There is much recent interest in the biologic and diagnostic implication of cell-free non-host DNA in the plasma and serum of human subjects. To determine if quantitative abnormalities of circulating ...non-host DNA may be associated with certain pathologic processes, we used circulating fetal DNA in preeclampsia as a model system.
We studied 20 preeclamptic women and 20 control subjects of comparable gestational age (means, 32 and 33 weeks, respectively). Male fetal DNA in maternal serum was measured using real-time quantitative PCR for the SRY gene on the Y chromosome.
The imprecision (CV) of the assay was 2.7%. The median circulating fetal DNA was increased fivefold in 20 preeclamptic women compared with 20 control pregnant women (381 vs 76 genome-equivalents/mL, P <0.001).
These observations suggest that preeclampsia is associated with disturbances in the liberation and/or clearance mechanisms of circulating DNA. These results also raise the possibility that measurement of circulating DNA may prove useful as a marker for the diagnosis and/or monitoring of preeclampsia.
Magnetoelastic coupling associated with the hexagonal-monoclinic transition in a natural sample of the mineral pyrrhotite, Fe7S8, has been analysed in terms of separate coupling of spontaneous ...strains with two discrete order parameters, qv for Fe/vacancy ordering and qm for magnetic ordering. Coupling of the two order parameters separately with strain gives rise to two terms for coupling between them, λqm2qv2 and λqm2qv8, and a pattern of evolution in which qv varies continuously and qm discontinuously through a single transition point. The transition is ferrimagnetic and ferroelastic but the relatively slow relaxation rate for Fe/vacancy ordering, in comparison with magnetic ordering, results in elastic and anelastic properties which are quite different from those observed in other ferroic or multiferroic materials with two instabilities. Instead of classical elastic softening, there is stiffening of the elastic constants which scales with qm2 and qv2. Instead of the normal pattern of acoustic loss associated with the mobility and subsequent freezing for ferroelastic twin walls, the loss is consistently low throughout the temperature range 300 K-875 K.
To investigate weight perception, dieting and emotional well being across the range of body mass index (BMI) in a population-based multiethnic sample of early adolescents.
Cross-sectional ...population-based survey.
In total, 2789 adolescents 11-14 years of age from three highly deprived regional authorities in East London, in 2001.
Data were collected by student-completed questionnaire on weight perception, dieting history, mental and physical health, health behaviours, social capital and sociodemographic factors. Height and weight were measured by trained researchers. Overweight was defined as BMI > or =85th centile and obesity as BMI > or =98th centile. Underweight was defined as BMI< or =15th centile.
In all, 73% were from ethnic groups other than white British. Valid BMI were available for 2522 subjects (90.4%) of whom 14% were obese. Only 20% of overweight boys and 51% of overweight girls assessed their weight accurately. Accuracy of weight perception did not vary between ethnic groups. In all, 42% of girls and 26% of boys reported current dieting to lose weight. Compared with white British teenagers, a history of dieting was more common among Bangladeshi, Indian and mixed ethnicity boys and less likely among Pakistani girls. Self-esteem was not associated with BMI in girls but was significantly lower in obese boys than those of normal weight (P=0.02). Within ethnic subgroups, self-esteem was significantly lower in overweight white British boys (P=0.03) and obese Bangladeshi boys (P=0.01) and Bangladeshi girls (P=0.04), but significantly higher in obese black African girls (P=0.01) than those of normal weight. Obese young people had a higher prevalence of psychological distress (P=0.04), except among Bangladeshi teenagers, where overweight and obese young people had less psychological distress than those of normal weight (P=0.02). Birth outside the UK was associated with reduced risk of obesity in girls (P=0.02) but not with history of dieting, weight perception or psychological factors in either gender.
High levels of current dieting for weight control and inaccurate perception of body mass are common across all ethnic groups. However, dieting history and the associations of obesity with self-esteem and psychological distress vary between ethnic groups. Interventions to prevent or treat obesity in black or minority ethnicity groups must consider cultural differences in the relationship between body mass, self-esteem and psychological distress.
Pyrrhotite, Fe7S8, is a commonly occurring carrier of magnetic remanence and has a low temperature transition, the Besnus transition, involving a change in spin state. Variations of the ...thermodynamic, magnetic and elastic properties through this transition at ∼33 K in a natural sample of 4C pyrrhotite have been tested against a group theoretical model for coupling between order parameters relating to Fe/vacancy ordering (irrep U1(1/2,0,1/4)) and magnetic ordering (irreps mΓ4+ and mΓ5+). Magnetoelastic coupling is weak but the pre-existing microstructure of ferroelastic and magnetic domains, that develop as a consequence of Fe/vacancy and ferrimagnetic ordering during slow cooling in nature (P63/mmc → C2′/c′), causes subtle changes in the low temperature transition (C2′/c′ → P1¯). The Besnus transition involves a rotation of magnetic moments out of the a-c plane of the monoclinic structure, but it appears that the transition temperature might vary locally according to whether it is taking place within the pre-existing domain walls or in the domains that they separate. Evidence of metamagnetic transitions suggests that the magnetic field-temperature phase diagram will display some interesting diversity. Low temperature magnetic transitions in minerals of importance to the palaeomagnetism community have been used to identify the presence of magnetite and haematite in rocks and the Besnus transition is diagnostic of the existence of pyrrhotite, Fe7S8.
We describe here the design and initial implementation of the eMERGE‐PGx project. eMERGE‐PGx, a partnership of the Electronic Medical Records and Genomics Network and the Pharmacogenomics Research ...Network, has three objectives: (i) to deploy PGRNseq, a next‐generation sequencing platform assessing sequence variation in 84 proposed pharmacogenes, in nearly 9,000 patients likely to be prescribed drugs of interest in a 1‐ to 3‐year time frame across several clinical sites; (ii) to integrate well‐established clinically validated pharmacogenetic genotypes into the electronic health record with associated clinical decision support and to assess process and clinical outcomes of implementation; and (iii) to develop a repository of pharmacogenetic variants of unknown significance linked to a repository of electronic health record–based clinical phenotype data for ongoing pharmacogenomics discovery. We describe site‐specific project implementation and anticipated products, including genetic variant and phenotype data repositories, novel variant association studies, clinical decision support modules, clinical and process outcomes, approaches to managing incidental findings, and patient and clinician education methods.
Clinical Pharmacology & Therapeutics (2014); 96 4, 482–489. doi:10.1038/clpt.2014.137
Chemical weapons have given the human experience of warfare a uniquely terrifying quality that has inspired a general repugnance and led to periodic attempts to ban their use. Nevertheless, since ...ancient times, toxic agents have been consistently employed to kill and terrorize target populations. The evolution of these weapons is examined here in ways that may allow military, law enforcement, and scientific professionals to gain a perspective on conditions that, in the past, have motivated their use - both criminally and as a matter of national policy during military campaigns. Special emphasis is placed on the genocidal use of chemical weapons by the regime of Saddam Hussein, both against Iranians and on Kurdish citizens of his own country, during the Iran-Iraq War of 1980-88. The historical development of chemical weapons use is summarized to show how progressively better insight into biochemistry and physiology was adapted to this form of warfare. Major attributes of the most frequently used chemical agents and a description of how they affected military campaigns are explained. Portions of this review describing chemical-casualty care devote particular focus to Iranian management of neurotoxic (nerve) agent casualties due to the unique nature of this experience. Both nerve and blistering "mustard" agents were used extensively against Iranian forces. However, Iran is the only nation in history to have sustained large-scale attacks with neurotoxic weapons. For this reason, an understanding of the successes and failures of countermeasures to nerve-agent use developed by the Iranian military are particularly valuable for future civil defense and military planning. A detailed consideration of these strategies is therefore considered. Finally, the outcomes of clinical research into severe chronic disease triggered by mustard-agent exposure are examined in the context of the potential of these outcomes to determine the etiology of illness among US and Allied veterans of the 1991 Persian Gulf War.
Objective
To develop standardized treatment regimens for chronic nonbacterial osteomyelitis (CNO), also known as chronic recurrent multifocal osteomyelitis (CRMO), to enable comparative effectiveness ...treatment studies.
Methods
Virtual and face‐to‐face discussions and meetings were held within the CNO/CRMO subgroup of the Childhood Arthritis and Rheumatology Research Alliance (CARRA). A literature search was conducted, and CARRA membership was surveyed to evaluate available treatment data and identify current treatment practices. Nominal group technique was used to achieve consensus on treatment plans for CNO refractory to nonsteroidal antiinflammatory drug (NSAID) monotherapy and/or with active spinal lesions.
Results
Three consensus treatment plans (CTPs) were developed for the first 12 months of therapy for CNO patients refractory to NSAID monotherapy and/or with active spinal lesions. The 3 CTPs are methotrexate or sulfasalazine, tumor necrosis factor inhibitors with optional methotrexate, and bisphosphonates. Short courses of glucocorticoids and continuation of NSAIDs are permitted for all regimens. Consensus was achieved on these CTPs among CARRA members. Consensus was also reached on subject eligibility criteria, initial evaluations that should be conducted prior to the initiation of CTPs, and data items to collect to assess treatment response.
Conclusion
Three consensus treatment plans were developed for pediatric patients with CNO refractory to NSAIDs and/or with active spinal lesions. Use of these CTPs will provide additional information on efficacy and will generate meaningful data for comparative effectiveness research in CNO.
Objective
To evaluate the construct validity of 2 proposed measures (the Ultrasound Disease Activity U‐DA and the Tissue Thickness Score TTS) for evaluating sonographic differences in juvenile ...localized scleroderma skin lesions.
Methods
We conducted a retrospective review of juvenile localized scleroderma patients who had ultrasound scans of their skin lesions between October 2005 and February 2009. Imaged lesions were classified as active or inactive based upon clinical assessment. Lesions had to have been imaged within 1 month of a clinic visit or have the same clinical assessment during both the visit before and the visit after the scan. Two physicians scored the scans using the U‐DA, which scores for differences in lesion echogenicity and vascularity compared with normal tissue. Tissue thickness differences were evaluated by percent differences and by using the TTS. Wilcoxon's rank sum test was performed to assess differences.
Results
We studied 52 scans from 21 patients, 32 scans of active skin lesions and 20 scans of inactive skin lesions. Features reported by clinicians as indicative of active disease included erythema, warmth, violaceous color, new lesion, expansion of lesion, and induration. The U‐DA was significantly different between active and inactive skin lesions (P = 0.0010) with significant differences found for the parameters of total echogenicity, hypodermis echogenicity, and deep tissue layer vascularity (P = 0.0014, P = 0.0023, and P = 0.0374, respectively). No significant differences were found for tissue layer thickness or TTS.
Conclusion
The U‐DA may be a useful tool in the identification of localized scleroderma activity. Further study is needed to prospectively evaluate the validity, reliability, and sensitivity of this potential monitoring tool.
We present the first public data release (DR1) of the Calar Alto Legacy Integral Field Area (CALIFA) survey. It consists of science-grade optical datacubes for the first 100 of eventually 600 nearby ...(0.005 < z < 0.03) galaxies, obtained with the integral-field spectrograph PMAS/PPak mounted on the 3.5 m telescope at the Calar Alto observatory. The galaxies in DR1 already cover a wide range of properties in color–magnitude space, morphological type, stellar mass, and gas ionization conditions. This offers the potential to tackle a variety of open questions in galaxy evolution using spatially resolved spectroscopy. Two different spectral setups are available for each galaxy, (i) a low-resolution V500 setup covering the nominal wavelength range 3745–7500 Å with a spectral resolution of 6.0 Å (FWHM), and (ii) a medium-resolution V1200 setup covering the nominal wavelength range 3650–4840 Å with a spectral resolution of 2.3 Å (FWHM). We present the characteristics and data structure of the CALIFA datasets that should be taken into account for scientific exploitation of the data, in particular the effects of vignetting, bad pixels and spatially correlated noise. The data quality test for all 100 galaxies showed that we reach a median limiting continuum sensitivity of 1.0 × 10-18 erg s-1 cm-2 Å-1 arcsec-2 at 5635 Å and 2.2 × 10-18 erg s-1 cm-2 Å-1 arcsec-2 at 4500 Å for the V500 and V1200 setup respectively, which corresponds to limiting r and g band surface brightnesses of 23.6 mag arcsec-2 and 23.4 mag arcsec-2, or an unresolved emission-line flux detection limit of roughly 1 × 10-17 erg s-1 cm-2 arcsec-2 and 0.6 × 10-17 erg s-1 cm-2 arcsec-2, respectively. The median spatial resolution is 3\hbox{$\farcs$}.″7, and the absolute spectrophotometric calibration is better than 15% (1σ). We also describe the available interfaces and tools that allow easy access to this first publicCALIFA data at http://califa.caha.es/DR1.
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