Against the Odds: Psychomotor Development of Children Under 2 years in a Sudanese Orphanage.

Providing abandoned children the necessary medical and psychological care as possible after their institutionalization may minimize developmental delays. We describe psychomotor development in infants admitted to an orphanage in Khartoum, Sudan, assessed at admission and over an 18-month follow-up. Psychological state and psychomotor quotients were determined using a simplified Neonatal Behavior Assessment Scale (NBAS), the Brunet-Lezine and Alarm distress baby (ADBB) scale. From May-September 2005, 151 children were evaluated 2, 4, 9, 12 and 18 months after inclusion. At admission, ∼15% of children ≤1 month had a regulation impairment according to the NBAS, and 33.8% presented a distress state (ADBB score >5). More than 85% (129/151) recovered normal psychomotor development. The results of the program reinforce the importance of early detection of psychological disorders followed by rapid implementation of psychological case management to improve the development of young children in similar institutions and circumstances

Automating Event-B invariant proofs by rippling and proof patching

This work is supported by EPSRC grants EP/H024204/1, EP/E005713/1, EP/M018407/1 and EP/J001058/1.The use of formal method techniques can contribute to the production of more reliable and dependable systems. However, a common bottleneck for industrial adoption of such techniques is the needs for interactive proofs. We use a popular formal method, called Event-B, as our working domain, and set invariant preservation (INV) proofs as targets, because INV proofs can account for a significant proportion of the proofs requiring human interactions. We apply an inductive theorem proving technique, called rippling, for Event-B INV proofs. Rippling automates proofs using meta-level guidance. The guidance is in particular useful to develop proof patches to recover failed proof attempts. We are interested in the case when a missing lemma is required. We combine a scheme-based theory-exploration system, called IsaScheme [MRMDB10], with rippling to develop a proof patch via lemma discovery. We also develop two new proof patches to unfold operator definitions and to suggest case-splits, respectively. The combined use of rippling with these three proof patches as a proof method significantly improves the proof automation for our evaluation set.Publisher PDFPeer reviewe

The effect of surface conductance on lateral gated quantum devices in Si/SiGe heterostructures

Quantum dots in Si/SiGe heterostructures are expected to have relatively long electron spin decoherence times, because of the low density of nuclear spins and the weak coupling between nuclear and electron spins. We provide experimental evidence suggesting that electron motion in a conductive layer parallel to the two-dimensional electron gas, possibly resulting from the donors used to dope the Si quantum well, is responsible for the well-known difficulty in achieving well-controlled dots in this system. Charge motion in the conductive layer can cause depletion on large length scales, making electron confinement in the dot impossible, and can give rise to noise that can overwhelm the single-electron charging signal. Results of capacitance versus gate bias measurements to characterize this conductive layer are presented.National Science Foundation (U.S.) ((PHY-0117795)National Science Foundation (U.S.) (DMR-0701386

MicroRNA-143 activation regulates smooth muscle and endothelial cell crosstalk in pulmonary arterial hypertension

Rationale: The pathogenesis of PAH remains unclear. The four microRNAs representing the miR-143 and miR-145 stem loops are genomically clustered. Objective: To elucidate the transcriptional regulation of the miR-143/145 cluster, and the role of miR-143 in PAH. Methods and Results: We identified the promoter region that regulates miR-143/145 miRNA expression in pulmonary artery smooth muscle cells (PASMCs). We mapped PAH-related signalling pathways, including estrogens receptor (ER), liver X factor/retinoic X receptor (LXR/RXR), TGF-β (Smads), and hypoxia (HRE) that regulated levels of all pri-miR stem loop transcription and resulting miRNA expression. We observed that miR-143-3p is selectively upregulated compared to miR-143-5p during PASMC migration. Modulation of miR-143 in PASMCs significantly altered cell migration and apoptosis. In addition, we found high abundance of miR-143-3p in PASMCs-derived exosomes. Using assays with pulmonary arterial endothelial cells (PAECs) we demonstrated a paracrine pro-migratory and pro-angiogenic effect of miR-143-3p enriched exosomes from PASMC. Quantitative PCR and in situ hybridisation showed elevated expression of miR-143 in calf models of PAH as well as in samples from PAH patients. Moreover, in contrast to our previous findings that had not supported a therapeutic role in vivo, we now demonstrate a protective role for miR-143 in experimental PH in vivo in miR-143-/- and antimiR143-3p-treated mice exposed to chronic hypoxia in both preventative and reversal settings. Conclusions: MiR-143-3p modulated both cellular and exosome-mediated responses in pulmonary vascular cells, while inhibition of miR-143-3p blocked experimental PH. Taken together these findings confirm an important role for the miR-143/145 cluster in PAH pathobiology

Solar Particle Acceleration at Reconnecting 3D Null Points

Context: The strong electric fields associated with magnetic reconnection in solar flares are a plausible mechanism to accelerate populations of high energy, non-thermal particles. One such reconnection scenario occurs at a 3D magnetic null point, where global plasma flows give rise to strong currents in the spine axis or fan plane. Aims: To understand the mechanism of charged particle energy gain in both the external drift region and the diffusion region associated with 3D magnetic reconnection. In doing so we evaluate the efficiency of resistive spine and fan models for particle acceleration, and find possible observables for each. Method: We use a full orbit test particle approach to study proton trajectories within electromagnetic fields that are exact solutions to the steady and incompressible magnetohydrodynamic equations. We study single particle trajectories and find energy spectra from many particle simulations. The scaling properties of the accelerated particles with respect to field and plasma parameters is investigated. Results: For fan reconnection, strong non-uniform electric drift streamlines can accelerate the bulk of the test particles. The highest energy gain is for particles that enter the current sheet, where an increasing "guide field" stabilises particles against ejection. The energy is only limited by the total electric potential energy difference across the fan current sheet. The spine model has both slow external electric drift speed and weak energy gain for particles reaching the current sheet. Conclusions: The electromagnetic fields of fan reconnection can accelerate protons to the high energies observed in solar flares, gaining up to 0.1 GeV for anomalous values of resistivity. However, the spine model, which gave a harder energy spectrum in the ideal case, is not an efficient accelerator after pressure constraints in the resistive model are included.Comment: 15 pages, 14 figures. Submitted to Astronomy and Astrophysic

The validation of a computer-based food record for older adults: the Novel Assessment of Nutrition and Ageing (NANA) method

Dietary assessment in older adults can be challenging. The Novel Assessment of Nutrition and Ageing (NANA) method is a touch-screen computer-based food record that enables older adults to record their dietary intakes. The objective of the present study was to assess the relative validity of the NANA method for dietary assessment in older adults. For this purpose, three studies were conducted in which a total of ninety-four older adults (aged 65–89 years) used the NANA method of dietary assessment. On a separate occasion, participants completed a 4 d estimated food diary. Blood and 24 h urine samples were also collected from seventy-six of the volunteers for the analysis of biomarkers of nutrient intake. The results from all the three studies were combined, and nutrient intake data collected using the NANA method were compared against the 4 d estimated food diary and biomarkers of nutrient intake. Bland–Altman analysis showed a reasonable agreement between the dietary assessment methods for energy and macronutrient intake; however, there were small, but significant, differences for energy and protein intake, reflecting the tendency for the NANA method to record marginally lower energy intakes. Significant positive correlations were observed between urinary urea and dietary protein intake using both the NANA and the 4 d estimated food diary methods, and between plasma ascorbic acid and dietary vitamin C intake using the NANA method. The results demonstrate the feasibility of computer-based dietary assessment in older adults, and suggest that the NANA method is comparable to the 4 d estimated food diary, and could be used as an alternative to the food diary for the short-term assessment of an individual’s dietary intake

Proteome Profiling of Breast Tumors by Gel Electrophoresis and Nanoscale Electrospray Ionization Mass Spectrometry

We have conducted proteome-wide analysis of fresh surgery specimens derived from breast cancer patients, using an approach that integrates size-based intact protein fractionation, nanoscale liquid separation of peptides, electrospray ion trap mass spectrometry, and bioinformatics. Through this approach, we have acquired a large amount of peptide fragmentation spectra from size-resolved fractions of the proteomes of several breast tumors, tissue peripheral to the tumor, and samples from patients undergoing noncancer surgery. Label-free quantitation was used to generate protein abundance maps for each proteome and perform comparative analyses. The mass spectrometry data revealed distinct qualitative and quantitative patterns distinguishing the tumors from healthy tissue as well as differences between metastatic and non-metastatic human breast cancers including many established and potential novel candidate protein biomarkers. Selected proteins were evaluated by Western blotting using tumors grouped according to histological grade, size, and receptor expression but differing in nodal status. Immunohistochemical analysis of a wide panel of breast tumors was conducted to assess expression in different types of breast cancers and the cellular distribution of the candidate proteins. These experiments provided further insights and an independent validation of the data obtained by mass spectrometry and revealed the potential of this approach for establishing multimodal markers for early metastasis, therapy outcomes, prognosis, and diagnosis in the future. © 2008 American Chemical Society

Genetic variation at MECOM, TERT, JAK2 and HBS1L-MYB predisposes to myeloproliferative neoplasms

Clonal proliferation in myeloproliferative neoplasms (MPN) is driven by somatic mutations in JAK2, CALR or MPL, but the contribution of inherited factors is poorly characterized. Using a three-stage genome-wide association study of 3,437 MPN cases and 10,083 controls, we identify two SNPs with genome-wide significance in JAK2V617F-negative MPN: rs12339666 (JAK2; meta-analysis P=1.27 × 10−10) and rs2201862 (MECOM; meta-analysis P=1.96 × 10−9). Two additional SNPs, rs2736100 (TERT) and rs9376092 (HBS1L/MYB), achieve genome-wide significance when including JAK2V617F-positive cases. rs9376092 has a stronger effect in JAK2V617F-negative cases with CALR and/or MPL mutations (Breslow–Day P=4.5 × 10−7), whereas in JAK2V617F-positive cases rs9376092 associates with essential thrombocythemia (ET) rather than polycythemia vera (allelic χ2 P=7.3 × 10−7). Reduced MYB expression, previously linked to development of an ET-like disease in model systems, associates with rs9376092 in normal myeloid cells. These findings demonstrate that multiple germline variants predispose to MPN and link constitutional differences in MYB expression to disease phenotype

Atomistic dynamics of sulfur-deficient high-symmetry grain boundaries in molybdenum disulfide

As a common type of structural defect, grain boundaries (GBs) play an important role in tailoring the physical and chemical properties of bulk crystals and their two-dimensional (2D) counterparts such as graphene and molybdenum disulfide (MoS2). In this study, we explore the atomic structures and dynamics of three kinds of high-symmetry GBs (α, β and γ) in monolayer MoS2. Atomic-resolution transmission electron microscopy (TEM) is used to characterize their formation and evolutionary dynamics, and atomistic simulation based analysis explains the size distribution of α-type GBs observed under TEM and the inter-GB interaction, revealing the stabilization mechanism of GBs by pre-existing sulfur vacancies. The results elucidate the correlation between the observed GB dynamics and the migration of sulfur atoms across GBs via a vacancy-mediated mechanism, offering a new perspective for GB engineering in monolayer MoS2, which may be generalized to other transition metal dichalcogenides