The uneven profile of memory development in Down Syndrome

This thesis explores memory development in children with Down syndrome (DS) between aged 3 years and 9 months and 14 years and 5 months (N=43). While memory has been extensively explored in older individuals with DS, relatively little work has considered the development of memory in childhood in DS, in part due to the difficulty of assessing memory in individuals with lower levels of ability. The project was innovative in applying a mixture of original and pre-existing tasks to this population, in order to characterise a wide range of memory abilities at varying levels of cognitive demand. These abilities were initially compared between those with DS and typically developing individuals by age group, early childhood (3 years 9 months to 8 years 4 months) and late childhood (9 years 9 months to 14 years 5 months). Standardised tasks were used to produce mental-age equivalents and raw scores for verbal and non-verbal memory abilities (BPVS, BAS II pattern construction). Study 1 examined object and object-in-place recognition using eye-tracking, using a low demand methodology that excluded few participants. Study 2 examined verbal working and long-term memory abilities overall, as well as learning and forgetting rates. Primacy, recency and mid-list recall rates were also analysed to shed light on strategies of encoding. Study 3 examined spatial working and long-term memory abilities, as well as forgetting rates. Study 4 examined multimodal associative immediate and delayed memory, using a spatialauditory associative eye-tracking paradigm. Study 5 examined the relationships between sustained attention, inhibition, and sleep behaviour measures, as these faculties are implicated in the development of memory abilities. Finally, in Study 6, cross-sectional developmental trajectories were constructed for all memory measures to ascertain if base levels or gradients of change significantly differed, either with respect to chronological age or domain-relevant mental age measures, in comparison to a sample of typically developing children. Overall, the project charted the emergence of an uneven profile of memory abilities across childhood in DS

The uneven profile of memory development in Down Syndrome

This thesis explores memory development in children with Down syndrome (DS) between aged 3 years and 9 months and 14 years and 5 months (N=43). While memory has been extensively explored in older individuals with DS, relatively little work has considered the development of memory in childhood in DS, in part due to the difficulty of assessing memory in individuals with lower levels of ability. The project was innovative in applying a mixture of original and pre-existing tasks to this population, in order to characterise a wide range of memory abilities at varying levels of cognitive demand. These abilities were initially compared between those with DS and typically developing individuals by age group, early childhood (3 years 9 months to 8 years 4 months) and late childhood (9 years 9 months to 14 years 5 months). Standardised tasks were used to produce mental-age equivalents and raw scores for verbal and non-verbal memory abilities (BPVS, BAS II pattern construction). Study 1 examined object and object-in-place recognition using eye-tracking, using a low demand methodology that excluded few participants. Study 2 examined verbal working and long-term memory abilities overall, as well as learning and forgetting rates. Primacy, recency and mid-list recall rates were also analysed to shed light on strategies of encoding. Study 3 examined spatial working and long-term memory abilities, as well as forgetting rates. Study 4 examined multimodal associative immediate and delayed memory, using a spatialauditory associative eye-tracking paradigm. Study 5 examined the relationships between sustained attention, inhibition, and sleep behaviour measures, as these faculties are implicated in the development of memory abilities. Finally, in Study 6, cross-sectional developmental trajectories were constructed for all memory measures to ascertain if base levels or gradients of change significantly differed, either with respect to chronological age or domain-relevant mental age measures, in comparison to a sample of typically developing children. Overall, the project charted the emergence of an uneven profile of memory abilities across childhood in DS

A general scaling relation for the critical current density in Nb3Sn

We review the scaling relations for the critical current density (Jc) in Nb3Sn wires and include recent findings on the variation of the upper critical field (Hc2) with temperature (T) and A15 composition. We highlight deficiencies in the Summers/Ekin relations, which are not able to account for the correct Jc(T) dependence. Available Jc(H) results indicate that the magnetic field dependence for all wires can be described with Kramer's flux shear model, if non-linearities in Kramer plots are attributed to A15 inhomogeneities. The strain (eps) dependence is introduced through a temperature and strain dependent Hc2*(T,eps) and Ginzburg- Landau parameter kappa1(T,eps) and a strain dependent critical temperature Tc(eps). This is more consistent than the usual Ekin unification, which uses two separate and different dependencies on Hc2*(T) and Hc2*(eps). Using a correct temperature dependence and accounting for the A15 inhomogeneities leads to a remarkable simple relation for Jc(H,T,eps). Finally, a new relation for s(eps) is proposed, based on the first, second and third strain invariants.Comment: Accepted Topical Review for Superconductor, Science and Technolog

Human candidate gene polymorphisms and risk of severe malaria in children in Kilifi, Kenya: a case-control association study

Background: Human genetic factors are important determinants of malaria risk. We investigated associations between multiple candidate polymorphisms—many related to the structure or function of red blood cells—and risk for severe Plasmodium falciparum malaria and its specific phenotypes, including cerebral malaria, severe malaria anaemia, and respiratory distress. Methods: We did a case-control study in Kilifi County, Kenya. We recruited as cases children presenting with severe malaria to the high-dependency ward of Kilifi County Hospital. We included as controls infants born in the local community between Aug 1, 2006, and Sept 30, 2010, who were part of a genetics study. We tested for associations between a range of candidate malaria-protective genes and risk for severe malaria and its specific phenotypes. We used a permutation approach to account for multiple comparisons between polymorphisms and severe malaria. We judged p values less than 0·005 significant for the primary analysis of the association between candidate genes and severe malaria. Findings: Between June 11, 1995, and June 12, 2008, 2244 children with severe malaria were recruited to the study, and 3949 infants were included as controls. Overall, 263 (12%) of 2244 children with severe malaria died in hospital, including 196 (16%) of 1233 with cerebral malaria. We investigated 121 polymorphisms in 70 candidate severe malaria-associated genes. We found significant associations between risk for severe malaria overall and polymorphisms in 15 genes or locations, of which most were related to red blood cells: ABO, ATP2B4, ARL14, CD40LG, FREM3, INPP4B, G6PD, HBA (both HBA1 and HBA2), HBB, IL10, LPHN2 (also known as ADGRL2), LOC727982, RPS6KL1, CAND1, and GNAS. Combined, these genetic associations accounted for 5·2% of the variance in risk for developing severe malaria among individuals in the general population. We confirmed established associations between severe malaria and sickle-cell trait (odds ratio [OR] 0·15, 95% CI 0·11–0·20; p=2·61 × 10−58), blood group O (0·74, 0·66–0·82; p=6·26 × 10−8), and –α3·7-thalassaemia (0·83, 0·76–0·90; p=2·06 × 10−6). We also found strong associations between overall risk of severe malaria and polymorphisms in both ATP2B4 (OR 0·76, 95% CI 0·63–0·92; p=0·001) and FREM3 (0·64, 0·53–0·79; p=3·18 × 10−14). The association with FREM3 could be accounted for by linkage disequilibrium with a complex structural mutation within the glycophorin gene region (comprising GYPA, GYPB, and GYPE) that encodes for the rare Dantu blood group antigen. Heterozygosity for Dantu was associated with risk for severe malaria (OR 0·57, 95% CI 0·49–0·68; p=3·22 × 10−11), as was homozygosity (0·26, 0·11–0·62; p=0·002). Interpretation: Both ATP2B4 and the Dantu blood group antigen are associated with the structure and function of red blood cells. ATP2B4 codes for plasma membrane calcium-transporting ATPase 4 (the major calcium pump on red blood cells) and the glycophorins are ligands for parasites to invade red blood cells. Future work should aim at uncovering the mechanisms by which these polymorphisms can result in severe malaria protection and investigate the implications of these associations for wider health. Funding: Wellcome Trust, UK Medical Research Council, European Union, and Foundation for the National Institutes of Health as part of the Bill & Melinda Gates Grand Challenges in Global Health Initiative

Effectiveness of nurse-led volunteer support and technology-driven pain assessment in improving the outcomes of hospitalised older adults: Protocol for a cluster randomised controlled trial

INTRODUCTION: Hospitalised older adults are prone to functional deterioration, which is more evident in frail older patients and can be further exacerbated by pain. Two interventions that have the potential to prevent progression of frailty and improve patient outcomes in hospitalised older adults but have yet to be subject to clinical trials are nurse-led volunteer support and technology-driven assessment of pain. METHODS AND ANALYSIS: This single-centre, prospective, non-blinded, cluster randomised controlled trial will compare the efficacy of nurse-led volunteer support, technology-driven pain assessment and the combination of the two interventions to usual care for hospitalised older adults. Prior to commencing recruitment, the intervention and control conditions will be randomised across four wards. Recruitment will continue for 12 months. Data will be collected on admission, at discharge and at 30 days post discharge, with additional data collected during hospitalisation comprising records of pain assessment and volunteer support activity. The primary outcome of this study will be the change in frailty between both admission and discharge, and admission and 30 days, and secondary outcomes include length of stay, adverse events, discharge destination, quality of life, depression, cognitive function, functional independence, pain scores, pain management intervention (type and frequency) and unplanned 30-day readmissions. Stakeholder evaluation and an economic analysis of the interventions will also be conducted. ETHICS AND DISSEMINATION: Ethical approval has been granted by Human Research Ethics Committees at Ramsay Health Care WA|SA (number: 2057) and Edith Cowan University (number: 2021-02210-SAUNDERS). The findings will be disseminated through conference presentations, peer-reviewed publications and social media. TRIAL REGISTRATION NUMBER: ACTRN12620001173987

Single hadron response measurement and calorimeter jet energy scale uncertainty with the ATLAS detector at the LHC

The uncertainty on the calorimeter energy response to jets of particles is derived for the ATLAS experiment at the Large Hadron Collider (LHC). First, the calorimeter response to single isolated charged hadrons is measured and compared to the Monte Carlo simulation using proton-proton collisions at centre-of-mass energies of sqrt(s) = 900 GeV and 7 TeV collected during 2009 and 2010. Then, using the decay of K_s and Lambda particles, the calorimeter response to specific types of particles (positively and negatively charged pions, protons, and anti-protons) is measured and compared to the Monte Carlo predictions. Finally, the jet energy scale uncertainty is determined by propagating the response uncertainty for single charged and neutral particles to jets. The response uncertainty is 2-5% for central isolated hadrons and 1-3% for the final calorimeter jet energy scale.Comment: 24 pages plus author list (36 pages total), 23 figures, 1 table, submitted to European Physical Journal

Standalone vertex finding in the ATLAS muon spectrometer

A dedicated reconstruction algorithm to find decay vertices in the ATLAS muon spectrometer is presented. The algorithm searches the region just upstream of or inside the muon spectrometer volume for multi-particle vertices that originate from the decay of particles with long decay paths. The performance of the algorithm is evaluated using both a sample of simulated Higgs boson events, in which the Higgs boson decays to long-lived neutral particles that in turn decay to bbar b final states, and pp collision data at √s = 7 TeV collected with the ATLAS detector at the LHC during 2011

Measurements of Higgs boson production and couplings in diboson final states with the ATLAS detector at the LHC

Measurements are presented of production properties and couplings of the recently discovered Higgs boson using the decays into boson pairs, H →γ γ, H → Z Z∗ →4l and H →W W∗ →lνlν. The results are based on the complete pp collision data sample recorded by the ATLAS experiment at the CERN Large Hadron Collider at centre-of-mass energies of √s = 7 TeV and √s = 8 TeV, corresponding to an integrated luminosity of about 25 fb−1. Evidence for Higgs boson production through vector-boson fusion is reported. Results of combined fits probing Higgs boson couplings to fermions and bosons, as well as anomalous contributions to loop-induced production and decay modes, are presented. All measurements are consistent with expectations for the Standard Model Higgs boson

Measurements of fiducial and differential cross sections for Higgs boson production in the diphoton decay channel at s√=8 TeV with ATLAS

Measurements of fiducial and differential cross sections are presented for Higgs boson production in proton-proton collisions at a centre-of-mass energy of s√=8 TeV. The analysis is performed in the H → γγ decay channel using 20.3 fb−1 of data recorded by the ATLAS experiment at the CERN Large Hadron Collider. The signal is extracted using a fit to the diphoton invariant mass spectrum assuming that the width of the resonance is much smaller than the experimental resolution. The signal yields are corrected for the effects of detector inefficiency and resolution. The pp → H → γγ fiducial cross section is measured to be 43.2 ±9.4(stat.) − 2.9 + 3.2 (syst.) ±1.2(lumi)fb for a Higgs boson of mass 125.4GeV decaying to two isolated photons that have transverse momentum greater than 35% and 25% of the diphoton invariant mass and each with absolute pseudorapidity less than 2.37. Four additional fiducial cross sections and two cross-section limits are presented in phase space regions that test the theoretical modelling of different Higgs boson production mechanisms, or are sensitive to physics beyond the Standard Model. Differential cross sections are also presented, as a function of variables related to the diphoton kinematics and the jet activity produced in the Higgs boson events. The observed spectra are statistically limited but broadly in line with the theoretical expectations

Measurement of the top quark pair cross section with ATLAS in pp collisions at √s=7 TeV using final states with an electron or a muon and a hadronically decaying τ lepton

A measurement of the cross section of top quark pair production in proton-proton collisions recorded with the ATLAS detector at the Large Hadron Collider at a centre-of-mass energy of 7 TeV is reported. The data sample used corresponds to an integrated luminosity of 2.05 fb -1. Events with an isolated electron or muon and a τ lepton decaying hadronically are used. In addition, a large missing transverse momentum and two or more energetic jets are required. At least one of the jets must be identified as originating from a b quark. The measured cross section, σtt-=186±13(stat.)±20(syst.)±7(lumi.) pb, is in good agreement with the Standard Model prediction