Evaluating quality and impact of acute paediatric inpatient care: Defining the domains for a Person Centred Outcome Measure (PCOM) in children and young people admitted with self-harm or eating disorders

Background and purpose: In the United Kingdom, the prevalence of children and young people (CYP), up to the age of 18 years, accessing acute paediatric inpatient care with mental health problems is increasing, with self-harm and eating disorders particularly prevalent. This initial period of acute inpatient care can involve multiple assessments and interventions in order to meet physical, psychological and social needs. However, there is a distinct paucity of published literature reporting CYP service users’ experiences and outcomes of being in receipt of non-specialist inpatient care. Therefore this project aimed to undertake the preliminary work in developing a Person Centred Outcome Measure (PCOM) for this patient group by identifying the domains for a PCOM and establishing how such a measure could be implemented. Methods: A two phase sequential design was adopted which involved: (1) a rapid review of the literature and (2) an evaluation of experiences and outcomes through stakeholder engagement events with children and young people admitted with self-harm or eating disorders, their parents and carers, and professionals from health, social care and education. Findings: Rapid review of the literature • There is a lack of reported outcomes relating to CYP admitted to inpatient care with self-harm within the literature. • Outcomes reported by CYP appear to relate to aspects of care delivery, communication and the inpatient environment; • CYP reports predominantly relate to deficits in service provision which is recognised to negatively impact on experience and inhibit recovery and outcome. Findings: Stakeholder workshops • In total 96 CYP, parents and carers, and professionals participated in the stakeholder event. • Disparities in experiences and the implied quality of being in receipt of care were identified. • Synthesis of findings identified five domains that could be used to develop a PCOM that included: Privacy and surveillance; Receiving holistic care; Making choices and being understood through timely, relevant and appropriate communication; Working together to plan and achieve care goals; and Respect and empowerment • Variation was evident between CYP stakeholders as to the acceptability of when and how outcomes are measured. Conclusion: Findings from this project provide the foundations for a PCOM for CYP admitted to acute paediatric care with self harm or eating disorders to be developed, tested, implemented and evaluated. The domains identified have the potential to be further developed and validated as an instrument with a larger and more diverse sample of CYP

Modelling the exposure of wildlife to radiation: key findings and activities of IAEA working groups

The International Atomic Energy Agency (IAEA) established the Biota Working Group (BWG) as part of its Environmental Modelling for Radiation Safety (EMRAS) programme in 2004 (http://www-ns.iaea.org/projects/emras/emras-biota-wg.htm). At that time both the IAEA and the International Commission on Radiological Protection (ICRP) were addressing environmental protection (i.e. protection of non-human biota or wildlife) within the on-going revisions to the Basic Safety Standards and Recommendations respectively. Furthermore, some countries (e.g. the USA, UK) were already conducting assessments in accordance with national guidelines. Consequently, a number of assessment frameworks/models had been or were being developed. The BWG was established recognising these developments and the need to improve Member State’s capabilities with respect to protection of the environment from ionizing radiation. The work of the BWG was continued within the IAEA’s EMRAS II programme by the Biota Modelling Group (http://wwwns. iaea.org/projects/emras/emras2/working-groups/working-group-four.asp)

Capillary Electrophoresis Separation of Protein Composition of γ-Irradiated Food Pathogens Listeria monocytogenes and Staphylococcus aureus

which were previously treated at different irradiation doses., one protein (50 S ribosomal protein) with the MW of 16.3 kDa was significantly decreased at a low dose of irradiation treatment and the other protein (transcriptional regulator CtsR) with the MW of 17.7 kDa was increased significantly (P≤0.05) at all doses of irradiation treatment compared to control.. The research further confirmed that capillary electrophoresis is a useful method to separate and analyse proteins expression which may be related to the resistance or sensitivity of food pathogens to γ-irradiation

The International X-Linked Hypophosphatemia (XLH) Registry:first interim analysis of baseline demographic, genetic and clinical data

Background: X-linked hypophosphatemia (XLH) is a rare, hereditary, progressive, renal phosphate-wasting disorder characterized by a pathological increase in FGF23 concentration and activity. Due to its rarity, diagnosis may be delayed, which can adversely affect outcomes. As a chronic disease resulting in progressive accumulation of musculoskeletal manifestations, it is important to understand the natural history of XLH over the patient’s lifetime and the impact of drug treatments and other interventions. This multicentre, international patient registry (International XLH Registry) was established to address the paucity of these data. Here we present the findings of the first interim analysis of the registry.Results: The International XLH Registry was initiated in August 2017 and includes participants of all ages diagnosed with XLH, regardless of their treatment and management. At the database lock for this first interim analysis (29 March 2021), 579 participants had entered the registry before 30 November 2020 and are included in the analysis (360 children [62.2%], 217 adults [37.5%] and 2 whose ages were not recorded [0.3%]; 64.2% were female). Family history data were available for 319/345 (92.5%) children and 145/187 (77.5%) adults; 62.1% had biological parents affected by XLH. Genetic testing data were available for 341 (94.7%) children and 203 (93.5%) adults; 370/546 (67.8%) had genetic test results; 331/370 (89.5%) had a confirmed PHEX mutation. A notably longer time to diagnosis was observed in adults ≥ 50 years of age (mean [median] duration 9.4 [2.0] years) versus all adults (3.7 [0.1] years) and children (1.0 [0.2] years). Participants presented with normal weight, shorter length or height and elevated body mass index (approximately − 2 and + 2 Z-scores, respectively) versus the general population. Clinical histories were collected for 349 participants (239 children and 110 adults). General data trends for prevalence of bone, dental, renal and joint conditions in all participants were aligned with expectations for a typical population of people with XLH.Conclusion: The data collected within the International XLH Registry, the largest XLH registry to date, provide substantial information to address the paucity of natural history data, starting with demographic, family history, genetic testing, diagnosis, auxology and baseline data on clinical presentation.</p

Genetic regulation of pituitary gland development in human and mouse

Normal hypothalamopituitary development is closely related to that of the forebrain and is dependent upon a complex genetic cascade of transcription factors and signaling molecules that may be either intrinsic or extrinsic to the developing Rathke’s pouch. These factors dictate organ commitment, cell differentiation, and cell proliferation within the anterior pituitary. Abnormalities in these processes are associated with congenital hypopituitarism, a spectrum of disorders that includes syndromic disorders such as septo-optic dysplasia, combined pituitary hormone deficiencies, and isolated hormone deficiencies, of which the commonest is GH deficiency. The highly variable clinical phenotypes can now in part be explained due to research performed over the last 20 yr, based mainly on naturally occurring and transgenic animal models. Mutations in genes encoding both signaling molecules and transcription factors have been implicated in the etiology of hypopituitarism, with or without other syndromic features, in mice and humans. To date, mutations in known genes account for a small proportion of cases of hypopituitarism in humans. However, these mutations have led to a greater understanding of the genetic interactions that lead to normal pituitary development. This review attempts to describe the complexity of pituitary development in the rodent, with particular emphasis on those factors that, when mutated, are associated with hypopituitarism in humans

Typical features of Parkinson disease and diagnostic challenges with microdeletion 22q11.2

Objective: To delineate the natural history, diagnosis, and treatment response of Parkinson disease (PD) in individuals with 22q11.2 deletion syndrome (22q11.2DS), and to determine if these patients differ from those with idiopathic PD. Methods: In this international observational study, we characterized the clinical and neuroimaging features of 45 individuals with 22q11.2DS and PD (mean follow-up 7.5 ± 4.1 years). Results: 22q11.2DS PD had a typical male excess (32 male, 71.1%), presentation and progression of hallmark motor symptoms, reduced striatal dopamine transporter binding with molecular imaging, and initial positive response to levodopa (93.3%). Mean age at motor symptom onset was relatively young (39.5 ± 8.5 years); 71.4% of cases had early-onset PD (<45 years). Despite having a similar age at onset, the diagnosis of PD was delayed in patients with a history of antipsychotic treatment compared with antipsychotic-naive patients (median 5 vs 1 year, p = 0.001). Preexisting psychotic disorders (24.5%) and mood or anxiety disorders (31.1%) were common, as were early dystonia (19.4%) and a history of seizures (33.3%). Conclusions: Major clinical characteristics and response to standard treatments appear comparable in 22q11.2DS-associated PD to those in idiopathic PD, although the average age at onset is earlier. Importantly, treatment of preexisting psychotic illness may delay diagnosis of PD in 22q11.DS patients. An index of suspicion and vigilance for complex comorbidity may assist in identifying patients to prioritize for genetic testing

The effects of different opacifiers on the translucency of experimental dental composite resins

OBJECTIVE: The aim of this study was to evaluate the effects of different opacifiers on the translucency of experimental dental composite-resins. METHODS: Three metal oxides that are used as opacifiers were tested in this study: titanium oxide (TiO2), aluminium oxide (Al2O3) and zirconium oxide (ZrO2). Experimental composite-resins were fabricated containing 25wt.% urethane dimethacrylate (UDMA)-based resin matrix and 75% total filler including different concentrations of metal oxides (0, 0.25, 0.5, 0.75 and 1wt.%) blended into silane treated barium-silicate filler. The specimens (15.5mm diameter and 1mm thickness) were light-cured and tested in the transmittance mode using a UV/VIS spectrophotometer at wavelengths from 380 to 700nm under a standard illuminant D65. The color differences (ΔE* ab) between different concentrations of opacifiers were also measured in transmittance mode based on their Lab values. RESULTS: Statistical analysis by ANOVA and Tukey's test showed a significant decrease (p<0.05) in light transmittance with the addition of opacifiers to the experimental composite-resins. There was a linear correlation between different concentrations of TiO2 and Al2O3 and total transmittance. Total transmittance was also found to be wavelength dependent. The color differences for the concentrations of 0-1wt.% of the opacifiers were above 1 ΔE* unit, with Al2O3 showing the smallest color shift. SIGNIFICANCE: The type and the amount of the opacifiers used in this study had a significant effect on the translucency of the experimental UDMA-based dental composite resins. The most effective opacifier was TiO2, followed by ZrO2 and Al2O3 in decreasing order, respectively

Congenital Hydrocephalus and Abnormal Subcommissural Organ Development in Sox3 Transgenic Mice

Congenital hydrocephalus (CH) is a life-threatening medical condition in which excessive accumulation of CSF leads to ventricular expansion and increased intracranial pressure. Stenosis (blockage) of the Sylvian aqueduct (Aq; the narrow passageway that connects the third and fourth ventricles) is a common form of CH in humans, although the genetic basis of this condition is unknown. Mouse models of CH indicate that Aq stenosis is associated with abnormal development of the subcommmissural organ (SCO) a small secretory organ located at the dorsal midline of the caudal diencephalon. Glycoproteins secreted by the SCO generate Reissner's fibre (RF), a thread-like structure that descends into the Aq and is thought to maintain its patency. However, despite the importance of SCO function in CSF homeostasis, the genetic program that controls SCO development is poorly understood. Here, we show that the X-linked transcription factor SOX3 is expressed in the murine SCO throughout its development and in the mature organ. Importantly, overexpression of Sox3 in the dorsal diencephalic midline of transgenic mice induces CH via a dose-dependent mechanism. Histological, gene expression and cellular proliferation studies indicate that Sox3 overexpression disrupts the development of the SCO primordium through inhibition of diencephalic roof plate identity without inducing programmed cell death. This study provides further evidence that SCO function is essential for the prevention of hydrocephalus and indicates that overexpression of Sox3 in the dorsal midline alters progenitor cell differentiation in a dose-dependent manner

Lack of an Antibacterial Response Defect in Drosophila Toll-9 Mutant

Toll and Toll-like receptors represent families of receptors involved in mediating innate immunity response in insects and mammals. Although Drosophila proteome contains multiple Toll paralogs, Toll-1 is, so far, the only receptor to which an immune role has been attributed. In contrast, every single mammalian TLR is a key membrane receptor upstream of the vertebrate immune signaling cascades. The prevailing view is that TLR-mediated immunity is ancient. Structural analysis reveals that Drosophila Toll-9 is the most closely related to vertebrate TLRs and utilizes similar signaling components as Toll-1. This suggests that Toll-9 could be an ancestor of TLR-like receptors and could have immune function. Consistently, it has been reported that over-expression of Toll-9 in immune tissues is sufficient to induce the expression of some antimicrobial peptides in flies. These results have led to the idea that Toll-9 could be a constitutively active receptor that maintain significant levels of antimicrobial molecules and therefore provide constant basal protection against micro-organisms. To test theses hypotheses, we generated and analyzed phenotypes associated with a complete loss-of-function allele of Toll-9. Our results suggest that Toll-9 is neither required to maintain a basal anti-microbial response nor to mount an efficient immune response to bacterial infection

Vocal Accuracy and Neural Plasticity Following Micromelody-Discrimination Training

Recent behavioral studies report correlational evidence to suggest that non-musicians with good pitch discrimination sing more accurately than those with poorer auditory skills. However, other studies have reported a dissociation between perceptual and vocal production skills. In order to elucidate the relationship between auditory discrimination skills and vocal accuracy, we administered an auditory-discrimination training paradigm to a group of non-musicians to determine whether training-enhanced auditory discrimination would specifically result in improved vocal accuracy.We utilized micromelodies (i.e., melodies with seven different interval scales, each smaller than a semitone) as the main stimuli for auditory discrimination training and testing, and we used single-note and melodic singing tasks to assess vocal accuracy in two groups of non-musicians (experimental and control). To determine if any training-induced improvements in vocal accuracy would be accompanied by related modulations in cortical activity during singing, the experimental group of non-musicians also performed the singing tasks while undergoing functional magnetic resonance imaging (fMRI). Following training, the experimental group exhibited significant enhancements in micromelody discrimination compared to controls. However, we did not observe a correlated improvement in vocal accuracy during single-note or melodic singing, nor did we detect any training-induced changes in activity within brain regions associated with singing.Given the observations from our auditory training regimen, we therefore conclude that perceptual discrimination training alone is not sufficient to improve vocal accuracy in non-musicians, supporting the suggested dissociation between auditory perception and vocal production