Autosomal recessive primary microcephaly: an analysis of locus heterogeneity and phenotypic variation

BACKGROUND AND OBJECTIVES: Locus heterogeneity is well established in autosomal recessive primary microcephaly (MCPH) and to date five loci have been mapped. However, the relative contributions of these loci have not been assessed and genotype-phenotype correlations have not been investigated. DESIGN: A study population of 56 consanguineous families resident in or originating from northern Pakistan was ascertained and assessed by the authors. A panel of microsatellite markers spanning each of the MCPH loci was designed, against which the families were genotyped. RESULTS: The head circumference of the 131 affected subjects ranged from 4 to 14 SD below the mean, but there was little intrafamilial variation among affecteds (± 1 SD). MCPH5 was the most prevalent, with 24/56 families consistent with linkage; 2/56 families were compatible with linkage to MCPH1, 10/56 to MCPH2, 2/56 to MCPH3, none to MCPH4, and 18/56 did not segregate with any of the loci. CONCLUSIONS: MCPH5 is the most common locus in this population. On clinical grounds alone, the phenotype of families linked to each MCPH locus could not be distinguished. We have also shown that further MCPH loci await discovery with a number of families as yet unlinked

Length of hospital stay prior to ICU admission and outcome

No abstract available

Core pinning by intragranular nanoprecipitates in polycrystalline MgCNi_3

The nanostructure and magnetic properties of polycrystalline MgCNi_3 were studied by x-ray diffraction, electron microscopy, and vibrating sample magnetometry. While the bulk flux-pinning force curve F_p(H) indicates the expected grain-boundary pinning mechanism just below T_c = 7.2 K, a systematic change to pinning by a nanometer-scale distribution of core pinning sites is indicated by a shift of F_p(H) with decreasing temperature. The lack of scaling of F_p(H) suggests the presence of 10 to 20% of nonsuperconducting regions inside the grains, which are smaller than the diameter of fluxon cores 2xi at high temperature and become effective with decreasing temperature when xi(T) approaches the nanostructural scale. Transmission electron microscopy revealed cubic and graphite nanoprecipitates with 2 to 5 nm size, consistent with the above hypothesis since xi(0) = 6 nm. High critical current densities, more than 10^6 A/cm^2 at 1 T and 4.2 K, were obtained for grain colonies separated by carbon. Dirty-limit behavior seen in previous studies may be tied to electron scattering by the precipitates, indicating the possibility that strong core pinning might be combined with a technologically useful upper critical field if versions of MgCNi_3 with higher T_c can be found.Comment: 5 pages, 6 figures, submitted to PR

Turning round the telescope. Centre-right parties and immigration and integration policy in Europe

This is an Author's Original Manuscript of 'Turning round the telescope. Centre-right parties and immigration and integration policy in Europe', whose final and definitive form, the Version of Record, has been published in the Journal of European Public Policy 15(3):315-330, 2008 [copyright Taylor & Francis], available online at: http://www.tandfonline.com/doi.org/10.1080/13501760701847341

Nonprofit governance: Improving performance in troubled economic times

Nonprofit management is currently pressured to perform effectively in a weak economy. Yet, nonprofit governance continues to suffer from unclear conceptions of the division of labor between board of directors and executive directors. This online survey of 114 executive directors aims to provide clarification and recommendations for social administration

Microstructure and Mechanical Properties of the in situ Β-Si 3 N 4 /Α′-SiAlON Composite

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65911/1/j.1151-2916.1994.tb04604.x.pd

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

"I couldn't do this with opposition from my colleagues": A qualitative study of physicians' experiences as clinical tutors

<p>Abstract</p> <p>Background</p> <p>Clinical contact in the early curriculum and workplace learning with active tutorship are important parts of modern medical education. In a previously published study, we found that medical students' tutors experienced a heavier workload, less reasonable demands and less encouragement, than students. The aim of this interview study was to further illuminate physicians' experiences as clinical tutors.</p> <p>Methods</p> <p>Twelve tutors in the Early Professional Contact course were interviewed. In the explorative interviews, they were asked to reflect upon their experiences of working as tutors in this course. Systematic text condensation was used as the analysis method.</p> <p>Results</p> <p>In the analysis, five main themes of physicians' experiences as clinical tutors in the medical education emerged: <it>(a) Pleasure and stimulation</it>. Informants appreciated tutorship and meeting both students and fellow tutors, <it>(b) Disappointment and stagnation</it>. Occasionally, tutors were frustrated and expressed negative feelings, <it>(c) Demands and duty</it>. Informants articulated an ambition to give students their best; a desire to provide better medical education but also a duty to meet demands of the course management, <it>(d) Impact of workplace relations</it>. Tutoring was made easier when the clinic's management provided active support and colleagues accepted students at the clinic, and <it>(e) Multitasking difficulties</it>. Combining several duties with those of a tutorship was often reported as difficult.</p> <p>Conclusions</p> <p>It is important that tutors' tasks are given adequate time, support and preparation. Accordingly, it appears highly important to avoid multitasking and too heavy a workload among tutors in order to facilitate tutoring. A crucial factor is acceptance and active organizational support from the clinic's management. This implies that tutoring by workplace learning in medical education should play an integrated and accepted role in the healthcare system.</p

Computerised cognitive assessment in patients with traumatic brain injury: an observational study of feasibility and sensitivity relative to established clinical scales

Background: Online technology could potentially revolutionise how patients are cognitively assessed and monitored. However, it remains unclear whether assessments conducted remotely can match established pen-and-paper neuropsychological tests in terms of sensitivity and specificity. Methods: This observational study aimed to optimise an online cognitive assessment for use in traumatic brain injury (TBI) clinics. The tertiary referral clinic in which this tool has been clinically implemented typically sees patients a minimum of 6 months post-injury in the chronic phase. Between March and August 2019, we conducted a cross-group, cross-device and factor analyses at the St. Mary's Hospital TBI clinic and major trauma wards at Imperial College NHS trust and St. George's Hospital in London (UK), to identify a battery of tasks that assess aspects of cognition affected by TBI. Between September 2019 and February 2020, we evaluated the online battery against standard face-to-face neuropsychological tests at the Imperial College London research centre. Canonical Correlation Analysis (CCA) determined the shared variance between the online battery and standard neuropsychological tests. Finally, between October 2020 and December 2021, the tests were integrated into a framework that automatically generates a results report where patients’ performance is compared to a large normative dataset. We piloted this as a practical tool to be used under supervised and unsupervised conditions at the St. Mary's Hospital TBI clinic in London (UK). Findings: The online assessment discriminated processing-speed, visual-attention, working-memory, and executive-function deficits in TBI. CCA identified two significant modes indicating shared variance with standard neuropsychological tests (r = 0.86, p < 0.001 and r = 0.81, p = 0.02). Sensitivity to cognitive deficits after TBI was evident in the TBI clinic setting under supervised and unsupervised conditions (F (15,555) = 3.99; p < 0.001). Interpretation: Online cognitive assessment of TBI patients is feasible, sensitive, and efficient. When combined with normative sociodemographic models and autogenerated reports, it has the potential to transform cognitive assessment in the healthcare setting. Funding: This work was funded by a National Institute for Health Research (NIHR) Invention for Innovation (i4i) grant awarded to DJS and AH ( II-LB-0715-20006)

The Cause of ‘Weak-Link’ Grain Boundary Behaviour in Polycrystalline Bi2Sr2CaCu2O8 and Bi2Sr2Ca2Cu3O10 Superconductors

The detrimental effects of grain boundaries have long been considered responsible for the low critical current densities (J_c) in high temperature superconductors. In this paper, we apply the quantitative approach used to identify the cause of the 'weak-link' grain boundary behaviour in YBa2Cu3O7 [1], to the Bi2Sr2CaCu2O8 and Bi2Sr2Ca2Cu3O10 materials that we have fabricated. Magnetic and transport measurements are used to characterise the grain and grain boundary properties of micro- and nanocrystalline material. Magnetisation measurements on all nanocrystalline materials show non-Bean-like behaviour and are consistent with surface pinning. Bi2Sr2CaCu2O8: Our microcrystalline material has very low grain boundary resistivity (ρ_GB), which is similar to that of the grains (ρ_G) such that ρ_GB≈ρ_G=2×〖10〗^(-5) Ωm (assuming a grain boundary thickness (d) of 1 nm) equivalent to an areal resistivity of ρ_G=2×〖10〗^(-14) Ωm^2. The transport J_c values are consistent with well-connected grains and very weak grain boundary pinning. However, unlike low temperature superconductors in which decreasing grain size increases the pinning along the grain boundary channels, any increase in pinning produced by making the grains in our Bi2Sr2CaCu2O8 materials nanocrystalline was completely offset by a decrease in the depairing current density of the grain boundaries caused by their high resistivity. We suggest a different approach to increasing J_c from that used in LTS materials, namely incorporating additional strong grain and grain boundary pinning sites in microcrystalline materials to produce high J_c values. Bi2Sr2Ca2Cu3O10: Both our micro- and nanocrystalline samples have ρ_GB/ρ_G of at least 10^3. This causes strong suppression of J_c across the grain boundaries, which explains the low transport J_c values we find experimentally. Our calculations show that low J_c in untextured polycrystalline Bi2Sr2Ca2Cu3O10 material is to be expected and the significant effort in the community in texturing samples and removing grain boundaries altogether is well-founded