Imaging errors in localization of COMS-type plaques in choroidal melanoma brachytherapy.
To investigate mathematically and experimentally the sources of errors in localization of COMS-type plaques in melanoma brachytherapy when using ultrasound and transillumination and to give recommendations to avoid such errors. A computer-aided simulation tool was developed to model the errors seen in the patient images when using ultrasound imaging and transillumination during localization of the COMS-type plaque in melanoma brachytherapy. Several laboratory experiments were performed on sheep eyes to confirm the validity of the error sources and the simulator outputs. Results were compared to the intraoperative ultrasonographic patient images for validation. Based on mathematical modeling and computer simulation results, transillumination provides acceptable accuracy for small to medium tumors with less than 7-mm height but shows poor accuracy as the tumor height increases. In ultrasound imaging, two sources of error are predicted in longitudinal scan using our computer simulation modeling, and the results are supported by the experiments on sheep eyes and patient images taken during the operation. Both errors are related to the lens. The first error is due to attenuation and refraction of the lens causing opaque areas and a change of curvature in the image of the plaque edge that is nearest to the lens. The second type of error is related to the total internal reflection from the lens. The simulation method presented in this article allows quantitative assessment of the sources, mechanisms, and measures of errors in localization of the CMOS-type plaques by ultrasound and transillumination techniques. Errors predicted by the simulation method are validated by experiments. Error assessment by this method provides guidelines for avoiding such errors.


Modeling the septation initiation network (SIN) in fission yeast cells.
Cytokinesis in fission yeast is controlled by a signal transduction pathway called the Septation Initiation Network (SIN). From a dynamical point of view the most interesting questions about the regulation of fission yeast cytokinesis are: how do wild type cells ensure that septation is initiated only once per cycle? Why does the control system stay in a continuously septating state in some mutant strains? And how is it that the SIN remains active when cytokinesis fails? To answer these questions we construct a simplified mathematical model of the SIN and graft this regulatory module onto our previous model of cyclin-dependent kinase (Cdk) dynamics in fission yeast cells. The SIN is both activated and inhibited by mitotic Cdk/cyclin complexes. As a consequence of this dual regulation, the SIN gets activated only once at the end of mitosis, when Cdk activity drops. The mathematical model describes the timing of septation not only in wild type cells but also in mutants where components of the SIN are knocked out. The model predicts phenotypes of some uncharacterized mutant cells and shows how a cytokinesis checkpoint can stop the cell cycle if septation fails.


Prevalence of hepatic granulomas in chronic hepatitis B.
An increasing frequency of hepatic granulomas, up to 10%, in chronic hepatitis C patients is reported, and their presence is considered to be a predictor of treatment success. However, there is only one prevalence study on granuloma in chronic hepatitis B, and its significance for treatment outcome is unknown. We aimed to determine the prevalence of hepatic granulomas in a larger group of chronic hepatitis B patients and to compare their presence with the response to interferon therapy. Biopsy specimens of chronic hepatitis B patients were reevaluated for the presence of hepatic granulomas. All patients with hepatic granuloma were screened for other granulomatous diseases by tuberculin skin test, chest X-ray and computed tomography, venereal disease research laboratory, Brucella agglutination tests, and exposure to hepatotoxic agents. We screened 663 cases of chronic hepatitis B. Hepatic granulomas were found in 10 cases (1.5%). The granulomas could not be ascribed to any other reason. Of the 10 patients with hepatic granulomas, 4 responded to interferon therapy, 2 dropped out, and 4 were nonresponders. We conclude that hepatic granuloma is a rare finding in chronic hepatitis B and its presence does not seem to predict the response to interferon therapy.


Effect of a peer-led intervention combining mental health promotion with coping-strategy-based workshops on mental health awareness, help-seeking behavior, and wellbeing among university students in Hong Kong.
The psychological well-being of university students is an important factor in successfully coping with the demands of academic life. This study aimed to assess the impact of a peer-led intervention of mental health promotion combined with coping-strategy-based group workshops on mental health awareness and help-seeking behavior among university students in Hong Kong. A mixed-method concurrent design was used for this study. Quantitative data, based on one-group pretest-posttest design, were collected using Mental Health Knowledge Schedule Questionnaire to assess mental health awareness, and Attitude Towards Seeking Professional Help Questionnaire-Short Form to examine help-seeking behavior of university students from The Hong Kong Polytechnic University. Qualitative data were collected from written post-activity reflections and focus group discussions which were thematically analyzed. A total of 62 university students (mean age: 23.2 ± 5.1 years) were included in this study. Mental health awareness was significantly improved (p = 0.015, 95% Confidence Interval of - 2.670, - 0.297) after program implementation. Help-seeking behavior mean score increased from pretest to posttest, however, no significant difference was observed (p = 0.188, 95% CI = - 1.775, 0.355). Qualitative analysis revealed that the program helped participants learn about coping strategies to help themselves and others with mental health challenges. The peer-led intervention provided a positive impact through increased mental health awareness and knowledge of coping strategies on self-help and helping others among university students. Further study could focus on the impact of the program when applied regularly throughout the entire academic year.


Vertical stratification of the foliar fungal community in the world's tallest trees.
The aboveground tissues of plants host numerous, ecologically important fungi, yet patterns in the spatial distribution of these fungi remain little known. Forest canopies in particular are vast reservoirs of fungal diversity, but intracrown variation in fungal communities has rarely been explored. Knowledge of how fungi are distributed throughout tree crowns will contribute to our understanding of interactions between fungi and their host trees and is a first step toward investigating drivers of community assembly for plant-associated fungi. Here we describe spatial patterns in fungal diversity within crowns of the world's tallest trees, coast redwoods (Sequoia sempervirens). We took a culture-independent approach, using the Illumina MiSeq platform, to characterize the fungal assemblage at multiple heights within the crown across the geographical range of the coast redwood. Within each tree surveyed, we uncovered evidence for vertical stratification in the fungal community; different portions of the tree crown harbored different assemblages of fungi. We also report between-tree variation in the fungal community within redwoods. Our results suggest the potential for vertical stratification of fungal communities in the crowns of other tall tree species and should prompt future study of the factors giving rise to this stratification.


Command and control: regulatory pathways controlling invasive behavior of the border cells.
The invasiveness of cancer cells resembles the normal behavior of cells that migrate into surrounding tissues during development. For example, the border cells in the Drosophila ovary undergo a partial epithelial to mesenchymal transition and invade the neighboring cluster of germline cells, migrating to the oocyte border. Once there, they provide patterning information to the oocyte and produce an eggshell specialization known as the micropyle. Border cell migration has been subjected to extensive genetic analyses using a variety of screening approaches. Recent findings demonstrate that conversion of the border cells from a stationary group of epithelial cells to invasive cells requires integration of the activities of at least two transcriptional regulatory pathways. One such pathway requires the slbo gene, which encodes Drosophila C/EBP, a basic region/leucine zipper transcriptional activator that is required for elevated expression of a number of downstream targets, including DE-cadherin and focal adhesion kinase (FAK). An independent pathway requires the activity of the ecdysone receptor and a recently identified co-activator for the ecdysone receptor known as Taiman (abbreviated TAI, pronounced ti-maan', meaning too slow). Ecdysone is produced in the Drosophila ovary in response to adequate nutrition and is required for progression of oogenesis through stage 9, when border cell migration occurs. Border cells mutant for tai accumulate abnormally high levels of adhesion complexes at their surfaces, which may account for their inability to migrate. Thus border cell migration requires a differentiation program mediated by the C/EBP pathway, which is required for elevated expression of a number of proteins required for motility. In addition, migration requires a hormonal signal that relays information regarding nutritional status and appears to be required for regulation of the proper localization of some of the C/EBP targets. These findings suggest that steroid hormones can regulate cell motility relatively directly, independent of the effects on proliferation. This may contribute to the metastatic effects of steroid hormones on certain cancers and the inhibition of metastasis by steroid hormone antagonists such as tamoxifen.


Characterization of the miRNA-RISC loading complex and miRNA-RISC formed in the Drosophila miRNA pathway.
In Drosophila, miRNA is processed by Dicer-1 (DCR-1) from its precursor and loaded onto Argonaute1 (AGO1). AGO1 recognizes target mRNAs based on the miRNA sequence and suppresses the expression at post-transcriptional levels. GW182, a P-body component, localizes the AGO1 complex to processing bodies (P-bodies) where mRNA targets are decayed or stored. However, the details of the pathway remain elusive. In this study, two distinct types of AGO1-containing complexes from Drosophila Schneider2 (S2) cells were isolated and compared at the molecular level. The AGO1 complex with DCR-1 contained neither mature miRNA nor GW182 but exhibited pre-miRNA processing activity. The resultant mature RNA was loaded onto AGO1 within the complex. The AGO1 complex with GW182 excluded DCR-1, but possessed mature miRNA and showed no pre-miRNA processing activity. Thus, the AGO1-DCR-1 and AGO1-GW182 complexes correspond to miRLC (miRISC loading complex) and miRISC, respectively. The requirement for various domains of AGO1 in miRNA-loading and DCR-1/GW182 interaction was also examined. The Mid domain mutant (F2V2) interacted with DCR-1 but not with mature miRNA and GW182. The AGO1-PAZ mutant lacks the mature miRNA-binding ability but associates with either DCR-1 or GW182. The AGO1-PIWI mutant showed no Slicer activity but associates with mature miRNA. These results indicate that these domains are required differently for miRLC and miRISC formation in the miRNA pathway.


Utilization of dental services in Southern China.
A population's utilization of dental services is an important parameter in oral health care planning, which has rarely been studied in China. The objectives of this report were to describe the dental service utilization pattern of middle-aged and elderly Chinese and to analyze the influence of selected variables on the use of dental services. A Guangdong Province population of 1,573 35- to 44-year-olds and 1,515 65- to 74-year-olds recruited from urban and rural communities was interviewed in their local dialect. It was found that 23% of the middle-aged and 24% of the elderly subjects had visited a dentist within the preceding year. The two most commonly cited reasons for not having seen a dentist for at least 3 years were: no perceived need, and no serious dental problems. Among subjects who had visited a dentist within 3 years, the 3 most commonly received treatments were: fillings, extractions, and dental prostheses. Furthermore, a logistic regression analysis showed that women, subjects who lived in urban areas, were better educated, were wealthier, and had better oral health knowledge were more likely to be a recent dental service user. In conclusion, dental service utilization among the adult Southern Chinese was found to be low, problem-driven, and influenced by some socio-economic factors.


Two cytosolic neutrophil oxidase components absent in autosomal chronic granulomatous disease.
Neutrophils kill microorganisms with oxygen radicals generated by an oxidase that uses the reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) as substrate. This system requires both membrane and cytosolic components and is defective in patients with chronic granulomatous disease. A cytosolic complex capable of activating latent membrane oxidase was eluted from guanosine triphosphate-agarose and was used to raise polyclonal antiserum that recognized 47- and 67-kilodalton proteins. These proteins were restricted to the cytosol of myeloid cells. Both proteins were associated with NADPH oxidase-activating capacity when neutrophil cytosol was purified on nucleotide affinity matrices or molecular sizing columns. Neutrophils from patients with two different forms of autosomal chronic granulomatous disease lacked either the 47- or 67-kilodalton protein.


Proportion of children meeting recommendations for 24-hour movement guidelines and associations with adiposity in a 12-country study.
The Canadian 24-h movement guidelines were developed with the hope of improving health and future health outcomes in children and youth. The purpose of this study was to evaluate adherence to the 3 recommendations most strongly associated with health outcomes in new 24-h movement guidelines and their relationship with adiposity (obesity and body mass index z-score) across countries participating in the International Study of Childhood Obesity, Lifestyle and the Environment (ISCOLE). Cross-sectional results were based on 6128 children aged 9-11 years from the 12 countries of ISCOLE. Sleep duration and moderate-to-vigorous physical activity (MVPA) were assessed using accelerometry. Screen time was measured through self-report. Body weight and height were measured. Body mass index (BMI, kg · m-2) was calculated, and BMI z-scores were computed using age- and sex-specific reference data from the World Health Organization. Obesity was defined as a BMI z-score > +2 SD. Meeting the overall 24-h movement guidelines was defined as: 9 to 11 h/night of sleep, ≤2 h/day of screen time, and at least 60 min/day of MVPA. Age, sex, highest parental education and unhealthy diet pattern score were included as covariates in statistical models. Associations between meeting vs. not meeting each single recommendation (and combinations) with obesity were assessed with odds ratios calculated using generalized linear mixed models. A linear mixed model was used to examine the differences in BMI z-scores between children meeting vs. not meeting the different combinations of recommendations. The global prevalence of children meeting the overall recommendations (all three behaviors) was 7%, with children from Australia and Canada showing the highest adherence (15%). Children meeting the three recommendations had lower odds ratios for obesity compared to those meeting none of the recommendations (OR = 0.28, 95% CI 0.18-0.45). Compared to not meeting the 24-h movement recommendations either independently or combined, meeting them was significantly associated with a lower BMI z-score. Whenever the MVPA recommendation was included in the analysis the odds ratios for obesity were lower. For ISCOLE participants meeting these 3 healthy movement recommendations the odds ratios of being obese or having high BMI z-scores were lower. However, only a small percentage of children met all recommendations. Future efforts should aim to find promising ways to increase daily physical activity, reduce screen time, and ensure an adequate night's sleep in children. The International Study of Childhood Obesity, Lifestyle and the Environment (ISCOLE) was registered at ClinicalTrials.gov (Identifier NCT01722500) (October 29, 2012).


Revision of the venous clinical severity score: venous outcomes consensus statement: special communication of the American Venous Forum Ad Hoc Outcomes Working Group.
In response to the need for a disease severity measurement, the American Venous Forum committee on outcomes assessment developed the Venous Severity Scoring system in 2000. There are three components of this scoring system, the Venous Disability Score, the Venous Segmental Disease Score, and the Venous Clinical Severity Score (VCSS). The VCSS was developed from elements of the CEAP classification (clinical grade, etiology, anatomy, pathophysiology), which is the worldwide standard for describing the clinical features of chronic venous disease. However, as a descriptive instrument, the CEAP classification responds poorly to change. The VCSS was subsequently developed as an evaluative instrument that would be responsive to changes in disease severity over time and in response to treatment. Based on initial experiences with the VCSS, an international ad hoc working group of the American Venous Forum was charged with updating the instrument. This revision of the VCSS is focused on clarifying ambiguities, updating terminology, and simplifying application. The specific language of proven quality-of-life instruments was used to better address the issues of patients at the lower end of the venous disease spectrum. Periodic review and revision are necessary for generating more universal applicability and for comparing treatment outcomes in a meaningful way.


PhenoMeter: A Metabolome Database Search Tool Using Statistical Similarity Matching of Metabolic Phenotypes for High-Confidence Detection of Functional Links.
This article describes PhenoMeter (PM), a new type of metabolomics database search that accepts metabolite response patterns as queries and searches the MetaPhen database of reference patterns for responses that are statistically significantly similar or inverse for the purposes of detecting functional links. To identify a similarity measure that would detect functional links as reliably as possible, we compared the performance of four statistics in correctly top-matching metabolic phenotypes of Arabidopsis thaliana metabolism mutants affected in different steps of the photorespiration metabolic pathway to reference phenotypes of mutants affected in the same enzymes by independent mutations. The best performing statistic, the PM score, was a function of both Pearson correlation and Fisher's Exact Test of directional overlap. This statistic outperformed Pearson correlation, biweight midcorrelation and Fisher's Exact Test used alone. To demonstrate general applicability, we show that the PM reliably retrieved the most closely functionally linked response in the database when queried with responses to a wide variety of environmental and genetic perturbations. Attempts to match metabolic phenotypes between independent studies were met with varying success and possible reasons for this are discussed. Overall, our results suggest that integration of pattern-based search tools into metabolomics databases will aid functional annotation of newly recorded metabolic phenotypes analogously to the way sequence similarity search algorithms have aided the functional annotation of genes and proteins. PM is freely available at MetabolomeExpress (https://www.metabolome-express.org/phenometer.php).


Evaluation of Sexual Function Before and After Hip Arthroscopic Surgery for Symptomatic Femoroacetabular Impingement.
It is unknown if chronic hip pain due to femoroacetabular impingement (FAI) may cause sexual difficulties. Available evidence suggests that hip arthroscopic surgery may be effective for the treatment of symptomatic FAI; however, sexual function before and after hip arthroscopic surgery has not been reported. The purpose of this study was to determine the presence and significance of sexual difficulties in patients with chronic hip pain due to symptomatic FAI both before and after hip arthroscopic surgery. The hypotheses were that (1) chronic hip pain due to symptomatic FAI has a negative effect on sexual function, (2) hip arthroscopic surgery improves the level of sexual function postoperatively, (3) the characteristics of sexual difficulties may be dependent on sex or age, (4) patients lack knowledge of potential sexual activity changes in the preoperative and postoperative periods, and (5) patients desire a greater level of discussion regarding potential changes in sexual function. Case series; Level of evidence, 4. A 23-item Likert-style questionnaire assessing preoperative and postoperative sexual function and a modified Harris Hip Score questionnaire were administered to 305 consecutive patients who underwent hip arthroscopic surgery for FAI with a minimum 1-year follow-up. Comparative analysis was performed between sexes and age groups (young: <40 years; old: >40 years). Of 131 respondents, preoperative sexual difficulties were reported by 66%, occurring 30.8 ± 49.1 days after the onset of FAI symptoms. Primary causes of difficulty included pain (77.9%), stiffness (47.1%), and loss of interest (21.4%). Sexual activity resumed 29.2 ± 20.1 days postoperatively, while sex with minimal pain occurred at 48.8 ± 40.6 days. Female patients and older patients (>40 years old) resumed sexual activity later (female: 34.8 ± 23.2 days; male: 21.0 ± 10.7 days; P < .0001) (young: 26.3 ± 21.7 days; old: 35.7 ± 13.5 days; P = .017). The frequency of sexual activity increased in 32.3%, decreased in 16.9%, and was unchanged in 48.5%. Among patients who reported an increase in the frequency of sexual activity, there was a greater proportion of male patients and younger patients (female: 38.1%; male: 61.9%; P < .0001) (young: 78.6%; old: 21.4%; P < .0001). More female patients reported alterations in sexual positioning (female: 82.3%; male: 17.7%; P < .0001). To obtain information on sexual function, 77.4% of patients preferred a discussion with the surgeon, and 67.4% preferred a booklet on the subject. Relief of pain after arthroscopic surgery was experienced by 88.9%, and only 10.8% reported current sexual difficulties. This study demonstrates the prevalence of sexual difficulties among the majority of patients with symptomatic FAI, the significant effect that these difficulties may have on quality of life, and the ability of hip arthroscopic surgery to improve sexual function postoperatively. While further studies are required to elucidate what specific factors are associated with sexual difficulties, the current study suggests that this is an important topic to explore.


Ligand influence over the formation of dinuclear [2+2] versus trinuclear [3+3] Cu(I) Schiff base macrocyclic complexes.
The preparation and characterization of three new macrocyclic ligands with pendant arms based on the [2+2] condensation of isophthalaldehyde and the corresponding triamine substituted at the central N-atom is reported. None of these new macrocyclic ligands undergo any equilibrium reaction, based on imine hydrolysis to generate [1+1] macrocyclic formation or higher oligomeric compounds, such as [3+3], [4+4], etc., at least within the time scale of days. This indicates the stability of the newly generated imine bond. In sharp contrast, the reaction of the [2+2] macrocyclic Schiff bases with Cu(I) generates the corresponding dinuclear Cu(I) complexes [Cu(2)(L(1))](2+), 1(2+); [Cu(2)(L(2))(CH(3)CN)(2)](2+), 2(2+); and [Cu(2)(L(3))(CH(3)CN)(2)](2+), 3(2+), together with their trinuclear Cu(I) homologues [Cu(3)(L(4))](3+), 4(3+); [Cu(3)(L(5))(CH(3)CN)(3)](3+), 5(3+); and [Cu(3)(L(6))(CH(3)CN)(3)](3+), 6(3+), where the [2+2] ligand has undergone an expansion to the corresponding [3+3] Schiff base that is denoted as L(4), L(5), or L(6). The conditions under which the dinuclear and trinuclear complexes are formed were analyzed in terms of solvent dependence and synthetic pathways. The new complexes are characterized in solution by NMR, UV-vis, and MS spectroscopy and in the solid state by X-ray diffraction analysis and IR spectroscopy. For the particular case of the L(2) ligand, MS spectroscopy is also used to monitor the metal assisted transformation where the dinuclear complex 2(2+) is transformed into the trinuclear complex 5(3+). The Cu(I) complexes described here, in general, react slowly (within the time scale of days) with molecular oxygen, except for the ones containing the phenolic ligands 2(2+) and 5(3+) that react a bit faster.


Ethanol-induced disordering of membranes from different age groups of C57BL/6NNIA mice.
In previous studies, we have shown that many of the pharmacological effects of ethanol administered in vivo are greater in older mice compared to younger mice. This study determined if there are age-related differences in membrane order when ethanol is administered in vitro. Synaptic plasma membranes, brain microsomal membranes and erythrocyte membranes were isolated from young (3-5 month), middle (11-13 months), and old (22-24 months) C57BL/6NNIA mice. The order parameter of each age group was measured using a 5-nitroxide stearic acid spin label in the presence of 0, 250 and 500 mM ethanol added in vitro. No age-related differences in order parameter were seen in the absence of ethanol. However, membranes from young animals were disordered to the greatest degree by ethanol. The synaptic plasma and erythrocyte membranes from young mice were disordered by both 250 and 500 mM ethanol. Membranes from old mice were disordered significantly by 500 mM ethanol only and the disordering was not as great as was seen in the membranes from the young mice. In the microsomal membrane preparation, 500 mM ethanol significantly disordered the membranes from the young animals, but it had no effect on membranes from old animals. Age differences were also observed generally for cholesterol and total phospholipid which both increased with increasing age for synaptic plasma and brain microsomes. Membrane disorder induced by ethanol differs with age and is associated with cholesterol and phospholipid content of membranes.


Low-dose Naltrexone Therapy for Psoriasis.
Safe, inexpensive, and convenient psoriasis therapy is desirable. Two recent case reports suggested that low-dose naltrexone is effective. Cases from our practice are presented in order to further the evidence of efficacy and safety of low-dose naltrexone in the treatment of psoriasis. Patients included 13 females, 2 males; mean age 57 years; mean psoriasis duration 16 years. Of the patients, 8 had psoriatic arthritis. In the past, 5 had completely failed and 10 had partially responded to =1 topical therapies. Patients used a self-assessed Likert scale on the effect of low-dose naltrexone on their psoriasis: 1 - worse; 2 - unchanged; 3 - slightly improved; 4 - somewhat improved; 5 - marked improvement. The response to 4.5 mg of oral naltrexone was as follows: 8/15 marked improvement; 2/15 somewhat improved; and 5/15 unchanged. Three adverse events included insomnia, diarrhea, and self-limited headache. Marked improvement was seen by 53% of the 15 patients. Low-dose naltrexone regulates lymphocyte responses, reduces cytokine production, and likely reduces mast cell activity. Low-dose naltrexone is safe, inexpensive, and appears be effective in this open-label study.


Adoption and maintenance of gym-based strength training in the community setting in adults with excess weight or type 2 diabetes: a randomized controlled trial.
Participant adoption and maintenance is a major challenge in strength training (ST) programs in the community-setting. In adults who were overweight or with type 2 diabetes (T2DM), the aim of this study was to compare the effectiveness of a standard ST program (SST) to an enhanced program (EST) on the adoption and maintenance of ST and cardio-metabolic risk factors and muscle strength. A 12-month cluster-randomized controlled trial consisting of a 6-month adoption phase followed by a 6-month maintenance phase. In 2008-2009, men and women aged 40-75 years (n = 318) with T2DM (n = 117) or a BMI >25 (n = 201) who had not participated in ST previously were randomized into either a SST or an EST program (which included additional motivationally-tailored behavioral counselling). Adoption and maintenance were defined as undertaking ≥ 3 weekly gym-based exercise sessions during the first 6-months and from 6-12 months respectively and were assessed using a modified version of the CHAMPS (Community Healthy Activity Models Program for Seniors) instrument. Relative to the SST group, the adjusted odds ratio (OR) of adopting ST for all participants in the EST group was 3.3 (95 % CI 1.2 to 9.4). In stratified analyses including only those with T2DM, relative to the SST group, the adjusted OR of adopting ST in the EST group was 8.2 (95 % CI 1.5-45.5). No significant between-group differences were observed for maintenance of ST in either pooled or stratified analyses. In those with T2DM, there was a significant reduction in HbA1c in the EST compared to SST group during the adoption phase (net difference, -0.13 % [-0.26 to -0.01]), which persisted after 12-months (-0.17 % [-0.3 to -0.05]). A behaviorally-focused community-based EST intervention was more effective than a SST program for the adoption of ST in adults with excess weight or T2DM and led to greater improvements in glycemic control in those with T2DM. Registered at ACTRN12611000695909 (Date registered 7/7/2011).


A comparative evaluation of PDQ-Evidence.
A strategy for minimising the time and obstacles to accessing systematic reviews of health system evidence is to collect them in a freely available database and make them easy to find through a simple 'Google-style' search interface. PDQ-Evidence was developed in this way. The objective of this study was to compare PDQ-Evidence to six other databases, namely Cochrane Library, EVIPNet VHL, Google Scholar, Health Systems Evidence, PubMed and Trip. We recruited healthcare policy-makers, managers and health researchers in low-, middle- and high-income countries. Participants selected one of six pre-determined questions. They searched for a systematic review that addressed the chosen question and one question of their own in PDQ-Evidence and in two of the other six databases which they would normally have searched. We randomly allocated participants to search PDQ-Evidence first or to search the two other databases first. The primary outcomes were whether a systematic review was found and the time taken to find it. Secondary outcomes were perceived ease of use and perceived time spent searching. We asked open-ended questions about PDQ-Evidence, including likes, dislikes, challenges and suggestions for improvements. A total of 89 people from 21 countries completed the study; 83 were included in the primary analyses and 6 were excluded because of data errors that could not be corrected. Most participants chose PubMed and Cochrane Library as the other two databases. Participants were more likely to find a systematic review using PDQ-Evidence than using Cochrane Library or PubMed for the pre-defined questions. For their own questions, this difference was not found. Overall, it took slightly less time to find a systematic review using PDQ-Evidence. Participants perceived that it took less time, and most participants perceived PDQ-Evidence to be slightly easier to use than the two other databases. However, there were conflicting views about the design of PDQ-Evidence. PDQ-Evidence is at least as efficient as other databases for finding health system evidence. However, using PDQ-Evidence is not intuitive for some people. The trial was prospectively registered in the ISRCTN registry 17 April 2015. Registration number: ISRCTN12742235 .


Swimming in the California sea lion: morphometrics, drag and energetics.
During swimming, the California sea lion, Zalophus californianus (Lesson), generates thrust forces solely by means of its pectoral flippers. This study examines the drag, energetic cost and efficiency associated with this method of locomotion. Sea lions are highly streamlined, with a fineness ratio of 5.5 and maximum girth at 40% of body length. This profile leads to reduced drag and swimming power requirements. Films of gliding animals showed the drag coefficient (based on wetted surface area) to be 0.0042 at a Reynolds number of 2.0 X 10(6). This value is comparable to that found for other aquatic vertebrates and suggests that the sea lion's morphology helps to delay turbulent separation and maintain laminar flow over the forward portion of its body. Swimming metabolism was measured in a water flume at velocities up to 1.3 ms-1. Effective swimming speeds up to 2.7 ms-1 were attained by increasing each animal's drag. Oxygen consumption rose exponentially with velocity and for two animals was best described as VO2 = 6.27e0.48U, where VO2 is in mlO2 min-1 kg-1 and U is in ms-1. Minimum cost of transport for these animals was 0.12 ml O2 kg-1 m-1 at a relative speed of 1.4 body lengths s-1. This is 2.5 times that predicted for a fish of similar size. Swimming efficiencies were determined from these results using power output values calculated from the measured drag coefficient and standard hydrodynamic equations. At the highest velocity, aerobic efficiency reached a maximum of 15% while mechanical efficiency of the foreflippers was 80%. The results demonstrate that foreflipper propulsion is a highly efficient and comparatively inexpensive method of locomotion in aquatic mammals.


Glycemic Monitoring and Management in Advanced Chronic Kidney Disease.
Glucose and insulin metabolism in patients with diabetes are profoundly altered by advanced chronic kidney disease (CKD). Risk of hypoglycemia is increased by failure of kidney gluconeogenesis, impaired insulin clearance by the kidney, defective insulin degradation due to uremia, increased erythrocyte glucose uptake during hemodialysis, impaired counterregulatory hormone responses (cortisol, growth hormone), nutritional deprivation, and variability of exposure to oral antihyperglycemic agents and exogenous insulin. Patients with end-stage kidney disease frequently experience wide glycemic excursions, with common occurrences of both hypoglycemia and hyperglycemia. Assessment of glycemia by glycated hemoglobin (HbA1c) is hampered by a variety of CKD-associated conditions that can bias the measure either to the low or high range. Alternative glycemic biomarkers, such as glycated albumin or fructosamine, are not fully validated. Therefore, HbA1c remains the preferred glycemic biomarker despite its limitations. Based on observational data for associations with mortality and risks of hypoglycemia with intensive glycemic control regimens in advanced CKD, an HbA1c range of 7% to 8% appears to be the most favorable. Emerging data on the use of continuous glucose monitoring in this population suggest promise for more precise monitoring and treatment adjustments to permit fine-tuning of glycemic management in patients with diabetes and advanced CKD.


The Depression Prevention Initiative: Trauma as a Moderator of Prevention Outcomes.
Interpersonal Psychotherapy-Adolescent Skills Training (IPT-AST) is an evidence-based indicated depression prevention program that has been shown to reduce depression symptoms. Research is needed to identify moderators of IPT-AST's effects. Although trauma history has emerged as a moderator of depression treatment outcomes, the impact of trauma on short- and long-term outcomes in the context of preventive interventions for adolescent depression is unknown. This study examines the impact of trauma on prevention outcomes in a school-based randomized controlled trial (RCT) in which 186 adolescents (mean age = 14.01 years, SD = 1.22; 67% female) were randomly assigned to IPT-AST delivered by research staff or group counseling (GC) provided by school counselors. Trauma history significantly moderated intervention outcomes during the active phase of the intervention, but not during long-term follow-up. During the active phase, youth in IPT-AST with low or no trauma exposure experienced significantly greater reductions in depression symptoms than youth in GC with low or no trauma exposure, but there were no significant differences in rates of change between the two interventions for youth with high or any trauma exposure. These findings highlight the importance of assessing trauma and investigating whether these interventions can be tailored or supplemented to enhance the effects for youth with trauma exposure.


Antimicrobial Resistance and Mortality in Hospitalized Patients with Bacteremia in the Greater Paris Area from 2016 to 2019.
Antibiotic-resistant bacteremia is a leading global cause of infectious disease morbidity and mortality. Clinical data warehouses (CDWs) allow for the secure, real-time coupling of diverse data sources from real-world clinical settings, including care-based medical-administrative data and laboratory-based microbiological data. The main purpose of this study was to assess the contribution of CDWs in the epidemiological study of antibiotic resistance by constructing a database of bacteremia patients, BactHub, and describing their main clinico-microbiological features and outcomes. Adult patients with bacteremia hospitalized between January 1, 2016 and December 31, 2019 in 14 acute care university hospitals from the Greater Paris area were identified; their first bacteremia episode was included. Data describing patients, episodes of bacteremia, bacterial isolates, and antimicrobial resistance were structured. Among 29,228 patients with bacteremia, 41% of episodes were community-onset (CO) and 59% were hospital-acquired (HA). Thirty-day and ninety-day mortality rates were 15% and 20% in CO episodes, and 18% and 36% in HA episodes. Overall resistance rates were high, including third-generation cephalosporin resistance among Klebsiella pneumoniae (CO 21%, HA 37%) and Escherichia coli (CO 13%, HA 17%), and methicillin resistance among Staphylococcus aureus (CO 11%, HA 14%). Annual incidence rates increased significantly from 2017 to 2019, from 20.0 to 20.9 to 22.1 stays with bacteremia per 1000 stays (p < 0.0001). The Bacthub database provides accurate clinico-microbiological data describing bacteremia across France's largest hospital group. Data from Bacthub may inform surveillance and the clinical decision-making process for bacteremia patients, including choice of antimicrobial therapy. The database also offers opportunities for research, including analysis of hospital care pathways and significant patient outcomes such as mortality and recurrence of infection.


Governance Options to Enhance Ecosystem Services in Cocoa, Soy, Tropical Timber and Palm Oil Value Chains.
Dutch policies have advocated sustainable commodity value chains, which have implications for the landscapes from which these commodities originate. This study examines governance and policy options for sustainability in terms of how ecosystem services are addressed in cocoa, soy, tropical timber and palm oil value chains with Dutch links. A range of policies addressing ecosystem services were identified, from market governance (certification, payments for ecosystem services) to multi-actor platforms (roundtables) and public governance (policies and regulations). An analysis of policy narratives and interviews identified if and how ecosystem services are addressed within value chains and policies; how the concept has been incorporated into value chain governance; and which governance options are available. The Dutch government was found to take a steering but indirect role in all the cases, primarily through supporting, financing, facilitating and partnering policies. Interventions mainly from end-of-chain stakeholders located in processing and consumption countries resulted in new market governance, notably voluntary sustainability standards. These have been successful in creating awareness of some ecosystem services and bringing stakeholders together. However, they have not fully addressed all ecosystem services or stakeholders, thus failing to increase the sustainability of value chains or of the landscapes of origin. We argue that chains sourced in tropical landscapes may be governed more effectively for sustainability if voluntary, market policy tools and governance arrangements have more integrated goals that take account of sourcing landscapes and impacts along the entire value chain. Given the international nature of these commodities. These findings have significance for debates on public-private approaches to value chain and landscape governance.


Hydration practices in residential and nursing care homes for older people.
To scope and explore hydration practices in care homes. Older residents do not regularly consume adequate fluids to support health. Achieving this is difficult with residents who have coexisting health, sensory and functional problems, as well as challenging hydration habits. This project used a sequential exploratory mixed method design to scope and explore existing hydration practices. Data were collected via two stages. First was a survey of hydration practices. Twenty-nine responses were received from 81 care homes (response rate: 35.8%). Second was the exploration of practitioners' experiences and perceptions of hydration practice via semi-structured interviews (54 staff: 43 interviews). Descriptive statistics summarised the survey findings. Open coding and thematic analysis were applied to the qualitative data, and details of the methods are reported in adherence to COREQ criteria. It is important to provide hydration support in addition to regularly offering drinks to residents. Hydration practices include the following: use of social interaction to encourage drinking; verbal and nonverbal prompts to drink; giving fluids with routine practices and social activities; providing drinks-related activity, use of aids and equipment to support drinking; and creating a drink-friendly environment. Practices are implemented in care homes; however, no one care home implements all these hydration strategies at any one time. Older care home residents need support and encouragement to drink adequate fluids which can be difficult to achieve with residents who have complex needs and challenging drinking habits. In addition to the routine offer of drinks, hydration support should be used to facilitate residents to drink sufficient amounts of fluid. Staff working in care homes have an important role in assessing the hydration needs of residents and using multiple hydration practices to support residents to achieve their hydration requirements.


Biology and clinical significance of circulating tumor cell subpopulations in lung cancer.
By identifying and tracking genetic changes in primary tumors and metastases, patients can be stratified for the most efficient therapeutic regimen by screening for known biomarkers. However, retrieving tissues biopsies is not always feasible due to tumor location or risk to patient. Therefore, a liquid biopsies approach offers an appealing solution to an otherwise invasive procedure. The rapid growth of the liquid biopsy field has been aided by improvements in the sensitivity and specificity of enrichment assays for isolating circulating tumor cells (CTCs) from normal surrounding blood cells. Furthermore, the identification and molecular characterization of CTCs has been shown in numerous studies to be of diagnostic and prognostic relevance in breast, prostate and colon cancer patients. Despite these advancements, and the highly metastatic nature of lung cancer, it remains a challenge to detect CTCs in advanced non-small cell lung cancer (NSCLC). It may be that loss of epithelial features, in favor of a mesenchymal phenotype, and the highly heterogeneous nature of NSCLC CTCs contribute to their evasion from current detection methods. By identifying a broader spectrum of biomarkers that could better differentiate the various NSCLC CTCs subpopulations, it may be possible to not only improve detection rates but also to shed light on which CTC clones are likely to drive metastatic initiation. Here we review the biology of CTCs and describe a number of proteins and genetic targets which could potentially be utilized for the dissemination of heterogenic subpopulations of CTCs in NSCLC.


Universal Design for Learning and Differentiated Instruction in Physical Education.
The aim of this case study was to describe the distinct approaches used by physical education (PE) teachers to accommodate students with disabilities in New York elementary school PE classes. The participants included 1 adapted PE specialist, 5 PE teachers, and 5 elementary school students with various impairments. Through thematic analysis, observations and interviews revealed 3 main approaches: (a) normalized instruction-traditional curriculum with no differentiation in the program; (b) differentiated instruction-adaptations tailored specifically to the needs of each student with disability; and (c) universally designed instruction based on the principles of Universal Design for Learning (UDL) and accessibility to all students. Differentiated instruction, entailing modifications in the program and pedagogical accommodations, was the most prevalent approach at the research site, but lessons based on UDL principles were also observed. In association, the 2 approaches (differentiated instruction and UDL) represented significant resources to accommodate students with disabilities in PE.


Plasma clearance and net uptake of alpha-tocopherol and low-density lipoprotein by tissues in WHHL and control rabbits.
The mechanism(s) of uptake of vitamin E (alpha-tocopherol) by tissues is poorly understood. It has, however, been suggested from studies in vitro that the apolipoprotein B/E (apo B/E) receptor pathway for low-density lipoprotein (LDL) may be involved. To investigate the role of the apo B/E receptor pathway in vivo, we have studied the transport and uptake of alpha-tocopherol by tissues in Watanabe Heritable Hyperlipidaemic (WHHL) rabbits, which lack functional LDL (apo B/E) receptors, and controls. [3H]alpha-Tocopherol incorporated within LDL labelled with [14C]sucrose was used in these studies, as this enabled the uptake of both alpha-tocopherol and LDL to be studied independently. The principal findings were as follows. (1) Concentrations of the circulating lipids (including alpha-tocopherol) and LDL were increased and the plasma fractional disappearance rates of alpha-tocopherol and LDL decreased in the WHHL rabbits. (2) The WHHL rabbits clear more LDL and alpha-tocopherol from the circulation than controls do, because of their increased pool sizes of alpha-tocopherol and LDL. (3) The lipoprotein composition of the WHHL rabbits differed from that of the controls, and there was exchange of alpha-tocopherol between the lipoprotein fractions in vivo and in vitro. (4) High-affinity apo B/E receptors were not essential for the uptake of alpha-tocopherol by tissues. (5) Evidence from the plasma-clearance and tissue data suggest that alpha-tocopherol can be taken up by tissues in association with, and also independent of, LDL. We conclude that there are several different mechanisms for the uptake of alpha-tocopherol by tissues, which include receptor-dependent and receptor-independent pathways, independent transport and co-transport of alpha-tocopherol and LDL, and uptake from a number of different lipoproteins.


Essential Roles of Bone Morphogenetic Protein-1 and Mammalian Tolloid-like 1 in Postnatal Root Dentin Formation.
Mutations in the proteinase bone morphogenetic protein-1 (BMP1) were recently identified in patients with osteogenesis imperfecta, which can be associated with type 1 dentinogenesis imperfecta. BMP1 is co-expressed in various tissues and has overlapping activities with the closely related proteinase mammalian tolloid-like 1 (TLL1). In this study we investigated whether removing the overlapping activities of BMP1 and TLL1 affects the mineralization of tooth root dentin. Floxed alleles of the BMP1 and TLL1 genes were excised via ubiquitously expressed Cre induced by tamoxifen treatment beginning at 3 days of age (harvested at 3 weeks of age) or beginning at 4 weeks of age (harvested at 8 weeks of age). Multiple techniques, including x-ray analysis, double-labeling with calcein and alizarin red stains for measurement of dentin formation rate, and histologic and immunostaining assays, were used to analyze the dentin phenotype. BMP1/TLL1 double knockout mice displayed short and thin root dentin, defects in dentin mineralization, and delayed tooth eruption. Molecular mechanism studies revealed accumulation of collagens in dentin and a sharp reduction in non-collagenous proteins such as dentin matrix protein 1 and dentin sialophosphoprotein. Furthermore, we found a strong reduction in tartrate-resistant acid phosphatase, which is likely caused by defects in bone cells. BMP1/TLL1 appear to play crucial roles in maintaining extracellular matrix homeostasis essential to root formation and dentin mineralization.


Assessment of dimensional accuracy of preadjusted metal injection molding orthodontic brackets.
the aim of this study is to evaluate the dimensional accuracy of McLaughlin, Bennett, and Trevisi (MBT) brackets manufactured by two different companies (American Orthodontics and Ortho Organizers) and determine variations in incorporation of values in relation to tip and torque in these products. In the present analytical/descriptive study, 64 maxillary right central brackets manufactured by two companies (American Orthodontics and Ortho Organizers) were selected randomly and evaluated for the accuracy of the values in relation to torque and angulation presented by the manufacturers. They were placed in a video measuring machine using special revolvers under them and were positioned in a manner so that the light beams would be directed on the floor of the slot without the slot walls being seen. Then, the software program of the same machine was used to determine the values of each bracket type. The means of measurements were determined for each sample and were analyzed with independent t-test and one-sample t-test. Based on the confidence interval, it can be concluded that at 95% probability, the means of tip angles of maxillary right central brackets of these two brands were 4.1-4.3° and the torque angles were 16.39-16.72°. The tips in these samples were at a range of 3.33-4.98°, and the torque was at a range of 15.22-18.48°. In the present study, there were no significant differences in the angulation incorporated into the brackets from the two companies; however, they were significantly different from the tiP values for the MBT prescription. In relation to torque, there was a significant difference between the American Orthodontic brackets exhibited significant differences with the reported 17°, too.


Towards a systems approach for understanding honeybee decline: a stocktaking and synthesis of existing models.
The health of managed and wild honeybee colonies appears to have declined substantially in Europe and the United States over the last decade. Sustainability of honeybee colonies is important not only for honey production, but also for pollination of crops and wild plants alongside other insect pollinators. A combination of causal factors, including parasites, pathogens, land use changes and pesticide usage, are cited as responsible for the increased colony mortality.However, despite detailed knowledge of the behaviour of honeybees and their colonies, there are no suitable tools to explore the resilience mechanisms of this complex system under stress. Empirically testing all combinations of stressors in a systematic fashion is not feasible. We therefore suggest a cross-level systems approach, based on mechanistic modelling, to investigate the impacts of (and interactions between) colony and land management.We review existing honeybee models that are relevant to examining the effects of different stressors on colony growth and survival. Most of these models describe honeybee colony dynamics, foraging behaviour or honeybee - varroa mite - virus interactions.We found that many, but not all, processes within honeybee colonies, epidemiology and foraging are well understood and described in the models, but there is no model that couples in-hive dynamics and pathology with foraging dynamics in realistic landscapes.Synthesis and applications. We describe how a new integrated model could be built to simulate multifactorial impacts on the honeybee colony system, using building blocks from the reviewed models. The development of such a tool would not only highlight empirical research priorities but also provide an important forecasting tool for policy makers and beekeepers, and we list examples of relevant applications to bee disease and landscape management decisions.


[Clinical features of Wegener granulomatosis and microscopic polyangiitis in Chilean patients].
Systemic vasculitis are a group of heterogeneous diseases characterized by inflammation and necrosis of blood vessel walls. The etiology is not known, but geographic and environmental factors are implicated. To describe the clinical features of microscopic polyangiitis (MPA) and Wegener's granulomatosis (WG) in a Chilean cohort of patients. Retrospective review of the medical records of 123 patients with the diagnosis of systemic vasculitis (65 MPA and 58 WG), seen from 1990 to 2001. The diagnosis were made based on the American College of Rheumatology and Chapel Hill criteria. The mean follow-up for MPA was 15 months (1-120) and for WG, 20 months (1-120). The median age (years) at diagnosis for MPA was 61 (19-82) and WG 50 (20-82). Gender distribution was similar in both groups (male: 68% and 57% respectively). The main clinical features in the MPA group were renal involvement (68%), peripheral nervous system involvement (57%), pulmonary hemorrhage (28%), and skin disease (32%). In the WG group were alveolar hemorrhage (62%), renal involvement (78%), paranasal sinus involvement (57%), and ocular disease (26%). In both, creatinine levels above 2.0 mg/dl were associated with a higher mortality (p< 0.01). ANCA by immunofluorescence was performed in 56 MPA patients (75% had pANCA, 4% had cANCA and 21% were ANCA negative) and in 55 WG patients (17% had pANCA, 79% had cANCA and 4% were ANCA negative). Global mortality was 18% and 17% respectively, and the most common causes of death were infections. The clinical features of our patients are similar to other published data. In our WG and MPA patients the main predictor for death was a serum creatinine above 2 mg/dl.


Long-term complications of JJ stent and its management: A 5 years review.
To assess the long term complications of JJ stent, the management of complications and the role of endoscopic approach to manage these complications. Nineteen patients with indwelling JJ stent for a duration of more than 6 months were included in this study. Patients were assessed with X-ray KUB, USG KUB, blood urea, creatinine and DTPA renogram. Data were analyzed by Microsoft excel 2007. Out of 19 patients 12 (63.16%) were male and 7 (36.84%) were female. The mean age was 39.78 ± 13.69 years., Mean duration for which the stent was in situ was 29.56 months. The most common complication was broken stent, in 11 cases (57.89%). Other complications were migration in 5 (26.32%), encrustation in 2 (10.52%) and 1 case of (5.26%) stone formation. Eighteen cases were managed by endoscopic approaches. A total of 22 procedures were performed to treat the complications. Eleven cases were managed by a single procedure and 8 patients required multiple procedures. All were managed successfully with no death reported. Post-operative complications were seen in eight cases (42.11%). JJ stent related long-term complications are not uncommon and are usually seen after 6 months of indwelling time. Endourological procedure should be the initial approach with a high success rate. Coordinated use multimodality and technology helps in management of difficult cases. Open surgery is rarely required. Prevention of the complication by judicious use and early removal is the cornerstone.


Cortactin and dynamin are required for the clathrin-independent endocytosis of gammac cytokine receptor.
Endocytosis is critical for many cellular functions. We show that endocytosis of the common gammac cytokine receptor is clathrin independent by using a dominant-negative mutant of Eps15 or RNA interference to knock down clathrin heavy chain. This pathway is synaptojanin independent and requires the GTPase dynamin. In addition, this process requires actin polymerization. To further characterize the function of dynamin in clathrin-independent endocytosis, in particular its connection with the actin cytoskeleton, we focused on dynamin-binding proteins that interact with F-actin. We compared the involvement of these proteins in the clathrin-dependent and -independent pathways. Thus, we observed that intersectin, syndapin, and mAbp1, which are necessary for the uptake of transferrin (Tf), a marker of the clathrin route, are not required for gammac receptor endocytosis. Strikingly, cortactin is needed for both gammac and Tf internalizations. These results reveal the ubiquitous action of cortactin in internalization processes and suggest its role as a linker between actin dynamics and clathrin-dependent and -independent endocytosis.


Phase-shift-locked interferometer with a wavelength-modulated laser diode.
A phase-shift-locked interferometer has been constructed for distance measurement. A phase shift produced by sawtooth-current modulation of a laser diode is locked to a phase difference preset by polarization optics that consists of a quarter-wave plate and polarizers through an electrical feedback technique. An optical path difference can be measured from the locked sawtooth-wave current amplitude in real time. The sensitivity of the interferometer is discussed.


Lateral access to the holes of photonic crystal fibers - selective filling and sensing applications.
A new, simple, technique is demonstrated to laterally access the cladding holes of solid-core photonic crystal fibers (PCFs) or the central hole of hollow-core PCFs by blowing a hole through the fiber wall (using a fusion splicer and the application of pressure). For both fiber types material was subsequently and successfully inserted into the holes. The proposed method compares favorably with other reported selective filling techniques in terms of simplicity and reproducibility. Also, since the holes are laterally filled, simultaneous optical access to the PCFs is possible, which can prove useful for practical sensing applications. As a proof-of-concept experiment, Rhodamine fluorescence measurements are shown.


Snake venom phospholipase A2s (Asp49 and Lys49) induce mechanical allodynia upon peri-sciatic administration: involvement of spinal cord glia, proinflammatory cytokines and nitric oxide.
Snakebites constitute a serious public health problem in Central and South America, where species of the lancehead pit vipers (genus Bothrops) cause the majority of accidents. Bothrops envenomations are very painful, and this effect is not neutralized by antivenom treatment. Two variants of secretory phospholipases A2 (sPLA2), corresponding to Asp49 and Lys49 PLA2s, have been isolated from Bothrops asper venom. These sPLA2s induce hyperalgesia in rats following subcutaneous injection. However, venom in natural Bothrops bites is frequently delivered intramuscularly, thereby potentially reaching peripheral nerve bundles. Thus, the present series of experiments tested whether these sPLA2s could exert pain-enhancing effects following administration around healthy sciatic nerve. Both were found to produce mechanical allodynia ipsilateral to the injection site; no thermal hyperalgesia was observed. As no prior study has examined potential spinal mechanisms underlying sPLA2 actions, a series of anatomical and pharmacological studies were performed. These demonstrated that both sPLA2s produce activation of dorsal horn astrocytes and microglia that is more prominent ipsilateral to the site of injection. As proinflammatory cytokines and nitric oxide have each been previously implicated in spinally mediated pain facilitation, the effect of pharmacological blockade of these substances was tested. The results demonstrate that mechanical allodynia induced by both sPLA2s is blocked by interleukin-1 receptor antagonist, anti-rat interleukin-6 neutralizing antibody, the anti-inflammatory cytokine interleukin-10, and a nitric oxide synthesis inhibitor (L-NAME). As a variety of immune cells also produce and release sPLA2s during inflammatory states, the data may have general implications for the understanding of inflammatory pain.


Differential targeting of feline photoreceptors by recombinant adeno-associated viral vectors: implications for preclinical gene therapy trials.
The cat is emerging as a promising large animal model for preclinical testing of retinal dystrophy therapies, for example, by gene therapy. However, there is a paucity of studies investigating viral vector gene transfer to the feline retina. We therefore sought to study the tropism of recombinant adeno-associated viral (rAAV) vectors for the feline outer retina. We delivered four rAAV serotypes: rAAV2/2, rAAV2/5, rAAV2/8 and rAAV2/9, each expressing green fluorescent protein (GFP) under the control of a cytomegalovirus promoter, to the subretinal space in cats and, for comparison, mice. Cats were monitored for gene expression by in vivo imaging and cellular tropism was determined using immunohistochemistry. In cats, rAAV2/2, rAAV2/8 and rAAV2/9 vectors induced faster and stronger GFP expression than rAAV2/5 and all vectors transduced the retinal pigment epithelium (RPE) and photoreceptors. Unlike in mice, cone photoreceptors in the cat retina were more efficiently transduced than rod photoreceptors. In mice, rAAV2/2 only transduced the RPE whereas the other vectors also transduced rods and cones. These results highlight species differences in cellular tropism of rAAV vectors in the outer retina. We conclude that rAAV serotypes are suitable for use for retinal gene therapy in feline models, particularly when cone photoreceptors are the target cell.


Expression and purification of affinity-tagged variants of the photochemical reaction center from Heliobacterium modesticaldum.
The heliobacterial photochemical reaction center (HbRC) from the chlorophototrophic Firmicutes bacterium Heliobacterium modesticaldum is the only homodimeric type I RC whose structure is known. Using genetic techniques recently established in our lab, we have developed a rapid heterologous expression system for the HbRC core polypeptide PshA. Our system relies on rescue of the non-chlorophototrophic ∆pshA::cbp2p-aph3 strain of Hbt. modesticaldum by expression of a heterologous pshA gene from a replicating shuttle vector. In addition, we constructed two tagged variants of PshA, one with an N-terminal octahistidine tag and one with an internal hexahistidine tag, which facilitate rapid purification of pure, active HbRC cores in milligram quantities. We constructed a suite of shuttle vectors bearing untagged or tagged versions of pshA driven by various promoters. Surprisingly, we found that the eno and gapDH_2 promoters from Clostridium thermocellum drive better expression of pshA than fragments of DNA derived from the region upstream of the pshA locus on the Hbt. modesticaldum genome. This "pshA rescue" strategy also provided a useful window into how Hbt. modesticaldum regulates pigment synthesis and growth rate when chlorophototrophic output decreases.


Ventilation-perfusion lung scanning and the diagnosis of pulmonary embolism: improvement of observer agreement by the use of a lung segment reference chart.
To test the hypothesis that the systematic use of a lung segment reference chart can improve the inter- and intra-observer agreement for the interpretation of ventilation-perfusion lung scans. A randomized trial. Ventilation-perfusion lung scans were obtained in a series of 220 consecutive patients with clinically suspected pulmonary embolism. Ventilation-perfusion scans were randomly allocated to one of two series each consisting of 110 ventilation-perfusion lung scans. The first series of lung scans was interpreted according to the routine diagnostic approach, and the second series was interpreted with the mandatory use of a lung segment reference chart on which observed ventilation and perfusion defects were drawn. The two nuclear medicine physicians agreed a priori on the diagnostic criteria of the classification scheme. Lung scans were classified as normal, non-high probability, or high probability for pulmonary embolism. The extent of disagreement between the nuclear medicine physicians (inter-observer disagreement) and the lack of internal consistency of each nuclear medicine physician (intra-observer disagreement) was assessed by the percentage disagreement and by kappa statistic. Inter-observer disagreement which was 20% in the first series, decreased significantly in the second series to 7%; P = 0.003. Intra-observer disagreement for the first series was 10% and 22% for the nuclear medicine physicians, respectively. Intra-observer disagreement for the second series of lung scans decreased significantly for one nuclear medicine physician (intra-observer disagreement, 0%; P less than 0.01), whereas intra-observer disagreement was reduced to 10% for the other nuclear medicine physician (P = 0.09). Inter- and intra-observer disagreement were significantly reduced when two nuclear medicine specialists interpreted ventilation-perfusion lung scans according to the routine diagnostic approach plus the use of a lung segment reference chart. The use of the lung segment reference chart for the interpretation of lung scans is likely to improve the management of patients with clinically suspected pulmonary embolism.


Heat shock protein 2 promoter drives Cre expression in spermatocytes of transgenic mice.
We generated transgenic mouse line C57BL/6-Tg(Hspa2-cre)1Eddy/J (Hspa2-cre), which expresses cre-recombinase under the control of a 907-bp fragment of the heat shock protein 2 (Hspa2) gene promoter. Transgene expression was determined using Gt(ROSA)26Sor(tm1Sor)/J (ROSA26) and Tg(CAG-Bgeo/GFP)21Lbe/J (Z/EG) reporter strains and RT-PCR and immunohistochemistry assays. Hspa2-cre expression mimicked the spermatogenic cell-specific expression of endogenous HSPA2 within the testis, being first observed in leptotene/zygotene spermatocytes. Expression of the transgene also was detected at restricted sites in the brain, as occurs for endogenous HSPA2. Although the results of mating the Hspa2-cre mice to mice with a floxed Cdc2a allele indicated that some expression of the transgene occurs during embryogenesis, the Hspa2-cre mice provide a valuable new tool for assessing the roles of genes during and after meiotic prophase in pachytene spermatocytes.


One Month of Cannabis Abstinence in Adolescents and Young Adults Is Associated With Improved Memory.
Associations between adolescent cannabis use and poor neurocognitive functioning have been reported from cross-sectional studies that cannot determine causality. Prospective designs can assess whether extended cannabis abstinence has a beneficial effect on cognition. Eighty-eight adolescents and young adults (aged 16-25 years) who used cannabis regularly were recruited from the community and a local high school between July 2015 and December 2016. Participants were randomly assigned to 4 weeks of cannabis abstinence, verified by decreasing 11-nor-9-carboxy-∆⁹-tetrahydrocannabinol urine concentration (MJ-Abst; n = 62), or a monitoring control condition with no abstinence requirement (MJ-Mon; n = 26). Attention and memory were assessed at baseline and weekly for 4 weeks with the Cambridge Neuropsychological Test Automated Battery. Among MJ-Abst participants, 55 (88.7%) met a priori criteria for biochemically confirmed 30-day continuous abstinence. There was an effect of abstinence on verbal memory (P = .002) that was consistent across 4 weeks of abstinence, with no time-by-abstinence interaction, and was driven by improved verbal learning in the first week of abstinence. MJ-Abst participants had better memory overall and at weeks 1, 2, 3 than MJ-Mon participants, and only MJ-Abst participants improved in memory from baseline to week 1. There was no effect of abstinence on attention: both groups improved similarly, consistent with a practice effect. This study suggests that cannabis abstinence is associated with improvements in verbal learning that appear to occur largely in the first week following last use. Future studies are needed to determine whether the improvement in cognition with abstinence is associated with improvement in academic and other functional outcomes. ClinicalTrials.gov identifier: NCT03276221.


A Modified Communication and Optimal Resolution Program for Intersystem Medical Error Discovery: Protocol for an Implementation Study.
Preventable medical errors represent a major public health problem. To prevent future errors, improve disclosure, and mitigate malpractice risks, organizations have adopted strategies for transparent communication and emphasized quality improvement through peer review. These principles are incorporated into the Agency for Healthcare Research and Quality (AHRQ) Communication and Optimal Resolution (CANDOR) Toolkit, which facilitates (1) transparent communication, (2) error prevention, and (3) achieving optimal resolution with patients and families; however, how medical errors should be addressed when they are discovered between systems-intersystem medical error discovery (IMED)-remains unclear. Without mechanisms for disclosure and feedback on the part of the discovering provider, uncertainty remains as to the extent to which IMED is communicated with patients or responsible providers. Furthermore, known barriers to disclosure and reporting one's own error may not be relevant or may be replaced by other unknown barriers when considering scenarios of IMED. This study aims to develop and test implementation of a modified CANDOR process for application to IMED scenarios. We plan a series of studies following an implementation framework. First, we plan a participatory, consensus-building stakeholder panel process to develop the modified CANDOR process. We will then conduct a robust preimplementation analysis to identify determinants of implementation of the modified process. Using the Consolidated Framework for Implementation Research as a theoretical framework, we will assess organizational readiness by key informant interviews and individual-level behaviors by a survey. Findings from this analysis will inform the implementation toolkit that will be developed and pilot-tested at 2 cancer centers, sites where IMED is hypothesized to occur more frequently than other settings. We will measure 5 implementation outcomes (acceptability, appropriateness, reach, adoption, and feasibility) using a combination of key informant interviews and surveys over the pre- and postimplementation phases. This protocol was funded in August 2018 with support from the AHRQ. The University of Michigan Medical School Institutional Review Board has reviewed and approved the scope of activities described. As of April 2019, step 1 of aim 1 is underway, and aim 1 is projected to be completed by April 2020. Data collection is projected to begin in January 2020 for aim 2 and in August 2020 for aim 3. Providing a communication and resolution strategy applicable to IMED scenarios will help address the current blind spot in the patient safety movement. This work will provide important insights into the potential utility of an implementation toolkit to improve transparent communication and optimal resolution of IMED scenarios. The natural progression of this work will be to test the toolkit more broadly, understand the feasibility and barriers of implementation on a broader scale, and pilot the implementation in new organizations. PRR1-10.2196/13396.


Monitoring intrauterine pressure during active labor. A prospective comparison of two methods.
Conventional recording of intrapartum uterine activity uses fluid-filled internal catheter systems requiring periodic maintenance. An intrauterine pressure catheter system, the INTRAN, uses an electronic pressure sensor and theoretically could obtain satisfactory uterine recordings with less maintenance. Simultaneous recordings with the INTRAN and standard fluid-filled systems were made in 40 third-trimester patients using comparably calibrated electronic monitoring systems. Comparisons of the recordings from each patient showed similar mean baseline uterine tone, contraction interval and duration. Mean peak uterine pressures were significantly higher with the INTRAN system (63 vs. 56 mm Hg). Coefficients of correlation for contraction interval, duration, peak intrauterine pressure and resting tone were .99, .87, .84 and .34, respectively. Both systems detected abnormal uterine activity equally well. Major technical failures were equally frequent with both systems; however, the fluid-filled catheters required more frequent readjustment.


Diagnosing Polyparasitism in a High-Prevalence Setting in Beira, Mozambique: Detection of Intestinal Parasites in Fecal Samples by Microscopy and Real-Time PCR.
Many different intestinal parasite species can co-occur in the same population. However, classic diagnostic tools can only frame a particular group of intestinal parasite species. Hence, one or two tests do not suffice to provide a complete picture of infecting parasite species in a given population. The present study investigated intestinal parasitic infections in Beira, Mozambique, i.e. in the informal settlement of Inhamudima. Diagnostic accuracy of five classical microscopy techniques and real-time PCR for the detection of a broad spectrum of parasites was compared. A cross-sectional population-based survey was performed. One stool sample per participant (n = 303) was examined by direct smear, formal-ether concentration (FEC), Kato smear, Baermann method, coproculture and real-time PCR. We found that virtually all people (96%) harbored at least one helminth, and that almost half (49%) harbored three helminths or more. Remarkably, Strongyloides stercoralis infections were widespread with a prevalence of 48%, and Ancylostoma spp. prevalence was higher than that of Necator americanus (25% versus 15%), the hookworm species that is often assumed to prevail in East-Africa. Among the microscopic techniques, FEC was able to detect the broadest spectrum of parasite species. However, FEC also missed a considerable number of infections, notably S. stercoralis, Schistosoma mansoni and G. intestinalis. PCR outperformed microscopy in terms of sensitivity and range of parasite species detected. We showed intestinal parasites-especially helminths-to be omnipresent in Inhamudima, Beira. However, it is a challenge to achieve high diagnostic sensitivity for all species. Classical techniques such as FEC are useful for the detection of some intestinal helminth species, but they lack sensitivity for other parasite species. PCR can detect intestinal parasites more accurately but is generally not feasible in resource-poor settings, at least not in peripheral labs. Hence, there is a need for a more field-friendly, sensitive approach for on-the-spot diagnosis of parasitic infections.


Homeopathic treatment of Japanese patients with intractable atopic dermatitis.
The objective of the study was to evaluate the efficacy of homeopathic treatment of intractable atopic dermatitis (IAD). Seventeen IAD patients were given individualized homeopathic treatment in addition to conventional dermatological therapy from 6 months to 2 years and 7 months. Although all of the patients had previously been treated with conventional medicine and various psychological approaches, they had had severe conditions and shown no significant sign of improvement. The efficacy of homeopathic treatment was measured by objective assessments of the skin condition and the patients' own assessments, using a 9 point scale similar to the Glasgow Homeopathic Outcome Scale, was used. Over 50% improvement was reported in overall impression and in their skin conditions by all patients, in itchiness by 15 of the patients, in sleep disturbance by 10 out of 13 patients, in satisfaction in daily life by nine out of 12, in fulfillment at work by seven out of 11 and in satisfaction with human relations by 10 out of 14. Two detailed case histories are reported.


The effects of tea extracts on proinflammatory signaling.
Skin toxicity is a common side effect of radiotherapy for solid tumors. Its management can cause treatment gaps and thus can impair cancer treatment. At present, in many countries no standard recommendation for treatment of skin during radiotherapy exists. In this study, we explored the effect of topically-applied tea extracts on the duration of radiation-induced skin toxicity. We investigated the underlying molecular mechanisms and compared effects of tea extracts with the effects of epigallocatechin-gallate, the proposed most-active moiety of green tea. Data from 60 patients with cancer of the head and neck or pelvic region topically treated with green or black tea extracts were analyzed retrospectively. Tea extracts were compared for their ability to modulate IL-1beta, IL-6, IL-8, TNFalpha and PGE2 release from human monocytes. Effects of tea extracts on 26S proteasome function were assessed. NF-kappaB activity was monitored by EMSAs. Viability and radiation response of macrophages after exposure to tea extracts was measured by MTT assays. Tea extracts supported the restitution of skin integrity. Tea extracts inhibited proteasome function and suppressed cytokine release. NF-kappaB activity was altered by tea extracts in a complex, caspase-dependent manner, which differed from the effects of epigallocatechin-gallate. Additionally, both tea extracts, as well as epigallocatechin-gallate, slightly protected macrophages from ionizing radiation Tea extracts are an efficient, broadly available treatment option for patients suffering from acute radiation-induced skin toxicity. The molecular mechanisms underlying the beneficial effects are complex, and most likely not exclusively dependent on effects of tea polyphenols such as epigallocatechin-gallate.


Signatures of the Primordial Universe from Its Emptiness: Measurement of Baryon Acoustic Oscillations from Minima of the Density Field.
Sound waves from the primordial fluctuations of the Universe imprinted in the large-scale structure, called baryon acoustic oscillations (BAOs), can be used as standard rulers to measure the scale of the Universe. These oscillations have already been detected in the distribution of galaxies. Here we propose to measure BAOs from the troughs (minima) of the density field. Based on two sets of accurate mock halo catalogues with and without BAOs in the seed initial conditions, we demonstrate that the BAO signal cannot be obtained from the clustering of classical disjoint voids, but it is clearly detected from overlapping voids. The latter represent an estimate of all troughs of the density field. We compute them from the empty circumsphere centers constrained by tetrahedra of galaxies using Delaunay triangulation. Our theoretical models based on an unprecedented large set of detailed simulated void catalogues are remarkably well confirmed by observational data. We use the largest recently publicly available sample of luminous red galaxies from SDSS-III BOSS DR11 to unveil for the first time a >3σ BAO detection from voids in observations. Since voids are nearly isotropically expanding regions, their centers represent the most quiet places in the Universe, keeping in mind the cosmos origin and providing a new promising window in the analysis of the cosmological large-scale structure from galaxy surveys.


Effective strategy of dendritic cell-based immunotherapy for advanced tumor-bearing hosts: the critical role of Th1-dominant immunity.
Although dendritic cell (DC)-based cancer-specific immunotherapy is a potent strategy for various types of carcinomas, few clinical studies have yielded optimal antitumor effects. Systemic immunodeficiency is observed in patients with advanced malignant disease. In this study, we explored the ability to induce antitumor immunity of the cultured monocyte-derived DCs from hosts with advanced malignant disease, using a mouse model. We found remarkable dysfunction of DCs from mice with advanced cancer, which exhibited T helper (Th)2-dominant immunity, and subsequent reduced antitumor immune response. On the other hand, we found dramatic restoration of the ability of DCs to induce optimal antitumor immune responses after systemic administration of streptococcal preparation OK-432 to the tumor-bearing mice, which induced Th1-dominant immunity. In therapeutic experiments, intratumoral injections of immature DCs from the OK-432-treated mice, designated OK-DCs, enhanced inhibition of tumor growth compared with injections of immature DCs from mice with advanced malignancies, designated T-DCs (P < 0.05), leading to significant prolongation in overall survival (P < 0.05). In analysis of cell surface antigens, antigen-presenting capability and interleukin 12 production, we showed functional skewing in T-DCs and significant restorations in OK-DCs. More CD8+ tumor-infiltrating lymphocytes were detected in the mice treated with OK-DCs; furthermore, CTL assays showed that intratumoral injection of OK-DCs induced tumor-specific immune response to spleen as great as those of N-DCs. These results suggested that Th1-dominant immunity might play a crucial role in the differentiation of DCs, and OK-432 might be useful for inducing optimal antitumor effects in DC-based immunotherapy in tumor-bearing hosts.


Variation in population levels of physical activity in European adults according to cross-European studies: a systematic literature review within DEDIPAC.
Physical inactivity is a well-known public health risk that should be monitored at the population level. Physical activity levels are often surveyed across Europe. This systematic literature review aims to provide an overview of all existing cross-European studies that assess physical activity in European adults, describe the variation in population levels according to these studies, and discuss the impact of the assessment methods. Six literature databases (PubMed, EMBASE, CINAHL, PsycINFO, SportDiscus and OpenGrey) were searched, supplemented with backward- and forward tracking and searching authors' and experts' literature databases. Articles were included if they reported on observational studies measuring total physical activity and/or physical activity in leisure time in the general population in two or more European countries. Each record was reviewed, extracted and assessed by two independent researchers and disagreements were resolved by a third researcher. The review protocol of this review is registered in the PROSPERO database under registration number CRD42014010334. Of the 9,756 unique identified articles, twenty-five were included in this review, reporting on sixteen different studies, including 2 to 35 countries and 321 to 274,740 participants. All but two of the studies used questionnaires to assess physical activity, with the majority of studies using the IPAQ-short questionnaire. The remaining studies used accelerometers. The percentage of participants who either were or were not meeting the physical activity recommendations was the most commonly reported outcome variable, with the percentage of participants meeting the recommendations ranging from 7% to 96% across studies and countries. The included studies showed substantial variation in the assessment methods, reported outcome variables and, consequently, the presented physical activity levels. Because of this, absolute population levels of physical activity in European adults are currently unknown. However, when ranking countries, Ireland, Italy, Malta, Portugal, and Spain generally appear to be among the less active countries. Objective data of adults across Europe is currently limited. These findings highlight the need for standardisation of the measurement methods, as well as cross-European monitoring of physical activity levels.


Pyogranulomatous pneumonias due to Nocardia asteroides and Staphylococcus epidermidis in two koalas (Phascolarctos cinereus).
Pyogranulomatous pneumonia was detected in two koalas (Phascolarctos cinereus). Nocardia asteroides was isolated from one koala with extensive pneumonia, pleurisy and splenitis. Staphylococcus epidermidis was isolated from a second koala with pneumonia restricted to the left cranial lobe. Both koalas were in poor condition and had underlying urogenital disease. It was concluded that each organism had acted as an opportunistic pathogen in its compromised host.


Transgender health in Massachusetts: results from a household probability sample of adults.
Despite higher rates of unemployment and poverty among transgender adults (n = 131; 0.5% weighted) than among nontransgender adults (n = 28,045) in our population-based Massachusetts household sample, few health differences were observed between transgender and nontransgender adults. Transgender adults who are stably housed and participated in a telephone health survey may represent the healthiest segment of the transgender population. Our findings demonstrate a need for diverse sampling approaches to monitor transgender health, including adding transgender measures to population-based surveys, and further highlight economic inequities that warrant intervention.


A study on the menopause in Malaysia.
In an attempt to gather data on the menopause in Malaysia, 400 women (13% Chinese, 70% Malays and 16% Indians), representing the three major ethnic groups in Malaysia, were interviewed. The majority (76%) of these women were still married and living with their husbands and 63% of them were working. Most of them (90%) had attained menarche by the age of 15 years and 50% of them had married before the age of 20. Their reproductive record was good, since 76% of them had 3 or more children who were still alive. The mean age at menopause in the Malaysian women studied was 50.7 years. Analysis of the climacteric symptoms reported showed significant differences in the vasomotor and nervosity indices in the perimenopausal and postmenopausal groups. Eighty percent (80%) of the women saw no need to consult a doctor about their climacteric symptoms. When they did, most of them (84%) received medication, but 43% of them did not comply with the prescribed treatment. Dyspareunia and urinary incontinence were evidently regarded as embarrassing complaints in all three groups, since around 80% of the women did not seek medical advice. This is not surprising in view of the fact that 89% of them rated their health as good.


Prevalence and Loads of Torquetenovirus in the European MARK-AGE Study Population.
Torquetenovirus (TTV) viremia has been associated with increased mortality risk in the elderly population. This work aims to investigate TTV viremia as a potential biomarker of immunosenescence. We compared levels of circulating TTV in 1813 participants of the MARK-AGE project, including human models of delayed (offspring of centenarians [GO]) and premature (Down syndrome [DS]) immunosenescence. The TTV load was positively associated with age, cytomegalovirus (CMV) antibody levels, and the Cu/Zn ratio and negatively associated with platelets, total cholesterol, and total IgM. TTV viremia was highest in DS and lowest in GO, with intermediate levels in the SGO (spouses of GO) and RASIG (Randomly Recruited Age-Stratified Individuals From The General Population) populations. In the RASIG population, TTV DNA loads showed a slight negative association with CD3+T-cells and CD4+T-cells. Finally, males with ≥4log TTV copies/mL had a higher risk of having a CD4/CD8 ratio<1 than those with lower viremia (odds ratio [OR] = 2.85, 95% confidence interval [CI]: 1.06-7.62), as well as reduced CD3+ and CD4+T-cells compared to males with lower replication rates (<4log), even after adjusting for CMV infection. In summary, differences in immune system preservation are reflected in the models of delayed and premature immunosenescence, displaying the best and worst control over TTV replication, respectively. In the general population, TTV loads were negatively associated with CD4+ cell counts, with an increased predisposition for an inverted CD4/CD8 ratio for individuals with TTV loads ≥4log copies/mL, thus promoting an immune risk phenotype.


Dyskinetic cerebral palsy in Europe: trends in prevalence and severity.
To describe the trends for and severity of dyskinetic cerebral palsy in a European collaborative study between cerebral palsy registers, the Surveillance of Cerebral Palsy in Europe (SCPE). The prevalence of dyskinetic cerebral palsy was calculated in children born in 1976-1996. Walking ability, accompanying impairments and perinatal adverse events were analysed. 578 children had dyskinetic cerebral palsy, of whom 70% were born at term. The prevalence per 1000 live births increased from 0.08 in the 1970s to 0.14 in the 1990s. For the 386 children (70%) with a birth weight of > or =2500 g, the increase was significant (0.05 to 0.12). There was a concurrent decrease in neonatal mortality among children with a birth weight of > or =2500 g. Overall, 16% of the children walked without aids, 24% with aids and 59% needed a wheelchair. Severe learning disability was present in 52%, epilepsy in 51% and severe visual and hearing impairment in 19% and 6%, respectively. Accompanying impairments increased with motor severity. In children born in 1991-1996, perinatal adverse events, that is an Apgar score of <5 at 5 min and convulsions before 72 h, had occurred more frequently compared with children with bilateral spastic cerebral palsy (BSCP, n = 4746). Children with dyskinetic cerebral palsy had more severe cognitive and motor impairments than children with BSCP. The prevalence of dyskinetic cerebral palsy appears to have increased in children with a normal birth weight. They have frequently experienced perinatal adverse events. Most children have a severe motor impairment and several accompanying impairments.


Low Energy Subsurface Environments as Extraterrestrial Analogs.
Earth's subsurface is often isolated from phototrophic energy sources and characterized by chemotrophic modes of life. These environments are often oligotrophic and limited in electron donors or electron acceptors, and include continental crust, subseafloor oceanic crust, and marine sediment as well as subglacial lakes and the subsurface of polar desert soils. These low energy subsurface environments are therefore uniquely positioned for examining minimum energetic requirements and adaptations for chemotrophic life. Current targets for astrobiology investigations of extant life are planetary bodies with largely inhospitable surfaces, such as Mars, Europa, and Enceladus. Subsurface environments on Earth thus serve as analogs to explore possibilities of subsurface life on extraterrestrial bodies. The purpose of this review is to provide an overview of subsurface environments as potential analogs, and the features of microbial communities existing in these low energy environments, with particular emphasis on how they inform the study of energetic limits required for life. The thermodynamic energetic calculations presented here suggest that free energy yields of reactions and energy density of some metabolic redox reactions on Mars, Europa, Enceladus, and Titan could be comparable to analog environments in Earth's low energy subsurface habitats.


Exploring the role of the amplitude envelope in duration estimation.
A sound's duration provides important information about the event producing it. Although many of the sounds we hear every day are 'percussive' in nature (ie resulting from two objects impacting) and therefore exhibit decaying/damped amplitude envelopes, perceptual experiments frequently use tones synthesized with 'flat' or abruptly ending envelopes. Such sounds afford an estimation strategy involving calculating the elapsed time between tone onset and offset--a strategy that would be problematic for ecologically pervasive decaying sounds. Here we compare duration judgments for tones with percussive (ie gradually decaying) and flat (ie abruptly ending) amplitude envelopes, finding evidence for the use of different strategies. This result is discussed in terms of its implications for dominant theories and models of sensory perception that are often assessed using artificial sounds (ie 'flat tones') affording strategies that may not be optimal or even available for everyday listening.


Real-Time Dynamics of the Formation of Hydrated Electrons upon Irradiation of Water Clusters with Extreme Ultraviolet Light.
Free electrons in a polar liquid can form a bound state via interaction with the molecular environment. This so-called hydrated electron state in water is of fundamental importance, e.g., in cellular biology or radiation chemistry. Hydrated electrons are highly reactive radicals that can either directly interact with DNA or enzymes, or form highly excited hydrogen (H^{*}) after being captured by protons. Here, we investigate the formation of the hydrated electron in real-time employing extreme ultraviolet femtosecond pulses from a free electron laser, in this way observing the initial steps of the hydration process. Using time-resolved photoelectron spectroscopy we find formation timescales in the low picosecond range and resolve the prominent dynamics of forming excited hydrogen states.


Mechanism of pomegranate ellagic polyphenols reducing insulin resistance on gestational diabetes mellitus rats.
Pomegranate ellagic polyphenols (PEP) has been used as a good medicine in many cultures throughout history. However, the mechanism of PEP regulated insulin resistance on gestational diabetes mellitus (GDM) rats is unclear. The main purpose of the present study was to explore the efficacy and mechanisms of PEP regulated in GDM rats. Then, ELISA assay indicated that the levels of serum RBP4, Hcy, GA and FFA were lower in PEP groups than GDM groups in a dose-dependent manner. TUNEL staining showed that PEP improved the pathological changes and inhibited the cell apoptosis in the pancreatic and placenta tissues, respectively. We found that PEP improved the weight of pregnant rats and fetal rats and the level of blood glucose, blood biochemical index, insulin resistance in GDM rats. Results from H&E and immunohistochemical analysis found that PEP decreased the expressions of APN and Chemerin. Further, PEP decreased the levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and C-reactive protein (CRP), and increased the levels of 11β-hydroxy steroid dehydrogenase type 2 (11β-HSD2) and PPARα-TRB3-AKT2-p-FOXO1-GLUT2 signal related to insulin sensitivity in a dose-dependent manner. In conclusion, we have demonstrated that PEP may be a candidate drug for the treatment of GDM and guide the clinical therapy.


More than g: selection quality and adverse impact implications of considering second-stratum cognitive abilities.
When using cognitive tests, personnel selection practitioners typically face a trade-off between the expected job performance and diversity of new hires. We review the increasingly mainstream evidence that cognitive ability is a multidimensional and hierarchically ordered set of concepts, and examine the implications for both composite test validity and subgroup differences. Ultimately, we recommend a strategy for differentially weighting cognitive subtests (i.e., second-stratum abilities) in a way that minimizes overall subgroup differences without compromising composite test validity. Using data from 2 large validation studies that included a total of 15 job families, we demonstrate that this strategy could lead to substantial improvement in diversity hiring (e.g., doubling the number of job offers extended to minority applicants) and to at least 8% improvement in job offers made to minority applicants, without decrements in expected selection quality compared to a unit-weighted cognitive test composite. Finally, we conduct a sensitivity analysis to examine whether the technique continues to perform well when applied to applicant pools of smaller size. We discuss prerequisites for the application of this strategy, potential limitations, and extensions.


Large-area synthesis of high-quality and uniform graphene films on copper foils.
Graphene has been attracting great interest because of its distinctive band structure and physical properties. Today, graphene is limited to small sizes because it is produced mostly by exfoliating graphite. We grew large-area graphene films of the order of centimeters on copper substrates by chemical vapor deposition using methane. The films are predominantly single-layer graphene, with a small percentage (less than 5%) of the area having few layers, and are continuous across copper surface steps and grain boundaries. The low solubility of carbon in copper appears to help make this growth process self-limiting. We also developed graphene film transfer processes to arbitrary substrates, and dual-gated field-effect transistors fabricated on silicon/silicon dioxide substrates showed electron mobilities as high as 4050 square centimeters per volt per second at room temperature.