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Kr L-shell spectroscopy modeling results are discussed in this paper, focusing on the n = 4 to n = 2 line transitions of Be- and Li-like Kr ions. Collisional radiative atomic kinetic and Stark-broadened spectral line shape calculations show electron temperature T e and density n e sensitivity in the spectrum. The combination of the T e dependence due to the relative intensity of Be-like to Li-like line emissions in the range from 1.5 to 3 keV and the n e sensitivity from the Stark broadening effect on the line shapes in the range from 5 × 10 23 to 2 × 10 24 / cc results in a spectrum that can be employed to diagnose T e and n e . Two different collisional radiative atomic kinetic models i.e., Prismspect [J. J. MacFarlane, et al., Int. Fusion Sci. Appl. Conf. Proc. 457 (2003)] and ABAKO [Florido, et al., PRE, 80, 056402 (2009)] produce similar results in level populations and spectra. In x-ray spectroscopy of implosion cores, this Kr L-shell spectrum may prove useful in an intermediate T e range in which Ar is too ionized for its K-shell to be of diagnostic value and Kr is not ionized enough for its K-shell emission to be useful. [ABSTRACT FROM AUTHOR]

Background: Impulsivity is implicated in the development and maintenance of Cocaine Use Disorder (CUD). Less work has examined impulsivity's role on interest in initiating treatment, treatment adherence, or treatment response. No pharmacotherapies are approved for CUD, so efforts to understand and bolster the effects of psychotherapy are important in guiding and refining treatment. The present study examined the impact of impulsivity on interest in treatment, treatment initiation, treatment adherence, and treatment outcomes in individuals with CUD. Methods: Following the completion of a larger study on impulsivity and CUD participants were offered 14 sessions of (12 weeks) Cognitive Behavioral Relapse Prevention (CBT-RP). Before starting treatment, participants completed seven self-report and four behavioral measures of impulsivity. Sixty-eight healthy adults (36% female) with CUD (aged 49.4 ± 7.9) expressed an interest in treatment. Results: Greater scores on several self-report measures of impulsivity, and fewer difficulties with delayed gratification were associated with increased interest in treatment in both males and females. 55 participants attended at least 1 treatment session, while 13 participants did attend a single session. Individuals who attended at least one treatment session scored lower on measures of lack of perseverance and procrastination. Still, measures of impulsivity did not reliably predict session attendance nor the frequency of cocaine-positive urine samples throughout treatment. Males attended nearly twice as many treatment sessions as females despite nonsignificant associations between impulsivity in males and the number of sessions attended. Conclusions: Greater impulsivity in individuals with CUD was associated with expressing an interest in treatment, but not treatment adherence or response. [ABSTRACT FROM AUTHOR]

Rigid-flex printed circuit boards (PCBs) are used in many applications that range from mobile electronic devices to low-volume medical tools. Dynamic characterization of a rigid-flex system is difficult because the system exhibits large deformation in the joints, panel-to-panel contact, and other sources of dynamic nonlinearities and complexities not present in traditional PCBs. To date, rigorous test methods for the dynamic characterization of rigid-flex PCB systems have not been proposed. The objective of this paper is to present a case study of a rigid-flex PCB system from the NASA Jet Propulsion Laboratory (JPL), demonstrating nonlinear characterization and a modal testing protocol that sufficiently characterizes the frequencies, mode shapes, damping, and nonlinear properties of the structure. Additionally, single panels and a rigid-flex assembly without aluminum components are tested to draw more generalized conclusions regarding appropriate test protocols for other rigid-flex systems. The nonlinear characterization of the rigid-flex structures was performed using the test for homogeneity, an examination of energy-dependent resonance and damping, and the use of the Hilbert transform. Based on the results of this study, it is recommended to first use the Hilbert transform to efficiently identify the presence of a nonlinearity then investigate energy-dependent frequency characteristics and nonlinear damping, which are likely to be influenced by the rigid-flex system's geometry. All of the rigid-flex systems exhibited energy-dependent frequency characteristics and damping nonlinearities that increased with increased range of motion of the PCB panels about the Nomex hinges and increased with an increase in the number of hinges activated in a particular mode. However, the addition of the aluminum reinforcing components reduced both forms of nonlinearity. To enable modal testing of the rigid-flex structure with aluminum components, it was necessary to understand the resonance replicability and the sensitivity to suspension and excitation orientation to separate noise from local and global resonances. [ABSTRACT FROM AUTHOR]

The failure of carbon fiber reinforced epoxy matrix composites has been attributed to different mechanisms involving tensile, compressive and shear failure of the fibers or the matrix. This research serves to understand whether linear elastic fracture mechanics can explain the matrix behavior under compressive loading. Experiments and finite element analysis (FEA) are used to confirm that the matrix under compressive loads follows the relationships established by linear elastic fracture mechanics. The failure load is related to the corresponding notch length, and the observed relationship is compared to the relationship defined by linear elastic fracture mechanics. [ABSTRACT FROM AUTHOR]

Background: Twenty to 45% of the general pediatric population experience feeding problems. When children with disabilities exhibit feeding problems, they are more likely to develop maladaptive mealtime behaviors that may lead to poor nutrition. Home training to help treat a child’s feeding delay or disorder is a vital component of feeding treatment and supports holistic, family-centered treatment models. It is important for occupational therapists working with this population to understand the impact of these behaviors on individual and family functioning. Method: This quantitative study examined caregivers’ perspectives of the training families receive to support their child’s feeding delay or disorder, and how family mealtimes may be affected. One hundred and eight participants completed an online survey using primarily Likert scale questions. Results: Caregivers report that (a) they are receiving current and evidenced-based interventions; (b) they feel supported, yet feel they need more support; (c) family relationships are adversely affected by a child’s feeding challenges; (d) caregivers desire to connect with other caregivers of children with feeding delays or disorders; and (e) they need stress management and coping strategies. Conclusion: Feeding treatment is strengthened with more family-focused topics like family relationships and interactions, caregiver burden and stress management, and increased caregiver support. [ABSTRACT FROM AUTHOR]

Prior to implosion in Magnetized Liner Inertial Fusion (MagLIF), the fuel is heated to temperatures on the order of several hundred eV with a multi-kJ, multi-ns laser pulse. We present two laser heated plasma experiments, relevant to the MagLIF preheat stage, performed at Z with beryllium liners filled with deuterium and a trace amount of argon. In one experiment, there is no magnetic field and, in the other, the liner and fuel are magnetized with an 8.5 T axial magnetic field. The recorded time integrated, spatially resolved spectra of the Ar K-shell emission are sensitive to electron temperature Te. Individual analysis of the spatially resolved spectra produces electron temperature distributions Te(z) that are resolved along the axis of laser propagation. In the experiment with magnetic field, the plasma reaches higher temperatures and the heated region extends deeper within the liner than in the unmagnetized case. Radiation magnetohydrodynamics simulations of the experiments are presented and post-processed. A comparison of the results from experimental and simulated data reveals that the simulations underpredict Te in both cases but the differences are larger in the case with magnetic field. [ABSTRACT FROM AUTHOR]

The Mekong River is a vital fisheries resource supporting millions of people in mainland Southeast Asia. However, numerous threats have the potential to negatively impact fish populations in this region including overfishing, pollution, climate change and increased urban, agriculture and upstream hydropower development. Although a few studies have examined the population genetic structure of fishes within the upper Mekong River, no known studies have explored that of fishes within the Mekong Delta (MD). Here, we examine the population structure of an important food fish within the MD, Polynemus melanochir, using a panel of 1735 single nucleotide polymorphisms (SNPs) generated by restriction site-associated DNA (RAD) sequencing across eight locations on the Tien (Mekong) and Hau (Bassac) Rivers in Vietnam. Pairwise FST values, principal component analysis and Structure analysis all indicate high levels of gene flow among the sites sampled across the MD. In contrast to the lack of genetic structure, high levels of relatedness were found, including 26 putatively related pairs, as well as an effective population size (Ne) of less than 500 across the MD. While panmixia indicates that fragmentation of this population is not presently an important threat, a low Ne estimate suggests this species may not be resilient to long-term environmental changes in the MD. The reliance on P. melanochir as a food resource may be contingent on management and mitigation of low effective population sizes. [ABSTRACT FROM AUTHOR]

Background/objectives: Recent research has speculated that the risk of developing atherosclerosis is due to the accumulation of the effects of daily diet choices. The purpose of this study was to examine which of our previously identified preclinical disease risk biomarkers were further elevated when consuming a high-fat (644±50 kcal; 100% recommended dietary allowance for fat), high-calorie (1118±100 kcal; 70% daily caloric needs) breakfast on consecutive days. Young, normal weight females (N=7) participated in this study.Subjects/methods: Blood samples were taken premeal and hourly for 5-h postprandial. Serum biomarkers (C-peptide, eotaxin, gastric inhibitory polypeptide, granulocyte colony-stimulating factor (G-CSF), granulocyte-monocyte colony-stimulating factor (GM-CSF), insulin, leptin, monocyte chemoattractant protein 1, pancreatic polypeptide (PPY) and tumor necrosis factor-α), monocyte concentration, and adhesion molecule expression (CD11a, CD18 and CD54) were measured. Area under the curve was calculated for each outcome variable as a function of day and data were analyzed for significance.Results: We found significant (P<0.05) increases on Day 2 for: GM-CSF (+47%; P=0.041), G-CSF (+31%; P=0.012), PPY (+51%; P=0.049), total monocyte (+110%; P=0.043), pro-inflammatory (PI) monocyte (+60%; P=0.012), PI monocyte CD18 (+960%; P=0.003), PI monocyte CD11a (+230%; P=0.006), and PI monocyte CD54 (+208%; P=0.015).Conclusions: To our knowledge, the present study is the first to report changes in selected biomarkers and monocytes following eating a high-fat, high-calorie breakfast on consecutive days in humans. More research is needed to determine how transient the observed changes are and what the long-term implications for disease risk are. [ABSTRACT FROM AUTHOR]

The USDA's collaborative study of methods of protein quality evaluation is introduced. It was intended primarily to provide a basis for the evaluation of possibly improved procedures for the labelling of foods as a source of dietary protein. In general, the usefulness of in vitro digestibility procedures has been confirmed, but problems remained for the in vitro evaluation of heat-damaged materials and of some types of pinto beans. [ABSTRACT FROM AUTHOR]

The Coral Triangle is a hotspot for marine species diversity as well as for intraspecific genetic diversity. Here, we used nuclear RAG2 and mitochondrial D-Loop genes to identify deep genetic divergence among Dascyllus aruanus (Linnaeus, 1758) populations across relatively short scales within the Coral Triangle. Mitochondrial clades different by >20 mutational steps were completely isolated from one another across the distance between Java and the Lesser Sunda Islands, and also showed frequency differences in the eastern and western Philippines. Evidence for population structure in the Sulu Sea and at the Lesser Sunda Islands was also identified. Our results suggest that the Sulu Sea Throughflow, Bohol Sea Throughflow, Indonesian Throughflow, signatures of extinction events from Pleistocene land barriers, and other past and present forces may be potential factors leading to lineage divergence of D. aruanus, and that these hypotheses should be tested in further studies. [ABSTRACT FROM AUTHOR]

The emerging field of next-generation sequencing (NGs) is rapidly expanding capabilities for cutting edge genomic research, with applications that can help meet marine conservation challenges of food security, biodiversity loss, and climate change. Navigating the use of these tools, however, is complex at best. Furthermore, applications of marine genomic questions are limited in developing nations where both marine biodiversity and threats to marine biodiversity are most concentrated. his is particularly true in southeast Asia. The first Pan-Pacific Advanced studies Institute (PacAsI) entitled "Genomic Applications to Marine science and resource Management in southeast Asia" was held in July 2012 in Dumaguete, Philippines, with the intent to draw together leading scientists from both sides of the Pacific Ocean to understand the potential of NGs in helping address the aforementioned challenges. Here we synthesize discussions held during the PacAsI to provide perspectives and guidance to help scientists new to NGs choose among the variety of available advanced genomic methodologies specifically for marine science questions. [ABSTRACT FROM AUTHOR]

The International Space Station offers a unique platform for rapid and inexpensive deployment of space telescopes. A scientific opportunity of great potential later this decade is the use of telescopes for the electromagnetic follow-up of ground-based gravitational wave detections of neutron star and black hole mergers. We describe this possibility for OpTIIX, an ISS technology demonstration of a 1.5 m diffraction limited optical telescope assembled in space, and ISS-Lobster, a wide-field imaging X-ray telescope now under study as a potential NASA mission. Both telescopes will be mounted on pointing platforms, allowing rapid positioning to the source of a gravitational wave event. Electromagnetic follow-up rates of several per year appear likely, offering a wealth of complementary science on the mergers of black holes and neutron stars. [ABSTRACT FROM AUTHOR]

Urea cycle defects presenting in the neonatal period with hyperammonaemia are associated with high morbidity and mortality, and necessitate liver transplantation for long-term management. Gene therapy is therefore an attractive possibility, with vectors based on adeno-associated virus (rAAV) currently showing exciting promise in liver-targeted clinical trials in adults. Successful use of rAAV vectors in infants, however, is more challenging as episomal rAAV genomes will be lost from proliferating hepatocytes during liver growth, leaving stable transgene expression dependent on the subset of vector genomes that undergo genomic integration. To explore this challenge, we exploited the partially ornithine transcarbamylase (OTC)-deficient spfash mouse model and small hairpin RNA-mediated knockdown of residual endogenous OTC enzyme activity in adult mice that had received neonatal treatment with an OTC-encoding rAAV. This leaves mice reliant on vector-encoded OTC activity that has persisted from the newborn period. Despite stable transduction in approximately 8% of hepatocytes and residual vector-encoded OTC activity of up to 33% of wild-type, well above endogenous spfash levels (5-7%), mice were not protected from hyperammonaemia. These data show that the distribution of OTC activity within the liver is critical and that rAAV vector re-delivery after early neonatal treatment is likely to be necessary for stable control of hyperammonaemia into adulthood. [ABSTRACT FROM AUTHOR]

Strenuous aerobic exercise is known to weaken the immune system, and while many nutritional supplements have been proposed to boost post-exercise immunity, few are known to be effective. The purpose of the present study was to evaluate whether 10 d of supplementation with a defined source of baker's yeast β-glucan (BG, Wellmune WGP®) could minimise post-exercise immunosuppression. Recreationally active men and women (n 60) completed two 10 d trial conditions using a cross-over design with a 7 d washout period: placebo (rice flour) and baker's yeast BG (250 mg/d of β-1,3/1,6-glucans derived from Saccharomyces cerevisiae) before a bout of cycling (49 ± 6 min) in a hot (38 ± 2°C), humid (45 ± 2 % relative humidity) environment. Blood was collected at baseline (before supplement), pre- (PRE), post- (POST) and 2 h (2H) post-exercise. Total and subset monocyte concentration was measured by four-colour flow cytometry. Plasma cytokine levels and lipopolysaccharide (LPS)-stimulated cytokine production were measured using separate multiplex assays. Total (CD14+) and pro-inflammatory monocyte concentrations (CD14+/CD16+) were significantly greater at POST and 2H (P< 0·05) with BG supplementation. BG supplementation boosted LPS-stimulated production of IL-2, IL-4, IL-5 and interferon-γ (IFN-γ) at PRE and POST (P< 0·05). Plasma IL-4, IL-5 and IFN-γ concentrations were greater at 2H following BG supplementation. It appears that 10 d of supplementation with BG increased the potential of blood leucocytes for the production of IL-2, IL-4, IL-5 and IFN-γ. The key findings of the present study demonstrate that BG may have potential to alter immunity following a strenuous exercise session. [ABSTRACT FROM PUBLISHER]

The purpose of this study was to compare weight gain and food intake during high-fat feeding in outbred CD-1 male mice while considering several different experimental designs. This study was completed using data from three separate experiments and was designed to address different experimental design issues. Experiment 1 compared mice housed in groups or singly. Experiment 2 compared adolescent and young adult mice. Experiment 3 examined mice that had been previously exercise-trained prior to diet-induced weight gain. Data from each experiment were analysed using repeated measures analysis of variance and linear regression. While housing and age did not significantly affect weight gain, mice that were previously exercise-trained consumed significantly more kilocalories than sedentary mice while maintaining comparable body weights. We generated a linear prediction model using data from Experiments 1 and 2 that will allow investigators to calculate the weeks of high-fat feeding needed to reach a target body weight. Our key findings characterize the issues related to and affecting experimental design when utilizing an outbred mouse diet-induced weight gain model and will serve as a guide for future researchers. [ABSTRACT FROM AUTHOR]

Context The World Alliance for Patient Safety was formed to accelerate worldwide research progress towards measurably improving patient safety. Although rates of adverse events have been studied in industrialised countries, little is known about the rates of adverse events in developing and emerging countries. Purpose To review the literature on patient safety issues in developing and emerging countries, to identify patient safety measures presently used in these countries and to propose a method of measurably improving patient safety measurement in these countries. Methods Using the Medline database for 1998 to 2007, we identified and reviewed 23 English-language articles that examined patient safety measurement in developing and emerging countries. Results Our review included 12 studies that prospectively measured patient safety and 11 studies that retrospectively measured safety. Two studies used measures of structure and the remaining used process measures, outcome measures or both. Whereas a few studies used surveys or direct observation, most studies used chart audits to measure patient safety. Most studies addressed safety at a single facility. Conclusions Investigation of patient safety in developing and emerging countries has been infrequent and limited in scope. Establishing fundamental safe patient practices, integrating those processes into routine health services delivery and developing patients' expectations that such processes be present are necessary prerequisites to measuring and monitoring progress towards safe patient care in emerging and developing countries. [ABSTRACT FROM PUBLISHER]

We describe three patients with congenital disorder of glycosylation (CDG) type Ia, all of whom had persistent hyperinsulinaemic hypoglycaemia responding to diazoxide therapy as a common feature. The first patient, an infant girl, presented with recurrent vomiting, failure to thrive, liver impairment, hypothyroidism and a pericardial effusion. The second patient, also female, had a milder disease with single organ involvement, presenting as isolated hyperinsulinaemic hypoglycaemia, not associated with any cognitive impairment. The third patient, a boy presented with multi-organ manifestations including congenital hypothyroidism, persistent hyperinsulinaemic hypoglycaemia, coagulopathy, olivopontocerebellar hypoplasia and recurrent pancreatitis. All three patients had a type 1 serum transferrin isoform pattern, and were subsequently found to have low phosphomannomutase activity, confirming the diagnosis of CDG type Ia. Our findings emphasize that CDG should be considered as a differential diagnosis in patients with persistent hyperinsulinaemic hypoglycaemia and that it may even occasionally be the leading symptom in CDG Ia. [ABSTRACT FROM AUTHOR]

New methods, designed for the commercial-scale production of Frisch collar CdZnTe gamma ray spectrometers, are described in detail in the following work. Past methods required considerable skilled labor, were not readily automatable, and batch processing was only supported through a portion of the fabrication process. Advances in dielectric materials technology allow for new processes that readily apply the required dielectric film between the CdZnTe crystal and the conductive collar. The processes use spray or chemical vapor deposition methods to accurately achieve a specific thickness. Furthermore, application of the conductive collar was improved to facilitate commercial manufacturing. Comparisons in device performance are presented between the previous and new methods to illustrate the effectiveness and robustness of the new fabrication method. Parylene N performed well as the dielectric layer, while nickel-based paint, high-purity silver-based paint, and a silver-suspension Electrodag all performed well as the conductive layer, each maintaining spectral performance. [ABSTRACT FROM AUTHOR]

Mutant proteins have the potential to exert dominant-negative effects that might limit the therapeutic efficacy of their wild-type counterparts after gene transfer. For ornithine transcarbamylase (OTC) deficiency, in vitro studies have suggested the presence of dominant-negative effects, however, supporting in vivo studies have not been conducted. In this study, we exploited the capacity of recombinant adeno-associated virus (rAAV) 2/8 vectors to deliver transgenes to the mouse liver with high efficiency to determine whether expression of selected OTC mutant proteins exert inhibitory effects on endogenous wild-type OTC enzymatic activity. Using site-directed mutagenesis we constructed three OTC mutants with a theoretical or reported in vitro capacity to exert dominant-negative effects, and delivered these to the liver using rAAV2/8. Each mutation had been earlier identified in patients with OTC deficiency. Treated mice showed no increase in urinary orotic acid levels or reduction in OTC activity despite supra-physiological expression of the mutant proteins, consistent with an absence of dominant-negative effects. These data have important implications for the development of gene therapy strategies for OTC deficiency and validate a model system in which potential dominant-negative effects of specific mutations in prospective patients can be examined empirically before gene therapy.Gene Therapy (2009) 16, 820–823; doi:10.1038/gt.2009.38; published online 9 April 2009 [ABSTRACT FROM AUTHOR]

Glutaric aciduria type I (GA I), a cerebral organic acidaemia with the potential for severe neurological consequences, can now be detected by tandem mass spectrometry newborn screening. Early detection with implementation of careful management strategies appears to lessen the likelihood of neurological damage. We assessed the outcome in all 10 GA I patients detected in New South Wales during the last decade. Three patients were detected clinically and 7 by newborn screening. Diagnosis was confirmed by detection of significantly elevated urinary 3-hydroxybutyrate and glutarate in urine, isolated elevation of glutarylcarnitine in plasma, typical clinical and MRI findings in several, and mutation analysis or enzyme analysis on cultured skin fibroblasts in 4 cases. The birth frequency was 1:90 000. Following diagnosis, treatment was initiated in all children with oral carnitine (100 mg/kg per day) and a low-protein diet supplemented with a lysine-free, low-tryptophan amino acid formula. Disability was assessed in fields of motor, cognitive and speech development and scored according to Kyllerman. Clinically diagnosed patients were all symptomatic, with severity scores (out of 9) of 3, 5 and 9. Six of seven patients detected by newborn screening are asymptomatic, 4 being aged 2–6 years. One patient had a severe decompensation at 7 months, despite full management advice and treatment, and later died. Our data support previous findings that early diagnosis reduces neurological complications, but show that even with early diagnosis and careful management severe complications may ensue in some. [ABSTRACT FROM AUTHOR]

Mass transfer across the gas--water interface is important in many fields, but the present understanding of the scalar transport as mediated by the complex near-surface turbulence is still far from complete. In this work, an innovative particle image velocimetry (PIV)--based measurement method was used to investigate the near surface turbulence. Turbulence measurement with respect to the fluctuating interface was performed and the gradient of the vertical fluctuating velocity (Hanratty's β) deemed as a critical controlling parameter was quantified. Several distinctly different but typical flow conditions were investigated and the associated mass-transfer velocity was measured. Based on these experimental works, an empirical relation, very similar to that proposed earlier by Law and Khoo, relating the mass transport across the turbulent interface to the turbulence parameter β, was determined in the midst of vastly different flow conditions where turbulence is induced simultaneously from above and beneath the gas--water interface. [ABSTRACT FROM AUTHOR]

Background/Aims: idiopathic interstitial pneumonias (IIPs) are a diverse grouping of chronic pulmonary diseases characterised by varying degrees of pulmonary fibrosis. The triggers of the fibroproliferative process in IIP remain enigmatic but recent attention has been directed towards chemokine involvement in this process. Methods: The expression of two chemokine receptors, CCR7 and CXCR4, and their respective ligands, CCL19, CCL21, and CXCL12, were examined in surgical lung biopsies (SLBs) from patients with IIP. Transcript and protein expression of these receptors and their ligands was compared with that detected in histologically normal margin SLBs. Results: CCR7 and CXCR4 were detected by gene array and real time polymerase chain reaction analysis and CCR7, but not CXCR4, expression was significantly raised in usual interstitial pneumonia (UIP) relative to biopsies from patients diagnosed with non-specific interstitial pneumonia (NSIP) or respiratory bronchiolitis/interstitial lung disease (RBILD). CCR7 protein was expressed in interstitial areas of all upper and lower lobe UIP SLBs analysed. CCR7 expression was present in 50% of NSIP SLBs, and CCR7 was restricted to blood vessels and mononuclear cells in 75% of RBILD SLBs. immune cell specific CXCR4 expression was seen in lip and normal margin biopsies. CCR7 positive areas in UIP biopsies were concomitantly positive for CD45 (the leucocyte common antigen) but CCR7 positive areas in all IIP SLBs lacked the haemopoietic stem cell antigen CD34, collagen 1, and α smooth muscle actin. Conclusion: This molecular and immunohistochemical analysis showed that IIPs are associated with abnormal CCR7 transcript and protein expression. [ABSTRACT FROM AUTHOR]

We have screened 13 patients with neurological abnormalities and 3-methylglutaconic aciduria (3MGA) for mutations in the OPA3 gene, which are known to be the cause of Costeff syndrome (optic atrophy, chorea and spasticity; type III 3MGA). We aimed to explore whether mutations in the OPA3 gene are present in patients with 3MGA but without classic Costeff syndrome. OPA3 mutations (IVS1−1G>C) were identified in 2 patients with the classic phenotype of type III 3MGA, but not in the other 11 patients with differing non-Costeff phenotypes associated with developmental delay and neurological signs and symptoms as described. We identified a previously described sequence variation in the OPA3 gene (c.231T>C) in 12/13 patients. The alteration was homozygous in 8/12 and heterozygous in 4/12. This alteration was also found in 60 of 98 normal control alleles. In a single patient, a novel sequence variation in the 5′ UTR was identified, (c.−38A>G). Our studies suggest that the c.231T>C sequence variation is of no clinical significance, whereas the significance of the 5′ UTR sequence variation remains open to speculation. Our study of the OPA3 gene in patients with 3MGA without Costeff syndrome suggests that mutations in OPA3 are not a common cause of 3MGA in the absence of signs of Costeff syndrome. [ABSTRACT FROM AUTHOR]

The innate immune and acquired immune responses are not separate, parallel systems but form interdependent components of a single integrated immune response. This is nicely highlighted by an expanding database demonstrating that the innate immune response provides the acquired immune response with information about the origin of the antigen and the type of response required via pattern recognition receptors (PRRs). Aspergillus is among a growing list of allergens that can aggravate asthmatic responses. Significant pulmonary pathology is associated with Aspergillus -induced allergic and asthmatic lung disease characterized by increased Th2 cytokine generation, IgE and IgG, eosinophilia, airway hyper-responsiveness and airway remodeling. Experimental data from a model of chronic fungal asthma demonstrate that thymus associated and regulated chemokine (TARC/CCL17) and macrophage derived chemokine (MDC/CCL22), working via CCR4, directly impair the innate anti-fungal immune response, thereby promoting the maintenance of acquired Th2-mediated asthmatic disease. Both chemokines appear to accomplish this by regulating the expression of PRRs such as toll like receptors (TLRs) and triggering receptor expressed on myeloid cells (TREM-1) by immune cells. Thus, the link between Aspergillus and asthma appears to reside in the magnitude and appropriateness of the host innate immune response, and ongoing research is revealing promising targets for therapy. [ABSTRACT FROM AUTHOR]

Asthmatic airway remodelling is characterized by myofibroblast hyperplasia and subbasement membrane collagen deposition. We hypothesized that cytokines and growth factors implicated in asthmatic airway remodelling are increased in bronchoalveolar lavage (BAL) fluid of asthmatics after segmental allergen challenge (SAC), and that these growth factors and cytokines increase α-smooth muscle actin (α-SMA) and collagen III synthesis by human lung fibroblasts (HLFs). Transforming growth factor (TGF)-β1, TGF-β2, IL-4 and IL-13 levels were measured in BAL fluid from 10 asthmatics and 9 non-asthmatic controls at baseline and then 1 day, 1 week and 2 weeks after SAC. Confluent cultures of HLFs were stimulated by exogenous addition of TGF-β1, TGF-β2, IL-4 or IL-13 (concentration range 0.01–10 ng/mL) over 48 h. Collagen III was measured in culture supernates and α-SMA in cell lysates by Western blot. At baseline, there was no difference in BAL fluid concentrations of TGF-β1, IL-4 and IL-13 between asthmatics and controls; however, non-asthmatics had higher concentrations of total TGF-β2. In asthmatics, BAL fluid concentrations of all four factors increased significantly 1 day after SAC. TGF-β1, TGF-β2 and IL-13 concentrations returned to baseline by 1 week after SAC, but BAL fluid IL-4 concentration remained elevated for at least 2 weeks. TGF-β1, TGF-β2 and IL-4 significantly increased α-SMA in fibroblasts, but only IL-4 caused corresponding increases in collagen III synthesis. IL-13 had no direct effects on collagen III synthesis and α-SMA expression. Because IL-4 caused a dose-dependent increase in α-SMA and collagen III synthesis, it may be an important cytokine mediating asthmatic airway remodelling. TGF-β1 and TGF-β2 may also play a role in airway remodelling by stimulating phenotypic change of fibroblasts to myofibroblasts. Additionally, collagen III synthesis appears to be independent of myofibroblast phenotype and is apparently regulated by different growth factors and cytokines. [ABSTRACT FROM AUTHOR]

Three patients with ketosis had increased excretion of 3-hydroxyglutarate (21.8–37.9 μmol/mmol creatinine; controls 2.3 ± 1.6), an indicator of glutaryl-CoA dehydrogenase deficiency (GDHD), which normalized when the patients were nonketotic. Clinical assessment of all three patients and enzyme studies in one patient were not consistent with GDHD. These findings were compared with those of other ketotic patients, who showed statistically significant increases in 3-hydroxyglutarate excretion (9.4 ± 5.0 μmol/mmol creatinine; p < 0.01), and with those of a child with confirmed GDHD when she was both ketotic and nonketotic. Secondary increase in 3-hydroxyglutarate excretion during ketosis is a potential confounder in the diagnosis of GDHD. [ABSTRACT FROM AUTHOR]

Considers issues related to the application of genomics and proteomics to improvements in the pharmacology and therapeutic approaches to pain. Details on pain control; Discussion on pain as a sensory message; Types of pain transmission.

Objective -- To evaluate newborn screening by tandem mass spectrometry for detection of medium chain acyl-CoA dehydrogenase (MCAD) deficiency, a fatty acid oxidation disorder with significant mortality in undiagnosed patients. Design -- The following were studied: (a) 13 clinically detected MCAD deficient subjects, most homozygous for the common A985G mutation, whose newborn screening sample was available; (b) 275 653 consecutive neonates undergoing routine newborn screening. Screened infants with blood octanoylcarnitine levels &ges; 1 μmol/l were analysed for the A985G mutation, had analysis of plasma and repeat blood spot acylcarnitines and urinary organic acids, and had fibroblast fatty acid oxidation or acylcarnitine studies. Result -- Twelve of the 13 patients later diagnosed clinically had newborn octanoylcarnitine levels > 2.3 μmol/l. Twenty three screened babies had initial octanoylcarnitine levels &ges; 1 μmol/l. Eleven of 12 babies with persistent abnormalities had metabolite and/or enzyme studies indicating MCAD deficiency. Only four were homozygous for the A985G mutation, the remainder carrying one copy. Conclusions -- Most patients with symptomatic MCAD deficiency could be detected by newborn screening. Infants actually detected had a lower frequency of A985G alleles than clinically diagnosed cases and may have a lower risk of becoming symptomatic. [ABSTRACT FROM AUTHOR]

A neonate at risk for hepatic carnitine palmitoyltransferase I (L-CPT I) deficiency was investigated from birth. The free carnitine and acylcarnitine profile in dried whole blood filter paper samples collected at ages 1 and 4 days showed a markedly elevated concentration of free carnitine (141 and 142 μmol/L, respectively), normal concentrations of acetyl- and propionylcarnitine, with the near absence of all other species. The diagnosis was confirmed by in vitro fatty acid oxidation screening assays and enzyme assay in cultured skin fibroblasts. Retrospective study of the newborn whole blood sample of the index case showed a similar profile (free carnitine 181 μmol/L). The newborn population distribution of free carnitine ( n=143981) showed that only three samples had free carnitine >140 μmol/L (>99.9th centile), two were from L-CPT I-deficient neonates and one from a baby with sepsis. While there are other conditions that can cause elevated concentrations of free carnitine, an isolated elevation of free carnitine only in an apparently healthy term neonate warrants further investigation to exclude L-CPT I deficiency. [ABSTRACT FROM AUTHOR]

Women who develop bilateral breast cancer at an early age are likely to harbour germline mutations in breast cancer susceptibility genes. The aim of this study was to test for concordant genetic changes in left and right breast cancer of young women (age <50) with bilateral breast cancer that may suggest an inherited breast cancer predisposition. Microsatellite markers were used to test for loss of heterozygosity (LOH) in left and right tumours for 31 women with premenopausal bilateral breast cancer. Markers adjacent to or within candidate genes on 17p (p53), 17q (BRCA1), 13q (BRCA2), 11q (Ataxia Telangiectasia-ATM) and 3p (FHIT) were chosen. Mutational testing for BRCA1 and BRCA2 was performed for cases where blood was available. Concordant LOH in both left and right tumours was demonstrated for at least one of the markers tested in 16/31(54%) cases. Where allelic loss was demonstrated for both left and right breast cancer, the same allele was lost on each occasion. This may suggest a common mutational event. Four cases showed concordant loss of alleles in both left and right breast cancer at D17S791 (BRCA1). BRCA1 mutations were identified in two of these cases where blood was available. Four cases showed concordant LOH at D13S155 (BRCA2). Concordant LOH was further demonstrated in seven cases for D11S1778 (ATM) and four cases for D3S1300 (which maps to the FHIT gene), suggesting a possible role for these tumour suppressor genes in this subgroup of breast cancer patients. No concordant allelic loss was demonstrated for D17S786 suggesting that germline mutations in p53 are unlikely in such cases of bilateral breast cancer. [ABSTRACT FROM AUTHOR]

It was previously shown that a high plasma concentration of non-esterified fatty acids (NEFA) persisted after a fatty breakfast, but not after an isoenergetic carbohydrate breakfast, adversely affecting glucose tolerance. The higher concentration after the fatty breakfast may in part have been a result of different mobilization rates of fatty acids. This factor can be investigated as NEFA mobilized from tissues are monounsaturated to a greater extent than those deposited from a typical meal. Twenty-four middle-aged healthy Caucasian men were given oral glucose tolerance tests (OGTT), and for 28 d isoenergetic breakfasts of similar fat composition but of low (L) or moderate (M) fat content. The composition of NEFA in fasting and postprandial plasma was determined on days 1 and 29. No significant treatment differences in fasting NEFA composition occurred on day 29. During the OGTT and 0–1 h following breakfast there was an increase in plasma long-chain saturated NEFA but a decrease in monounsaturated NEFA (μg/100 μg total NEFA; P<0·001). Between 1 and 3 h following breakfast treatment differences occurred for total saturated and total monounsaturated fatty acids (μg/100 μg total NEFA; P<0·05), expressed as an increase in 18 : 1 and decreases in 16 : 0 and 17 : 0 in treatment M relative to treatment L (P<0·05). Serum insulin attained 35 and 65 mU/l in treatments M and L respectively during this period. Negative correlations were found between 16 : 0 in fasting plasma and both waist:hip circumference (P=0·0009) and insulin response curve area during OGTT (within treatment M, P=0·0001). It is concluded that a normal postprandial insulin response is associated with a rapid change in plasma saturated:monounsaturated NEFA. It is proposed that this change is the result of a variable suppression of fat mobilization, which may partly account for a large difference in postprandial total plasma NEFA between fatty and carbohydrate meals. [ABSTRACT FROM PUBLISHER]

In the early 1920s, workers in both England and the US had discovered that rats on a rachitic diet would remain healthy if irradiated with ultraviolet light. However, they also found, to their surprise, that "control" rats too would recover if either their jar was irradiated without the rat in it or if a cage-mate was removed for irradiation and then returned. The ideas that either air or material objects that had been irradiated continued themselves to convey healthful secondary radiations were investigated but not confirmed. There was then the commercially important finding that with irradiation, some rachitic diets would become anti-rachitic. However, this effect did not explain all the previous findings. Consumption of either small irradiated fecal particles or of feces from irradiated rats was the likely explanation for the recovery of nonirradiated rats, but this was not tested by direct experiment, and it now appears unlikely that feces from irradiated rats would show significant antirachitic activity. It is suggested that an alternative possibility--activity of grease from irradiated fur--deserves investigation. [ABSTRACT FROM AUTHOR]

High signal-to-noise ratio spectra of RR Tel obtained at medium resolution with the Goddard High-Resolution Spectrograph (GHRS) on the Hubble Space Telescope (HST) are used to test available atomic data for the OIV 2s[sup 2]2p [sup 2]P--2s2p[sup 2][sup 4]P multiplet (UV 0.01). The fine-structure intervals of the 2s2p[sup 2][sup 4]P term given by Moore (1983) appear to need revision. The flux ratios of lines within multiplet UV (0.01), which have a common upper level, depend only on transition probabilities. The observed flux ratio of lines from the [sup 4]P[sub 3/2] level differs from that predicted by theory, but this difference cannot be attributed to a blend with a line of SIV]. At the electron densities in the RR Tel nebula, other flux ratios give information on the relative electron excitation rates between the [sup 2]P and [sup 4]P fine-structure levels. Using the collision strengths calculated by Zhang, Graziani & Pradhan, the rate to the [sup 4]P[sub 5/2] level, relative to the rates to the other J states, appears to be underestimated by ∼ 10 per cent, which is within the expected uncertainty of 20 per cent. We also discuss the SIV 3s[sup 2]3p [sup 2]P--3s3p[sup 2][sup 4]P multiplet. [ABSTRACT FROM AUTHOR]

We report a male infant with cobalamin C defect whose clinical course was complicated by diarrhoea suggestive of a protein-losing enteropathy, failure to thrive, macrocytosis and thrombocytopenia which resolved with hydroxocobalamin treatment. Protein-losing enteropathy has not previously been reported in association with cobalamin C defect and, if unrecognized, could cause considerable morbidity. [ABSTRACT FROM AUTHOR]