Fundamental nuclear properties of indium isotopes measured with laser spectroscopy

The primary focus of this thesis is the analysis and interpretation of spectroscopic measurements of the neutron-deficient indium isotopes, 101−115In, in order to evaluate the evolution of nuclear structure towards the heaviest self-conjugate doubly-magic nucleus, 100Sn. These measurements were performed at the Collinear Resonance Ionisation Spectroscopy experiment at the ISOLDE facility at CERN. Two laser excitations were separately employed: between the 5s2 5p 2P1/2 and 5s2 8s 2S1/2 atomic states and between the 5s2 5p 2P3/2 and 5s2 9s 2S1/2 states. Both excitations were followed by non-resonant laser ionisation before ion detection. The work resulted in new nuclear-model-independent measurements of magnetic dipole moments, electric quadrupole moments, nuclear spins and changes in mean-squared charge radii. These properties were determined for the first time in three nuclear ground states, 101,102,103In, and in a number of isomeric states. Comparisons to nuclear theory were performed using predictions of the shell model, droplet model and density functional theory. Previous predictions of simple single-particle behaviour in the Iπ = 9/2+ states of the mid-shell indium isotopes are brought further into question by these new results, due to non-zero trends in the measured magnetic dipole moments. Confidence in the 100Sn shell closure is reinforced by newly measured quadrupole moments, confirming the similar strength of N = 82 and N = 50 at Z = 50. Density functional theory calculations predict the moments relatively well, while finite-range droplet model calculations underestimate the quadrupole-deformation parameters

Pilot Open Case Series of Voice over Internet Protocol-Delivered Assessment and Behavior Therapy for Chronic Tic Disorders

Comprehensive Behavioral Intervention for Tics (CBIT) is an efficacious treatment for children with chronic tic disorders (CTDs). Nevertheless, many families of children with CTDs are unable to access CBIT due to a lack of adequately trained treatment providers, time commitment, and travel distance. This study established the interrater reliability between in-person and Voice over Internet Protocol (VoIP) administrations of the Yale Global Tic Severity Scale (YGTSS), and examined the preliminary efficacy, feasibility, and acceptability of VoIP-delivered CBIT for reducing tics in children with CTDs in an open case series. Across in-person and VoIP administrations of the YGTSS, results showed mean agreement of 91%, 96%, and 95% for motor, phonic, and total tic severity subscales. In the pilot feasibility study, 4 children received 8 weekly sessions of CBIT via VoIP and were assessed at pre- and posttreatment by an independent evaluator. Results showed a 29.44% decrease in clinician-rated tic severity from pre- to posttreatment on the YGTSS. Two of the 4 patients were considered treatment responders at posttreatment, using Clinical Global Impressions–Improvement ratings. Therapeutic alliance, parent and child treatment satisfaction, and videoconferencing satisfaction ratings were high. CBIT was considered feasible to implement via VoIP, although further testing is recommended

Identifying Tennessee school-based agricultural education student growth and program accountability metrics

Over the years, accountability in education has transformed from the primary focus being the school as a whole to the individual teacher. The purpose of this study was to determine the metrics Tennessee school-based agricultural education teachers perceive as indicators of excellent total programs (classroom instruction, FFA, SAE), and a modified Delphi study was used to seek a consensus. The following nine metrics were retained: (a) pesticide certification, (b) program of activities, (c) number of students participating in CDEs, (d) chapter community service hours, (e) total number of FFA activities, (f) number of CDEs coached, (g) at least one proficiency at regional level, (h) one American degree every 3 years, and (i) percentage of students with SAE. Overall, the metrics agreed upon are narrow in focus and all but one is a record of activity and not direct measures of students’ knowledge or skills. As a result, the measures do not include student growth or value-added scores or authentic assessments of 21st century skills. Additional research is needed to further investigate the metrics that should be used to measure a school-based agricultural education program’s success in Tennessee and across the nation

Analysis of Germline Variants in CDH1, IGFBP3, MMP1, MMP3, STK15 and VEGF in Familial and Sporadic Renal Cell Carcinoma

BACKGROUND:The investigation of rare familial forms of kidney cancer has provided important insights into the biology of sporadic renal cell carcinoma (RCC). In particular, the identification of the von Hippel Lindau (VHL) familial cancer syndrome gene (VHL) provided the basis for the discovery that VHL is somatically inactivated in most sporadic clear cell RCC. Many cases of familial RCC do not have mutations in known RCC susceptibility genes and there is evidence that genetic modifiers may influence the risk of RCC in VHL disease patients. Hence we hypothesised that low-penetrance functional genetic variants in pathways related to the VHL protein (pVHL) function might (a) modify the phenotypic expression of VHL disease and/or (b) predispose to sporadic RCC. METHODOLOGY/PRINCIPAL FINDINGS:We tested this hypothesis for functional polymorphisms in CDH1 (rs16260), IGFBP3 (rs2854744), MMP1 (rs1799750), MMP3 (rs679620), STK15 (rs2273535) and VEGF (rs1570360). We observed that variants of MMP1 and MMP3 were significant modifiers of RCC risk (and risks of retinal angioma and cerebellar haemangioblastoma) in VHL disease patients. In addition, higher frequencies of the MMP1 rs1799750 2G allele (p = 0.017, OR 1.49, 95%CI 1.06-2.08) and the MMP1/MMP3 rs1799750/rs679620 2G/G haplotype (OR 1.45, 95%CI 1.01-2.10) were detected in sporadic RCC patients than in controls (n = 295). CONCLUSIONS/SIGNIFICANCE:These findings (a) represent the first example of genetic modifiers of RCC risk in VHL disease, (b) replicate a previous report of an association between MMP1/MMP3 variants and sporadic RCC and (c) further implicate MMP1/MMP3-related pathways in the pathogenesis of familial and sporadic RCC

Upstream watershed condition predicts rural children\u27s health across 35 developing countries

Diarrheal disease (DD) due to contaminated water is a major cause of child mortality globally. Forests and wetlands can provide ecosystem services that help maintain water quality. To understand the connections between land cover and childhood DD, we compiled a database of 293,362 children in 35 countries with information on health, socioeconomic factors, climate, and watershed condition. Using hierarchical models, here we find that higher upstream tree cover is associated with lower probability of DD downstream. This effect is significant for rural households but not for urban households, suggesting differing dependence on watershed conditions. In rural areas, the effect of a 30% increase in upstream tree cover is similar to the effect of improved sanitation, but smaller than the effect of improved water source, wealth or education. We conclude that maintaining natural capital within watersheds can be an important public health investment, especially for populations with low levels of built capital

Stability of the CpG island methylator phenotype during glioma progression and identification of methylated loci in secondary glioblastomas

BACKGROUND: Grade IV glioblastomas exist in two forms, primary (de novo) glioblastomas (pGBM) that arise without precursor lesions, and the less common secondary glioblastomas (sGBM) which develop from earlier lower grade lesions. Genetic heterogeneity between pGBM and sGBM has been documented as have differences in the methylation of individual genes. A hypermethylator phenotype in grade IV GBMs is now well documented however there has been little comparison between global methylation profiles of pGBM and sGBM samples or of methylation profiles between paired early and late sGBM samples.METHODS: We performed genome-wide methylation profiling of 20 matched pairs of early and late gliomas using the Infinium HumanMethylation450 BeadChips to assess methylation at &gt;485,000 cytosine positions within the human genome.RESULTS: Clustering of our data demonstrated a frequent hypermethylator phenotype that associated with IDH1 mutation in sGBM tumors. In 80% of cases, the hypermethylator status was retained in both the early and late tumor of the same patient, indicating limited alterations to genome-wide methylation during progression and that the CIMP phenotype is an early event. Analysis of hypermethylated loci identified 218 genes frequently methylated across grade II, III and IV tumors indicating a possible role in sGBM tumorigenesis. Comparison of our sGBM data with TCGA pGBM data indicate that IDH1 mutated GBM samples have very similar hypermethylator phenotypes, however the methylation profiles of the majority of samples with WT IDH1 that do not demonstrate a hypermethylator phenotype cluster separately from sGBM samples, indicating underlying differences in methylation profiles. We also identified 180 genes that were methylated only in sGBM. Further analysis of these genes may lead to a better understanding of the pathology of sGBM vs pGBM.CONCLUSION: This is the first study to have documented genome-wide methylation changes within paired early/late astrocytic gliomas on such a large CpG probe set, revealing a number of genes that maybe relevant to secondary gliomagenesis.</p

A Latent Profile Analysis of Age of Onset in Pathological Skin Picking

Background Pathological Skin Picking (PSP) may begin at any age, but the most common age of onset is during adolescence. Age of onset is a potentially useful clinical marker to delineate subtypes of psychiatric disorders. The present study sought to examine empirically defined age of onset groups in adults with PSP and assess whether groups differed on clinical characteristics. Method Participants were 701 adult respondents to an internet survey, who endorsed recurrent skin picking with tissue damage and impairment. Latent profile analysis (LPA) was conducted to identify subtypes of PSP based on age of onset. Then subgroups were compared on demographic and clinical characteristics. Results The best fitting LPA model was a two-class solution comprised of a large group with average age of onset in adolescence (n = 650; 92.9% of the sample; Mean age of onset = 13.6 years) and a small group with average onset in middle adulthood (n = 50; 7.1% of the sample; Mean age of onset = 42.8 years). Relative to the early onset group, the late onset group reported significantly less focused picking, less skin picking-related impairment, lower rates of co-occurring body-focused repetitive behaviors, and trends towards reduced family history of PSP. Individuals in the late onset group also reported increased rates of comorbid depression, anxiety and posttraumatic stress disorder, and were more likely to report that initial picking onset seemed related to or followed depression/anxiety and physical illness. Conclusion Findings suggest the presence of two distinct PSP age of onset groups: (1) an early onset group with average onset in adolescence, clinical characteristics suggestive of greater picking-related burden and familiality, and a profile more representative of the general PSP population; and (2) a late onset group with average onset in middle adulthood, increased co-occurring affective and trauma conditions, and initial onset associated with or following other mental health and physical problems. Future replication is needed to assess the validity and clinical utility of these subgroups

Characterisation of canine KCNIP4: A novel gene for cerebellar ataxia identified by whole-genome sequencing two affected Norwegian Buhund dogs

Author summary Hereditary ataxias, which are a group of disorders characterised by incoordination of movement, are typically incurable and there are often no disease-modifying treatments available. Canine hereditary ataxias are a notable group of movement disorders in dogs, and represent well characterised naturally occurring disease models of ataxia that can help improve our understanding of the underlying biology of the disorder in both dogs and humans. We used the whole genome sequences of two affected siblings to investigate the genetic cause of a slowly progressive form of hereditary ataxia in the Norwegian Buhund dog breed, and identified a single base change within the KCNIP4 gene. We have characterised the expression of KCNIP4 in the dog, and investigated the effect of the identified mutation. This gene has not previously been implicated in inherited ataxia in any species, and our findings suggest that this and related genes represent potential candidates for ataxia in future studies in other species. Our findings will allow dog breeders to avoid producing affected dogs, reduce the disease allele frequency, and eventually eliminate the disease from the breed, through the use of a DNA test. A form of hereditary cerebellar ataxia has recently been described in the Norwegian Buhund dog breed. This study aimed to identify the genetic cause of the disease. Whole-genome sequencing of two Norwegian Buhund siblings diagnosed with progressive cerebellar ataxia was carried out, and sequences compared with 405 whole genome sequences of dogs of other breeds to filter benign common variants. Nine variants predicted to be deleterious segregated among the genomes in concordance with an autosomal recessive mode of inheritance, only one of which segregated within the breed when genotyped in additional Norwegian Buhunds. In total this variant was assessed in 802 whole genome sequences, and genotyped in an additional 505 unaffected dogs (including 146 Buhunds), and only four affected Norwegian Buhunds were homozygous for the variant. The variant identified, a T to C single nucleotide polymorphism (SNP) (NC_006585.3:g.88890674T>C), is predicted to cause a tryptophan to arginine substitution in a highly conserved region of the potassium voltage-gated channel interacting protein KCNIP4. This gene has not been implicated previously in hereditary ataxia in any species. Evaluation of KCNIP4 protein expression through western blot and immunohistochemical analysis using cerebellum tissue of affected and control dogs demonstrated that the mutation causes a dramatic reduction of KCNIP4 protein expression. The expression of alternative KCNIP4 transcripts within the canine cerebellum, and regional differences in KCNIP4 protein expression, were characterised through RT-PCR and immunohistochemistry respectively. The voltage-gated potassium channel protein KCND3 has previously been implicated in spinocerebellar ataxia, and our findings suggest that the Kv4 channel complex KCNIP accessory subunits also have an essential role in voltage-gated potassium channel function in the cerebellum and should be investigated as potential candidate genes for cerebellar ataxia in future studies in other species.Peer reviewe