Creation and judicious application of a wheat resistance gene atlas.
Disease-resistance (R) gene cloning in wheat (Triticum aestivum) has been accelerated by the recent surge of genomic resources, facilitated by advances in sequencing technologies and bioinformatics. However, with the challenges of population growth and climate change, it is vital not only to clone and functionally characterize a few handfuls of R genes, but also to do so at a scale that would facilitate the breeding and deployment of crops that can recognize the wide range of pathogen effectors that threaten agroecosystems. Pathogen populations are continually changing, and breeders must have tools and resources available to rapidly respond to those changes if we are to safeguard our daily bread. To meet this challenge, we propose the creation of a wheat R-gene atlas by an international community of researchers and breeders. The atlas would consist of an online directory from which sources of resistance could be identified and deployed to achieve more durable resistance to the major wheat pathogens, such as wheat rusts, blotch diseases, powdery mildew, and wheat blast. We present a costed proposal detailing how the interacting molecular components governing disease resistance could be captured from both the host and the pathogen through biparental mapping, mutational genomics, and whole-genome association genetics. We explore options for the configuration and genotyping of diversity panels of hexaploid and tetraploid wheat, as well as their wild relatives and major pathogens, and discuss how the atlas could inform a dynamic, durable approach to R-gene deployment. Set against the current magnitude of wheat yield losses worldwide, recently estimated at 21%, this endeavor presents one route for bringing R genes from the lab to the field at a considerable speed and quantity.


Lower limb stress fractures in sport: Optimising their management and outcome.
Stress fractures in sport are becoming increasing more common, comprising up to 10% of all of sporting injuries. Around 90% of such injuries are located in the lower limb. This articles aims to define the optimal management of lower limb stress fractures in the athlete, with a view to maximise return rates and minimise return times to sport. Treatment planning of this condition is specific to the location of the injury. However, there remains a clear division of stress fractures by "high" and "low" risk. "Low risk" stress fractures are those with a low probability of fracture propagation, delayed union, or non-union, and so can be managed reliably with rest and exercise limitation. These include stress fractures of the Postero-Medial Tibial Diaphysis, Metatarsal Shafts, Distal Fibula, Medial Femoral Neck, Femoral Shaft and Calcaneus. "High risk" stress fractures, in contrast, have increased rates of fracture propagation, displacement, delayed and non-union, and so require immediate cessation of activity, with orthopaedic referral, to assess the need for surgical intervention. These include stress fractures of the Anterior Tibial Diaphysis, Fifth Metatarsal Base, Medial Malleolus, Lateral Femoral Neck, Tarsal Navicular and Great Toe Sesamoids. In order to establish the optimal methods for managing these injuries, we present and review the current evidence which guides the treatment of stress fractures in athletes. From this, we note an increased role for surgical management of certain high risk stress fractures to improve return times and rates to sport. Following this, key recommendations are provided for the management of the common stress fracture types seen in the athlete. Five case reports are also presented to illustrate the application of sport-focussed lower limb stress fracture treatment in the clinical setting.


Reperfusion therapies in pulmonary embolism-state of the art and expert opinion: A position paper from the "Unité de Soins Intensifs de Cardiologie" group of the French Society of Cardiology.
Acute pulmonary embolism is a frequent cardiovascular emergency with an increasing incidence. The prognosis of patients with high-risk and intermediate-high-risk pulmonary embolism has not improved over the last decade. The current treatment strategies are mainly based on anticoagulation to prevent recurrence and reduce pulmonary vasculature obstruction. However, the slow rate of thrombus lysis under anticoagulation is unable to acutely decrease right ventricle overload and pulmonary vasculature resistance in patients with severe obstruction and right ventricle dysfunction. Therefore, patients with high-risk and intermediate-high-risk pulmonary embolism remain a therapeutic challenge. Reperfusion therapies may be discussed for these patients, and include systemic thrombolysis, catheter-directed therapies and surgical thrombectomy. High-risk patients require systemic thrombolysis, but may have contraindications as a result of the high risk of bleeding. In addition, intermediate-high-risk patients should not receive systemic thrombolysis, despite its high efficacy, because of prohibitive bleeding complications. Recently, percutaneous reperfusion techniques have been developed to acutely decrease pulmonary vascular obstruction with lower-dose or no thrombolytic agents and, thus, potentially higher safety than systemic thrombolysis. Some of these techniques improve key haemodynamic variables. Cardiac surgical techniques and venoarterial extracorporeal membrane oxygenation as temporary circulatory support may be useful in selected cases. The development of pulmonary embolism centres with multidisciplinary pulmonary embolism teams is mandatory to enable adequate use of reperfusion and improve outcomes. We aim to present the state of the art regarding reperfusion therapies in pulmonary embolism, but also to provide guidance on their indications and patient selection.


The importance of small for gestational age in the risk assessment of infants with critical congenital heart disease.
Infants with critical congenital heart disease who require cardiothoracic surgical intervention may have significant post-operative mortality and morbidity. Infants who are small for gestational age <10th percentile with foetal growth restriction may have end-organ dysfunction that may predispose them to increased morbidity or mortality. A single-institution retrospective review was performed in 230 infants with congenital heart disease who had cardiothoracic surgical intervention <60 days of age. Pre-, peri-, and post-operative morbidity and mortality markers were collected along with demographics and anthropometric measurements. There were 230 infants, 57 (23.3%) small for gestational age and 173 (70.6%) appropriate for gestational age. No significant difference was noted in pre-operative markers - gestational age, age at surgery, corrected gestational age, Society for Thoracic Surgeons and European Association for Cardiothoracic Surgery mortality score; or post-operative factors - length of stay, ventilation days, arrhythmias, need for extracorporeal membrane oxygenation, vocal cord dysfunction, hearing loss; or end-organ dysfunction - gastro-intestinal, renal, central nervous system, or genetic. Small for gestational age infants were more likely to have failed vision tests (p = 0.006). Small for gestational age infants were more likely to have increased 30-day (p = 0.005) and discharge mortality (p = 0.035). Small for gestational age infants with normal birth weight (>2500 g) were also at increased risk of 30-day mortality compared with appropriate for gestational age infants (p = 0.045). Small for gestational age infants with congenital heart disease who undergo cardiothoracic surgery <60 days of age have increased risk of mortality and failed vision screening. Assessment of foetal growth restriction as part of routine pre-operative screening may be beneficial.


A dose comparison of olanzapine for the treatment of borderline personality disorder: a 12-week randomized, double-blind, placebo-controlled study.
To examine the efficacy and safety of olanzapine at low and moderate doses for the treatment of borderline personality disorder. In this 12-week randomized double-blind placebo-controlled trial, 451 outpatients aged 18-65 years with DSM-IV borderline personality disorder received olanzapine 2.5 mg/d (n = 150), olanzapine 5-10 mg/d (n = 148), or placebo (n = 153). The trial was conducted from February 2004 through January 2006 at 59 community-based and academic study centers in 9 countries (United States, Italy, Poland, Romania, Turkey, Chile, Peru, Argentina, and Venezuela). The primary efficacy measure was mean change from baseline to last-observation-carried-forward endpoint on the Zanarini Rating Scale for Borderline Personality Disorder (ZAN-BPD) total score. Secondary measures included the Montgomery-Asberg Depression Rating Scale, the Modified Overt Aggression Scale, the Global Assessment of Functioning, the Symptom Checklist-90-Revised, and the Sheehan Disability Scale. An overall mean baseline ZAN-BPD total score of 17.2 (SD = 4.9) indicated moderate symptom severity. Only treatment with olanzapine 5-10 mg/d was associated with significantly greater mean change from baseline to endpoint in ZAN-BPD total score relative to placebo (-8.5 vs -6.8, respectively; P = .010; effect size = 0.29; 95% CI, 0.06-0.52). Response rates (response indicated by ≥ 50% decrease from baseline in ZAN-BPD total score) were significantly higher for olanzapine 5-10 mg/d (73.6%) versus olanzapine 2.5 mg/d (60.1%; P = .018) and versus placebo (57.8%; P = .006). Time to response was also significantly shorter for patients taking olanzapine 5-10 mg/d than for placebo-treated patients (P = .028). Treatment-emergent adverse events reported significantly more frequently among olanzapine-treated patients included somnolence, fatigue, increased appetite, and weight increase (all P values < .05). Mean weight change from baseline to endpoint was significantly greater for olanzapine-treated than for placebo-treated patients (olanzapine 2.5 mg/d: 2.09 kg; olanzapine 5-10 mg/d: 3.17 kg; placebo: 0.02 kg; P < .001). The overall completion rate for the 12-week double-blind treatment period was 65.2% (ie, 64.7% for olanzapine 2.5 mg/d, 69.6% for olanzapine 5-10 mg/d, and 61.4% for placebo). Olanzapine 5-10 mg/d showed a clinically modest advantage over placebo in the treatment of overall borderline psychopathology. This advantage in effectiveness should be weighed against the risk of adverse events (particularly weight gain), which were consistent with the known safety profile of olanzapine. clinicaltrials.gov Identifier: NCT00088036.


A virus-induced gene silencing (VIGS) system for functional genomics in the parasitic plant Striga hermonthica.
Striga hermonthica is a hemiparasitic weed that infects cereals in Sub Sahara Africa (SSA) resulting in up to 100% grain yield loss. This significant loss in grain yields is a major contributor to food insecurity and poverty in the region. Current strategies to control the parasite are costly, unavailable and remain unpracticed by small-scale farmers, underscoring the need for more economical and sustainable control strategies. Development of resistant germplasm is the most sustainable strategy in the control of S. hermonthica, but is constrained by paucity of resistance genes for introduction into crop germplasm. RNA interference (RNAi) has potential for developing host-derived resistance against S. hermonthica by transformation of host crops with RNAi sequences targeted at critical Striga genes. The application of RNAi in management of S. hermonthica is however constrained by lack of efficient high throughput screening protocols for the candidate genes for silencing, as well as sub optimal delivery of siRNAs into the parasite. In comparison to stable transformation, viral induced gene silencing (VIGS) is a rapid and powerful tool for plant functional genomics and provides an easy and effective strategy in screening for putative candidate genes to target through RNAi. In addition, VIGS allows for a secondary amplification of the RNAi signal increasing the siRNA threshold and facilitates siRNA transport through viral movement proteins. We tested the efficiency of the Tobacco rattle virus (TRV1 and TRV2) VIGS vectors in silencing S. hermonthica phytoene desaturase (PDS) gene through agrodrench and agro-infiltration. We report the validation of VIGS in S. hermonthica using a silencing cassette generated from TRV with a PDS gene insert. Agro-infiltrated and agro-drenched S. hermonthica leaves showed photo-bleaching phenotypes typical for PDS silencing within 7 and 14 days post infection respectively. In both cases S. hermonthica plants recovered from photo-bleaching effects within 28 days post inoculation. The transformation efficiency of the VIGS protocol in S. hermonthica was (60 ± 2.9)%. These results demonstrate that the TRV-VIGS system work in S. hermonthica and can be used for candidate gene validation for their role in the parasite development and parasitism, with the ultimate goal of developing resistant transgenic maize.


Predictors of Visual Acuity After Treatment of Neovascular Age-Related Macular Degeneration - Current Perspectives.
Visual acuity is a key outcome measure in the treatment of neovascular age-related macular degeneration (nAMD) using anti-vascular endothelial growth factor agents. Large variations in visual responses between individuals within clinical trials and real-world studies may relate to underlying differences in patient and treatment factors. Most notably, a better baseline visual acuity, younger age and smaller choroidal neovascularization lesion size have been strongly associated with achieving better visual outcomes. In addition, there is emerging evidence for other roles including genetic factors and anatomical variables such as fluid status. Apart from patient-related factors, treatments that favor a higher number of injections tend to provide better visual outcomes. Overall, the identification of predictive factors does not currently play an essential role in the clinical management of patients with nAMD. However, they have allowed for the understanding that early detection, timely management and close monitoring of the disease are required to achieve optimal visual outcomes. Further investigation into predictive factors alongside the development of novel therapeutic agents may one day provide a means to accurately predict patient outcomes. Treatment regimens that offer flexible dosing patterns such as the treat-and-extend strategy currently provide a degree of personalization during treatment.


Whole exome HBV DNA integration is independent of the intrahepatic HBV reservoir in HBeAg-negative chronic hepatitis B.
The involvement of HBV DNA integration in promoting hepatocarcinogenesis and the extent to which the intrahepatic HBV reservoir modulates liver disease progression remains poorly understood. We examined the intrahepatic HBV reservoir, the occurrence of HBV DNA integration and its impact on the hepatocyte transcriptome in hepatitis B 'e' antigen (HBeAg)-negative chronic hepatitis B (CHB). Liver tissue from 84 HBeAg-negative patients with CHB with low (n=12), moderate (n=25) and high (n=47) serum HBV DNA was analysed. Covalently closed circular DNA (cccDNA), pregenomic RNA (pgRNA) were evaluated by quantitative PCR, whole exome and transcriptome sequencing was performed by Illumina, and the burden of HBV DNA integrations was evaluated by digital droplet PCR. Patients with low and moderate serum HBV DNA displayed comparable intrahepatic cccDNA and pgRNA, significantly lower than in patients with high HBV DNA, while hepatitis B core-related antigen correlated strongly with the intrahepatic HBV reservoir, reflecting cccDNA quantity. Whole exome integration was detected in a significant number of patients (55.6%, 14.3% and 25% in high, moderate and low viraemic patients, respectively), at a frequency ranging from 0.5 to 157 integrations/1000 hepatocytes. Hepatitis B surface antigen >5000 IU/mL predicted integration within the exome and these integrations localised in genes involved in hepatocarcinogenesis, regulation of lipid/drug metabolism and antiviral/inflammatory responses. Transcript levels of specific genes, including the proto-oncogene hRAS, were higher in patients with HBV DNA integration, supporting an underlying oncogenic risk in patients with low-level to moderate-level viraemia. HBV DNA integration occurs across all HBeAg-negative patients with CHB, including those with a limited HBV reservoir; localising in genes involved in carcinogenesis and altering the hepatocyte transcriptome.


Fluorescence monitoring of antibiotic-induced bacterial damage using flow cytometry.
Conventional techniques used to assess bactericidal activities of antibodies are time-consuming; flow cytometry has been used as a rapid alternative. In this study, the membrane potential-sensitive fluorescent probes bis-(1,3-dibutylbarbituric acid) trimethine oxonol (DiBAC4(3)) and Sytox Green, the redox dye cyano-2,3-ditolyl tetrazolium chloride (CTC), and the Baclite viability test kit were used to assess the effects of ceftazidime, ampicillin, and vancomycin on clinical isolates of Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus aureus, respectively. Bacterial cultures were grown to early exponential phase, at which point the antibiotics were added at their breakpoint values, and incubation was allowed to continue. At timed intervals, samples were stained and flow cytometric analysis was performed on a Skatron Argus 100 arc-lamp based dual-parameter flow cytometer. All the dyes successfully identified antibiotic-induced damage in the three strains, although different fluorescence responses between the dyes were observed. DiBAC4(3) and Sytox Green overestimated numbers of nonviable bacteria relative to loss of viability as judged by plate counts. CTC, a measure of respiratory activity, revealed antibiotic-induced population heterogeneity illus trated by the development of several subpopulations. The "live" component of the viability kit identified two populations corresponding to viable and nonviable organisms, whereas the "dead" component only revealed single populations, the fluorescence intensity of which increased with antibiotic exposure. Flow cytometry provides a rapid and sensitive technique for the evaluation of the antibacterial activities of antibiotics. The use of a range of fluorophores specific for different cellular characteristics may be beneficial, bearing in mind the different fluorescence responses observed among the dyes used here.


Myopathy phenotype in transgenic mice expressing mutated PABPN1 as a model of oculopharyngeal muscular dystrophy.
Autosomal dominant oculopharyngeal muscular dystrophy (OPMD) is a late-onset disorder characterized clinically by progressive ptosis, dysphagia and limb weakness, and by unique intranuclear inclusions in the skeletal muscle fibers. The disease is caused by the expansion of a 10-alanine stretch to 12-17 alanine residues in the poly(A)-binding protein, nuclear 1 (PABPN1; PABP2). While PABPN1 is a major component of the inclusions in OPMD, the exact cause of the disease is unknown. To elucidate the molecular mechanism and to construct a useful model for therapeutic trials, we have generated transgenic mice expressing the hPABPN1. Transgenic mice lines expressing a normal hPABPN1 with 10-alanine stretch did not reveal myopathic changes, whereas lines expressing high levels of expanded hPABPN1 with a 13-alanine stretch showed an apparent myopathy phenotype, especially in old age. Pathological studies in the latter mice disclosed intranuclear inclusions consisting of aggregated mutant hPABPN1 product. Furthermore, some TUNEL positive nuclei were shown around degenerating fibers and a cluster of it in the lesion in necrotic muscle fibers. Interestingly, the degree of myopathic changes was more prominent in the eyelid and pharyngeal muscles. Further, muscle weakness in the limbs was apparent as shown by the fatigability test. Nuclear inclusions seemed to develop gradually with aging, at least after 1 week of age, in model mouse muscles. We established the first transgenic mouse model of OPMD by expressing mutated PABPN1, and our model mice appear to have more dramatic alternations in myofiber viability.


Signal transduction pathways triggered by fibroblast growth factor receptor 1 expressed in Xenopus laevis oocytes after fibroblast growth factor 1 addition. Role of Grb2, phosphatidylinositol 3-kinase, Src tyrosine kinase, and phospholipase Cgamma.
Xenopus oocytes expressing fibroblast growth factor receptor 1 (FGFR1) were used as a biological model system to analyse the signal transduction pathways that are triggered by fibroblast growth factor 1 (FGF1). Germinal vesicle breakdown (GVBD) and phosphorylation of extracellular signal-regulated protein kinase 2 (ERK2) occured 15 h after FGF1 addition. These events were Ras-dependent as they were blocked by a Ras dominant negative form. The Ras activity was promoted by three upstream effectors, growth factor-bound protein 2 (Grb2), phosphatidylinositol 3-kinase (PI3K) and Src cytoplasmic kinase. Ras activation was inhibited by a Grb2 dominant negative form (P49L), by PI3K inhibitors, including wortmannin, LY294002, the N-SH2 domain of p85alpha PI3K and by the SH2 domain of Src. Src activation induced by FGF1 was blocked by the SH2 domain of Src and PP2, a specific inhibitor of Src. The Grb2 adaptor was recruited by the upstream Src homology 2/alpha-collagen-related (Shc) effector, as the SH2-Shc domain prevented the GVBD and the ERK2 phosphorylation induced by FGF1. The importance of another signalling pathway involving phospholipase Cgamma (PLCgamma) was also investigated. The use of the PLCgamma inhibitory peptide, neomycin and the calcium chelator BAPTA-AM on oocytes expressing FGFR1 or the stimulation by PDGF-BB of oocytes expressing PDGFR-FGFR1 mutated on the PLCgamma binding site, prevented GVBD and ERK2 phosphorylation. This study shows that the transduction cascade induced by the FGFR1-FGF1 interaction in Xenopus oocytes represents the sum of Ras-dependent and PLCgamma-dependent pathways. It emphasizes the role played by PI3K and Src and their connections with the Ras cascade in the FGFR1 signal transduction.


Insomnia and use of hypnotics: study of a French population.
A cross-sectional study of insomnia and hypnotic use was performed in a sample of the French population. The quota method was used to select the sample of 1,003 subjects, with less than 3% substitution. Subjects were 15 years old and older and were representative of the French population based on gender, age, marital status and living environment. Subjects were asked questions relevant to the complaint of insomnia and hypnotic use and filled out questionnaires measuring anxiety and depression. The complaint of insomnia is common, even in the 15-24-year-old group. Overall, more women than men were afflicted. The largest group of insomniac subjects, and the group who most often used hypnotics "frequently and chronically", were women 45 years and older. Men presented a sharp increase in hypnotic use after 65 years of age. Ten percent of the entire sample used hypnotics, 8% for more than 6 months and 6.17% on a chronic and frequent basis. Retired and unemployed elderly were also chronic and frequent hypnotic users: aging and social isolation correlate with chronic and frequent hypnotic usage. Higher scores on anxiety and depression scales correlate with more frequent complaints of nocturnal sleep disturbances. Young individuals are a significant complainer group but use hypnotics rarely. A rural environment was associated, overall, with fewer insomnia complaints, but environment had much less impact on complaints and hypnotic use in the elderly than in other age groups. One may question whether, in the French population, hypnotic prescription and intake are not responses to a social rather than a medical problem.


Hydrolyzed Fat Formula Increases Brain White Matter in Small for Gestational Age and Appropriate for Gestational Age Neonatal Piglets.
Background: Intrauterine growth restriction is a common cause of small for gestational age (SGA) infants worldwide. SGA infants are deficient in digestive enzymes required for fat digestion and absorption compared to appropriate for gestational age (AGA) infants, putting them at risk for impaired neurocognitive development. Objective: The objective was to determine if a hydrolyzed fat (HF) infant formula containing soy free fatty acids, 2-monoacylglycerolpalmitate, cholesterol, and soy lecithin could increase brain tissue incorporation of essential fatty acids or white matter to enhance brain development in SGA and AGA neonatal piglet models. Methods: Sex-matched, littermate pairs of SGA (0.5-0.9 kg) and AGA (1.2-1.8 kg) 2 days old piglets (N = 60) were randomly assigned to control (CON) or HF formula diets in a 2 × 2 factorial design. On day 14, 24 piglets were used for hippocampal RNA-sequencing; the rest began a spatial learning task. On days 26-29, brain structure was assessed by magnetic resonance imaging (MRI). Cerebellum and hippocampus were analyzed for fatty acid content. Results: SGA piglets grew more slowly than AGA piglets, with no effect of diet on daily weight gain or weight at MRI. HF diet did not affect brain weight. HF diet increased relative volumes of 7 brain regions and white matter (WM) volume in both SGA and AGA piglets. However, HF did not ameliorate SGA total WM integrity deficits. RNA sequencing revealed SGA piglets had increased gene expression of synapse and cell signaling pathways and decreased expression of ribosome pathways in the hippocampus compared to AGA. HF decreased expression of immune response related genes in the hippocampus of AGA and SGA piglets, but did not correct gene expression patterns in SGA piglets. Piglets learned the T-maze task at the same rate, but SGA HF, SGA CON, and AGA HF piglets had more accurate performance than AGA CON piglets on reversal day 2. HF increased arachidonic acid (ARA) percentage in the cerebellum and total ARA in the hippocampus. Conclusions: HF enhanced brain development in the neonatal piglet measured by brain volume and WM volume in specific brain regions; however, more studies are needed to assess long-term outcomes.


Computation of 31P NMR chemical shifts in Keggin-based lacunary polyoxotungstates.
Density Functional Theory (DFT) calculations were employed to systematically study the accuracy of various exchange-correlation functionals in reproducing experimental 31P NMR chemical shifts, δExp(31P) for Keggin, [PW12O40]3- and corresponding lacunary clusters: [PW11O39]7-, [A-PW9O34]9-, and [B-PW9O34]9-. Initially, computed chemical shifts, δCalc(31P) were obtained with without neutralising their charge in which associated error, δError(31P), decreased as a function of Hartree-Fock (HF) exchange, attributed to constriction of the P-O tetrahedron. By comparison, δCalc(31P) performed with explicitly located counterions to render the system charge neutral, reduced discrepancies, δError(31P) by 1-2 ppm. However, uncertainties in δCalc(31P) remain, particularly for [B-PW9O34]9- anions attributed to direct electrostatic interactions between the counterions and the central tetrahedron. Optimal results were achieved using the PBE/TZP//PBE0/TZP method, achieving a mean absolute error (MAE) and a mean squared error (MSE) of 4.03 ppm. Our results emphasize that understanding the nature of the electrolyte and solvent environment is essential to obtaining reasonable agreement between theoretical and experimental results.


Compensatory capsid protein mutations in cucumber mosaic virus confer systemic infectivity in squash (Cucurbita pepo).
Cucumber mosaic virus (CMV) systemically infects both tobacco and zucchini squash. CMV capsid protein loop mutants with single-amino-acid substitutions are unable to systemically infect squash, but they revert to a wild-type phenotype in the presence of an additional, specific single-site substitution. The D118A, T120A, D192A, and D197A loop mutants reverted to a wild-type phenotype but did so in combination with P56S, P77L, A162V, and I53F or T124I mutations, respectively. The possible effect of these compensatory mutations on other, nonsystemically infecting loop mutants was tested with the F117A mutant and found to be neutral, thus indicating a specificity to the observed changes.


Numerical simulations of the impact of the 20 March 2015 eclipse on UK weather.
Short lead-time forecasts using the operational United Kingdom variable-resolution (UKV) configuration of the Met Office's numerical weather prediction model, with horizontal grid-length 1.5 km over the UK, with and without a representation of the 20 March 2015 eclipse, have been used to simulate the impact of the eclipse on UK weather. The major impact was surface-driven through changes to surface heat and moisture fluxes that changed the boundary-layer development. In cloud-free areas, the nocturnal stable boundary layer persisted or quickly re-established during the eclipse. Surface temperatures were reduced by 7-8°C, near-surface air temperature by 1-3°C, and near-surface winds were backed, typically by 20°. Impacts on wind speed were small and variable, and would have been very difficult to detect. Smaller impacts occurred beneath cloud. However, the impact was enhanced because most of the incoming radiation that reached the surface was driving surface sensible heat flux rather than moisture flux, and the near-surface air temperature impact (0.5-1°C) agrees reasonably well with observations. The modelled impact of the eclipse was substantially reduced in urban areas due to their large thermal inertia. Experience from other assessments of the model suggests that this lack of response may be exaggerated. Surface impacts propagated upwards and downstream with time, resulting in a complex pattern of response, though generally near-surface temperature differences persisted for many hours after the eclipse. The impact on atmospheric pressure fields was insufficient to account for any significant perturbations to the wind field when compared with the direct impacts of surface stress and boundary-layer mixing.This article is part of the themed issue 'Atmospheric effects of solar eclipses stimulated by the 2015 UK eclipse'.


Improved satisfaction of preoperative patients after group video-teaching during interview at preanesthetic evaluation clinic: the experience of a medical center in Taiwan.
Anesthesiologist-directed anesthetic preoperative evaluation clinic (APEC) is used to prepare patients to receive anesthesia for surgery. Studies have shown that APEC can reduce preoperative tests, consultations, surgery delays and cancellations. APEC with video-teaching has been purposed as a medium to provide comprehensive information about the process of anesthesia but it has not been practiced in small groups of patients. It is rational to assume that video-teaching in a small group patients can provide better information to patients to understand the process of anesthesia and in turn improve their satisfaction in anesthesia practice. This study was designed to evaluate the difference of satisfaction between patients who joined in small group video-teaching at APEC and patients who paid a traditional preoperative visit in the waiting area, using questionnaire for evaluation. Totally, 237 eligible patients were included in the study in a space of two months. Patients were divided in two groups; 145 patients joined the small group video-teaching designated as study group and 92 patients who were paid traditional preoperative visit at the waiting area served as control. All patients were requested to fill a special questionnaire after postoperative visit entrusted to two non-medical persons. There were significantly higher scores of satisfaction in anesthesia inclusive of waiting time for surgery in the operation room, attitude towards anesthetic staffs during postoperative visit and management of complications in patients who were offered small group video-teaching in comparison with patients of traditional preoperative visit. The results indicated that APEC with group video-teaching could not only make patients more satisfied with process of anesthesia in elective surgery but also reduce the expenditure of hospitalization and anesthetic manpower.


From the Cover: Roles of mmu_piR_003399 in Microcystin-Leucine Arginine-Induced Reproductive Toxicity in the Spermatogonial Cells and Testis.
Our previous work has demonstrated that microcystin-leucine arginine (MC-LR) is a potent toxin for the reproductive system of male mice and it exerts cytotoxicity in spermatogonial cells, resulting in the constitutional and functional changes of the mouse testis. The present study was designed to investigate the functions of P-element-induced wimpy (piwi)-interacting RNAs (piRNAs) in MC-LR-induced reproductive toxicity in male mice. We observed an increase in the mmu_piR_003399 level in spermatogonial cells and mouse testicular tissues following treatment with MC-LR. Moreover, our data confirmed that cyclin-dependent kinase 6 (CDK6) was the target gene of mmu_piR_003399. Increases in the concentration of mmu_piR_003399 were correlated with the reduced expression of CDK6 both in vitro and in vivo. mmu_piR_003399 induced cell cycle arrest at the G1-phase, down-regulated sperm counts and sperm motility, and compromised sperm morphology. On the contrary, suppressing the expression of mmu_piR_003399 could substantially attenuate MC-LR-induced pathology in mice including cell cycle arrest, reduced mature sperm counts, sperm viability loss and abnormal sperm morphology. Furthermore, our data supported that mmu_piR_003399 existed in mouse serum and plasma, and its level was increased in MC-LR-treated mice. In conclusion, we demonstrate that mmu_piR_003399 plays a crucial role in regulating MC-LR-induced reproductive toxicity.


Analysis of Epigenetic Age Predictors in Pain-Related Conditions.
Chronic pain prevalence is high worldwide and increases at older ages. Signs of premature aging have been associated with chronic pain, but few studies have investigated aging biomarkers in pain-related conditions. A set of DNA methylation (DNAm)-based estimates of age, called "epigenetic clocks," has been proposed as biological measures of age-related adverse processes, morbidity, and mortality. The aim of this study is to assess if different pain-related phenotypes show alterations in DNAm age. In our analysis, we considered three cohorts for which whole-blood DNAm data were available: heat pain sensitivity (HPS), including 20 monozygotic twin pairs discordant for heat pain temperature threshold; fibromyalgia (FM), including 24 cases and 20 controls; and headache, including 22 chronic migraine and medication overuse headache patients (MOH), 18 episodic migraineurs (EM), and 13 healthy subjects. We used the Horvath's epigenetic age calculator to obtain DNAm-based estimates of epigenetic age, telomere length, levels of 7 proteins in plasma, number of smoked packs of cigarettes per year, and blood cell counts. We did not find differences in epigenetic age acceleration, calculated using five different epigenetic clocks, between subjects discordant for pain-related phenotypes. Twins with high HPS had increased CD8+ T cell counts (nominal p = 0.028). HPS thresholds were negatively associated with estimated levels of GDF15 (nominal p = 0.008). FM patients showed decreased naive CD4+ T cell counts compared with controls (nominal p = 0.015). The severity of FM manifestations expressed through various evaluation tests was associated with decreased levels of leptin, shorter length of telomeres, and reduced CD8+ T and natural killer cell counts (nominal p < 0.05), while the duration of painful symptoms was positively associated with telomere length (nominal p = 0.034). No differences in DNAm-based estimates were detected for MOH or EM compared with controls. In summary, our study suggests that HPS, FM, and MOH/EM do not show signs of epigenetic age acceleration in whole blood, while HPS and FM are associated with DNAm-based estimates of immunological parameters, plasma proteins, and telomere length. Future studies should extend these observations in larger cohorts.


Coenzyme Q10 protects against acute consequences of experimental myocardial infarction in rats.
Myocardial infarction (MI) due to sudden occlusion of a major coronary artery leads to a complex series of events that result in left ventricle (LV) impairment eventual heart failure. Therapeutic options are limited to reverse such trends post MI. The aim of this study was to compare the acute cardioprotective effects of the antioxidants, resveratrol (RES) and coenzyme Q10 (CoQ10), either individually or in combination, on infracts size, LV hemodynamics, inflammation and oxidative stress markers in rats with experimentally induced MI. Male Wistar rats were randomly divided into six groups: control without surgery, sham without occlusion, MI without antioxidants, RES pre-treated then MI (20 mg/kg, orally), CoQ10 then MI (20 mg/kg, intramuscular.), and combined RES and CoQ10 then MI with (each group n = 10). Pretreatment commenced 7 days prior to the permanent occlusion of the left anterior descending (LAD) coronary artery. Infarct area, hemodynamics, inflammation and oxidative stress markers were assessed 24 hours post-MI. Compared to RES alone, CoQ10 pre-administration either by itself or in combination with RES, significantly reduced LV infarct area (57%), and normalized LV hemodynamic parameters like LVEDP (100%), LVSP (95.4%), LV +dp/dt and -dp/dt (102 and 73.1%, respectively). CoQ10 also decreased serum levels of brain natriuretic peptide (70%), and various circulating inflammatory markers like TNF-α (83.2%) and IL-6 (83.2%). Regarding oxidative stress, TBARS scores were lowered with a concurrent increase in both superoxide dismutase and glutathione peroxidase activities with CoQ10 alone or in combination with RES. Coenzyme Q10 protects against the acute sequelae of myocardial infarction. It profoundly reduced infarct area, inflammation and oxidative stress while normalizing LV hemodynamics post MI.


Randomized, double-blind, parallel-group, 48-week study for efficacy and safety of a higher-dose rivastigmine patch (15 vs. 10 cm²) in Alzheimer's disease.
Determine whether patients with Alzheimer's disease demonstrating functional and cognitive decline, following 24-48 weeks of open-label treatment with 9.5 mg/24 h (10 cm(2)) rivastigmine patch, benefit from a dose increase in a double-blind (DB) comparative trial of two patch doses. Patients meeting prespecified decline criteria were randomized to receive 9.5 or 13.3 mg/24 h (15 cm(2)) patch during a 48-week, DB phase. Coprimary outcomes were change from baseline to week 48 on the Instrumental Activities of Daily Living domain of the Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-IADL) scale and the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog). Safety and tolerability were assessed. Of 1,584 patients enrolled, 567 met decline criteria and were randomized. At all timepoints, ADCS-IADL and ADAS-cog scores favoured the 13.3 mg/24 h patch. The 13.3 mg/24 h patch was statistically superior to the 9.5 mg/24 h patch on the ADCS-IADL scale from week 16 (p = 0.025) onwards including week 48 (p = 0.002), and ADAS-cog at week 24 (p = 0.027), but not at week 48 (p = 0.227). No unexpected safety concerns were observed. The 13.3 mg/24 h rivastigmine patch significantly reduced deterioration in IADL, compared with the 9.5 mg/24 h patch, and was well tolerated.


Prevalence and validity of ACR/EULAR remission in four European early rheumatoid arthritis cohorts.
In 2011 an ACR/EULAR collaboration developed new remission definitions for RA. In the present study, we evaluated the prevalence and predictive validity of these new ACR/EULAR remission criteria in 4 different European early rheumatoid arthritis cohorts. Data from a tot al of 722 patients with early RA were analysed. Presence of remission at 6 months, as defined by one of the 4 proposed ACR/EULAR remission definitions was used to predict good functional and radiological outcome between 1 and 2 years of follow-up. Remission rates at 6 months ranged from 2-17% (Boolean definition) between the four cohorts. The level of HAQ and radiological damage varied between cohorts. Patients in remission at 6 months have an increased likelihood of long-term good outcome in terms of HAQ stability, but not radiographic stability. The performance of the practice definitions of remission was highly similar to the trial definitions. CRP status seems to add little information to the classification of remission in early RA. In clinical practice, a minority of patients with early RA achieves remission in the first 6 months of treatment. Remission at 6 months is predictive for good HAQ outcome between year 1 and 2 after inclusion, but not radiographic stability.


Nonsense-mediated decay of mRNA for the selenoprotein phospholipid hydroperoxide glutathione peroxidase is detectable in cultured cells but masked or inhibited in rat tissues.
Previous studies of mRNA for classical glutathione peroxidase 1 (GPx1) demonstrated that hepatocytes of rats fed a selenium-deficient diet have less cytoplasmic GPx1 mRNA than hepatocytes of rats fed a selenium-adequate diet. This is because GPx1 mRNA is degraded by the surveillance pathway called nonsense-mediated mRNA decay (NMD) when the selenocysteine codon is recognized as nonsense. Here, we examine the mechanism by which the abundance of phospholipid hydroperoxide glutathione peroxidase (PHGPx) mRNA, another selenocysteine-encoding mRNA, fails to decrease in the hepatocytes and testicular cells of rats fed a selenium-deficient diet. We demonstrate with cultured NIH3T3 fibroblasts or H35 hepatocytes transiently transfected with PHGPx gene variants under selenium-supplemented or selenium-deficient conditions that PHGPx mRNA is, in fact, a substrate for NMD when the selenocysteine codon is recognized as nonsense. We also demonstrate that the endogenous PHGPx mRNA of untransfected H35 cells is subject to NMD. The failure of previous reports to detect the NMD of PHGPx mRNA in cultured cells is likely attributable to the expression of PHGPx cDNA rather than the PHGPx gene. We conclude that 1) the sequence of the PHGPx gene is adequate to support the NMD of product mRNA, and 2) there is a mechanism in liver and testis but not cultured fibroblasts and hepatocytes that precludes or masks the NMD of PHGPx mRNA.


Structure and mechanism of proton transport through the transmembrane tetrameric M2 protein bundle of the influenza A virus.
The M2 proton channel from influenza A virus is an essential protein that mediates transport of protons across the viral envelope. This protein has a single transmembrane helix, which tetramerizes into the active channel. At the heart of the conduction mechanism is the exchange of protons between the His37 imidazole moieties of M2 and waters confined to the M2 bundle interior. Protons are conducted as the total charge of the four His37 side chains passes through 2(+) and 3(+) with a pK(a) near 6. A 1.65 A resolution X-ray structure of the transmembrane protein (residues 25-46), crystallized at pH 6.5, reveals a pore that is lined by alternating layers of sidechains and well-ordered water clusters, which offer a pathway for proton conduction. The His37 residues form a box-like structure, bounded on either side by water clusters with well-ordered oxygen atoms at close distance. The conformation of the protein, which is intermediate between structures previously solved at higher and lower pH, suggests a mechanism by which conformational changes might facilitate asymmetric diffusion through the channel in the presence of a proton gradient. Moreover, protons diffusing through the channel need not be localized to a single His37 imidazole, but instead may be delocalized over the entire His-box and associated water clusters. Thus, the new crystal structure provides a possible unification of the discrete site versus continuum conduction models.


The poliovirus sensitivity (PVS) gene is on chromosome 19q12----q13.2.
Sensitivity to nonmodified poliovirus infection is an autosomal dominant trait, specific to primates. The gene for poliovirus sensitivity (PVS) is encoded on human chromosome 19. In order to sublocalize the PVS gene, we infected rodent-human hybrid cell lines that divide human chromosome 19 into four regions with poliovirus 1 and/or 3. When infected, these hybrid cell lines showed the typical cytopathic effect of poliovirus infection only if they contained 19q12----q13.2 as the smallest region of overlap. Appropriate negative and positive controls were used. PVS may be of relevance to myotonic dystrophy (DM) and the inherited motor neuron diseases: to DM because it localizes to the same region of chromosome 19 and to the inherited motor neuron diseases because it encodes a cell-surface receptor expressed on motor neurons.


Work injury management model and implication in Hong Kong: a literature review.
The objective of this review is to explore the work injury management models in literatures and the essential components in different models. The resulting information could be used to develop an integrated holistic model that could be applied in the work injury management system in Hong Kong. A keyword search of MEDLINE and CINAHL databases was conducted. A total of 68 studies related to the management of an injury were found within the above mentioned electronic database. Together with the citation tracking, there were 13 studies left for selection after the exclusion screening. Only 7 out of those 13 studies met the inclusion criteria for review. It is noticeable that the most important component in the injury management model in the reviewed literatures is early intervention. Because of limitations in Employees' Compensation Ordinance in Hong Kong, there is an impetus to have a model and practice guideline for work injury management in Hong Kong to ensure the quality of injury management services. At the end of this paper, the authors propose a work injury management model based on the employees' compensation system in Hong Kong. This model can be used as a reference for those countries adopting similar legislation as in Hong Kong.


Female urine-induced male mice ultrasonic vocalizations, but not scent-marking, is modulated by social experience.
Despite the evidence for a communicative function of rodent scent marks and ultrasonic vocalizations, relatively little is known about the impact of social factors on these two forms of communication. Here, we tested the effects of two important social factors, prior exposure to a female and freshness of female urine, on male scent marks and ultrasonic vocalizations elicited by female urine. We also asked whether a recently reported strain difference between the highly social strain C57BL/6J (B6) and the mouse model of autism BTBR T+tf/J (BTBR) herein is specifically seen in response to female urine or also detectable in response to male urine traces. Results show that the emission of female urine-elicited ultrasonic vocalizations was dependent on previous female experience, while scent-marking behavior was not affected. A positive correlation was detected between scent-marking behavior and ultrasonic calling in the most biologically relevant context, male mice exposed to fresh female urine after female experience. Correlations were less prominent or missing in less biologically relevant contexts, e.g. in male mice exposed to fresh female urine without previous female experience, indicating that previous female experience is affecting both the emission of female urine-elicited ultrasonic vocalizations and the correlation between olfactory and acoustic communication. The strain difference in scent-marking behavior and ultrasonic calling between B6 and BTBR appears to be specific to female urine-elicited behavior as it was not seen in response to male urine traces, highlighting the relevance of the social context in which mouse communication is evaluated.


The Role of Xenobiotic Receptors on Hepatic Glycolipid Metabolism.
PXR (Pregnane X Receptor) and CAR (Constitutive Androstane Receptor) are termed as xenobiotic receptors, which are known as core factors in regulation of the transcription of metabolic enzymes and drug transporters. However, accumulating evidence has shown that PXR and CAR exert their effects on energy metabolism through the regulation of gluconeogenesis, lipogenesis and β-oxidation. Therefore, in this review, we are trying to summary recent advances to show how xenobiotic receptors regulate energy metabolism. A structured search of databases has been performed by using focused review topics. According to conceptual framework, the main idea of research literature was summarized and presented. For introduction of each receptor, the general introduction and the critical functions in hepatic glucose and lipid metabolism have been included. Recent important studies have shown that CAR acts as a negative regulator of lipogenesis, gluconeogenesis and β -oxidation. PXR activation induces lipogenesis, inhibits gluconeogenesis and inhabits β-oxidation. In this review, the importance of xenobiotic receptors in hepatic glucose and lipid metabolism has been confirmed. Therefore, PXR and CAR may become new therapeutic targets for metabolic syndrome, including obesity and diabetes. However, further research is required to promote the clinical application of this new energy metabolism function of xenobiotic receptors.


[Interneuronal signaling mediated by the trans-synaptic diffusion of neurotransmitters].
A great number of modern neurophysiological studies give evidence about the possibility of the extrasynaptic diffusion of the released neurotransmitters. Such observations challenge the established view on synapses as isolated communication channels between pre- and postsynaptic neurones. In the present review article, we consider the latest experimental data on the interneuronal cross-talk mediated by extrasynaptic diffusion of L-glutamate (L-Glu) and gamma-amino-butyric acid (GABA). Possible physiological significance of this phenomenon is also discussed.


Modulation of the inwardly rectifying potassium channel IRK1 by the m1 muscarinic receptor.
Modulation of the inwardly rectifying potassium channel (IRK1) by the m1 muscarinic receptor was studied with the whole-cell patch-clamp recording technique with the use of a mammalian expression system. After transfection with IRK1 and m1 muscarinic receptor genes, tsA cells expressed a cesium-sensitive inwardly rectifying potassium conductance that was reduced on application of the muscarinic receptor agonist carbachol. This reduction was reversible on washout of carbachol and could be completely inhibited by the muscarinic receptor antagonist atropine. Conversely, stimulation of the m2 muscarinic receptor, when coexpressed with IRK1, resulted in no change in IRK1 current amplitude. Phorbol-12, 13-dibutyrate, an activator of protein kinase c (PKC), mimicked the effect of m1 muscarinic receptor stimulation by inhibiting the IRK1 conductance. Preincubation with staurosporine or the specific PKC inhibitor calphostin C, before application of carbachol, fully prevented the inhibition of IRK1 by m1 muscarinic receptor stimulation. Administration of 8-bromo-cAMP, an activator of protein kinase A, and thapsigargin, a stimulator of intracellular calcium release, had no effect on IRK1, suggesting that these second messengers were not involved in the m1 muscarinic receptor-induced response. Therefore, the data indicate that the m1 muscarinic receptor inhibits IRK1, presumably via stimulation of PKC. As IRK1 is widely distributed throughout the central nervous system, it is possible that such an action on IRK1 underlies the inhibitory effects of muscarinic receptor stimulation on inwardly rectifying potassium conductances observed in the brain.


Temporal analysis of natural variation for the rate of leaf production and its relationship with flowering initiation in Arabidopsis thaliana.
Vegetative growth and flowering initiation are two crucial developmental processes in the life cycle of annual plants that are closely associated. The timing of both processes affects several presumed adaptive traits, such as flowering time (FT), total leaf number (TLN), or the rate of leaf production (RLP). However, the interactions among these complex processes and traits, and their mechanistic bases, remain largely unknown. To determine the genetic relationships between them, the natural genetic variation between A. thaliana accessions Fei-0 and Ler has been studied using a new population of 222 LerxFei-0 recombinant inbred lines. Temporal analysis of the parental development under a short day photoperiod distinguishes two vegetative phases differing in their RLP. QTL mapping of RLP in consecutive time intervals of vegetative development indicates that Ler/Fei-0 variation is caused by 10 loci whose small to moderate effects mainly display two different temporal patterns. Further comparative QTL analyses show that most of the genomic regions affecting FT or TLN also alter RLP. In addition, the partially independent genetic bases observed for FT and TLN appear determined by several genomic regions with two different patterns of phenotypic effects: regions with a larger effect on FT than TLN, and vice versa. The distinct temporal and pleiotropic patterns of QTL effects suggest that natural variation for flowering time is caused by different genetic mechanisms involved in vegetative and/or reproductive phase changes, most of them interacting with the control of leaf production rate. Thus, natural selection might contribute to maintain this genetic variation due to its phenotypic effects not only on the timing of flowering initiation but also on the rate of vegetative growth.


Understanding the Roles of Remoteness and Indigenous Status in Rural and Remote Road Trauma in North Queensland: Using a Mixed-Methods Approach.
Road trauma is a significant health problem in rural and remote regions of Australia, particularly for Indigenous communities. This study aims to identify and compare the circumstances leading to (proximal causation) and social determinants of (distal causation) crashes of Indigenous and non-Indigenous people in these regions and their relation to remoteness. This is a topic seriously under-researched in Australia. Modelled on an earlier study, 229 persons injured in crashes were recruited from local health facilities in rural and remote North Queensland and interviewed, mainly by telephone, according to a fixed protocol which included a detailed narrative of the circumstances of the crash. A qualitative analysis of these narratives identified several core themes, further explored statistically in this sample, supplemented by participants in the earlier study with compatible questionnaire data, designed to determine which factors were more closely associated with Indigenous status and which with remoteness. Indigenous participants were less often vehicle controllers, more likely to have recently been a drink driver or passenger thereof; to be unemployed, unlicensed, distracted or fatigued before the crash, alcohol dependent and have lower perceived social, but not personal, locus of control in a traffic crash than non-Indigenous persons. Differences between Indigenous and non-Indigenous participants are largely ascribable to hardship and transport disadvantage due to lack of access to licensing and associated limitations on employment opportunities. Based on these findings, a number of policy recommendations relating to educational, enforcement and engineering issues have been made.


Conservation objectives and sea-surface temperature anomalies in the Great Barrier Reef.
Spatial and temporal dynamics of ecological processes have long been considered important in marine systems, but seldom have conservation objectives been set for them. Climate change makes the consideration of the dynamics of ecological processes in the design of marine protected areas critical. We analyzed sea-surface temperature (SST) trends and variability in Great Barrier Reef Marine Park (GBRMP) for 25 years and formulated and tested whether three sets of notional conservation objectives were met to illustrate the potential for planning to address climate change. Given mixed and limited evidence that no-take areas increase resilience to disturbances such as anomalously high temperatures (i.e., temperatures ≥1 °C above weekly mean temperature), our conservation objectives focused on areas less likely to be affected by such events at extents ranging from the entire Great Barrier Reef to the system of no-take zones and individual no-take zones. The objective sets were (1) at least 50% of temperature refugia (i.e., pixels that had high-temperature anomalies <5% or <7% of the time) within no-take zones, (2) maximum occurrence of high-temperature anomalies is <10%,< 20%, or <30% of total no-take area 90% of the time, and (3) coverage of any single no-take zone by high-temperature anomalies occurs <5% or <10% of the time. We used satellite imagery from 1985-2009 to measure SST to determine high-temperature anomalies. SSTs in the Great Barrier Reef increased significantly in some regions, and some of the conservation objectives were met by the park's current zoning plan. Dialogue between conservation scientists and managers is needed to develop appropriate conservation objectives under climate change and strategies to meet them.


Effect of roasted soybeans and corn on performance and ruminal and blood metabolites of dairy calves.
Newborn Holstein calves (n = 132) were used to evaluate three protein sources (soybean meal and soybeans roasted to an exit temperature of 138 or 146 degrees C) that contained 30, 45, or 52% RUP, respectively. Each was used with either raw corn or corn roasted to an exit temperature of 135 degrees C. Roasting of corn increased starch gelatinization from 34.8 to 118.6 mg of maltose equivalents/g of sample. Six pelleted isonitrogenous calf starters (18% CP) were fed for ad libitum consumption from 0.5 to 8 wk of age. Performance of calves fed soybeans roasted at 146 degrees C plus raw corn was superior to that of calves fed soybean meal plus raw corn but was similar to the performance of calves fed soybean meal plus roasted corn. Roasted corn tended to improve calf performance when used with soybean meal and, to a lesser degree, when used with soybeans roasted at 138 degrees C but depressed performance when used with soybeans roasted at 146 degrees C. Ruminal concentrations of NH3, butyrate, and total VFA and plasma concentrations of urea were higher for calves fed soybean meal. Ruminal pH and lactate, plasma NEFA, and blood BHBA concentrations were unaffected by starter. Performance was superior when calves consumed protein and corn sources with similar degrees of ruminal availability.


Field testing of lake water chemistry with a portable and an AUV-based mass spectrometer.
Two mass spectrometers (MS) are tested for the measurement of volatile substances, such as hydrocarbons and metabolic gases, in natural waters. KOALA is a backpackable MS operated from above the water surface, in which samples are pumped through a flow cell using a syringe. NEREUS is an underwater instrument hosted by an autonomous underwater vehicle (AUV) that is linked to a communications network to provide chemical data in real time. The mass analyzers of the two MS are nearly identical cycloids, and both use flat-plate membrane inlets. Testing took place in an eutrophic, thermally stratified lake exhibiting steep chemical gradients and significant levels of methane. KOALA provided rapid multispecies analysis of dissolved gases, with a detection limit for methane of 0.1 ppm (readily extendable to 0.01 ppm) and savings of time of at least a factor of 10 compared to that of conventional analysis. The AUV-mounted NEREUS additionally provided rapid spatial coverage and the capability of performing chemical surveys autonomously. Tests demonstrated the need for temperature control of a membrane inlet when steep thermal gradients are present in a water body, as well as the benefits of co-locating all sensors on the AUV to avoid interference from chemically different waters entering and draining from the free-flooding outer hull. The ability to measure dissolved volatiles provided by MS offers potential for complementarity with ionic sensors in the study of natural waters, such as in the case of the carbonate system.


Focus on anorexia nervosa: modern psychological treatment and guidelines for the adolescent patient.
Anorexia nervosa is a serious condition associated with high mortality. Incidence is highest for female adolescents, and prevalence data highlight a pressing unmet need for treatment. While there is evidence that adolescent-onset anorexia has relatively high rates of eventual recovery, the illness is often protracted, and even after recovery from the eating disorder there is an ongoing vulnerability to psychosocial problems in later life. Family therapy for anorexia in adolescence has evolved from a generic systemic treatment into an eating disorder-specific format (family therapy for anorexia nervosa), and this approach has been evidenced as an effective treatment. Individual treatments, including cognitive behavioral therapy, also have some evidence of effectiveness. Most adolescents can be effectively and safely managed as outpatients. Day-patient treatment holds promise as an alternative to inpatient treatment or as an intensive program following a brief medical admission. Evidence is emerging of advantages in detecting and treating adolescent anorexia nervosa in specialist community-based child and adolescent eating-disorder services accessible directly from primary care. Limitations and future directions for modern treatment are considered.


Molecular diversity within clonal complex 22 methicillin-resistant Staphylococcus aureus encoding Panton-Valentine leukocidin in England and Wales.
Panton-Valentine leukocidin (PVL)-positive methicillin-resistant Staphylococcus aureus (MRSA) that are multi-locus sequence type clonal complex 22 (CC22) comprise a significant public health problem in the UK. In the present study we sought to determine the genetic diversity, and the respective patient demographics, among 47 PVL-MRSA with a CC22 pulsotype that occurred sporadically or in clusters in community and healthcare settings in eight of nine geographic regions in England and Wales between January 2005 and September 2007. Patient demographics and disease presentations were typical for PVL-S. aureus infections (mostly skin and soft tissue infections in individuals <40 years old); one patient with community-acquired pneumonia died. Although the isolates were closely genotypically related by spa typing and pulsed field gel electrophoresis, at least two variant groups were suggested. PCR detections demonstrated that the majority of the CC22 PVL-MRSA identified (n = 42; 89%) harboured SCCmecIVc, three had SCCmecIVd, one had SCCmecIV but was non-subtypeable, and one isolate harboured SCCmecV. At least three different PVL-encoding phages were detected: ФPVL, Ф108PVL and an unidentified icosahedral phage. Agar dilution MIC determinations showed that the CC22 PVL-MRSA identified were typically resistant to gentamicin and trimethoprim (43 of 47 isolates) and ciprofloxacin resistance was also noted in six isolates. In conclusion, the CC22 PVL-MRSA tested were geographically disseminated but highly genetically related. The observed variances in acquired elements (most notably SCCmec and PVL-encoding phages) suggested that CC22 PVL-MRSA in England and Wales have evolved on multiple occasions.


Classification of the Physical Surface in Sound-based Uroflowmetry.
This work constitutes a first approach to automatically classify the urination medium for non-invasive sound based uroflowmetry tests. Often the voiding flow impacts the toilet wall (often made of ceramic) instead of the water. This causes a reduction in the amplitude of the recorded audio signal, and thus a reduction in the amplitude of the extracted envelope. Analysing the envelope alone, it is not possible to tell accurately if the reduction in the amplitude is due to a low voiding flow or an impact on the toilet walls. In this work, we carry out a study on the classification of sound uroflowmetry data depending on the medium where the urine impacts within the toilet: water or ceramic. In the analysis, a classification algorithm is proposed to identify the physical medium automatically based on the urination acoustics. The classification algorithm takes as input the frequency spectrum, the variance, and the kurtosis of the audio signal corresponding to a voiding event.Clinical relevance- Sound uroflowmetry has a strong correlation with the standard uroflowmetry. It is useful for the non-invasive detection of pathologies associated with the urinary tract as a support tool for information processing and screening. It consists of a characterization of the urinary flow patterns by capturing the sound generated when the urine stream impacts the water in the toilet. Identifying the medium which originates the sound is of paramount importance to better interpret the sound uroflowmetry.


Malignant lymphomas following allogenic disease: transition from an immunological to a neoplastic disorder.
The graft versus host reaction which occurs in F(1) hybrid mice injected with parental spleen cells was used to examine several immunological theories of neoplasia. Long-term survivors of this reaction developed lymphoid neoplasms which resembled Hodgkin's disease and lymphosarcoma. Mice with these tumors were chimeras, but the parental cells present within their spleens had specific immunological tolerance toward host antigens. This, together with the finding that the tumors were transplantable only to isogenic recipients, indicates that the tumors were of host rather than donor origin.


Intrathecal production of interleukin-12 and gamma interferon in patients with bacterial meningitis.
To assess the role of interleukin-12 (IL-12) and gamma interferon (IFN-gamma) in children with bacterial meningitis, bioactive IL-12 (p70) and the inactive subunit p40 and IFN-gamma were measured in serum and cerebrospinal fluid (CSF) from 35 children with bacterial meningitis and 10 control subjects. The production of IFN-gamma is induced by IL-12 with tumor necrosis factor alpha (TNF-alpha) as a costimulator and inhibited by IL-10. CSF concentrations of IL-12 p40 as well as those of IFN-gamma were markedly elevated, whereas IL-12 p70 was hardly detectable. Detectable CSF levels of IFN-gamma correlated positively with IL-12 p40 (r = 0.40, P = 0.02) and TNF-alpha (r = 0.46, P = 0.04) but not with IL-6, IL-8, or IL-10. In contrast to CSF levels of TNF-alpha, IL-12, and IL-10, those of IFN-gamma were significantly higher in patients with pneumococcal meningitis than in children with meningitis caused by Haemophilus influenzae and Neisseria meningitidis, presumably because of a high CSF TNF-alpha/IL-10 ratio in the former. We suggest that IL-12- and TNF-alpha-induced IFN-gamma production may contribute to the natural immunity against microorganisms in the CSF compartment during the acute phase of bacterial meningitis.


Low oxygen tension is a more potent promoter of chondrogenic differentiation than dynamic compression.
During fracture healing and microfracture treatment of cartilage defects mesenchymal stem cells (MSCs) infiltrate the wound site, proliferate extensively and differentiate along a cartilaginous or an osteogenic lineage in response to local environmental cues. MSCs may be able to directly sense their mechanical environment or alternatively, the mechanical environment could act indirectly to regulate MSC differentiation by inhibiting angiogenesis and diminishing the supply of oxygen and other regulatory factors. Dynamic compression has been shown to regulate chondrogenesis of MSCs. In addition, previous studies have shown that a low oxygen environment promotes in vitro chondrogenesis of MSCs. The hypothesis of this study is that a low oxygen environment is a more potent promoter of chondrogenic differentiation of MSCs embedded in agarose hydrogels compared to dynamic compression. In MSC-seeded constructs supplemented with TGF-beta3, GAG and collagen accumulation was higher in low oxygen conditions compared to normoxia. For normoxic and low oxygen culture GAG accumulation within the agarose hydrogel was inhomogeneous, with low levels of GAG measured in the annulus of constructs maintained in normoxic conditions. Dynamic compression did not significantly increase GAG or collagen accumulation in normoxia. However under low oxygen conditions, dynamic compression reduced GAG accumulation compared to free-swelling controls, but remained higher than comparable constructs maintained in normoxic conditions. This study demonstrates that continuous exposure to low oxygen tension is a more potent pro-chondrogenic stimulus than 1h/day of dynamic compression for porcine MSCs embedded in agarose hydrogels.


The epidermal growth factor receptor axis: support for a new target for oral premalignancy.
This perspective on the report by Benchekroun et al. in this issue of the journal (beginning on page 800) examines new studies of factors in the epidermal growth factor receptor (EGFR) axis (including copy number alterations at the EGFR locus) that potentially predict the development of oral cancer; this work was conducted in a chemoprevention trial cohort of patients with oral premalignant lesions. The new data raise the possibility that a subset of oral premalignant lesions may benefit from specific therapeutic targeting of the EGFR axis.


A 47-Year-Old Woman with a Retained Central Venous Catheter Line Guidewire Presenting with a Right Atrial Thrombus Requiring Removal During Open Heart Surgery: A Case Report.
BACKGROUND A central venous catheter (CVC) is an indwelling catheter that is inserted into a large central vein for different purposes, including hemodynamic monitoring and administration of fluids and medications. This report is of a 47-year-old woman with a retained CVC line guidewire presenting with a large right atrial thrombus requiring removal during open heart surgery. CVC insertion is one of the most frequently attempted procedures in intensive care units, emergency departments, and operation rooms, especially for critically ill patients. Possible complications range from failure to place the catheter to cardiac arrest. One of the rarest complications is missing the guidewire after insertion, which is usually discovered early after inserting it. CASE REPORT We report the case of a 47-year-old woman who had a CVC line inserted following complicated open cholecystectomy. A few years later, she developed shortness of breath, with an incidental finding of a huge right atrial thrombus and a wire shown on transthoracic echocardiography. The right atrial thrombus required open heart surgery to excise the thrombus and the wire, which was done successfully. The thrombus was histopathologically and clinically proven to be an organized right atrial thrombus formed around the CVC guidewire. CONCLUSIONS This case report presents a rare complication of CVC insertion. Because this procedure is increasingly used, clinicians should be aware of the potential complications of retained CVC lines. Moreover, this report outlines different techniques to prevent such fatal complications and emphasizes the significance of radiography after insertion.


Intraductal Papillary Mucinous Neoplasms Arise From Multiple Independent Clones, Each With Distinct Mutations.
Intraductal papillary mucinous neoplasms (IPMNs) are lesions that can progress to invasive pancreatic cancer and constitute an important system for studies of pancreatic tumorigenesis. We performed comprehensive genomic analyses of entire IPMNs to determine the diversity of somatic mutations in genes that promote tumorigenesis. We microdissected neoplastic tissues from 6-24 regions each of 20 resected IPMNs, resulting in 227 neoplastic samples that were analyzed by capture-based targeted sequencing. Somatic mutations in genes associated with pancreatic tumorigenesis were assessed across entire IPMN lesions, and the resulting data were supported by evolutionary modeling, whole-exome sequencing, and in situ detection of mutations. We found a high prevalence of heterogeneity among mutations in IPMNs. Heterogeneity in mutations in KRAS and GNAS was significantly more prevalent in IPMNs with low-grade dysplasia than in IPMNs with high-grade dysplasia (P < .02). Whole-exome sequencing confirmed that IPMNs contained multiple independent clones, each with distinct mutations, as originally indicated by targeted sequencing and evolutionary modeling. We also found evidence for convergent evolution of mutations in RNF43 and TP53, which are acquired during later stages of tumorigenesis. In an analysis of the heterogeneity of mutations throughout IPMNs, we found that early-stage IPMNs contain multiple independent clones, each with distinct mutations, indicating their polyclonal origin. These findings challenge the model in which pancreatic neoplasms arise from a single clone. Increasing our understanding of the mechanisms of IPMN polyclonality could lead to strategies to identify patients at increased risk for pancreatic cancer.


Mortality and morbidity associated with pressure- and volume-limited infant ventilators.
The effect of pressure-limited (PL) and volume-limited (VL) ventilation on mortality and morbidity in infants with severe hyaline membrane disease (HMD) was examined in a prospective controlled study. Criteria for mechanical ventilation were PaO2 value of 50 mm Hg or less or a Paco2 value of 70 mm Hg or greater, while the infant was receiving nasal continuous positive airway pressure (CPAP) at oxygen concentrations (FIO2) of 0.8 or greater and CPAP of 8 cm H2O or greater; HMD associated with severe perinatal asphyxia requiring mechanical ventilation in the delivery room. Consecutive patients were alternately assigned to receive either PL or VL ventilation. Twenty infants were ventilated with PL machines using low peak inspiratory pressures (mean maximum inspiratory pressure of 28 cm H2O) and prolonged inspiratory times. Twenty other infants were ventilated with VL machines, using essentially unlimited peak inspiratory pressures (mean maximum inspiratory pressure of 62 mm H2O) and prolonged expiratory times. There were no significant differences in survival, incidence of pneumothorax or pulmonary interstitial emphysema, or noteworthy bronchopulmonary dysplasia.


Oligometastatic breast cancer treated with curative-intent stereotactic body radiation therapy.
Prospective pilot study to assess patient outcome after stereotactic body radiation therapy (SBRT) for limited metastases from breast cancer. Forty patients with < or =5 metastatic lesions received curative-intent SBRT, while 11 patients with >5 lesions, undergoing SBRT to < or =5 metastatic lesions, were treated with palliative-intent. Among those treated with curative-intent, 4-year actuarial outcomes were: overall survival of 59%, progression-free survival of 38% and lesion local control of 89%. On univariate analyses, 1 metastatic lesion (versus 2-5), smaller tumor volume, bone-only disease, and stable or regressing lesions prior to SBRT were associated with more favorable outcome. Patients treated with palliative-intent SBRT were spared morbidity and mortality from progression of treated lesions, though all developed further metastatic progression shortly (median 4 months) after enrollment. SBRT may yield prolonged survival and perhaps cure in select patients with limited metastases. Palliative-intent SBRT may be warranted for symptomatic or potentially symptomatic metastases.


Spin polarization and tunable valley degeneracy in a MoS2 monolayer via proximity coupling to a Cr2O3 substrate.
Introducing magnetism in two-dimensional materials is of particular importance for both fundamental research and practical applications in nanoscale spintronics. Herein, we report the lifting of valley degeneracy in a MoS2 monolayer via magnetic proximity coupling to an insulating antiferromagnetic Cr2O3 substrate and the gate-voltage tunability of the MoS2/Cr2O3 heterojunction on the basis of first-principles calculations. Our calculations suggest that there is a large Zeeman splitting of 23.4 meV in the MoS2 monolayer due to strong spin-orbit coupling, corresponding to a magnetic exchange field of 100 T. Both spin and valley indices flip when the magnetic ordering of Cr2O3 is reversed. More interestingly, the charge transfer, magnetic moment, band gap and Schottky barrier of the heterojunction can be tuned continually by applying an external out-of-plane gate voltage, resulting in variable valley Zeeman splitting ranging from 11.3 to 34.5 meV. These findings demonstrate great potential applications of the Cr2O3/MoS2 heterojunction in nanoscale spintronics.


Improving the healthcare response to domestic violence and abuse in sexual health clinics: feasibility study of a training, support and referral intervention.
Sexual health and gynaecological problems are the most consistent and largest physical health differences between abused and non-abused female populations. Sexual health services are well placed to identify and support patients experiencing domestic violence and abuse (DVA). Most sexual health professionals have had minimal DVA training despite English National Institute for Health and Care Excellence recommendations. We sought to determine the feasibility of an evidence-based complex DVA training intervention in female sexual health walk-in services (IRIS ADViSE: Identification and Referral to Improve Safety whilst Assessing Domestic Violence in Sexual Health Environments). An adaptive mixed method pilot study in the female walk-in service of two sexual health clinics. Following implementation and evaluation at site 1, the intervention was refined before implementation at site 2. The intervention comprised electronic prompts, multidisciplinary training sessions, clinic materials and simple referral pathways to IRIS ADViSE advocate-educators (AEs). The pilot lasted 7 weeks at site 1 and 12 weeks at site 2. Feasibility outcomes were to assign a supportive DVA clinical lead, an IRIS ADViSE AE employed by a local DVA service provider, adapt electronic records, develop local referral pathways, assess whether enquiry, identification and referral rates were measurable. Both sites achieved all feasibility outcomes: appointing a supportive DVA clinical lead and IRIS ADViSE AE, establishing links with a local DVA provider, adapting electronic records, developing local referral pathways and rates of enquiry, identification and referral were found to be measurable. Site 1: 10% enquiry rate (n=267), 4% identification rate (n=16) and eight AE referrals. Site 2: 61% enquiry rate (n=1090), a 7% identification rate (n=79) and eight AE referrals. IRIS ADViSE can be successfully developed and implemented in sexual health clinics. It fulfils the unmet need for DVA training. Longer-term evaluation is recommended.


Local Protocol Variations for Image Guided Radiation Therapy in the Multicenter Dutch Hypofractionation (HYPRO) Trial: Impact of Rectal Balloon and MRI Delineation on Anorectal Dose and Gastrointestinal Toxicity Levels.
The phase 3 HYpofractionated irradiation for PROstate cancer (HYPRO) trial randomized patients with intermediate- to high-risk localized prostate cancer to conventionally fractionated (78 Gy in 39 fractions) or hypofractionated (64.6 Gy in 19 fractions) radiation therapy. Differences in techniques and treatment protocols were present between participating centers. This study aimed to compare dose parameters and patient-reported gastrointestinal symptoms between these centers. From the trial population, we selected patients (N=572) from 4 treatment centers who received image guided (IG) intensity modulated radiation therapy (IMRT). Center A (n=242) applied planning target volume (PTV) margins of 5 to 6 mm and was considered the reference center. In center B (n=170, 7-mm margins), magnetic resonance imaging (MRI) was integrated in treatment planning. An endorectal balloon (ERB) was applied in center C (n=85, 7-mm margins). Center D (n=75) applied the largest PTV margins of 8 mm. The study protocol provided identical anorectal dose constraints, and local protocols were applied for further treatment optimization. Anorectal dose-surface histograms were compared by applying t tests. Rectal complaints during follow-up (6 months to 4 years) were compared in a generalized linear model, adjusting for age, follow-up, treatment arm, and hormone therapy. Favorable anorectal dose distributions were found for center B (MRI delineation) and center C (ERB application) as compared with centers A and D. These were associated with significantly lower incidences of patient-reported complaints of rectal incontinence, use of incontinence pads, and rectal discomfort in these centers. Furthermore, lower incidences of increased stool frequency (≥4 per day) and mucous loss were observed for center C. Despite comparable IG-IMRT techniques and predefined dose constraints, pronounced differences in dose distributions and toxicity rates were observed. MRI delineation and ERB application were associated with favorable rectal dose parameters and toxicity profiles, whereas a 2- to 3-mm difference in PTV margins did not translate into observed differences. We conclude that choices for treatment optimization of IG-IMRT are important and clinically relevant for patients since these affect symptoms experienced in daily life.


Personality disorder and self-rated health: a population-based cross-sectional survey.
Little is known about the impact of personality disorder (PD) on the health of people living in the community. The authors set out to examine the association between PD and general health, using a cross-sectional survey of a representative community sample in London, UK. A total of 1,698 adults aged 16 years or over from 1,075 randomly selected households were recruited and interviewed face-to-face by trained interviewers. Using multivariable logistic regression, the authors examined the cross-sectional association between PD screen status, as assessed by the Standardised Assessment of Personality-Abbreviated Scale (SAPAS), and self-rated health, adjusting for demographic and health covariates. Of the participants, 14.5% screened positively for PD. A greater proportion of those scoring positively for PD reported poor self-rated health, compared to screen negative participants (41.3% versus 15.0%). This association was reduced, but remained significant, after adjustment for potential confounders (unadjusted odds ratio (OR) = 3.99, 95% CI [2.93, 5.42]; fully adjusted OR = 1.53, 95% CI [1.02, 2.29]. Of note, subthreshold symptoms of PD were significantly associated with poor self-rated health (unadjusted OR per unit SAPAS score increment = 1.53, 95% CI [1.40, 1.67]; fully adjusted OR = 1.19, 95% CI [1.07, 1.33]. Furthermore, people screening positive for PD were more likely to report multiple (three or more) long-standing illnesses. The authors conclude that in the general population, individuals who are at high risk for PD are independently at increased risk of poor general health.


The ethics of practice guidelines.
Practice guidelines, which are assistive tools for clinicians, have a long tradition in clinical medicine. Traditionally, these documents were developed by physicians to improve quality of care and can provide practitioners with valuable medical information and improve objectivity in medical decision making. Guidelines development by nonphysician groups is increasing. Guidelines are now intended to assist in decreasing costs, in reducing liability risk, and in utilization review, among other activities. Despite this enthusiasm for guidelines, their development is variable and validity remains largely untested. The intended clinical and nonclinical applications of guidelines require critical analysis. Practice guidelines are not inherently unethical. However, applications of nonmedical values combined with intense pressures on health care provision create an environment for guideline misuse. The ethical implications of practice guidelines are examined in our article.


SERS detection of the biomarker hydrogen cyanide from Pseudomonas aeruginosa cultures isolated from cystic fibrosis patients.
Pseudomonas aeruginosa is the primary cause of chronic airway infections in cystic fibrosis (CF) patients. Persistent infections are seen from the first P. aeruginosa culture in about 75% of young CF patients, and it is important to discover new ways to detect P. aeruginosa at an earlier stage. The P. aeruginosa biomarker hydrogen cyanide (HCN) contains a triple bond, which is utilized in this study because of the resulting characteristic C≡N peak at 2135 cm-1 in a Raman spectrum. The Raman signal was enhanced by surface-enhanced Raman spectroscopy (SERS) on a Au-coated SERS substrate. After long-term infection, a mutation in the patho-adaptive lasR gene can alter the expression of HCN, which is why it is sometimes not possible to detect HCN in the breath of chronically infected patients. Four P. aeruginosa reference strains and 12 clinical P. aeruginosa strains isolated from CF children were evaluated, and HCN was clearly detected from overnight cultures of all wild type-like isolates and half of the later isolates from the same patients. The clinical impact could be that P. aeruginosa infections could be detected at an earlier stage, because daily breath sampling with an immediate output could be possible with a point-of-care SERS device.


Lymphocyte-bound complement activation products as biomarkers for diagnosis of systemic lupus erythematosus.
Systemic lupus erythematosus (SLE) is frequently misdiagnosed due to the lack of definitive diagnostic tests. The purpose of this study was to determine specifically whether complement activation products (CAP) are deposited on lymphocytes of SLE patients and whether lymphocyte-bound CAP (LB-CAP) may serve as novel biomarkers for the diagnosis of SLE. We conducted a cross-sectional study of 224 patients with SLE, 179 patients with other diseases, and 114 healthy controls. LB-CAP on peripheral blood lymphocytes was measured by flow cytometry. Diagnostic utility of LB-CAP was determined by receiver operating characteristic (ROC) analysis. Significantly elevated levels of C4d and C3d were detected specifically on T and B lymphocytes (designated T-C4d, T-C3d, B-C4d, and B-C3d) of SLE patients. As diagnostic tools, T-C4d and B-C4d, respectively, were 56% sensitive/80% specific and 60% sensitive/82% specific in differentiating SLE from other diseases. Moreover, compared with measurement of anti-dsDNA, serum C3, or serum C4, measurement of T-C4d/B-C4d was significantly more sensitive in identifying SLE patients during a single clinic visit. This is the first investigation of lymphocytes bearing complement activation products in human disease. T-C4d and B-C4d have high diagnostic sensitivity and specificity for SLE and may have added value to current laboratory tests for SLE diagnosis.


How are treatment integrity data assessed? Reviewing the performance feedback literature.
Collecting treatment integrity data is critical for (a) strengthening internal validity within a research study, (b) determining the impact of an intervention on student outcomes, and (c) assessing the need for implementation supports. Although researchers have noted the increased inclusion of treatment integrity data in published articles, there has been limited attention to how treatment integrity is assessed. The purpose of this study was to review how treatment integrity is typically assessed in single-case design performance feedback articles. Doctoral students in school psychology coded 58 performance feedback studies to determine how treatment integrity data are assessed in this literature, and common intervention characteristics linked to treatment integrity assessment. Findings indicate that, although data were collected most frequently via direct observation by a researcher targeting intervention adherence, intervention characteristics varied widely across studies. Implications of results are discussed. (PsycINFO Database Record (c) 2018 APA, all rights reserved).


Routine biochemistry in suspected vitamin D deficiency.
Vitamin D deficiency, which continues to be widespread amongst persons of Asian descent in the UK, is often detected from abnormal results on routine biochemistry. The aim of this study was to assess the frequency of abnormal results from routine baseline tests of serum calcium, phosphate, and alkaline phosphatase in patients who subsequently proved to have vitamin D deficiency and secondary hyperparathyroidism. A retrospective examination was undertaken to assess these baseline indices in a cohort of 84 such patients seen in Bradford-5 male; 80 of Asian descent; median age 46 years (range 16-82); serum 25-hydroxyvitamin D<10 microg/L; parathyroid hormone >54 ng/L. Calcium was normal in 55 patients (66%), phosphate in 68 (81%) and alkaline phosphatase in 24 (29%). In only 5 patients were all three indices outside the normal range. The median parathyroid hormone concentration was significantly greater in patients with abnormal routine biochemistry (145 [range 55-1662] ng/L) than in patients with normal routine biochemistry (88 [59-322] ng/L) but the median 25-hydroxyvitamin D levels did not differ (3.1 [1.3-9.9] and 3.0 [1.5-7.3] microg/L). Routine biochemistry was normal in 20% of cases. If routine biochemistry is relied upon to detect vitamin D deficiency and osteomalacia, a substantial minority of cases will be missed.


Visual function in young adults following intrauterine growth retardation.
Intrauterine growth retardation (IUGR) resulting in infants born small for gestational age is a known risk factor for neurologic deficits and may predispose to poor cognitive development later in life. We recently found an association between IUGR and a reduced neuroretinal rim area at 18 years of age. We evaluated the possible association between IUGR and visual function. We studied 26 subjects who had been born small for gestational age and 20 subjects whose birth weights were appropriate for gestational age (controls) using letter acuity thresholds, color vision testing, full-threshold frequency doubling technology perimetry, and rarebit perimetry at 18 years of age. gestational age had a rarebit hit rate below the normal range as compared with none of the controls (P = .006). These 8 subjects had a significantly smaller rim-disc ratio compared with the subjects who were small for gestational age who had a normal rarebit hit rate (P = .047). The frequency doubling technology indices did not differ significantly between the control group and the group that was small for gestational age, nor did the visual acuity, refraction, and color vision test results. These data indicate that IUGR is associated with an increased rate of impaired visual function, which can be detected by using rarebit perimetry but not frequency doubling technology perimetry, visual acuity, or color vision tests.


Integrating person-centered and variable-centered approaches in the study of developmental courses and transitions in alcohol use: introduction to the special section.
This special section consists of research from the symposium "Integrating Person-Centered and Variable-Centered Approaches to the Study of Developmental Courses and Transitions in Alcohol Use," presented at the 1999 Annual Meeting of the Research Society on Alcoholism. The section focuses on ways to integrate variable-centered and person-centered approaches to better understand longitudinal trajectories of alcohol use and associated problems. Our aim is to increase awareness and discussion of alternative conceptual and quantitative approaches that involve both a person-centered and a variable-centered component, and to make these methods more accessible to alcohol and other drug researchers. The first paper provides a general latent variable modeling framework within which to conceptualize developmental questions that involve the combination of continuous latent variables and categorical variables that represent classifications of individuals into meaningful subgroups. This is followed by three empirical papers that use integrative methods to examine early adult outcomes of adolescent binge drinking; potential mediators of familial alcoholism effects on alcohol and tobacco use disorder comorbidity; and the ability of psychopathology, substance use, and parental history of alcohol problems to predict individual differences in the likelihood of transitions in drinking behavior during adolescence. The section concludes with a discussion of the statistical basis for integrating person-centered and variable-centered methods, a comparison of study findings, and directions for future research.


Prevalence of metabolic syndrome and its components among Chinese professional athletes of strength sports with different body weight categories.
There is an increasing concern on cardiometabolic health in young professional athletes at heavy-weight class. Our cross-sectional survey aimed to evaluate the prevalence of metabolic syndrome and clustering of metabolic risk factors in a population of young and active professional athletes of strength sports in China. From July 2006 to December 2008, a total of 131 male and 130 female athletes of strength sports were enrolled. We used two criteria provided by the Chinese Diabetes Society (2004) and the National Cholesterol Education Program's Adult Treatment Panel III (2002) to define the metabolic syndrome and its individual components, respectively. Regardless of their similar ages (mean: 21 years) and exercise levels, athletes in the heaviest-weight-class with unlimited maximum body weight (UBW) boundaries (mean weight and BMI: 130 kg and 38 kg/m(2) for men, 110 kg and 37 kg/m(2) for women) had significantly higher prevalence of metabolic syndrome than did those in all other body-weight-class with limited body weight (LBW) boundaries (mean weight and BMI: 105 kg and 32 kg/m(2) for men, 70 kg and 26 kg/m(2) for women). Prevalence of metabolic syndrome using CDS criteria (UBW vs. LBW: 89% vs. 18% for men, 47% vs. 0% for women) and its individual components, including central obesity, hypertension, hypertriglyceridemia, low high-density lipoprotein-cholesterol levels, and impaired fasting glucose, were all significantly higher in athletes at the heaviest weight group with UBW than all other weight groups with LBW. Our study suggests that professional athletes of strength sports at the heaviest-weight-class are at a significant increased risk of cardiometabolic disease compared with those at all other weight categories. The findings support the importance of developing and implementing the strategy of early screening, awareness, and interventions for weight-related health among young athletes.


[Treatment of ununited fractures and pseudarthrosis of long bones of the lower limbs complicated by osteomyelitis].
123 patients with ununited diaphyseal fractures and false joints of the shin bones (93) and the hip (30), complicated by purulent infection, were treated in the clinic for pyogenic complications and consequences of locomotor traumas of the CITO from 1988 to 1994 years. Most patients were men (110 patients). The posttraumatic period varied from several months to 12 years. Many patients before their admittance to the clinic were not once unsuccessfully operated 69 (56.1%) patients had osseous defects of the thigh and the shin, all patients contractures of joints of the lower extremities as well as substantial trophic disturbances and atrophy of the muscles. 12 patients underwent closed transosseous osteosynthesis by the apparatus of an external fixation. One stage surgery was carried out in 111 patients, which included radical fistulosequestrenecretomy (and when indicated--extended segmental sequestrectomy) and transosseous osteosynthesis by the apparatus of external fixation with the use of the needles, rods, or their combination. The feature of the osteosynthesis depended on the extent of bone defect, which has been developed after sequestrectomy, in the defect up to 4 cm monolocal osteosynthesis was used, in the defect from 5 to 8 cm--bilocal and if it were over 8 cm--multilocal osteosynthesis was preferable. One stage treatment resulted in favourable outcomes in 95.9% of patients: the osteomyelitis was eliminated, the integrity of the bone was restored and in a great majority of cases--the length of the extremity was preserved. The treatment duration was 1.5-2 times less than in commonly used methods.


Chromogenesis mirabilis in Streptomyces griseus.
A number of chromogenic Streptomyces, producing diffusible melanoid pigment on complex organic media, fail to form melanin pigment on conventionally used synthetic tyrosine agar. By means of our new melanin formation test, almost all the chromogenic streptomyces can now be detected in chemically defined medium. In contrast to ordinary chromogenic streptomyces, two streptomyces species of the International Streptomyces Project, S. griseus ISP 5236 and S. ornatus ISP 5307, produce melanin pigment only on synthetic tyrosine agar, without showing chromogenicity on complex organic media. From the results obtained with S. griseus ISP 5236 and S. phaeochromogenes ISP 5073, it was revealed that melanin formation by Streptomyces, in general, is inhibited by L-cysteine present in organic nitrogen sources incorporated into natural media. Most chromogenic species of streptomyces produce a higher level of tyrosinase and rapidly utilize L-cysteine in the culture media which result in the manifestation of good chromogenicity on natural media. Peculiarity of chromogenicity of S. griseus and S. ornatus might be due to the lower ability to produce tyrosinase and to utilize L-cysteine in the culture medium.