rats.

This study compared the effects of ad libitum (AL) overfeeding and moderate or marked dietary restriction (DR) on aged-related degenerative and proliferative changes of the endocrine pancreas in Sprague-Dawley (SD) rats. SD rats were fed Purina Certified Rodent Diet AL (group 1), DR at 72-79% of AL (group 2), DR at 68-72% of AL (group 3) or DR at 47-48% of AL (group 4) for 106 weeks. Interim necropsies were performed at 13, 26, and 53 weeks, after a 7-day 5-bromo-2-deoxyuridine (BrdU)-filled minipump implantation. Before each necropsy, glucose and serum insulin levels were measured. In addition to the routine histopathologic examination performed in both sexes, determination of 9 pancreatic islet stereologic parameters was done in males at 13, 26, and 53 weeks. In AL-fed rats, early changes in the islet morphology occurred, which resulted in a high incidence of islet fibrosis, focal hyperplasias and adenomas by two years. DR was dose-proportionally associated with decreased glucose and serum insulin levels, and delayed the onset, and decreased the incidence and severity of islet fibrosis and hyperplasia. Results of the stereology supported the histopathologic and clinical chemistry findings. It demonstrated that, compared to AL-fed rats, DR-fed rats had smaller pancreas, smaller pancreatic islets, smaller insulin secreting cell volumes, a lower degree of islet fibrosis and a lower islet cell BrdU labeling index, which correlated with a lower incidence of islet adenoma and carcinoma at study termination. Moderate and marked degrees of DR delayed the onset and severity of islet hyperplasia and fibrosis in a temporal- and dose-related manner. In contrast to marked DR, which dramatically prevented these changes, moderate DR delayed but not prevented onset of islet tumors. These findings support the concept that moderate DR results in a better-controlled animal model with a lower incidence or delayed onset of chronic spontaneous endocrine diseases in the rat bioassay.

Clinical significance and correlates of disruptive behavior in environmentally at-risk preschoolers.

Examines the clinical significance and correlates of disruptive behavior disorder symptoms (DBDSX) in preschoolers. Participants were 129 predominantly minority preschoolers (2 1/2 to 5 1/2) residing in low-income environments, half of whom were clinic-referred for disruptive behavior. Children with higher levels of DBDSX were more impaired in parent-child, preschool and clinic contexts. Correlates of DBDSX included both prenatal and infancy risks (low soothability as infants, prenatal exposure to cigarettes) and concurrent parenting factors (harshness, low levels of behavioral responsiveness, and parenting stress). In general, the clinical and risk profile of DBDSX in preschoolers at environmental risk appears to be similar to that of older children. Based on the results of this study, etiologic and prevention research on disruptive behavior disorders should begin in the first few years of life.

Caloric restriction mimetics: metabolic interventions.

Caloric restriction (CR) retards diseases and aging in laboratory rodents and is now being tested in nonhuman primates. One way to apply these findings to human health is to identify and test agents that may mimic critical actions of CR. Panel 2 focused on two outcomes of CR, reduction of oxidative stress and improved glucoregulation, for which candidate metabolic mimics exist. It was recommended that studies on oxidative stress should emphasize mitochondrial function and to test the efficacy of nitrone and other antioxidants in mimicking CR's effects. Studies should also focus on the long-term effects of compounds known to lower circulating glucose and insulin concentrations or to increase insulin sensitivity. Also, four other developing areas were identified: intermediary metabolism, response to infection, stress responses, and source of dietary fat. These areas are important because either they hold promise for the discovery of new mimetics or they need to be explored prior to initiation of CR trials in humans. Other recommendations were that transgenic approaches and adult-onset CR should be emphasized in future studies.

Chronic nephropathy in ad libitum overfed Sprague-Dawley rats and its early attenuation by increasing degrees of dietary (caloric) restriction to control growth.

The early development and progression of chronic nephropathy and its amelioration by moderate and marked dietary restriction (DR) was determined in Sprague-Dawley (SD) rats at 20, 33, 60, and 113 weeks of age. Both sexes of SD rats were overfed ad libitum (AL) or DR-fed at 72-79%, 68-72%, or 47-48% of the adult AL intake. The AL-fed rats rapidly developed increased body and kidney size, increased glomerular area (GA) and urinary protein loss, followed by declining creatinine clearance. Early increased kidney growth and glomerular hypertrophy by 20 weeks preceded increases in glomerular sclerotic index (GSI), 7-day BrdU tubular labeling index (TLI), and the lesions associated with chronic nephropathy. The glomerular number (GN) or the number of nephrons did not differ between the groups over the course of the study. Moderate DR (68-79% of AL) prevented the increased kidney size and GA at 20 weeks and delayed increases in GSI and TLI until 60 weeks of age. Marked DR (47-48% of AL) prevented increases in kidney size, GA and TLI at 20 weeks, and GSI at 60 weeks of age. In AL-fed rats, the early increase in GA predicted the early onset of proteinuria and the later decrease in creatinine clearance, and increased GSI, TLI, and mortality from severe nephropathy. The temporal and dose-related effects of increasing degrees of DR demonstrated that while nephron numbers were unchanged with age, the early development of glomerular hypertrophy was the critical morphological biomarker predicting the progression and severity of chronic nephropathy. Caloric restriction by DR prevented or delayed the development of glomerulosclerosis, tubulointerstitial damage, functional changes, morbidity, and mortality associated with chronic nephropathy in AL-overfed SD rats by controlling initial body and kidney growth, glomerular size, and nephron hypertrophy. These results indicate that control of body and renal growth by DR may be essential to prevent the development and progression of glomerulosclerosis in spontaneous nephropathy of laboratory rats.