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Cerebral palsy is a clinical descriptor covering a diverse group of permanent, non-degenerative disorders of motor function. Around one-third of cases have now been shown to have an underlying genetic aetiology, with the genetic landscape overlapping with those of neurodevelopmental disorders including intellectual disability, epilepsy, speech and language disorders and autism. Here we review the current state of genomic testing in cerebral palsy, highlighting the benefits for personalized medicine and the imperative to consider aetiology during clinical diagnosis. With earlier clinical diagnosis now possible, we emphasize the opportunity for comprehensive and early genomic testing as a crucial component of the routine diagnostic work-up in people with cerebral palsy. The diagnosis of cerebral palsy is currently made on clinical observations only and does not consider aetiology or pathology. Here, van Eyk and colleagues review the current state of genomic testing in cerebral palsy and highlight the benefits of a 'genotype-first' approach for this group of disorders. Key points: Currently, a clinical diagnosis of cerebral palsy (CP) is made on observation of signs and symptoms and does not consider aetiology or pathology. CP encompasses a clinically heterogeneous group of disorders — together referred to as cerebral palsies — with at least one-third of cases having a genetic aetiology. CP has a high degree of genetic overlap with neurodevelopmental disorders, such as intellectual disability, epilepsy and autism, and should itself be considered, at least partly, a genetic neurodevelopmental disorder. The presence of known cerebral palsy risk factors, such as prematurity and growth restriction, and the absence of other comorbid neurodevelopmental phenotypes, including intellectual disability and epilepsy, do not rule out a genetic aetiology. Diagnostic practice has not evolved with the fast-accumulating evidence for a genetic contribution to CP aetiology; the nomenclature for genetic cases and the circumstances under which a genetic diagnosis should negate the CP clinical diagnosis lack consensus. An aetiology-driven diagnosis of CP involving a 'genotype-first' approach will bring tangible benefits to individuals with CP through precision medicine and improved clinical management. [ABSTRACT FROM AUTHOR]

Objective: To determine the frequency of paroxysmal nonepileptic events in children with cerebral palsy due to brain injury who have epilepsy and to describe the factors associated with paroxysmal nonepileptic events. Methods: Retrospective, population-based study of children from the Victorian CP Register born 1999–2006. Neuroimaging, medical records, electroencephalograms (EEG), and EEG requests were analyzed. Results: Of the included 256 children, 87 had epilepsy. EEGs (with video correlation) were available for 82 of 87. Eighteen (18/82, 22%) had epileptic events captured on EEG. Twenty-one (21/82, 26%) had paroxysmal nonepileptic events captured on EEG. The majority (13/18, 77%) of children with epileptic events also had paroxysmal nonepileptic events captured. Ten parents and carers continued to report events as epileptic despite there being no ictal EEG correlate for specific events on multiple EEGs. There were no clear associations to identify which children would have ongoing paroxysmal nonepileptic events reported. Conclusions: Paroxysmal nonepileptic events were captured on EEG in one-fourth of children from this cerebral palsy cohort with epilepsy and available EEG. Half the parents and carers reported previously identified paroxysmal nonepileptic events as epileptic on subsequent EEGs, highlighting the need for clearer counseling so that parents better understand seizure semiology in children with EEG-proven paroxysmal nonepileptic events. [ABSTRACT FROM AUTHOR]

Cerebral palsy (CP) is a broad diagnosis unbound by aetiology and is based on a clinical examination demonstrating abnormalities of movement or posture. CP represents a static neurological condition, provided that neurodegenerative conditions, leukoencephalopathies and neuromuscular disorders are excluded. In paediatrics, the genetic conditions associated with CP are rapidly increasing, with primary and overlapping neurodevelopmental conditions perhaps better categorised by the predominant clinical feature such as CP, intellectual disability, autism spectrum disorder or epilepsy. Progress in molecular genetics may challenge what constitutes CP, but a genetic diagnosis does not negate the CP diagnosis. As clinicians working in the field, we discuss the changing tide of CP. Neuroimaging provides essential information through pattern recognition and demonstration of static brain changes. We present examples of children where a layered clinical diagnosis or dual aetiologies are appropriate. We also present examples of children with genetic causes of CP to highlight the challenges and limitations of neuroimaging to provide an aetiological diagnosis. In consultation with a geneticist, access to genomic testing (exome or genome sequencing) is now available in Australia under Medicare billing for children under the age of 10 with dysmorphic features, one or more major structural organ anomalies, (an evolving) intellectual disability or global developmental delay. We encourage the uptake of genomic testing in CP, because it can be difficult to tell whether a child has an environmental or genetic cause for CP. A specific genetic diagnosis may change patient management, reduce guilt and enable more distinctive research in the future to assist with understanding disease mechanisms. [ABSTRACT FROM AUTHOR]

More than 50% of infants with cerebral palsy (CP) are born at or near term, with the vast majority having pre- or perinatally acquired CP. While some have a clinical history predictive of CP, such as neonatal encephalopathy or neonatal stroke, others have no readily identifiable risk factors. Paediatricians are often required to discriminate generalised motor delay from a variety of other diagnoses, including CP. This paper outlines known causal pathways to CP in term-born infants with a focus on differential diagnosis. Early and accurate diagnosis is important as it allows prompt access to early intervention during the critical periods of brain development. A combination of clinical history taking, standard clinical examination, neuroimaging and genetic testing should be started at the time of referral. Attention to the investigation of common comorbidities of CP, including feeding and sleep difficulties, and referral to early intervention are recommended. [ABSTRACT FROM AUTHOR]

Mental health can affect young people’s sense of wellbeing and life satisfaction, their ability to participate in employment and education, and their onward opportunities in life. This paper offers a rare opportunity to longitudinally examine mental health in a population-representative study of children aged 4–5 years to 14–15 years. Using data from the Longitudinal Study of Australian Children (LSAC), this study examined maternally-reported child mental health over a 10 year period, in order to understand their initial mental health status early in life and its change over time, as measured by the Strengths and Difficulties Questionnaire. Longitudinal models were fitted from ages 4–5 to 14–15 years. Results showed that child sex, maternal mental health, socio-economic status (family income, maternal education, neighbourhood disadvantage), maternal hostility, and child temperament (persistence, sociability, reactivity) are all independent contributors to child mental health at age 4. These effects largely persist over time, with the effects of maternal mental health increasing slightly over time. Persistence of these effects suggests the need for early intervention and supports. The independent contribution of these factors to child mental health suggests that multi-faceted approaches to child and maternal mental health are needed. [ABSTRACT FROM AUTHOR]

Although prematurity and hypoxic-ischaemic injury are well-recognized contributors to the pathogenesis of cerebral palsy (CP), as many as one-third of children with CP may lack traditional risk factors. For many of these children, a genetic basis to their condition is suspected. Recent findings have implicated copy number variants and mutations in single genes in children with CP. Current studies are limited by relatively small patient numbers, the underlying genetic heterogeneity identified, and the paucity of validation studies that have been performed. However, several genes mapping to intersecting pathways controlling neurodevelopment and neuronal connectivity have been identified. Analogous to other neurodevelopmental disorders such as autism and intellectual disability, the genomic architecture of CP is likely to be highly complex. Although we are just beginning to understand genetic contributions to CP, new insights are anticipated to serve as a unique window into the neurobiology of CP and suggest new targets for intervention. [ABSTRACT FROM AUTHOR]

For the Roman Catholic community, the Second Vatican Council inaugurated a notable paradigm shift, especially in the ecumenical movement. Joining earlier efforts of the Orthodox and Reformation churches, Catholics established official theological consultations with other churches. Since then there have appeared collaborative studies on the teachings of the Council and the imperative of unity movements. In addition to these studies, individual scholars have analyzed afresh the origins of ecclesial divergences and the paths to reconciliation. This article provides a bibliographical overview of these two genres of publications, especially those appearing in Canada and the United States. Because of the emergence of "receptive ecumenism" and "unity in diversity," church leaders and scholars are hopeful that, in the near future, the divisions that have marked Christianity for centuries will gradually be healed. Attention is also paid to university centres such as Leuven, Bologna, and Durham that have been prominent in research, including collection of archival materials and publication of conciliar diaries by now deceased council participants. Also provided are lists of major international conferences in Europe and America that have explored reasons for implementation of and even resistance to the teachings of Vatican II. [ABSTRACT FROM AUTHOR]

Purpose Statin selection for the largest hospital formulary in Qatar is not systematic, not comparative, and does not consider the multi-indication nature of statins. There are no reports in the literature of multi-indication−based comparative scoring models of statins or of statin selection criteria weights that are based primarily on local clinicians’ preferences and experiences. This study sought to comparatively evaluate statins for first-line therapy in Qatar, and to quantify the economic impact of this. Methods An evidence-based, multi-indication, multi-criteria pharmacotherapeutic model was developed for the scoring of statins from the perspective of the main health care provider in Qatar. The literature and an expert panel informed the selection criteria of statins. Relative weighting of selection criteria was based on the input of the relevant local clinician population. Statins were comparatively scored based on literature evidence, with those exceeding a defined scoring threshold being recommended for use. Findings With 95% CI and 5% margin of error, the scoring model was successfully developed. Selection criteria comprised 28 subcriteria under the following main criteria: clinical efficacy, best publish evidence and experience, adverse effects, drug interaction, dosing time, and fixed dose combination availability. Outcome measures for multiple indications were related to effects on LDL cholesterol, HDL cholesterol, triglyceride, total cholesterol, and C-reactive protein. Atorvastatin, pravastatin, and rosuvastatin exceeded defined pharmacotherapeutic thresholds. Atorvastatin and pravastatin were recommended as first-line use and rosuvastatin as a nonformulary alternative. It was estimated that this would produce a 17.6% cost savings in statins expenditure. Sensitivity analyses confirmed the robustness of the evaluation’s outcomes against input uncertainties. Implications Incorporating a comparative evaluation of statins in Qatari practices based on a locally developed, transparent, multi-indication, multi-criteria scoring model has the potential to considerably reduce expenditures on statins. Atorvastatin and pravastatin should be the first-line statin therapies in the main Qatari health care provider, with rosuvastatin as an alternative. [ABSTRACT FROM AUTHOR]

Aim: Idiopathic toe walking (ITW) is a diagnosis for children who toe walk without another diagnosis known to cause toe walking. Recent research has suggested that children with ITW may have mild motor planning challenges and sensory processing differences. The primary aim of this systematic review was to determine whether children diagnosed with ITW have differences in their sensory processing compared to typically developing children. Secondary aims included determining how sensory processing was assessed in this population and documenting the broad clinometric and psychometric properties of any assessment tools. Methods: MEDLINE, CINAHL, AMED and Embase were searched for relevant literature in English. Studies were eligible for inclusion if they described children aged 3 and 18 with idiopathic toe walking and reported a sensory processing domain. Results: Twelve articles met the inclusion criteria; however, only two papers included data permitting meta‐analysis. Meta‐analyses of vibration perception threshold using a random effect model were not significant (p = 0.31). Other data were synthesised by narrative and showed a high heterogeneity across multiple sensory processing domains. Conclusion: This study highlights that despite children with ITW often conceptualised as possessing sensory processing challenges, there is little evidence supporting this theory. Further research on sensory processing in children with this gait pattern is necessary. [ABSTRACT FROM AUTHOR]

Introduction Cerebral ventriculomegaly is one of the most commonly detected fetal anomalies at the midtrimester ultrasound. Current evidence suggests that magnetic resonance imaging ( MRI) is indicated when the isolated ventriculomegaly ( IVM) on ultrasound is severe (>15 mm), but there is less agreement when IVM is mild or moderate (10-15 mm). The current study aimed to determine the frequency and nature of additional findings on MRI in IVM and their relationship to the severity of VM and gestational age. Methods Data were gathered prospectively from all pregnant women with ultrasound-diagnosed IVM referred for MRI between November 2006 and February 2013. Cases with IVM and no other suspected cranial abnormality on a tertiary ultrasound performed at our institution, at or after 20 weeks gestation, were included. Results Of the 59 fetuses with unilateral or bilateral IVM, additional findings were seen on MRI in 10 cases (17%) and half of these findings were identified in fetuses with mild IVM. Five of 40 (12.5%) fetuses with mild IVM had additional findings and 3/5 (60%) were potentially clinically significant. No additional abnormalities were identified in fetuses less than or equal to 24 weeks gestation with mild or moderate IVM. There was no statistically significant relationship between gestational age and additional findings on MRI in mild IVM. Callosal and septum pellucidum lesions, periventricular abnormalities and malformations of cortical development accounted for all of the significant additional findings. Conclusion This study helps to inform referral of pregnant women with a fetus who has IVM for prenatal MRI. [ABSTRACT FROM AUTHOR]

Background: It is widely accepted that both autologous and alloplastic reconstruction are safe. A recent publication reported a significant association between textured implants and metastatic recurrence of breast cancer. This study aims to assess if the published results are reproducible in our cohort and to review the safety of breast reconstruction. Methods: This is a retrospective cohort study of adult patients undergoing mastectomy and either alloplastic or autologous breast reconstruction at a single quaternary hospital. Outcomes include disease free survival (DFS), local and recurrence free survival (LRRFS) and BIA‐ALCL. For time to event endpoints, unadjusted and multivariate adjusted hazard ratios (HRs) were estimated using Cox regression, and penalized Cox regression respectively. Results: Four hundred and twenty‐six patients of whom 187 underwent autologous reconstruction and 239 underwent alloplastic. There were 43 cancer recurrences (24 alloplastic and 19 autologous) and 14 local regional recurrences (8 alloplastic and 4 autologous). There were 26 deaths and no instances of BIA‐ALCL. Median follow‐up time was 4.7 years. No evidence of association was found between breast reconstruction method and DFS (HR 0.87 CI: 0.47–1.58). It is uncertain whether implant texture grade was associated with increased breast cancer recurrence (HR 2.17 CI: 0.65–7.52). Conclusion: Both autologous and alloplastic breast reconstruction have been carried out in our cohort and reconstructive modality was not associated with either reduced DFS or LRRFS. The results in this cohort show there is uncertainty between the use of textured breast implants and either local or distant breast cancer recurrence. [ABSTRACT FROM AUTHOR]

An important goal of many epidemiological studies is to estimate the magnitude of association between an exposure and an outcome. Exposure measurement error causes bias in such estimates of association and can be substantial. In this article, we describe the problem of exposure measurement error and its effects. We show how a simple hand calculation, in conjunction with validation study data and a calibration equation, can be used to correct estimates for the bias caused by exposure measurement error. Correcting estimates of association for measurement error helps researchers appropriately assess effect size. [ABSTRACT FROM AUTHOR]

Background Finite mixture models posit the existence of a latent categorical variable and can be used for probabilistic classification. The authors illustrate the use of mixture models for dietary pattern analysis. An advantage of this approach is taking classification uncertainty into account. Methods Participants were a random sample of women from the European Prospective Investigation into Cancer. Food consumption was measured using dietary questionnaires. Mixture models identified latent classes in food consumption data, which were interpreted as dietary patterns. Results Among various assumptions examined, models allowing the variance of foods to vary within and between classes fit better than alternatives assuming constant variance (the K-means method of cluster analysis also makes the latter assumption). An eight-class model was best fitting and five patterns validated well in a second random sample. Patterns with lower classification uncertainty tended to be better validated. One pattern showed low consumption of foods despite being associated with moderate body mass index. Conclusion Mixture modelling for dietary pattern analysis has advantages over both factor and cluster analysis. In contrast to these other methods, it is easy to estimate pattern prevalence, to describe patterns and to use patterns to predict disease taking classification uncertainty into account. Owing to substantial error in food consumptions, any analysis will usually find some patterns that cannot be well validated. While knowledge of classification uncertainty may aid pattern evaluation, any method will better identify patterns from food consumptions measured with less error. Mixture models may be useful to identify individuals who under-report food consumption. [ABSTRACT FROM AUTHOR]

The State of Qatar is a small oil and gas-rich Gulf country that is experiencing rapid development in health care services, including pharmaceutical services. To date, there is no autonomous professional pharmacy association or society that regulates or promotes the practice of pharmacy in Qatar, and the challenges that face the profession of pharmacy in Qatar mirror the challenges facing the profession in all other Middle Eastern countries. However, a set of initiatives and projects that include pioneering educational initiatives, close alignment of practice with the educational providers, stronger leadership from a National Health Strategy, and the development of pharmacy leadership groups at the practice level all contribute in the fast development of the practice of pharmacy in this country. In this commentary, we provide a snapshot of the pharmaceutical scene in Qatar, and in doing so, we shall discuss the challenges that face the practice, and the main landmarks and initiatives that are destined to move pharmacy forward in Qatar. [ABSTRACT FROM AUTHOR]

The term 'stem cell' most commonly refers to embryonic stem cells, particularly in the lay media; however, it also describes other cell types. A stem cell represents a cell of multi-lineage potential with the ability for self-renewal. It is now clear that the plasticity and immortality of a given stem cell will depend on what type of stem cell it is, whether an embryonic stem cell, a fetal-placental stem cell or an adult stem cell. Stem cells offer great promise as cell-based therapies for the future. With evolving technology, much of the socio-political debate regarding stem cells can now be avoided. [ABSTRACT FROM AUTHOR]

Abstract: Aim: To investigate the relationship between motor ability and early social development in a cohort of preschool children with cerebral palsy (CP). Design: Population-based cohort study. Methods: Participants were 122 children with CP assessed at 18, 24 and 30 months, corrected age (ca). Motor ability was measured by the Gross Motor Function Classification System (GMFCS) with classification assigned by physiotherapists. The sample was representative of a population-based cohort (I=48, 38.4%, II=19, 15.2%, III=17, 13.6%, IV=22, 17.6% and V=19, 15.2%). Social development was measured by the Paediatric Evaluation of Disability Inventory (PEDI) and included capabilities in social interaction, social communication, interactive play and household/community tasks. Results: Cross-sectional analyses indicated a significant relationship between motor ability and social development at 18 months, F(4, 56)=11.44, p <.0001, η 2 =.45, at 24 months, F(4, 79)=15.66, p <.0001, η 2 =.44 and at 30 months, F(4, 76)=16.06, p <.0001, η 2 =.49. A longitudinal analysis with a subset of children (N =24) indicated a significant interaction between age at assessment and GMFCS, F(2, 21)=7.02, p =.005, η 2 =.40. Comparison with community norms indicated that at 18 months corrected age, 44.3% of the cohort was greater than two standard deviations below the mean (>2SD) for social development and a further 27.9% of the cohort was greater than one standard deviation below the mean (>1SD). Interpretation: There is a relationship between motor ability and social development in preschool children with CP. Children with CP may require support for social development in additional to physical interventions, from as early as 18 months. [ABSTRACT FROM AUTHOR]

Background: Many methods are used to measure arterial elasticity in children using echocardiography. There is no data to support the equivalence of the different techniques. The goal of this study was to evaluate the reproducibility of several techniques used to measure arterial elasticity using echocardiography. Methods: Aortic distension in two different sites (arterial distension) through the cardiac cycle was measured by (four) two-dimensional (2D) and M-mode echocardiographic techniques in 20 children without significant structural heart disease. These measurements combined with noninvasive blood pressure measurements were used to calculate arterial elastic indices. Arterial elasticity was expressed in terms of distensibility and stiffness. Data were collected by two sonographers and interpreted by two reviewers. Paired Student's t-test and Pitman's test for equality of variance for correlated observations were used to detect differences between different sonographers, different reviewers, and different techniques. Results: No significant difference in the measured elasticity between sonographers or reviewers was observed. There was a somewhat increased variance in two of the four techniques evaluated. There was no significant difference in elasticity measured using different techniques to evaluate the same arterial site, although a significantly decreased elasticity was noted from measurements taken in the proximal ascending aorta as compared with the distal ascending aorta. Conclusions: Many echocardiographic techniques produce reproducible measurements of arterial elasticity. There may be intrinsic differences in arterial elasticity between different segments of the ascending aorta, which have not been previously described in children with normal cardiac anatomy. Comparisons of data from separate studies must take these differences into account. [ABSTRACT FROM AUTHOR]

Drawing upon his thirty years experience of teaching ecclesiology, the author tries to identify some developments and paradigm shifts he recognizes as having influenced theological reflection on the Church in Roman Catholic, Orthodox, Anglican, and Protestant contexts. He contrasts the present-day situation of Catholics to the isolationist doldrums that characterized the post-Modernist and pre-Vatican II eras. The impact of the Faith and Order Commission of the World Council of Churches was already notable when Catholics belatedly began to participate in ecumenical dialogue. Various advances in ecclesiology can be identified, especially the use of 'communion' ecclesiology. Negatively, the achievements of ecumenical exchanges are little known by the faithful and rarely cited by church leaders. Canonical regulations especially affecting eucharistic hospitality do not take into consideration the doctrinal consensuses that have emerged. A select bibliography is appended. [ABSTRACT FROM AUTHOR]

This article reports on politics in Taiwan under the presidency of Chen Shui-bian of the Democratic Progressive Party (DPP), whose election in 2000 unseated the Kuomintang (Nationalist Party, or KMT). Relations with China are discussed, as well as issues of independence, national identity, United Nations membership, relations with the U.S., and the 2008 Taiwanese presidential elections.

This commentary is on the invited review by Baxter on pages 563–568 of this issue. [ABSTRACT FROM AUTHOR]

This article provides information on past editors of the Theological Studies journal, as of December 2005. Theological Studies was founded in 1940 while the effects of the papal condemnation of Catholic Modernism were still lingering, while Europe was already in the throes of World War II, but the U.S. was debating, before Pearl Harbor, whether or not it should enter the war. Surely the then six theological faculties manned by the Society of Jesus in the U.S. could produce a first-rate theological journal. And since several voices of American Catholic theological scholarship had been silenced by the suppression of the short-lived The New York Review, published out of St. Joseph's Seminary, Dunwoodie, New York, and by the suspension, at least temporarily, of the American Ecclesiastical Review, the need was real.

Introduces several authors who contributed to the June 2004 issue of "Theological Studies." Roberto Goizueta, a Cuban American lay theologian; Allan Figuerora Deck, a Mexican American priest from Southern California; Jeanette Rodriguez of New York.

Mitochondrial donation to reduce the risk of primary mitochondrial disease transmission from mother to child is now permitted under Australian law as part of a clinical trial. The energy demands of pregnancy have the potential to worsen mitochondrial disease symptoms and severity in affected women. We conducted a systematic literature review on mitochondrial disease in pregnancy; five cohort studies and 19 case reports were included. For many women with mitochondrial disease, pregnancy does not have a negative effect on health status. However, serious adverse outcomes may occur. We provide suggested guidelines for preconception counselling and antenatal care. [ABSTRACT FROM AUTHOR]

This study aims to determine if children follow the same cortical activation patterns as adults when responding to two‐point discrimination sensory stimuli during functional magnetic resonance imaging (fMRI). We recruited 15 children with typical development, aged between 8 and 16 years. These participants were asked to complete a two‐point discrimination test (task block) while undergoing an fMRI scan. In the two‐point stimulus test, strong activation compared to baseline was observed in the left and right frontal orbital cortex. The inferior parietal lobe also exhibited activity, particularly on the right side, with activation in both the supramarginal and angular gyri. Further activity was evident in the left supramarginal gyrus and the left paracingulate gyrus. This novel study on fMRI two‐point discrimination testing in children shows the activation patterns in key brain regions involved in somatosensory discrimination and decision making. Practical Applications: This study provides crucial normative data on cortical activation patterns during two‐point discrimination testing in typically developing children. Such data serve as a valuable reference point for future research investigating sensory processing and cognitive function in pediatric populations. Researchers can use these findings to establish benchmarks and compare cortical activation patterns in children with neurodevelopmental conditions. This information is essential for exploring pathology, which may affect tactile sensation techniques and developing targeted interventions tailored to individual needs in pediatric treatment. Additionally, it lays the groundwork for further exploration into the neural mechanisms underpinning somatosensory discrimination, potentially leading to advancements in understanding and treating sensory‐related disorders in children. [ABSTRACT FROM AUTHOR]

Describes the preparatory stages, format, various points of convergence and contention and the anticipated long-range impact of the special synod of Catholic bishops at the Vatican in 1997. Origin of synod; Other expressions of collegiality in the church; Comments on the four sections of the Synod of America.

Cerebral palsy (CP) is a nonprogressive neurological disorder and the most common physical disability of childhood. There is no cure for CP, but stem cells have the potential to improve brain injury and hence function. This phase 1 clinical trial investigated the safety of the intravenous infusion of full-matched sibling cord blood cells for children with CP aged 1 to 16 years. Preliminary efficacy outcomes were also investigated. Twelve participants received 12/12 HLA-matched sibling cord blood cell infusions. One treatable serious adverse reaction to cryoprotectant was observed, and no adverse reactions occurred beyond 24 h after infusion. Gross motor function measure (GMFM-66) scores did not improve compared with baseline beyond what could be expected from developmental levels, and participants had varied changes in the Quality of Upper Extremity Skills Test (QUEST) and Vineland Adaptive Behavior Scales (VABS-II) scores. In conclusion, matched sibling cord blood cell infusion for children with CP is relatively safe when conducted in an appropriate facility. Australian and New Zealand Clinical Trials Registry (ACTRN12616000403437) and Clinicaltrials.gov (NCT03087110). [ABSTRACT FROM AUTHOR]

Factors that significantly affect performance of in-service sprayed seals have been identified through developing comprehensive models using a multilevel analysis approach. Subjective condition data of surface distresses from five rural road networks in Victoria/Australia have been used. They include cracking, deformation, texture loss, stone loss and patching. Evaluations of individual distresses for representative segments are combined into a composite index called Surface Inspection Rating (SIR) which is used to trigger the need for resealing. Contributing factors considered include surface age, traffic volume, aggregate size, subgrade soil type, shoulder seal width, rainfall and temperature. For each network, statistically significant factors for each distress are identified and used in developing their SIR models. An overall SIR model has also been developed using condition data from all five networks. Predictions of this model have been compared with an existing model that has been developed using Markov Chains with surface age as the only predictor. The results show that both models have roughly similar deterioration rates of SIR up to 8 years of seal life, after which deterioration rate of the newly developed model becomes higher. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article regarding the osteoporosis care pathway from the American Academy of Cerebral Palsy and Developmental Medicine (AACPDM).

A study has been performed to develop long-term performance models for asphalt surfaces using condition data from two urban road networks. The performance of asphalt surfaces is assessed subjectively every two to three years considering the extent and severity of different distress types. They include cracking, deformation, texture loss, stone loss and patching of potholes and localised depressions. Different ratings are used for each condition then combined into one overall condition index referred to as Surface Inspection Rating (SIR). SIR is used to trigger the need for resurfacing operations. Performance models have been developed for these distresses and SIR considering the following factors; surface age, traffic loading, aggregate size and climatic conditions (rainfall and temperature). Multilevel analysis approach has been used to model the historical time series condition data. The results indicate that surface age, temperature and rainfall affect SIR in both networks and that traffic loading has a significant effect in one network. [ABSTRACT FROM AUTHOR]

Blood–brain barrier (BBB) dysfunction and neuroinflammation are key mechanisms of brain injury. We performed a time-course study following neonatal hypoxia–ischemia (HI) to characterize these events. HI brain injury was induced in postnatal day 10 rats by single carotid artery ligation followed by hypoxia (8% oxygen, 90 min). At 6, 12, 24, and 72 h (h) post-HI, brains were collected to assess neuropathology and BBB dysfunction. A significant breakdown of the BBB was observed in the HI injury group compared to the sham group from 6 h in the cortex and hippocampus (p < 0.001), including a significant increase in albumin extravasation (p < 0.0033) and decrease in basal lamina integrity and tight-junction proteins. There was a decrease in resting microglia (p < 0.0001) transitioning to an intermediate state from as early as 6 h post-HI, with the intermediate microglia peaking at 12 h (p < 0.0001), which significantly correlated to the peak of microbleeds. Neonatal HI insult leads to significant brain injury over the first 72 h that is mediated by BBB disruption within 6 h and a transitioning state of the resident microglia. Key BBB events coincide with the appearance of the intermediate microglial state and this relationship warrants further research and may be a key target for therapeutic intervention. [ABSTRACT FROM AUTHOR]

Objective: Variants in several potassium channel genes, including KCNA1 and KCNA2, cause Developmental and Epileptic Encephalopathies (DEEs). We investigated whether variants in KCNA3, another mammalian homologue of the Drosophila shaker family and encoding for Kv1.3 subunits, can cause DEE. Methods: Genetic analysis of study individuals was performed by routine exome or genome sequencing, usually of parent‐offspring trios. Phenotyping was performed via a standard clinical questionnaire. Currents from wild‐type and/or mutant Kv1.3 subunits were investigated by whole‐cell patch‐clamp upon their heterologous expression. Results: Fourteen individuals, each carrying a de novo heterozygous missense variant in KCNA3, were identified. Most (12/14; 86%) had DEE with marked speech delay with or without motor delay, intellectual disability, epilepsy, and autism spectrum disorder. Functional analysis of Kv1.3 channels carrying each variant revealed heterogeneous functional changes, ranging from "pure" loss‐of‐function (LoF) effects due to faster inactivation kinetics, depolarized voltage‐dependence of activation, slower activation kinetics, increased current inactivation, reduced or absent currents with or without dominant‐negative effects, to "mixed" loss‐ and gain‐of‐function (GoF) effects. Compared to controls, Kv1.3 currents in lymphoblasts from 1 of the proband displayed functional changes similar to those observed upon heterologous expression of channels carrying the same variant. The antidepressant drug fluoxetine inhibited with similar potency the currents from wild‐type and 1 of the Kv1.3 GoF variant. Interpretation: We describe a novel association of de novo missense variants in KCNA3 with a human DEE, and provide evidence that fluoxetine might represent a potential targeted treatment for individuals carrying variants with significant GoF effects. ANN NEUROL 2024;95:365–376 [ABSTRACT FROM AUTHOR]

• Resurfacing is significant in reducing crash frequency and severity levels. • As the increase in skid resistance is found to improve safety by severity, therefore, priority should be provided in intersections maintenance program to ensure continued acceptable levels of skid resistance. • Pavement surface condition parameters, roughness and rutting, need to be considered in either intervention criteria or treatment selection to ensure that they are reduced to acceptable levels for users' comfort and safety. • To account for the repeated observations , Generalised Estimating Equation (GEE) with Negative Binomial (NB) regression is an appropriate model in predicting crash frequency. • Road users' safety at signalised intersections are affected by pavement surface condition and geometric characteristics. This study investigated the effects of pavement surface condition and other control factors on casualty crashes at signalized intersections. It involved conducting a before and after study for road surface condition and situational factors. It also included assessing the effects of geometric characteristics on safety performance of signalized intersections post resurfacing to control for the effect of pavement surface condition. Pavement surface condition included roughness, rutting, and skid resistance. The control factors included traffic volume, light and surface moisture condition, and speed limit. The geometric characteristics included approach width, number of lanes, intersection depth, presence of median, presence of shared lane, and presence of bus stop. To account for the repeated observations of the effect of light and surface moisture conditions in four occasions (day-dry, day-wet, night-dry and night-wet) Generalized Estimating Equation (GEE) with Negative Binomial (NB) and log link function was applied. For each signalized intersection in the sample, condition data are collected for the year before and after the year of surface treatment. Crash data, however, are collected for a minimum of three and maximum of five years before and after treatment years. The results show that before treatment, light condition, road surface moisture condition, and skid resistance interaction with traffic volume are the significant contributors to crash occurrence. For after treatment; light condition, road surface moisture condition, their interaction product, and roughness interaction with light condition, surface moisture condition, and traffic volume are the significant contributors. The geometric variables that were found to have significant effects on crash frequency post resurfacing were approach width interactions with presence of shared lane, bus stop, or median. The findings confirm that resurfacing is significant in reducing crash frequency and severity levels. Practical Applications: The study findings would help for better understanding of how geometric characteristics can be improved to reduce crash occurrence. [ABSTRACT FROM AUTHOR]

Fragile X syndrome (FXS) is usually associated with a CGG repeat expansion >200 repeats within the FMR1 gene, known as a full mutation (FM). FM alleles produce abnormal methylation of the FMR1 promoter with reduction or silencing of FMR1 gene expression. Furthermore, premutation (PM: 55–199 CGGs) and full mutation alleles usually expand in size when maternally transmitted to progeny. This study describes a PM allele carried by the mother decreasing to a normal sized allele in a male from a dichorionic diamniotic (DCDA) twin pregnancy, with the female twin inheriting FM (200–790 CGGs), PM (130 CGGs) and normal-sized (39 CGGs) alleles. Further evidence of instability of the maternal PM allele was shown by a male proband (older brother) mosaic for PM (CGG 78 and 150 CGGs) and FM (200–813 CGGs), and a high level of FMR1 promoter methylation, between 50 and 70%, in multiple tissues. The fully-retracted, normal-sized allele was identified by PCR CGG sizing in the male twin, with no evidence of a FM allele identified using Southern blot analysis in multiple tissues collected postnatally and prenatally. Consistent with this, prenatal PCR sizing (35 CGGs) showed inconsistent inheritance of the maternal normal allele (30 CGGs), with single-nucleotide polymorphism (SNP) linkage analysis confirming that the abnormal FMR1 chromosome had been inherited from the mother’s PM chromosome. Importantly, the male twin showed no significant hypermethylation of the FMR1 promoter in all pre and postnatal tissues tested, as well as normal levels of FMR1 mRNA in blood. In summary, this report demonstrates the first postnatal follow up of a prenatal case in which FMR1 mRNA levels were approaching normal, with normal levels of FMR1 promoter methylation and normal CGG size in multiple pre and postnatally collected tissues. [ABSTRACT FROM AUTHOR]

Aim: This paper describes the use of the single patient therapy plan (SPTP). The SPTP has been designed to assess the efficacy at an individual level of a commercially available cannabinoid product, cannabidiol, in reducing seizure frequency in paediatric patients with intractable epilepsy. Methods: The SPTP is a randomised, double‐blind, placebo‐controlled N‐of‐1 trial designed to assess the efficacy of treatment in a neurology outpatient setting. The primary objective of the SPTP is to assess the efficacy of cannabidiol in reducing seizure frequency in each patient with intractable epilepsy, with change in seizure frequency being the primary outcome of interest. The analysis adopts a Bayesian approach, which provides results in the form of posterior probabilities that various levels of benefit (based on the primary outcome measure, seizure frequency) have been achieved under active treatment compared to placebo, accompanied by decision rules that provide thresholds for deciding whether treatment has been successful in the individual patient. The SPTP arrangement is most accurately considered part of clinical practice rather than research, since it is aimed at making clinical treatment decisions for individual patients and is not testing a hypothesis or collecting aggregate data. Therefore, Human Research Ethics Committee approval was considered not to be required, although it is recommended that hospital Clinical Ethics Committees provide ethical oversight. Conclusion: These SPTP resources are made available so that they may inform clinical practice in the treatment of severe epilepsy or adapted for use in other conditions. [ABSTRACT FROM AUTHOR]

The article presents a clinical guide for conducting gait examination in children. It outlines the preliminary steps for gait examination that include asking the child to walk and considering provisional diagnosis and the potential usefulness of tests such as Romberg test, Trendelenberg test and the Gower maneuver. Also discussed are the neurological and extended examination to distinguish between myopathy, neuropathy and neuromuscular junction abnormality.

The article presents tips to pediatricians on performing eye examination. A 10-year-old boy has had trouble with his eyes for years. This sort of situation always causes fear among candidates. It is probably an introduction to examining other components of the neurological system, and normally, the signs should be clear to elicit.

The article discusses the major challenge in this examination of surrogate baby to distinguish whether a child has a central cause of floppiness or a peripheral cause. It mentions that peripheral causes include the diseases of motor neuron, neuromuscular junction and peripheral nerve, the weakness due to spinal muscular atrophy type 2 (SMA 2), and central causes tend to be associated with decreased alertness and measure by brain magnetic resonance imaging (MRI) scan.

Background: Intracardiac foreign bodies have been described in the literature, however, they are rare entities, particularly in pediatric patients. We present a case of a teenage boy diagnosed with perimyocarditis who was found to have an unexpected underlying etiology: an unknowingly swallowed sewing pin.Case Report: A 17-year-old boy presented to the Emergency Department with 3 days of chest pain suggestive of perimyocarditis, in the absence of prodromal symptoms or trauma. Electrocardiogram at the time of presentation demonstrated diffuse ST-segment elevation consistent with perimyocarditis. A chest radiograph was significant for a linear density in the anterior mid chest, concerning for foreign body. Chest computed tomography confirmed the presence of a 3.5-cm linear metallic foreign body within the right ventricle. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: This case demonstrates the need to consider alternative etiologies for perimyocarditis, especially in the absence of the typical prodromal symptoms. In addition, it highlights the potential devastating complications of foreign body ingestion and challenges the paradigm that ingested sharp linear foreign bodies < 5 cm in length rarely cause problems. [ABSTRACT FROM AUTHOR]

Objective To identify risk factors for thunderstorm asthma (TA) in subjects ≥15 years of age from information available in routine clinical records. Methods: Retrospective and hospital‐based case–control study of various clinical factors in all TA cases (n = 53) who presented to a single‐site ED in November 2016 (TA16) and in a control group of patients (n = 156) who presented to the same ED with asthma during the pollen season over eight non‐TA years. Bivariate analysis and multivariable logistic regression modelling was performed to calculate the odds of TA asthma in the presence of potential risk factors. Results: A logistic regression model revealed that the odds of TA were lower for age (odds ratio [OR] 0.97, 95% confidence interval [CI] 0.95–0.99), higher for Asian country of birth (OR 4.09, 95% CI 1.40–11.95) and higher for oral beta‐blocker use (OR 6.43, 95% CI 1.58–26.33) compared to controls. No difference was found between TA16 cases and controls for allergies (to medication, grass pollen, animal), hayfever, smoking, oral non‐steroidal anti‐inflammatory drugs, or aspirin. Newly diagnosed asthma was higher in TA16 cases versus controls (32.1% vs 12.2%, P = 0.001). Conclusions: Oral beta‐blocker medications, younger age and Asian‐born heritage are risk factors for TA. Further study is required to explore the potential association between beta‐blockers and TA. [ABSTRACT FROM AUTHOR]

Umbilical cord blood cells have therapeutic potential for neurological disorders, through a paracrine mechanism of action. A greater understanding of the safety and immunological effects of allogeneic donor cord blood cells in the context of a healthy recipient immune system, such as in cerebral palsy, is needed. This study aimed to determine how quickly donor cord blood cells were cleared from the circulation in children with cerebral palsy who received a single intravenous infusion of 12/12 human leucocyte antigen (HLA)-matched sibling cord blood cells. Twelve participants with cerebral palsy aged 2–12 years received cord blood cell infusions as part of a phase I trial of umbilical blood infusion for cerebral palsy. Digital droplet PCR analysis of DNA copy number variants specific to donor and recipient was used to assess donor DNA clearance at five timepoints post-infusion, a surrogate measure of cell clearance. Donor cells were cleared by 3 months post-infusion in 11/12 participants. When detected, donor DNA was at a fraction of 0.01–0.31% of total DNA with no signs of graft-versus-host disease in any participant. The donor DNA clearance times provided by this study have important implications for understanding the safety of allogeneic cord blood cell infusion for cerebral palsy and translational tissue engineering or regenerative medicine research in other disorders. [ABSTRACT FROM AUTHOR]

(1) Background: Neonatal brain injury can lead to permanent neurodevelopmental impairments. Notably, suppressing inflammatory pathways may reduce damage. To determine the role of neuroinflammation in the progression of neonatal brain injury, we investigated the effect of treating neonatal rat pups with the immunosuppressant tacrolimus at two time points: before and after hypoxic–ischaemic (HI)-induced injury. (2) Methods: To induce HI injury, postnatal day (PND) 10 rat pups underwent single carotid artery ligation followed by hypoxia (8% oxygen, 90 min). Pups received daily tacrolimus (or a vehicle) starting either 3 days before HI on PND 7 (pre-HI), or 12 h after HI (post-HI). Four doses were tested: 0.025, 0.05, 0.1 or 0.25 mg/kg/day. Pups were euthanised at PND 17 or PND 50. (3) Results: All tacrolimus doses administered pre-HI significantly reduced brain infarct size and neuronal loss, increased the number of resting microglia and reduced cellular apoptosis (p < 0.05 compared to control). In contrast, only the highest dose of tacrolimus administered post-HI (0.25 mg/kg/day) reduced brain infarct size (p < 0.05). All doses of tacrolimus reduced pup weight compared to the controls. (4) Conclusions: Tacrolimus administration 3 days pre-HI was neuroprotective, likely mediated through neuroinflammatory and cell death pathways. Tacrolimus post-HI may have limited capacity to reduce brain injury, with higher doses increasing rat pup mortality. This work highlights the benefits of targeting neuroinflammation during the acute injurious period. More specific targeting of neuroinflammation, e.g., via T-cells, warrants further investigation. [ABSTRACT FROM AUTHOR]

Although prematurity and hypoxic-ischaemic injury are well-recognized contributors to the pathogenesis of cerebral palsy (CP), as many as one-third of children with CP may lack traditional risk factors. For many of these children, a genetic basis to their condition is suspected. Recent findings have implicated copy number variants and mutations in single genes in children with CP. Current studies are limited by relatively small patient numbers, the underlying genetic heterogeneity identified, and the paucity of validation studies that have been performed. However, several genes mapping to intersecting pathways controlling neurodevelopment and neuronal connectivity have been identified. Analogous to other neurodevelopmental disorders such as autism and intellectual disability, the genomic architecture of CP is likely to be highly complex. Although we are just beginning to understand genetic contributions to CP, new insights are anticipated to serve as a unique window into the neurobiology of CP and suggest new targets for intervention. [ABSTRACT FROM AUTHOR]

Context: Cerebral palsy (CP) is a motor disorder affecting movement, muscle tone and posture due to damage to the foetal or infant brain. The subsequent lack of ambulation, nutritional deficiencies, anticonvulsant use and hormonal deficiencies have been implicated in the low bone mass associated with this condition. Objective: To assess changes in areal bone mineral density (aBMD) during adolescence and young adulthood in individuals with CP. The effect of ambulation, nutrition, hypogonadism on longitudinal changes in aBMD is also examined. Design: Retrospective longitudinal study. Setting and participants: Forty‐five subjects with CP who had longitudinal dual‐energy X‐ray absorptiometry (DXA) scans at a single tertiary hospital between 2006 and 2018. Results: Mean age at first DXA was 19.4 years (range: 10‐36 years), 57.8% were male and 80% were nonambulatory. The mean Z‐scores at baseline were <−2.0 at all sites – lumbar spine (LS), femoral neck (FN), total hip (TH) and total body (TB). The median change in aBMD was +1.2%‐1.9% per year in all subjects but in those <20 years of age, the median change was 4%‐8% per year. Z‐scores across all sites remained stable over time. Reduced functional state as measured by the gross motor functional classification scale (GMFCS) had a small negative effect on aBMD over time. Conclusion: In adolescents with CP, low bone mass was evident from the baseline DXA. However, significant bone accrual occurred during the second decade, followed by bone maintenance in young adulthood. Future studies should focus on optimizing bone health from early childhood. [ABSTRACT FROM AUTHOR]

Presents an overview of the practice of Catholicism in Ireland. Reason behind the change in the public attitude toward Catholic priests; Perceptions of persons living in affluent conditions; Economic condition in Ireland in 1949.

Offers insights on Pope Benedict XVI. Experiences of a student with the pope in Germany when he was still a professor; Views on the pope's change of ministry from prefect of the Congregation for the Doctrine of the Faith to Roman Pontiff; Concerns of theologians under the pope.

Offers views regarding the December 26, 2004 tsunami tragedy that hit several countries in Southeast Asia and East Africa. Estimated number of people who died in the tragedy; Efforts of Christian missionaries to help the victims; Reaction of some religious leaders on the tragedy; Theological implication of the tragedy.

Discusses issues concerning medical care. Impact of the war in Iraq on the U.S.; Estimation of the number of casualties and injured people from the U.S.; Importance of medical personnel; Inability of some countries to provide health care for the poor due to lack of medical insurance coverage.

-The Board of Directors of Theological Studies, concluding a national search, has named David Schultenover, S.J., the present book review editor and professor of historical theology at Marquette University, as associate editor. -Recent visits to two of the major Catholic theological centers in Europe--Heythrop College (London) and the Catholic University of Leuven--have brought home to me how" young" are the North American universities and divinity schools by comparison to counterparts overseas. -Today, what is so impressive about Heythrop College and its rich programs in philosophy and theology, offered in conjunction with the University of London, is not its physical plant (which, because of the age of its buildings, is not completely user friendly), nor its precious incunabula, but rather the rich diversity and commitment of its teaching staff and student body, mostly lay women and men from a variety of backgrounds and cultures, persons committed to the academic life and renewal of the Church in the modern world. -Leuven is justly proud of the major contributions made to the Second Vatican Council by a number of 20th-century Belgian professors such as Gustave Thils, G& eacute; rard Philips, and Louis Janssens. In fact, in September 2005, the University will host a symposium, under the co-sponsorship of the Cardinal Suenens Institute of John Carroll University, Cleveland, devoted to analyzing the impact of Belgian scholars on the formulation of conciliar texts. -The University's setting with its cobblestone alleyways, its ornate 15th-century City Hall, the Collegiate Church of St. Peter, and its restored Groot Begijnhof, is nonetheless very much plugged into the electronic age of digital computers, cellular phones, high-tech equipment, and jet-set professors.