Magnetar-like X-ray Bursts from an Anomalous X-ray Pulsar

Anomalous X-ray Pulsars (AXPs) are a class of rare X-ray pulsars whose energy source has been perplexing for some 20 years. Unlike other, better understood X-ray pulsars, AXPs cannot be powered by rotation or by accretion from a binary companion, hence the designation ``anomalous.'' AXP rotational and radiative properties are strikingly similar to those of another class of exotic objects, the Soft Gamma Repeaters (SGRs). However, the defining property of SGRs, namely their low-energy gamma-ray and X-ray bursts, have heretofore not been seen in AXPs. SGRs are thought to be ``magnetars,'' young neutron stars powered by the decay of an ultra-high magnetic field. The suggestion that AXPs are magnetars has been controversial. Here we report the discovery, from the direction of AXP 1E 1048-5937, of two X-ray bursts that have many properties similar to those of SGR bursts. These events imply a close relationship between AXPs and SGRs, with both being magnetars.Comment: 14 pages, 2 figures, accepted for publication in Nature. Note: The content of this paper is embargoed until 1900 hrs London time / 1400 US Eastern Time on Sept 1

Quantitative SPECT/CT parameters of myocardial 99mTechnetium-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) uptake in suspected cardiac transthyretin amyloidosis

Background: 99mTc-labelled bisphosphonates are used for imaging assessment of patients with transthyretin cardiac amyloidosis (ATTR). Present study evaluates whether quantitative SPECT/CT measurement of absolute myocardial 99mTc-labelled 3,3-diphosphono-1,2-propanodicarboxylic acid (Tc-DPD) uptake can diagnose patients with suspected ATTR. / Methods: Twenty-eight patients (25 male, age 80.03 ± 6.99 years) with suspected ATTR referred for Tc-DPD imaging had planar and SPECT/CT imaging of the chest. Three operators independently obtained Tc-DPD myocardial SUVmax and SUVmean above threshold (SMaT) (20, 40 and 60% of SUVmax), using a semi-automated threshold segmentation method. Results were compared to visual grading (0–3) of cardiac uptake. / Results: Twenty-two patients (78%) had cardiac uptake (2 grade 1, 15 grade 2, 5 grade 3). SUVmax and SMaT segmentation thresholds enabled separating grades 2/3 from 0/1 with excellent inter- and intra-reader correlation. Cut-off values 6.0, 2.5, 3 and 4 for SUVmax, SMaT20,40,60, respectively, separated between grades 2/3 and 0 /1 with PPV and NPV of 100%. SMaT20,40,60(cardiac)/SUVmean (liver) and SMaT20,40,60(cardiac)/SUVmean(liver/lung) separated grades 2 and 3. / Conclusion: Quantitative SPECT/CT parameters of cardiac Tc-DPD uptake are robust, enabling separation of patients with grades 2 and 3 cardiac uptake from grades 0 and 1. Larger patient cohorts will determine the incremental value of SPECT/CT quantification for ATTR management

Cognitive reserve in granulin-related frontotemporal dementia: from preclinical to clinical stages

OBJECTIVE Consistent with the cognitive reserve hypothesis, higher education and occupation attainments may help persons with neurodegenerative dementias to better withstand neuropathology before developing cognitive impairment. We tested here the cognitive reserve hypothesis in patients with frontotemporal dementia (FTD), with or without pathogenetic granulin mutations (GRN+ and GRN-), and in presymptomatic GRN mutation carriers (aGRN+). METHODS Education and occupation attainments were assessed and combined to define Reserve Index (RI) in 32 FTD patients, i.e. 12 GRN+ and 20 GRN-, and in 17 aGRN+. Changes in functional connectivity were estimated by resting state fMRI, focusing on the salience network (SN), executive network (EN) and bilateral frontoparietal networks (FPNs). Cognitive status was measured by FTD-modified Clinical Dementia Rating Scale. RESULTS In FTD patients higher level of premorbid cognitive reserve was associated with reduced connectivity within the SN and the EN. EN was more involved in FTD patients without GRN mutations, while SN was more affected in GRN pathology. In aGRN+, cognitive reserve was associated with reduced SN. CONCLUSIONS This study suggests that cognitive reserve modulates functional connectivity in patients with FTD, even in monogenic disease. In GRN inherited FTD, cognitive reserve mechanisms operate even in presymptomatic to clinical stages

A Variational Method in Out of Equilibrium Physical Systems

A variational principle is further developed for out of equilibrium dynamical systems by using the concept of maximum entropy. With this new formulation it is obtained a set of two first-order differential equations, revealing the same formal symplectic structure shared by classical mechanics, fluid mechanics and thermodynamics. In particular, it is obtained an extended equation of motion for a rotating dynamical system, from where it emerges a kind of topological torsion current of the form $\epsilon_{ijk} A_j \omega_k$, with $A_j$ and $\omega_k$ denoting components of the vector potential (gravitational or/and electromagnetic) and $\omega$ is the angular velocity of the accelerated frame. In addition, it is derived a special form of Umov-Poynting's theorem for rotating gravito-electromagnetic systems, and obtained a general condition of equilibrium for a rotating plasma. The variational method is then applied to clarify the working mechanism of some particular devices, such as the Bennett pinch and vacuum arcs, to calculate the power extraction from an hurricane, and to discuss the effect of transport angular momentum on the radiactive heating of planetary atmospheres. This development is seen to be advantageous and opens options for systematic improvements.Comment: 22 pages, 1 figure, submitted to review, added one referenc

The CF-CIRC study: a French collaborative study to assess the accuracy of Cystic Fibrosis diagnosis in neonatal screening

BACKGROUND: Cystic fibrosis (CF) is caused by mutations in the gene encoding for the CF transmembrane conductance regulator (CFTR) protein, which acts as a chloride channel after activation by cyclic AMP (cAMP). Newborn screening programs for CF usually consist of an immunoreactive trypsinogen (IRT) assay, followed when IRT is elevated by testing for a panel of CF-causing mutations. Some children, however, may have persistent hypertrypsinogenemia, only one or no identified CFTR gene mutation, and sweat chloride concentrations close to normal values. In vivo demonstration of abnormal CFTR protein function would be an important diagnostic aid in this situation. Measurements of transepithelial nasal potential differences (NPD) in adults accurately characterize CFTR-related ion transport. The aim of the present study is to establish reference values for NPD measurements for healthy children and those with CF aged 3 months to 3 years, the age range of most difficult-to-diagnose patients with suspected CF. The ultimate goal of our study is to validate NPD testing as a diagnostic tool for children with borderline results in neonatal screening. METHODS/DESIGN: We adapted the standard NPD protocol for young children, designed a special catheter for them, used a slower perfusion rate, and shortened the protocol to include only measurement of basal PD, transepithelial sodium (Na(+)) transport in response to the Na(+ )channel inhibitor amiloride, and CFTR-mediated chloride (Cl(-)) secretion in response to isoproterenol, a β-agonist in a Cl(- )free solution. The study will include 20 children with CF and 20 healthy control children. CF children will be included only if they carry 2 CF-causing mutations in the CFTR gene or have sweat chloride concentrations > 60 mEq/L or both. The healthy children will be recruited among the siblings of the CF patients, after verification that they do not carry the familial mutation. DISCUSSION: A preliminary study of 3 adult control subjects and 4 children older than 12 years with CF verified that the new protocol was well tolerated and produced NPD measurements that did not differ significantly from those obtained with the standard protocol. This preliminary study will provide a basis for interpreting NPD measurements in patients with suspected CF after neonatal screening. Earlier definitive diagnosis should alleviate parental distress and allow earlier therapeutic intervention and genetic counseling

Molecular evolution of HoxA13 and the multiple origins of limbless morphologies in amphibians and reptiles

Developmental processes and their results, morphological characters, are inherited through transmission of genes regulating development. While there is ample evidence that cis-regulatory elements tend to be modular, with sequence segments dedicated to different roles, the situation for proteins is less clear, being particularly complex for transcription factors with multiple functions. Some motifs mediating protein-protein interactions may be exclusive to particular developmental roles, but it is also possible that motifs are mostly shared among different processes. Here we focus on HoxA13, a protein essential for limb development. We asked whether the HoxA13 amino acid sequence evolved similarly in three limbless clades: Gymnophiona, Amphisbaenia and Serpentes. We explored variation in ω (dN/dS) using a maximum-likelihood framework and HoxA13sequences from 47 species. Comparisons of evolutionary models provided low ω global values and no evidence that HoxA13 experienced relaxed selection in limbless clades. Branch-site models failed to detect evidence for positive selection acting on any site along branches of Amphisbaena and Gymnophiona, while three sites were identified in Serpentes. Examination of alignments did not reveal consistent sequence differences between limbed and limbless species. We conclude that HoxA13 has no modules exclusive to limb development, which may be explained by its involvement in multiple developmental processes

Tidal Volume Single Breath Washout of Two Tracer Gases - A Practical and Promising Lung Function Test

Small airway disease frequently occurs in chronic lung diseases and may cause ventilation inhomogeneity (VI), which can be assessed by washout tests of inert tracer gas. Using two tracer gases with unequal molar mass (MM) and diffusivity increases specificity for VI in different lung zones. Currently washout tests are underutilised due to the time and effort required for measurements. The aim of this study was to develop and validate a simple technique for a new tidal single breath washout test (SBW) of sulfur hexafluoride (SF(6)) and helium (He) using an ultrasonic flowmeter (USFM)

A model of professional self-identity formation in student doctors and dentists: a mixed method study.

BACKGROUND: Professional self-identity [PSI] can be defined as the degree to which an individual identifies with his or her professional group. Several authors have called for a better understanding of the processes by which healthcare students develop their professional identities, and suggested helpful theoretical frameworks borrowed from the social science and psychology literature. However to our knowledge, there has been little empirical work examining these processes in actual healthcare students, and we are aware of no data driven description of PSI development in healthcare students. Here, we report a data driven model of PSI formation in healthcare students. METHODS: We interviewed 17 student doctors and dentists who had indicated, on a tracking questionnaire, the most substantial changes in their PSI. We analysed their perceptions of the experiences that had influenced their PSI, to develop a descriptive model. Both the primary coder and the secondary coder considered the data without reference to the existing literature; i.e. we used a bottom up approach rather than a top down approach. RESULTS: The results indicate that two overlapping frames of reference affect PSI formation: the students' self-perception and their perception of the professional role. They are 'learning' both; neither is static. Underpinning those two learning processes, the following key mechanisms operated: [1] When students are allowed to participate in the professional role they learn by trying out their knowledge and skill in the real world and finding out to what extent they work, and by trying to visualise themselves in the role. [2] When others acknowledge students as quasi-professionals they experience transference and may respond with counter-transference by changing to meet expectations or fulfil a prototype. [3] Students may also dry-run their professional role (i.e., independent practice of professional activities) in a safe setting when invited. CONCLUSIONS: Students' experiences, and their perceptions of those experiences, can be evaluated through a simple model that describes and organises the influences and mechanisms affecting PSI. This empirical model is discussed in the light of prevalent frameworks from the social science and psychology literature

Regional cortical thickness changes accompanying generalized tonic-clonic seizures

OBJECTIVE: Generalized tonic-clonic seizures are accompanied by cardiovascular and respiratory sequelae that threaten survival. The frequency of these seizures is a major risk factor for sudden unexpected death in epilepsy (SUDEP), a leading cause of untimely death in epilepsy. The circumstances accompanying such fatal events suggest a cardiovascular or respiratory failure induced by unknown neural processes rather than an inherent cardiac or lung deficiency. Certain cortical regions, especially the insular, cingulate, and orbitofrontal cortices, are key structures that integrate sensory input and influence diencephalic and brainstem regions regulating blood pressure, cardiac rhythm, and respiration; output from those cortical regions compromised by epilepsy-associated injury may lead to cardiorespiratory dysregulation. The aim here was to assess changes in cortical integrity, reflected as cortical thickness, relative to healthy controls. Cortical alterations in areas that influence cardiorespiratory action could contribute to SUDEP mechanisms. METHODS: High-resolution T1-weighted images were collected with a 3.0-Tesla MRI scanner from 53 patients with generalized tonic-clonic seizures (Mean age ± SD: 37.1 ± 12.6 years, 22 male) at Case Western Reserve University, University College London, and the University of California at Los Angeles. Control data included 530 healthy individuals (37.1 ± 12.6 years; 220 male) from UCLA and two open access databases (OASIS and IXI). Cortical thickness group differences were assessed at all non-cerebellar brain surface locations (P < 0.05 corrected). RESULTS: Increased cortical thickness appeared in post-central gyri, insula, and subgenual, anterior, posterior, and isthmus cingulate cortices. Post-central gyri increases were greater in females, while males showed more extensive cingulate increases. Frontal and temporal cortex, lateral orbitofrontal, frontal pole, and lateral parietal and occipital cortices showed thinning. The extents of thickness changes were sex- and hemisphere-dependent, with only males exhibiting right-sided and posterior cingulate thickening, while females showed only left lateral orbitofrontal thinning. Regional cortical thickness showed modest correlations with seizure frequency, but not epilepsy duration. SIGNIFIANCE: Cortical thickening and thinning occur in patients with generalized tonic-clonic seizures, in cardiovascular and somatosensory areas, with extent of changes sex- and hemisphere-dependent. The data show injury in key autonomic and respiratory cortical areas, which may contribute to dysfunctional cardiorespiratory patterns during seizures, as well as to longer-term SUDEP risk

Tyrosine kinase signalling in breast cancer

Cells are continuously exposed to diverse stimuli ranging from soluble endocrine and paracrine factors to signalling molecules on neighbouring cells. Receptors of the tyrosine kinase family play an important role in the integration and interpretation of these external stimuli, allowing a cell to respond appropriately to its environment. The activation of receptor tyrosine kinases (RTKs) is tightly controlled, allowing a normal cell to correctly integrate its external environment with internal signal transduction pathways. In contrast, due to numerous molecular alterations arising during the course of malignancy, a tumour is characterized by an abnormal response to its environment, which allows cancer cells to evade the normal mechanisms controlling cellular proliferation. Alterations in the expression of various RTKs, in their activation, and in the signalling molecules lying downstream of the receptors play important roles in the development of cancer. This topic is the major focus of the thematic review section of this issue of Breast Cancer Research