Targeting lysine demethylase 6B ameliorates ASXL1 truncation-mediated myeloid malignancies in preclinical models.
ASXL1 mutation frequently occurs in all forms of myeloid malignancies and is associated with aggressive disease and poor prognosis. ASXL1 recruits Polycomb Repressive Complex 2 (PRC2) to specific gene loci to repress transcription through tri-methylation of histone H3 on lysine 27 (H3K27me3). ASXL1 alterations reduce H3K27me3 levels, which results in leukemogenic gene expression and the development of myeloid malignancies. Standard therapies for myeloid malignancies have limited efficacy when mutated ASXL1 is present. We discovered up-regulation of lysine demethylase 6B (KDM6B), a demethylase for H3K27me3, in ASXL1-mutant leukemic cells, which further reduces H3K27me3 levels and facilitates myeloid transformation. Here, we demonstrated that heterozygous deletion of Kdm6b restored H3K27me3 levels and normalized dysregulated gene expression in Asxl1Y588XTg hematopoietic stem/progenitor cells (HSPCs). Furthermore, heterozygous deletion of Kdm6b decreased the HSPC pool, restored their self-renewal capacity, prevented biased myeloid differentiation, and abrogated progression to myeloid malignancies in Asxl1Y588XTg mice. Importantly, administration of GSK-J4, a KDM6B inhibitor, not only restored H3K27me3 levels but also reduced the disease burden in NSG mice xenografted with human ASXL1 mutant leukemic cells in vivo. This preclinical finding provides compelling evidence that targeting KDM6B may be a therapeutic strategy for myeloid malignancies with ASXL1 mutations.


The Fecal Microbiota Profile and Bronchiolitis in Infants.
Little is known about the association of gut microbiota, a potentially modifiable factor, with bronchiolitis in infants. We aimed to determine the association of fecal microbiota with bronchiolitis in infants. We conducted a case-control study. As a part of multicenter prospective study, we collected stool samples from 40 infants hospitalized with bronchiolitis. We concurrently enrolled 115 age-matched healthy controls. By applying 16S rRNA gene sequencing and an unbiased clustering approach to these 155 fecal samples, we identified microbiota profiles and determined the association of microbiota profiles with likelihood of bronchiolitis. Overall, the median age was 3 months, 55% were male, and 54% were non-Hispanic white. Unbiased clustering of fecal microbiota identified 4 distinct profiles: Escherichia-dominant profile (30%), Bifidobacterium-dominant profile (21%), Enterobacter/Veillonella-dominant profile (22%), and Bacteroides-dominant profile (28%). The proportion of bronchiolitis was lowest in infants with the Enterobacter/Veillonella-dominant profile (15%) and highest in the Bacteroides-dominant profile (44%), corresponding to an odds ratio of 4.59 (95% confidence interval, 1.58-15.5; P = .008). In the multivariable model, the significant association between the Bacteroides-dominant profile and a greater likelihood of bronchiolitis persisted (odds ratio for comparison with the Enterobacter/Veillonella-dominant profile, 4.24; 95% confidence interval, 1.56-12.0; P = .005). In contrast, the likelihood of bronchiolitis in infants with the Escherichia-dominant or Bifidobacterium-dominant profile was not significantly different compared with those with the Enterobacter/Veillonella-dominant profile. In this case-control study, we identified 4 distinct fecal microbiota profiles in infants. The Bacteroides-dominant profile was associated with a higher likelihood of bronchiolitis.


The perception of globally coherent motion.
How do human observers perceive a coherent pattern of motion from a disparate set of local motion measures? Our research has examined how ambiguous motion signals along straight contours are spatially integrated to obtain a globally coherent perception of motion. Observers viewed displays containing a large number of apertures, with each aperture containing one or more contours whose orientations and velocities could be independently specified. The total pattern of the contour trajectories across the individual apertures was manipulated to produce globally coherent motions, such as rotations, expansions, or translations. For displays containing only straight contours extending to the circumferences of the apertures, observers' reports of global motion direction were biased whenever the sampling of contour orientations was asymmetric relative to the direction of motion. Performance was improved by the presence of identifiable features, such as line ends or crossings, whose trajectories could be tracked over time. The reports of our observers were consistent with a pooling process involving a vector average of measures of the component of velocity normal to contour orientation, rather than with the predictions of the intersection-of-constraints analysis in velocity space.


A synoptic review of Promonobothrium Mackiewicz, 1968 (Cestoda: Caryophyllidea), parasites of suckers (Catostomidae) in North America, with description of two new species.
Monozoic cestodes of the recently amended genus Promonobothrium Mackiewicz, 1968 (Cestoda: Caryophyllidea), parasites of suckers (Cypriniformes: Catostomidae) in North America, are reviewed, with information on their host specificity, distribution and data on the scolex morphology of seven species studied for the first time using scanning electron microscopy (SEM). Evaluation of type and voucher specimens from museum collections and newly collected material of most species indicated the following valid nominal species: Promonobothrium minytremi Mackiewicz, 1968 (type species); P. ingens (Hunter, 1927); P. hunteri (Mackiewicz, 1963); P. ulmeri (Calentine et Mackiewicz, 1966); P. fossae (Williams, 1974) and P. mackiewiczi (Williams, 1974). Rogersus Williams, 1980 with its only species R. rogersi is transferred to Promonobothrium based on morphological and molecular data. Promonobothrium currani sp. n. and P. papiliovarium sp. n. are described from Ictiobus bubalus (Rafinesque) and Ictiobus niger (Rafinesque), and Erimyzon oblongus (Mitchill), respectively. The newly described species can be distinguished from the other congeners by the morphology of the scolex, the position of the anteriormost vitelline follicles and testes, the presence of postovarian vitelline follicles and the shape of the ovary. Molecular phylogenetic analyses of six species based on sequences of the small and large subunits of the nuclear ribosomal RNA genes (ssrDNA, lsrDNA) confirmed the monophyletic status of the genus and supported the validity of the species analysed. A key to identification of all species of Promonobothrium based on morphological characteristics is provided.


Color-shape associations revealed with implicit association tests.
Kandinsky proposed a correspondence theory that suggests associations between specific colors and shapes (i.e., circle-blue, square-red, triangle-yellow). Makin and Wuerger tested the theory using the Implicit Association Test (IAT) and did not find clear evidence for Kandinsky's color-shape associations among British participants. In the present study, we first replicated the previous study among Japanese participants and found similar results to those of Makin and Wuerger, showing little support for Kandinsky's theory. In the subsequent experiment, we tested another set of color-shape associations that had been revealed by using an explicit matching method (circle-red, square-blue, triangle-yellow) in Japanese participants. The IAT tests showed that response times were significantly faster when circle-red, square-blue, and triangle-yellow combinations were mapped onto the same response key, rather than different key combinations, indicating that these color-shape combinations were encoded. These results provide the first empirical evidence that color-shape associations can be measured by indirect behavioral methods, and in particular, Japanese people's color-shape associations (circle-red, square-blue, triangle-yellow) can be observed by both direct and indirect experimental methods.


Salmonella biofilm development depends on the phosphorylation status of RcsB.
The Rcs phosphorelay pathway is a complex signaling pathway involved in the regulation of many cell surface structures in enteric bacteria. In response to environmental stimuli, the sensor histidine kinase (RcsC) autophosphorylates and then transfers the phosphate through intermediary steps to the response regulator (RcsB), which, once phosphorylated, regulates gene expression. Here, we show that Salmonella biofilm development depends on the phosphorylation status of RcsB. Thus, unphosphorylated RcsB, hitherto assumed to be inactive, is essential to activate the expression of the biofilm matrix compounds. The prevention of RcsB phosphorylation either by the disruption of the phosphorelay at the RcsC or RcsD level or by the production of a nonphosphorylatable RcsB allele induces biofilm development. On the contrary, the phosphorylation of RcsB by the constitutive activation of the Rcs pathway inhibits biofilm development, an effect that can be counteracted by the introduction of a nonphosphorylatable RcsB allele. The inhibition of biofilm development by phosphorylated RcsB is due to the repression of CsgD expression, through a mechanism dependent on the accumulation of the small noncoding RNA RprA. Our results indicate that unphosphorylated RcsB plays an active role for integrating environmental signals and, more broadly, that RcsB phosphorylation acts as a key switch between planktonic and sessile life-styles in Salmonella enterica serovar Typhimurium.


Two-dimensional gel analysis of the heat-shock response in marine snails (genus Tegula): interspecific variation in protein expression and acclimation ability.
The degree to which temperature acclimation modifies the acute synthesis of the entire heat-shock protein (Hsp) complement is still unknown, but it may constitute an important mechanism for understanding the differences in acclimation ability among closely related ectothermic species that occupy widely varying thermal environments. In general, eurythermal (heat-tolerant) species modify physiological function in response to an increase in acclimation temperature to a greater extent than stenothermal (heat-sensitive) species. In the present work I used 35S-labelled amino acids and two-dimensional gel electrophoresis to test this assumption for how acclimation affects acute Hsp expression (referred to as phenotypic plasticity) in two heat-sensitive, low-intertidal to subtidal zone turban snails, Tegula brunnea and T. montereyi, in comparison to a heat-tolerant, mid- to low-intertidal zone congener, T. funebralis. I was able (i) to detect the synthesis of over 30 proteins in gill tissue, primarily in the 70 kDa range, in response to an increase in temperature (13 degrees C, 24 degrees C, 27 degrees C and 30 degrees C), (ii) to assess the effect of acclimation (13 degrees C vs 22 degrees C) on acute Hsp synthesis, and (iii) to compare this effect among the three Tegula congeners. After increasing acclimation temperature from 13 degrees C to 22 degrees C, synthesis of the most highly expressed Hsps decreased more in T. brunnea and T. montereyi than in T. funebralis. Two highly expressed proteins of molecular mass 71 and 74 kDa, however, were also synthesized constitutively at 13 degrees C and changed with increasing acclimation temperature in all three species. Although similar in phenotypic plasticity, T. brunnea and T. montereyi synthesized either a 76 or a 72 kDa cluster of proteins, respectively, and differed in how acclimation affected the acute synthesis of several 77 kDa proteins. Thus, in Tegula, the effect of acclimation on Hsp expression is (i) Hsp-specific, (ii) dependent on a protein's expression pattern (constitutive and inducible vs only inducible), (iii) and is actually limited in the more eurythermal mid- to low-intertidal congener. These results contradict the general assumption that greater heat tolerance correlates with an increased ability to modify physiological function in response to acclimation.


Non-NMDA receptor-mediated neurotoxicity in cortical culture.
The neurotoxicity of 3 non-NMDA glutamate receptor agonists--kainate, alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA), and quisqualate--was investigated quantitatively in dissociated murine cortical cultures. Five minute exposure to 500 microM kainate, but not AMPA, produced widespread acute neuronal swelling. Kainate-induced swelling was resistant to 2-amino-5-phosphonovalerate (APV) or replacement of extracellular sodium with choline but attenuated by either kynurenate or low concentrations of quisqualate. Unlike NMDA agonists, kainate or AMPA did not produce much late neuronal loss after a 5 min exposure. In contrast, 5 min exposure to 500 microM quisqualate produced both acute neuronal swelling and widespread late neuronal degeneration. This acute swelling was blocked by APV or by replacement of extracellular sodium by choline, consistent with mediation by NMDA receptors; we speculate that high concentrations of quisqualate may directly activate NMDA receptors or induce the release of endogenous glutamate. Quisqualate-induced late neuronal degeneration may be due to another unexpected process: cellular quisqualate uptake and delayed release, converting brief addition into prolonged exposure. Hours after thorough washout of exogenously added quisqualate, micromolar concentrations could be detected in the bathing medium by high performance liquid chromatography. With lengthy exposure (20-24 hr), all 3 non-NMDA agonists were potent neurotoxins, able to destroy neurons with EC50's of about 20 microM for kainate, 4 microM for AMPA, and 1 microM for quisqualate. Kynurenate and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), but not APV or L-glutamate diethyl ester, were effective in attenuating the neuronal degeneration induced by these agonists. CNQX was about 3 times more selective than kynurenate against kainate-induced neuronal injury, but CNQX was still nearly equipotent with APV against NMDA-induced injury. Gamma-D-glutamylaminomethyl sulfonate exhibited partial antagonist specificity for AMPA-induced toxicity.


Preferential therapy for osteoarthritis by cord blood MSCs through regulation of chondrogenic cytokines.
Osteoarthritis (OA) is a common rheumatic disease associated with imbalanced cartilage homeostasis which could be corrected by mesenchymal stem cells (MSCs) therapy. However, MSCs from different origins might exhibit distinct differentiation capacities. This study was undertaken to compare the therapeutic efficacies between MSCs from cord blood (CB-MSCs) and bone marrow (BM-MSCs) on OA treatment. The surface phenotypes and multipotent capacities of CB-MSCs and BM-MSCs were first characterized. The coculture commitment system was subsequently utilized for comparing the patterned molecules in stage-specific chondrogenesis of committed MSCs. For examining the therapeutic efficacies, committed CB-MSCs and BM-MSCs were encapsulated in neo-cartilage and subjected into pro-inflammatory cytokine environment. Finally, chondrogenic and inflammatory cytokine profiles in committed MSCs were evaluated. CB-MSCs and BM-MSCs were both negative for hematopoietic markers and positive for adhesion and mesenchymal cell markers. The CB-MSCs showed a markedly higher chondrogenic potential and relatively lower osteogenic and adipogenic capacities than BM-MSCs. During chondrogenesis, the committed CB-MSCs also showed significant increases in cell proliferation, adhesion molecules, signaling molecules, and chondrogenic-specific gene expressions in a coculture system. For the therapeutic efficacies, the committed CB-MSCs could strongly recover the pro-inflammatory cytokines diminished-Col II and proteoglycan expressions in a 3D arthritic model. The IL-10, ICAM-1 and TGF-β1 were also up-regulated in committed CB-MSCs analyzed by using cytokine profiling. Our data demonstrate that CB-MSCs possess specific advantages in cartilage regeneration over BM-MSCs. The CB-MSCs showed a better therapeutic potential that can contribute to advanced cell-based transplantation for clinical OA therapy.


Endothelin-B Receptor Activation in Astrocytes Regulates the Rate of Oligodendrocyte Regeneration during Remyelination.
Reactive astrogliosis is an essential and ubiquitous response to CNS injury, but in some cases, aberrant activation of astrocytes and their release of inhibitory signaling molecules can impair endogenous neural repair processes. Our lab previously identified a secreted intercellular signaling molecule, called endothelin-1 (ET-1), which is expressed at high levels by reactive astrocytes in multiple sclerosis (MS) lesions and limits repair by delaying oligodendrocyte progenitor cell (OPC) maturation. However, as ET receptors are widely expressed on neural cells, the cell- and receptor-specific mechanisms of OPC inhibition by ET-1 action remain undefined. Using pharmacological approaches and cell-specific endothelin receptor (EDNR) ablation, we show that ET-1 acts selectively through EDNRB on astrocytes--and not OPCs--to indirectly inhibit remyelination. These results demonstrate that targeting specific pathways in reactive astrocytes represents a promising therapeutic target in diseases with extensive reactive astrogliosis, including MS.


Premature discontinuation of patients: a potential bias in COPD clinical trials.
Premature discontinuation from clinical trials may bias results against effective therapies. In the present study mortality rates were retrospectively reviewed in a 6-month, randomised, placebo-controlled trial in which tiotropium 18 mug daily was shown to decrease chronic obstructive pulmonary disease exacerbations. Patients participated for 6 months even if trial medication was prematurely discontinued. Exposure-adjusted incidence rates (IRs) were calculated for randomisation-end trial, randomisation-end trial drug (0-ED) and end trial drug-end trial (ED-ET). Of 1,829 patients (forced expiratory volume in one second 1.04 L (36% predicted), mean age 68 yrs, 99% male), 16% tiotropium and 27% placebo patients prematurely stopped trial medication. The number of fatal events for the entire cohort was: 62 all cause, including 16 cardiac and 16 lower respiratory. IRs for fatal events per 100 patient-yrs were higher in the discontinued period: 1.9 (0-ED) versus 23.0 (ED-ET) in the tiotropium group and 1.8 versus 19.0 in the placebo group. Respective IRs for fatal cardiac events were 0.7 versus 2.8 (tiotropium) and 0.5 versus 6.2 (placebo); for fatal lower respiratory events were 0.7 versus 2.8 (tiotropium) and 0.8 versus 5.4 (placebo). Rate ratios (tiotropium/placebo) for fatal events were lower in the discontinued period: 1.4 versus 0.5 for cardiac and 0.9 versus 0.5 for lower respiratory. Higher incidence rates of fatal events occurred following premature discontinuation of study medication. Incomplete information from rate ratios occurs as a result of failure to consider outcomes of patients who discontinue early from clinical trials.


Malaise and fatigue following mitral valve repair: case report.
Mitral valve regurgitation is the second most common valvular heart disease. In primary, degenerative mitral regurgitation (MR), valve repair is the preferred treatment option. We present a case of a 73-year-old man who was admitted to our cardiology department with progressively worsening shortness of breath (New York Heart Association-Classification IV) and fatigue 2 months after surgical mitral valve repair for MR. Transthoracic and transoesophageal echocardiography showed a remaining severe MR and mitral valve stenosis II°. Laboratory results showed an extra-corpuscular, mechanical, and haemolytic anaemia. After exclusion of other causes of haemolytic anaemia and the lack of clinical and laboratory improvement, the patient underwent valve replacement with a biological valve. Haemolysis parameter normalized and the clinical status improved. Although haemolysis after mechanical prosthetic mitral valve replacement is frequently recognized, haemolytic anaemia after mitral valve reconstruction is still an underestimated complication, and there are only a small number of reported cases. This case demonstrates the clinical diagnostic steps for excluding other causes of haemolytic anaemia after mitral valve repair in patients with a history of heart surgery.


Tweeting PP: an analysis of the 2015-2016 Planned Parenthood controversy on Twitter.
We analyzed Twitter tweets and Twitter-provided user data to give geographical, temporal and content insight into the use of social media in the Planned Parenthood video controversy. We randomly sampled the full Twitter repository (also known as the Firehose) (n=30,000) for tweets containing the phrase "planned parenthood" as well as group-defining hashtags "#defundpp" and "#standwithpp." We used demographic content provided by the user and word analysis to generate charts, maps and timeline visualizations. Chi-square and t tests were used to compare differences in content, statistical references and dissemination strategies. From July 14, 2015, to January 30, 2016, 1,364,131 and 795,791 tweets contained "#defundpp" and "#standwithpp," respectively. Geographically, #defundpp and #standwithpp were disproportionally distributed to the US South and West, respectively. Word analysis found that early tweets predominantly used "sensational" words and that the proportion of "political" and "call to action" words increased over time. Scatterplots revealed that #standwithpp tweets were clustered and episodic compared to #defundpp. #standwithpp users were more likely to be female [odds ratio (OR) 2.2, confidence interval (CI) 2.0-2.4] and have fewer followers (median 544 vs. 1578, p<.0001). #standwithpp and #defundpp did not differ significantly in their usage of data in tweets. #defundpp users were more likely to link to websites (OR 1.8, CI 1.7-1.9) and to other online dialogs (mean 3.3 vs. 2.0 p<.0001). Social media analysis can be used to characterize and understand the content, tempo and location of abortion-related messages in today's public spheres. Further research may inform proabortion efforts in terms of how information can be more effectively conveyed to the public. This study has implications for how the medical community interfaces with the public with regards to abortion. It highlights how social media are actively exploited instruments for information and message dissemination. Researchers, providers and advocates should be monitoring social media and addressing the public through these modern channels.


An autonomous debating system.
Artificial intelligence (AI) is defined as the ability of machines to perform tasks that are usually associated with intelligent beings. Argument and debate are fundamental capabilities of human intelligence, essential for a wide range of human activities, and common to all human societies. The development of computational argumentation technologies is therefore an important emerging discipline in AI research1. Here we present Project Debater, an autonomous debating system that can engage in a competitive debate with humans. We provide a complete description of the system's architecture, a thorough and systematic evaluation of its operation across a wide range of debate topics, and a detailed account of the system's performance in its public debut against three expert human debaters. We also highlight the fundamental differences between debating with humans as opposed to challenging humans in game competitions, the latter being the focus of classical 'grand challenges' pursued by the AI research community over the past few decades. We suggest that such challenges lie in the 'comfort zone' of AI, whereas debating with humans lies in a different territory, in which humans still prevail, and for which novel paradigms are required to make substantial progress.


Development of an expert system as a diagnostic support of cervical cancer in atypical glandular cells, based on fuzzy logics and image interpretation.
Cervical cancer is the second largest cause of death among women worldwide. Nowadays, this disease is preventable and curable at low cost and low risk when an accurate diagnosis is done in due time, since it is the neoplasm with the highest prevention potential. This work describes the development of an expert system able to provide a diagnosis to cervical neoplasia (CN) precursor injuries through the integration of fuzzy logics and image interpretation techniques. The key contribution of this research focuses on atypical cases, specifically on atypical glandular cells (AGC). The expert system consists of 3 phases: (1) risk diagnosis which consists of the interpretation of a patient's clinical background and the risks for contracting CN according to specialists; (2) cytology images detection which consists of image interpretation (IM) and the Bethesda system for cytology interpretation, and (3) determination of cancer precursor injuries which consists of in retrieving the information from the prior phases and integrating the expert system by means of a fuzzy logics (FL) model. During the validation stage of the system, 21 already diagnosed cases were tested with a positive correlation in which 100% effectiveness was obtained. The main contribution of this work relies on the reduction of false positives and false negatives by providing a more accurate diagnosis for CN.


Responses to Salt Stress in Portulaca: Insight into Its Tolerance Mechanisms.
Climate change and its detrimental effects on agricultural production, freshwater availability and biodiversity accentuated the need for more stress-tolerant varieties of crops. This requires unraveling the underlying pathways that convey tolerance to abiotic stress in wild relatives of food crops, industrial crops and ornamentals, whose tolerance was not eroded by crop cycles. In this work we try to demonstrate the feasibility of such strategy applying and investigating the effects of saline stress in different species and cultivars of Portulaca. We attempted to unravel the main mechanisms of stress tolerance in this genus and to identify genotypes with higher tolerance, a procedure that could be used as an early detection method for other ornamental and minor crops. To investigate these mechanisms, six-week-old seedlings were subjected to saline stress for 5 weeks with increasing salt concentrations (up to 400 mM NaCl). Several growth parameters and biochemical stress markers were determined in treated and control plants, such as photosynthetic pigments, monovalent ions (Na+, K+ and Cl-), different osmolytes (proline and soluble sugars), oxidative stress markers (malondialdehyde-a by-product of membrane lipid peroxidation-MDA) and non-enzymatic antioxidants (total phenolic compounds and total flavonoids). The applied salt stress inhibited plant growth, degraded photosynthetic pigments, increased concentrations of specific osmolytes in both leaves and roots, but did not induce significant oxidative stress, as demonstrated by only small fluctuations in MDA levels. All Portulaca genotypes analyzed were found to be Na+ and Cl- includers, accumulating high amounts of these ions under saline stress conditions, but P. grandiflora proved to be more salt tolerant, showing only a small reduction under growth stress, an increased flower production and the lowest reduction in K+/Na+ rate in its leaves.


Implementing meta-analysis from genome-wide association studies for pork quality traits.
Pork quality plays an important role in the meat processing industry. Thus, different methodologies have been implemented to elucidate the genetic architecture of traits affecting meat quality. One of the most common and widely used approaches is to perform genome-wide association (GWA) studies. However, a limitation of many GWA in animal breeding is the limited power due to small sample sizes in animal populations. One alternative is to implement a meta-analysis of GWA (MA-GWA) combining results from independent association studies. The objective of this study was to identify significant genomic regions associated with meat quality traits by performing MA-GWA for 8 different traits in 3 independent pig populations. Results from MA-GWA were used to search for genes possibly associated with the set of evaluated traits. Data from 3 pig data sets (U.S. Meat Animal Research Center, commercial, and Michigan State University Pig Resource Population) were used. A MA was implemented by combining -scores derived for each SNP in every population and then weighting them using the inverse of estimated variance of SNP effects. A search for annotated genes retrieved genes previously reported as candidates for shear force (calpain-1 catalytic subunit [] and calpastatin []), as well as for ultimate pH, purge loss, and cook loss (protein kinase, AMP-activated, γ 3 noncatalytic subunit []). In addition, novel candidate genes were identified for intramuscular fat and cook loss (acyl-CoA synthetase family member 3 mitochondrial []) and for the objective measure of muscle redness, CIE a* (glycogen synthase 1, muscle [] and ferritin, light polypeptide []). Thus, implementation of MA-GWA allowed integration of results for economically relevant traits and identified novel genes to be tested as candidates for meat quality traits in pig populations.


Fluorescence imaging, an emerging tool for preserving the parathyroid glands during thyroidectomy.
With vocal cord palsy, hypoparathyroidism is one of the two major complications after thyroid surgery. Traditional approaches to preserving the parathyroid glands during thyroid surgery include identifying the glands precisely and preserving their vasculature with the naked eye, which mainly depend on the experience and skill of the surgeon. Recently, a relatively new technique, fluorescence image-guided surgery, has been widely researched and is becoming increasingly popular. The authors present a video clip of transoral robotic total thyroidectomy, which shows the three typical statuses of the parathyroid glands after thyroid surgery (well-perfused, poorly or non-perfused, and congested) and explains how to deal with each status of the parathyroid glands.


Which body features are associated with female adolescents' body dissatisfaction? A cross-cultural study in Australia, China and Malaysia.
This study investigated how dissatisfaction with various aspects of the body is associated with overall body dissatisfaction among female adolescents in Western and Asian cultures. Data used in the study were obtained from 58 Malaysian Malays, 95 Malaysian Chinese, 242 Chinese from China, and 81 non-Asian Australians aged 12-19 years (M=15.72, SD=1.72) who were recruited from high schools. Participants completed a questionnaire assessing dissatisfaction with their body overall, and dissatisfaction with varying aspects of their body. Malaysian Chinese were the most dissatisfied with their bodies. After controlling for body mass index (BMI), age and dissatisfaction with weight/shape, upper, middle and lower body, and muscles, dissatisfaction with the face was positively correlated with overall body dissatisfaction among Malaysian Malays and Australians. These findings demonstrate the importance of using assessment measures that address all possible areas of body focus as well as being tailored to the relevant culture.


After-hours care in Canada: analysis of the 2001 National Family Physician Workforce Survey.
To determine family physicians' availability to their general practice patients after hours and to explore the characteristics and determinants of after-hours services. Secondary analysis of the 2001 National Family Physician Workforce Survey. Canada. Canadian family physicians and general practitioners currently in practice (n = 10,553). Provision of after-hours care, defined as providing care to all practice patients outside of normal office hours. Sixty-two percent of Canadian family physicians reported providing after-hours service. The lowest rates were found in Quebec (34%) and the highest in Alberta and Saskatchewan (88%). Respondents practising in academic and community clinics, offering selective medical services (emergency care, palliative care, housecalls, after-hours care), or living outside of Ontario or Quebec were more likely to provide after-hours care. Women physicians, those practising in walk-in clinics, or physicians primarily paid by fee-for-service were less likely to do so. Urban versus rural location, organization of practice (solo or group), age of physician, country of graduation, and physician satisfaction were not found to significantly affect the likelihood of providing after-hours services. Knowledge of these factors can be used to inform policy development for after-hours service arrangements, which is particularly relevant today, given provincial governments' interests in exploring alternative payment plans and primary care reform options.


Effect of metformin in addition to dietary and lifestyle advice for pregnant women who are overweight or obese: the GRoW randomised, double-blind, placebo-controlled trial.
Maternal overweight and obesity are associated with well recognised pregnancy complications. Antenatal dietary and lifestyle interventions have a modest effect on gestational weight gain without affecting pregnancy outcomes. We aimed to assess the effects on maternal and infant outcomes of antenatal metformin given in addition to dietary and lifestyle advice among overweight and obese pregnant women. GRoW was a multicentre, randomised, double-blind, placebo-controlled trial in which pregnant women at 10-20 weeks' gestation with a BMI of 25 kg/m2 or higher were recruited from three public maternity units in Adelaide, SA, Australia. Women were randomly assigned (1:1) via a computer-generated schedule to receive either metformin (to a maximum dose of 2000 mg per day) or matching placebo. Participants, their antenatal care providers, and research staff (including outcome assessors) were masked to treatment allocation. All women received an antenatal dietary and lifestyle intervention. The primary outcome was the proportion of infants with birthweight greater than 4000 g. Secondary outcomes included measures of maternal weight gain, maternal diet and physical activity, maternal pregnancy and birth outcomes, maternal quality of life and emotional wellbeing, and infant birth outcomes. Outcomes were analysed on an intention-to-treat basis (including all randomly assigned women who did not withdraw consent to use their data, and who did not have a miscarriage or termination of pregnancy before 20 weeks' gestation, or a stillbirth). The trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12612001277831. Of 524 women who were randomly assigned between May, 28 2013 and April 26, 2016, 514 were included in outcome analyses (256 in the metformin group and 258 in the placebo group). Median gestational age at trial entry was 16·29 weeks (IQR 14·43-18·00) and median BMI was 32·32 kg/m2 (28·90-37·10); 167 (32%) participants were overweight and 347 (68%) were obese. There was no significant difference in the proportion of infants with birthweight greater than 4000 g (40 [16%] with metformin vs 37 [14%] with placebo; adjusted risk ratio [aRR] 0·97, 95% CI 0·65 to 1·47; p=0·899). Women receiving metformin had lower average weekly gestational weight gain (adjusted mean difference -0·08 kg, 95% CI -0·14 to -0·02; p=0·007) and were more likely to have gestational weight gain below recommendations (aRR 1·46, 95% CI 1·10 to 1·94; p=0·008). Total gestational weight gain, pregnancy and birth outcomes, maternal diet and physical activity, and maternal quality of life and emotional wellbeing did not differ significantly between groups. Similar numbers of women in both treatment groups (76% [159/208] in the metformin group and 73% [144/196] in the placebo group) reported side-effects including nausea, diarrhoea, and vomiting. Two stillbirths (placebo group) and one neonatal death (metformin group) occurred; none of the perinatal deaths were determined to be attributable to participation in the trial. For pregnant women who are overweight or obese, metformin given in addition to dietary and lifestyle advice initiated at 10-20 weeks' gestation does not improve pregnancy and birth outcomes. Australian National Health and Medical Research Council.


Assisted reproductive technology surveillance--United States, 2011.
Since the first U.S. infant conceived with Assisted Reproductive Technology (ART) was born in 1981, both the use of advanced technologies to overcome infertility and the number of fertility clinics providing ART services have increased steadily in the United States. ART includes fertility treatments in which both eggs and embryos are handled in the laboratory (i.e., in vitro fertilization [IVF] and related procedures). Women who undergo ART procedures are more likely to deliver multiple-birth infants than those who conceive naturally because more than one embryo might be transferred during a procedure. Multiple births pose substantial risks to both mothers and infants, including pregnancy complications, preterm delivery, and low birthweight infants. This report provides state-specific information on U.S. ART procedures performed in 2011 and compares infant outcomes that occurred in 2011 (resulting from procedures performed in 2010 and 2011) with outcomes for all infants born in the United States in 2011. 2011. In 1996, CDC began collecting data on all ART procedures performed in fertility clinics in the United States as mandated by the Fertility Clinic Success Rate and Certification Act of 1992 (FCSRCA) (Public Law 102-493). Data are collected through the National ART Surveillance System (NASS), a web-based data collecting system developed by CDC. In 2011, a total of 151,923 ART procedures performed in 451 U.S. fertility clinics were reported to CDC. These procedures resulted in 47,818 live-birth deliveries and 61,610 infants. The largest numbers of ART procedures were performed among residents of six states: California (18,808), New York (excluding New York City) (14,576), Massachusetts (10,106), Illinois (9,886), Texas (9,576), and New Jersey (8,698). These six states also had the highest number of live-birth deliveries as a result of ART procedures and together accounted for 47.2% of all ART procedures performed, 45.3% of all infants born from ART, and 45.1% of all multiple live-birth deliveries, but only 34% of all infants born in the United States. Nationally, the average number of ART procedures performed per 1 million women of reproductive age (15-44 years), which is a proxy indicator of ART use, was 2,401. In 11 states (Connecticut, Delaware, Hawaii, Illinois, Maryland, Massachusetts, New Hampshire, New Jersey, New York, Rhode Island, and Virginia), the District of Columbia, and New York City, this proxy measure was higher than the national rate, and of these, in three states (Massachusetts, New Jersey, and New York) and the District of Columbia, it exceeded twice the national rate. Nationally, among ART cycles with patients using fresh embryos from their own eggs in which at least one embryo was transferred, the average number of embryos transferred increased with increasing age (2.0 among women aged <35 years, 2.3 among women aged 35-40 years, and 2.9 among women aged >40 years). Elective single-embryo transfer (eSET) rates decreased with increasing age (12.2% among women aged <35 years, 4.7% among women aged 35-40 years, and 0.7% among women aged >40 years). Rates of eSET also varied substantially between states (range: 0.7% in Idaho to 53% in Delaware among women aged <35 years). The number of ART births as a percentage of total infants born in the state is considered as another measure of ART use. Overall, ART contributed to 1.5% of U.S. births (range: 0.2% in Puerto Rico to 4.5% in Massachusetts) with the highest rates (≥3.5% of all infants born) observed in four states (Connecticut, Massachusetts, New Jersey, and New York state), and the District of Columbia. Infants conceived with ART comprised 20% of all multiple-birth infants (range: 4.7% in Puerto Rico to 41.3% in New York state), 19% of all twin infants (range: 4.1% in Mississippi to 39.7% in Massachusetts), and 32% of triplet or higher order infants (range: 0 in several states to 71.4% in Hawaii). Among infants conceived with ART, 45.6% were born in multiple-birth deliveries (range: 23.1% in Delaware to 61.3% in Wyoming), compared with only 3.4% of infants among all births in the general population (range: 1.9% in Puerto Rico to 4.8% in New Jersey). Approximately 43% of ART-conceived infants were twins, and 3% were triplets and higher order infants. Nationally, infants conceived with ART comprised 5.7% of all low birthweight (<2,500 grams) infants (range: 0.6% in Puerto Rico to 15% in Massachusetts) and 5.9% of all very low birthweight (<1,500 grams) infants (range: 0.8% in Mississippi to 17.3% in Massachusetts). Overall, among ART-conceived infants, 31% were low birthweight (range: 18% in District of Columbia to 44.6% in Puerto Rico), compared with 8.1% among all infants (range: 6% in Alaska to 12.5% in Puerto Rico); 5.7% of ART infants were very low birthweight (range: 0 in North Dakota to 8.5% in Hawaii), compared with 1.4% among all infants (range: 0.9% in Alaska to 2.2% in Mississippi). Finally, ART-conceived infants comprised 4.6% of all infants born preterm (<37 weeks; range: 0.5% in Puerto Rico to 13% in Massachusetts) and 5.2% of all infants born very preterm (<32 weeks; range: 0 in Wyoming to 17.1% in Massachusetts). Overall, among infants conceived with ART, 36.2% were born preterm (range: 12.5% in Vermont to 56.9% in Puerto Rico), compared with 11.8% among all infants born in the general population (range: 8.8% in Vermont to 17.6% in Puerto Rico); 6.7% of ART infants were born very preterm (range: 0 in Wyoming to 12.5% in Alaska), compared with 1.9% among all infants born in the general population (range: 1.3% in Wyoming to 3.0% in Puerto Rico). The percentage of infants conceived with ART who were low birthweight varied from 8.8% (range: 3.9% in the District of Columbia to 17.9% in Puerto Rico) among singletons, to 56.4% (range: 34.6% in Vermont to 70.4% in Mississippi) among twins, and 95.7% (range: 79.5% in North Carolina to 100% in several states) among triplets or higher-order multiples; comparable percentages for all infants were 6.4% (range: 4.5% in Idaho and Oregon to 11.3% in Puerto Rico), 56.3% (range: 47.7% in Vermont to 72.1% in Puerto Rico), and 93.9% (range: 50% in Wyoming to 100% in several states), respectively. The percentage of ART infants who were preterm varied from 13.2% (range: 7.3% in the District of Columbia to 28.6% in Puerto Rico) among singletons, to 61.8% (range: 46% in the District of Columbia to 82.7% in Oklahoma) among twins, and 97.1% (range: 76.9% in Iowa to 100% in several states) among triplets or higher-order multiples; comparable percentages for all infants were 10.1% (range:7.5% in Oregon to 16.6% in Puerto Rico), 57.3% (range: 46.8% in New Hampshire to 68.8% in Louisiana), and 93.4% (range: 73.3% in Rhode Island to 100% in several states), respectively. Only nonsuppressed values from reporting areas are provided to protect confidentiality. The percentage of infants conceived with ART varied considerably by state (range: 0.2% to 4.5%). In most states, multiples from ART comprised a substantial proportion of all twin, triplet, and higher-order infants born in the state, and the rates of low birthweight and preterm infants were disproportionately higher among ART infants than in the birth population overall. Even among women aged <35 years, for whom elective single embryo transfers should be considered (particularly in patients with a favorable prognosis), on average, two embryos were transferred per cycle in ART procedures, influencing the overall multiple infant rates in the United States. Compared with ART singletons, ART twins were approximately 5 times more likely to be born preterm, and approximately six times more likely to be low birthweight. Singleton infants conceived with ART had slightly higher rates of preterm delivery and low birthweight than among all singleton infants born in the United States. However, all multiple-birth infants, regardless of whether they were ART-conceived or not, were more likely to be preterm and low birthweight compared with singletons. Further, ART use per population unit was distributed disproportionately in the United States, with 11 states showing ART use above the national rate. Of the four states (Illinois, Massachusetts, New Jersey, and Rhode Island) with comprehensive statewide-mandated health insurance coverage for ART procedures (e.g., coverage for at least four cycles of in vitro fertilization, three states (Illinois, Massachusetts, and New Jersey) also had rates of ART use >1.5 times the national level. This type of mandated insurance has been associated with greater use of ART and might account for the differences in per capita ART use observed among states. Reducing the number of embryos transferred per ART procedure and promoting eSET procedures, when clinically appropriate, are needed to reduce multiple births and related adverse consequences of ART. Improved patient education and counseling on the health risks of having twins might be useful in reducing twin births given that twins account for the majority of ART-conceived multiple births. Although ART contributes to increasing rates of multiple births, it does not explain all of the increases, and therefore other explanations for multiple births not investigated in this report, such as the possible role of non-ART fertility treatments, warrants further study.


Joint Influence of SNPs and DNA Methylation on Lipids in African Americans From Hypertensive Sibships.
Plasma concentrations of lipids (i.e., total cholesterol, high-density cholesterol, low-density cholesterol, and triglycerides) are amenable to therapeutic intervention and remain important factors for assessing risk of cardiovascular diseases. Some of the observed variability in serum lipid concentrations has been associated with genetic and epigenetic variants among cohorts with European ancestry (EA). Serum lipid levels have also been associated with genetic variants in multiethnic populations. The purpose of this study was to determine whether single-nucleotide polymorphisms (SNPs) and DNA methylation (DNAm) differences contribute to lipid variation among African Americans ([AAs], N = 739) in the Genetic Epidemiology Network of Arteriopathy (GENOA) study. Previous meta-analyses identified 161 SNPs that are associated with lipid traits in populations of EA. We evaluated these SNPs and 66 DNAm sites within the genes containing the SNPs in the GENOA cohort using linear mixed-effects modeling. We did not identify any significant associations of SNPs or DNAm with serum lipid levels. These results suggest that the SNPs identified as being significant for lipid levels through the EA genome-wide association studies may not be significant across AA populations. Reductions in morbidity and mortality due to variation in lipids among AAs may be achieved through a better understanding of the genetic and epigenetic factors associated with serum lipid levels for early and appropriate screening. Further large-scale studies specifically within AA and other non-EA populations are warranted.


Epidural versus intramuscular pethidine in postoperative pain relief.
Twenty-one patients received epidural pethidine 0,75 mg/kg in 10 ml normal saline for postoperative analgesia. A control group of 20 patients received intramuscular pethidine 1,5 mg/kg. Respiratory and cardiovascular parameters in both groups were stable, and in both side-effects were similar and not serious. In the epidural group analgesia was more intense and of longer duration and the level of consciousness was better. Central depression was present in both groups but less so in the epidural group.


Novel delivery system for T-oligo using a nanocomplex formed with an alpha helical peptide for melanoma therapy.
Oligonucleotides homologous to 3'-telomere overhang (T-oligos) trigger inherent telomere-based DNA damage responses mediated by p53 and/or ATM and induce senescence or apoptosis in various cancerous cells. However, T-oligo has limited stability in vivo due to serum and intracellular nucleases. To develop T-oligo as an innovative, effective therapeutic drug and to understand its mechanism of action, we investigated the antitumor effects of T-oligo or T-oligo complexed with a novel cationic alpha helical peptide, PVBLG-8 (PVBLG), in a p53 null melanoma cell line both in vitro and in vivo. The uptake of T-oligo by MM-AN cells was confirmed by immunofluorescence, and fluorescence-activated cell sorting analysis indicated that the T-oligo-PVBLG nanocomplex increased uptake by 15-fold. In vitro results showed a 3-fold increase in MM-AN cell growth inhibition by the T-oligo-PVBLG nanocomplex compared with T-oligo alone. Treatment of preformed tumors in immunodeficient mice with the T-oligo-PVBLG nanocomplex resulted in a 3-fold reduction in tumor volume compared with T-oligo alone. This reduction in tumor volume was associated with decreased vascular endothelial growth factor expression and induction of thrombospondin-1 expression and apoptosis. Moreover, T-oligo treatment downregulated procaspase-3 and procaspase-7 and increased catalytic activity of caspase-3 by 4-fold in MM-AN cells. Furthermore, T-oligo induced a 10-fold increase of senescence and upregulated the melanoma tumor-associated antigens MART-1, tyrosinase, and thrombospondin-1 in MM-AN cells, which are currently being targeted for melanoma immunotherapy. Interestingly, siRNA-mediated knockdown of p73 (4-10-fold) abolished this upregulation of tumor-associated antigens. In summary, we suggest a key role of p73 in mediating the anticancer effects of T-oligo and introduce a novel nanoparticle, the T-oligo-PVBLG nanocomplex, as an effective anticancer therapeutic.


Postoperative mortality 90 days after robot-assisted laparoscopic prostatectomy and retropubic radical prostatectomy: a nationwide population-based study.
To assess 90-day postoperative mortality after robot-assisted laparoscopic radical prostatectomy (RARP) and retropubic radical prostatectomy (RRP) using nationwide population-based registry data. We conducted a cohort study using the National Prostate Cancer Register of Sweden, including 22 344 men with localized prostate cancer of clinical stage T1-T3, whose prostate-specific antigen levels were <50 μg/mL and who had undergone primary radical prostatectomy in the period 1998-2012. Vital status was ascertained through the Total Population Register. The rates for 90-day postoperative mortality were analysed using logistic regression analysis, and comparisons of 90-day mortality with the background population were made using standardized mortality ratios (SMRs). Of the 14 820 men who underwent RRP, 29 (0.20%) died, and of the 7 524 men who underwent RARP, 10 (0.13%) died. Mortality in the cohort during the 90-day postoperative period was lower than in an age-matched background population: SMR 0.57 (95% confidence interval [CI] 0.39-0.75). There was no statistically significant difference in 90-day mortality according to surgical method: RARP vs RRP odds ratio (OR) 1.14; 95% CI 0.46-2.81. Postoperative 90-day mortality decreased over time: 2008-2012 vs 1998-2007 OR 0.44; 95% CI 0.21-0.95, mainly because of lower mortality after RARP. The 90-day postoperative mortality rates were low after RARP and RRP and there was no statistically significant difference between the methods. Given the long life expectancy among men with low- and intermediate-risk prostate cancer, very low postoperative mortality is a prerequisite for RP, which was fulfilled by both RRP and RARP. The selection of healthy men for RP is highlighted by the lower 90-day mortality after RP compared with the background population.


Role of Egr-2 in up-regulation of Fas ligand in normal T cells and aberrant double-negative lpr and gld T cells.
We previously identified a Fas ligand regulatory element (FLRE) in the Fas ligand (fasL) promoter that binds Egr family proteins and demonstrated that Egr-3 (PILOT) but not Egr-1 (NGFI-A, Krox-24, Tis-8, and Zif-268) induces transcription of fasL. The aberrant CD4(-)CD8(-) T cells from lpr/lpr and gld/gld mice, which have mutations in the genes encoding Fas and FasL, respectively, have an activated phenotype and constitutively express high levels of fasL mRNA, prompting us to ask what role if any the FLRE and Egr family proteins have in this aberrant expression of fasL. Unstimulated MRL-lpr/lpr and C3H-gld/gld CD4(-)CD8(-) T cells constitutively contained high levels of two proteins that bound to the FLRE. Supershift analysis revealed these proteins to be Egr-1 and Egr-2 (Krox-20); Egr-3 was not detected. Activation of normal lymph node cells resulted in increased expression of Egr-1, -2, and -3. As with egr-3, expression of egr-2 was blocked by cyclosporin A. Although overexpressed Egr-1 was ineffective, overexpressed Egr-2 was as potent as Egr-3 in inducing fasL promoter-dependent reporter constructs in T cell hybridomas and HeLa cells, and both up-regulated endogenous fasL mRNA in HeLa cells. FasL-dependent reporter constructs in MRL-lpr/lpr and C3H-gld/gld CD4(-)CD8(-) T cells were constitutively active, and this activity was largely prevented by mutation of the critical Egr family binding element. Thus, Egr-2, in addition to Egr-3, regulates FasL expression in activated normal T cells, and Egr-2 is likely to play a direct role in aberrant fasL up-regulation in lpr/lpr and gld/gld CD4(-)CD8(-) T cells.


Fracture Burden and Risk Factors in Childhood CKD: Results from the CKiD Cohort Study.
Childhood chronic kidney disease (CHD) poses multiple threats to bone accrual; however, the associated fracture risk is not well characterized. This prospective cohort study included 537 CKD in Children (CKiD) participants. Fracture histories were obtained at baseline, at years 1, 3, and 5 through November 1, 2009, and annually thereafter. We used Cox regression analysis of first incident fracture to evaluate potential correlates of fracture risk. At enrollment, median age was 11 years, and 16% of patients reported a prior fracture. Over a median of 3.9 years, 43 males and 24 females sustained incident fractures, corresponding to 395 (95% confidence interval [95% CI], 293-533) and 323 (95% CI, 216-481) fractures per 10,000 person-years, respectively. These rates were 2- to 3-fold higher than published general population rates. The only gender difference in fracture risk was a 2.6-fold higher risk in males aged ≥15 years (570/10,000 person-years, adjusted P=0.04). In multivariable analysis, advanced pubertal stage, greater height Z-score, difficulty walking, and higher average log-transformed parathyroid hormone level were independently associated with greater fracture risk (all P≤0.04). Phosphate binder treatment (predominantly calcium-based) was associated with lower fracture risk (hazard ratio, 0.37; 95% CI, 0.15-0.91; P=0.03). Participation in more than one team sport was associated with higher risk (hazard ratio, 4.87; 95% CI, 2.21-10.75; P<0.001). In conclusion, children with CKD have a high burden of fracture. Regarding modifiable factors, higher average parathyroid hormone level was associated with greater risk of fracture, whereas phosphate binder use was protective in this cohort.


Adsorption of sophorolipid biosurfactants on their own and mixed with sodium dodecyl benzene sulfonate, at the air/water interface.
The adsorption of the lactonic (LS) and acidic (AS) forms of sophorolipid and their mixtures with the anionic surfactant sodium dodecyl benzene sulfonate (LAS) has been measured at the air/water interface by neutron reflectivity, NR. The AS and LS sophorolipids adsorb with Langmuir-like adsorption isotherms. The more hydrophobic LS is more surface active than the AS, with a lower critical micellar concentration, CMC, and stronger surface adsorption, with an area/molecule ∼70 Å(2) compared with 85 Å(2) for the AS. The acidic sophorolipid shows a maximum in its adsorption at the CMC which appears to be associated with a mixture of different isomeric forms. The binary LS/AS and LS/LAS mixtures show a strong surface partitioning in favor of the more surface active and hydrophobic LS component but are nevertheless consistent with ideal mixing at the interface. In contrast, the surface composition of the AS/LAS mixture is much closer to the solution composition, but the surface mixing is nonideal and can be accounted for by regular solution theory, RST. In the AS/LS/LAS ternary mixtures, the surface adsorption is dominated by the sophorolipid, and especially the LS component, in a way that is not consistent with the observations for the binary mixtures. The extreme partitioning in favor of the sophorolipid for the LAS/LS/AS (1:2) mixtures is attributed to a reduction in the packing constraints at the surface due to the AS component. Measurements of the surface structure reveal a compact monolayer for LS and a narrow solvent region for LS, LS/AS, and LS/LAS mixtures, consistent with the more hydrophobic nature of the LS component. The results highlight the importance of the relative packing constraints on the adsorption of multicomponent mixtures, and the impact of the lactonic form of the sophorolipid on the adsorption of the sophorolipid/LAS mixtures.


Mechanisms for racial and ethnic disparities in glycemic control in middle-aged and older Americans in the health and retirement study.
Mechanisms for racial/ethnic disparities in glycemic control are poorly understood. A nationally representative sample of 1901 respondents 55 years or older with diabetes mellitus completed a mailed survey in 2003; 1233 respondents completed valid at-home hemoglobin A(1c) (HbA(1c)) kits. We constructed multivariate regression models with survey weights to examine racial/ethnic differences in HbA(1c) control and to explore the association of HbA(1c) level with sociodemographic and clinical factors, access to and quality of diabetes health care, and self-management behaviors and attitudes. There were no significant racial/ethnic differences in HbA(1c) levels in respondents not taking antihyperglycemic medications. In 1034 respondents taking medications, the mean HbA(1c) value (expressed as percentage of total hemoglobin) was 8.07% in black respondents and 8.14% in Latino respondents compared with 7.22% in white respondents (P < .001). Black respondents had worse medication adherence than white respondents, and Latino respondents had more diabetes-specific emotional distress (P < .001). Adjusting for hypothesized mechanisms accounted for 14.0% of the higher HbA(1c) levels in black respondents and 19.0% in Latinos, with the full model explaining 22.0% of the variance. Besides black and Latino ethnicity, only insulin use (P < .001), age younger than 65 years (P = .007), longer diabetes duration (P = .004), and lower self-reported medication adherence (P = .04) were independently associated with higher HbA(1c) levels. Latino and African American respondents had worse glycemic control than white respondents. Socioeconomic, clinical, health care, and self-management measures explained approximately a fifth of the HbA(1c) differences. One potentially modifiable factor for which there were racial disparities--medication adherence--was among the most significant independent predictors of glycemic control.


Tailor-made directional emission in nanoimprinted plasmonic-based light-emitting devices.
We demonstrate an enhanced and tailor-made directional emission of light-emitting devices using nanoimprinted hexagonal arrays of aluminum nanoparticles. Fourier microscopy reveals that the luminescence of the device is not only determined by the material properties of the organic dye molecules but is also strongly influenced by the coherent scattering resulting from periodically arranged metal nanoparticles. Emitters can couple to lattice-induced hybrid plasmonic-photonic modes sustained by plasmonic arrays. Such modes enhance the spatial coherence of an emitting layer, allowing the efficient beaming of the emission along narrow angular and spectral ranges. We show that tailoring the separation of the nanoparticles in the array yields an accurate angular distribution of the emission. This combination of large-area metal nanostructures fabricated by nanoimprint lithography and light-emitting devices is beneficial for the design and optimization of solid-state lighting systems.


Structure, agency, and sexual development of Latino gay men.
There is a high prevalence of childhood sexual abuse and HIV among Latino gay men, with limited proven HIV prevention interventions. This study used qualitative methods to explicate earlier findings showing differential health outcomes among Latino gay men who had no sex, voluntary, or forced sex before age 16. Analyses of in-depth interviews with 27 Latino gay men revealed that structural factors in childhood contribute to their developing sexuality by enhancing or inhibiting a sense of agency. Agency is essential for making decisions that are in line with their intentions to have healthy sexual lives. Findings suggest that interventions should focus on developing a sense of sexual agency among Latino gay men by (a) increasing their recognition of structural factors that contribute to feelings of worthlessness in order to relocate internalized blame and homophobia to external structural forces, (b) facilitating awareness of the social structural oppressions that lead to psychological and sexual risk in order to enhance their options for sexual health, and (c) shifting from individually focused constructions of sexual health to those that consider the structural factors that reduce agency and contribute to diminished sexual health among Latino gay men.


Reaching out to see: arm position can attenuate human visual loss.
Electrophysiological recordings in monkeys have now revealed several brain regions that contain bimodal visuotactile neurons capable of responding to either tactile or visual stimuli placed on or near the hands, arms, and face. These cells have now been found in frontal, parietal, and subcortical areas of the monkey brain, suggesting a cortical network of neurons that preferentially represent near peripersonal space. The degree to which the visual responses of such cells rely on input from the primary visual cortex and the extent to which they may contribute to visual perception is not completely understood. Nonetheless, recent neuropsychological studies suggest that a similar representation of near space may be bimodally coded in humans as well. Given the accumulating evidence for specialized processing of visual stimuli placed near the hands and arms, we hypothesized that arm position may be capable of modulating human visual ability. Here we report the case of WM, who lost his ability to see in his left visual hemifield after sustaining damage to his right primary visual cortex. Interestingly, the placement of WM's left arm into his "blind" field resulted in significantly better detection of left visual field stimuli compared to when his hand was placed in his lap at midline. Moreover, we found this attenuation to be confined to stimuli presented within reaching distance (unless a tool that extended WM's reach was held while he performed the test). These findings are highly consistent with the characteristics of the bimodal visuo-tactile neurons that have been described in monkeys. Thus, it seems that arm position can modulate human visual ability, even after damage to the primary visual cortex. This study provides an exciting bridge between monkey neurophysiology and human visual capacity while also offering a novel approach for improving visual defects acquired via cortical injury.


First Report of Anthracnose Caused by Colletotrichum gloeosporioides on Pistachio (Pistacia vera) in China.
In the 1990s, pistachio (Pistacia vera L. 'Kerman' and 'Peters') was introduced in China. They are found in many orchards in Beijing and Gansu and Hebei provinces, northern China. In 2009, a new disease was observed on leaves, stems, and fruits in pistachio orchards in Gansu Province. Disease incidence in 8- to 12-year-old orchards was 30%. Yield losses reached 25%. Symptoms began as discrete, sunken, black spots, approximately 10 mm in diameter, followed by circular lesions that eventually coalesced with tissue death recorded and orange fructifications developed on lesions. Pieces of diseased leaves, stems, and fruits were surfaced sterilized and placed on 2% potato dextrose agar (PDA) at 25°C. A fungus was consistently isolated. After 10 days, cultures on PDA showed aerial, white mycelium that turned gray to grayish black with a salmon-to-orange conidial mass at 25°C and a 12-h photoperiod. Brown, 80 to 120 μm long setae were observed in the acervulus. Conidia were hyaline, fusiform to nearly straight, and averaged 12 to 18 × 3 to 5 μm. On the basis of morphological characteristics, the fungus was identified as Colletotrichum gloeosporioides (Penz.) Sacc. (2). On PDA, 0.5 μg/ml of benomyl was applied for the sensitivity test (3). Benomyl completely inhibited the growth of the fungus. Mycelial DNA was extracted, PCR amplified using ITS1 and ITS4 primers for the ribosomal DNA internal transcribed spacers 1 and 2, and sequenced. The DNA sequence was recorded in GenBank as No. HQ631378. The DNA sequence was blasted showing 99% identity with Accession Nos. GQ144454 and GU004376, for C. gloeosporioides. Pathogenicity tests were conducted under greenhouse conditions at 25°C. Three replicates of 2-year-old 'Kerman' plants were inoculated with mycelial PDA plugs placed on 0.5-cm2 stem wounds and then wrapped with Parafilm. Controls were inoculated with PDA plugs without the fungus. After 3 weeks, stem cankers were observed on inoculated plants. Control plants remained healthy. Pathogenicity was also tested on injured leaves and fruits. A 10-μl drop of a spore suspension of 104 conidia/ml was applied on 'Kerman' and 'Peters' leaves and 'Kerman' fruits and placed on plates with a wet filter paper at 25°C. Small, black lesions were observed at 2 days after inoculation. At 7 days, necrotic lesions covered the entire surface. C. gloeosporioides was reisolated from necrotic lesions. Controls did not develop symptoms. C. acutatum has been reported on pistachio in Australia (1), but to our knowledge, this is the first report of anthracnose caused by C. gloeosporioides on pistachio. References: (1) G. J. Ash and V. M. Lanoiselet. Australas. Plant Pathol. 30:365, 2001. (2) J. Y. Lu. Plant Pathogenic Mycology. China Agricultural Press, Beijing, 2001. (3) N. A. R. Peres et al. Plant Dis. 86:620, 2002.


Perspectives on using remotely-sensed imagery in predictive veterinary epidemiology and global early warning systems.
Recent disease epidemics and their spread around the world have illustrated the weaknesses of disease surveillance and early warning systems (EWS), both at national and international levels. These diseases continuously threaten the livestock sector on a worldwide basis, some with major public health impact. EWS and accurate forecasting of new outbreaks of epidemic livestock diseases that may also affect wildlife, and the capacity for spread of such diseases to new areas is an essential pre-requisite to their effective containment and control. Because both the geographical and seasonal distribution of many infectious diseases are linked to climate, the possibility of using climaterelated environmental factors as predictive indicators, in association with regular disease surveillance activities, has proven to be relevant when establishing EWS for climate-related diseases. This article reviews the growing importance of using geographical information systems in predictive veterinary epidemiology and its integration into EWS, with a special focus on Rift Valley fever. It shows that, once fully validated in a country or region, this technology appears highly valuable and could play an increasing role in forecasting major epidemics, providing lead time to national veterinary services to take action to mitigate the impact of the disease in a cost-effective manner.


Comparing Different Methods to Create a Linear Model for Uncontrolled Manifold Analysis.
An essential step in uncontrolled manifold analysis is creating a linear model that relates changes in elemental variables to changes in performance variables. Such linear models are usually created by means of an analytical method. However, a multiple regression analysis is also suggested. Whereas the analytical method includes only averages of joint angles, the regression method uses the distribution of all joint angles. We examined whether the latter model is more suitable to describe manual reaching movements. The relation between estimated and measured fingertip-position deviations from the mean of individual trials, the relation between fingertip variability and nongoal-equivalent variability, goal-equivalent variability, and nongoal-equivalent variability indicated that the linear model created with the regression method gives a more accurate description of the reaching data. Therefore, we suggest the usage of the regression method to create the linear model for uncontrolled manifold analysis in tasks that require the approximation of the linear model.


On the unusual fluorescence properties of xanthone in water.
Photo-excited xanthone is known to undergo ultrafast intersystem crossing (ISC) in the 1 ps time domain. Correspondingly, its fluorescence quantum yield in most solvents is very small ( approximately 10(-4)). Surprisingly, the quantum yield in water is 100 times larger, while ISC is still rapid ( approximately 1 ps), as seen by ultrafast pump probe absorption spectroscopy. Temperature dependent steady state and time resolved fluorescence experiments point to a delayed fluorescence mechanism, where the triplet (3)npi* state primarily accessed by ISC is nearly isoenergetic with the photo-excited (1)pipi* state. The delayed fluorescence of xanthone in water decays with a time constant of 700 ps, apparently by internal conversion between the (3)npi* state and the lowest lying triplet state (3)pipi*.


Constructing multiplicative measures of beliefs in the theory of planned behaviour.
Commonly used theories in health psychology involve multiplicative composites of measures, which have been used as predictors, mediators, and outcomes. The chosen scaling system can affect correlations with other variables. This study evaluated how best to construct composites in the context of the theory of planned behaviour (TPB), using hierarchical linear regression, a priori defined scaling systems, and optimal scaling. Longitudinal. At baseline, 6 and 12 months, 365 trial participants (ProActive) completed questionnaires assessing salient beliefs, which were used to construct composites (indirect measures), and direct measures of instrumental and affective attitude, subjective norm, and perceived behavioural control towards becoming more physically active over the next 12 months. Linear regression supported a multiplicative model for indirect instrumental attitude and perceived control. Except for perceived control, associations between composites and direct measures were unaffected by different a priori scaling systems. Optimal scaling produced widely differing composites over time for subjective norm and affective attitude and a negative association between composite and direct measure for subjective norm. We recommend that researchers who use multiplicative composites first establish clear support for a multiplicative model, before they examine a range of meaningful scaling systems on theoretical and empirical grounds. Caution is needed when using optimal scaling without checking that a multiplicative model is supported and the resulting scaling system meaningful. What is already known on this subject? Multiplicative composites are included in commonly used theories in health psychology (e.g., theory of planned behaviour). Valid measures are needed as the choice of scaling system (e.g., unipolar or bipolar) can affect estimates of associations between composites and other variables. Ajzen has advocated the use of optimal scaling. What does this study add? The study shows that optimal scaling can result in meaningless measures. We recommend that health psychologists use optimal scaling with great caution and we provide alternative recommendations for constructing composites.


Learning to minimize efforts versus maximizing rewards: computational principles and neural correlates.
The mechanisms of reward maximization have been extensively studied at both the computational and neural levels. By contrast, little is known about how the brain learns to choose the options that minimize action cost. In principle, the brain could have evolved a general mechanism that applies the same learning rule to the different dimensions of choice options. To test this hypothesis, we scanned healthy human volunteers while they performed a probabilistic instrumental learning task that varied in both the physical effort and the monetary outcome associated with choice options. Behavioral data showed that the same computational rule, using prediction errors to update expectations, could account for both reward maximization and effort minimization. However, these learning-related variables were encoded in partially dissociable brain areas. In line with previous findings, the ventromedial prefrontal cortex was found to positively represent expected and actual rewards, regardless of effort. A separate network, encompassing the anterior insula, the dorsal anterior cingulate, and the posterior parietal cortex, correlated positively with expected and actual efforts. These findings suggest that the same computational rule is applied by distinct brain systems, depending on the choice dimension-cost or benefit-that has to be learned.


Popliteal artery branches: percutaneous transluminal angioplasty.
Percutaneous transluminal angioplasty of the branches of the popliteal artery was performed in six patients, two of whom also had femoropopliteal angioplasty. Dilatation was performed with catheters ranging from 5.5 to 7 French. None of the popliteal branch dilatations was performed with an inflated balloon. Excellent dilatation, as documented by angiography and Doppler ultrasound pressure recordings, was obtained in four cases and moderate and slight improvement in one case each. Two of the four patients with excellent results had prompt healing of toe amputations and are doing well at 19 and 22 months after angioplasty. In the other two patients with excellent results, below-knee amputation was necessary despite patency of the dilated segment in one. In the other patient with initially excellent results, reocclusion occurred 4 months after angioplasty. In the patients who had moderate and slight improvement on angiography and in distal pressures, no significant clinical course change occurred. No patient had clinical deterioration after angioplasty and no significant complications occurred.


Optical vortices induced in nonlinear multilevel atomic vapors.
In a numerical investigation, we demonstrate the existence and curious evolution of vortices in a ladder-type three-level nonlinear atomic vapor with linear, cubic, and quintic susceptibilities considered simultaneously with the dressing effect. We find that the number of beads and topological charge of the incident beam, as well as its size, greatly affect the formation and evolution of vortices. To determine the number of induced vortices and the corresponding rotation direction, we give common rules associated with the initial conditions coming from various incident beams.


Genetic models in applied physiology: selected contribution: effects of spaceflight on immunity in the C57BL/6 mouse. II. Activation, cytokines, erythrocytes, and platelets.
This portion of the study quantified the effects of a 12-day space shuttle mission (Space Transport System-108/UF-1) on body and lymphoid organ masses, activation marker expression, cytokine secretion, and erythrocyte and thrombocyte characteristics in C57BL/6 mice. Animals in flight (Flt group) had 10-12% lower body mass compared with ground controls housed either in animal enclosure modules or under standard vivarium conditions (P < 0.001) and the smallest thymus and spleen masses. Percentages of CD25(+) lymphocytes, CD3(+)/CD25(+) T cells, and NK1.1(+)/CD25(+) natural killer cells from Flt mice were higher compared with both controls (P < 0.05). In contrast, CD71 expression was depressed in the Flt and animal enclosure module control mice compared with vivarium control animals (P < 0.001). Secretion of interferon-gamma, IL-2, and IL-4, but not tumor necrosis factor-alpha and IL-5, by splenocytes from Flt mice was decreased relative to either one or both ground controls (P < 0.05). Flt mice also had high red blood cell and thrombocyte counts compared with both sets of controls; low red blood cell volume and distribution width, percentage of reticulocytes, and platelet volume were also noted (P < 0.05) and were consistent with dehydration. These data indicate that relatively short exposure to the spaceflight environment can induce profound changes that may become significant during long-term space missions.


Deficiency in mouse oxytocin prevents milk ejection, but not fertility or parturition.
Oxytocin is a nonapeptide hormone that participates in the regulation of parturition and lactation. It has also been implicated in various behaviors, such as mating and maternal, and memory. To investigate whether or not oxytocin (OT) is essential for any of these functions, we eliminated, by homologous recombination, most of the first intron and the last two exons of the OT gene in mice. Those exons encode the neurophysin portion of the oxytocin preprohormone which is hypothesized to help in the packaging and transport of OT. The homozygous mutant mice have no detectable neurophysin or processed oxytocin in the paraventricular nucleus, supraoptic nucleus or posterior pituitary. Interestingly, homozygous mutant males and females are fertile and the homozygous mutant females are able to deliver their litters. However, the pups do not successfully suckle and die within 24 h without milk in their stomachs. OT injection into the dams restores the milk injection in response to suckling. These results indicate an absolute requirement for oxytocin for successful milk injection, but not for mating, parturition and milk production, in mice.


Education rather than age structure brings demographic dividend.
The relationship between population changes and economic growth has been debated since Malthus. Initially focusing on population growth, the notion of demographic dividend has shifted the attention to changes in age structures with an assumed window of opportunity that opens when falling birth rates lead to a relatively higher proportion of the working-age population. This has become the dominant paradigm in the field of population and development, and an advocacy tool for highlighting the benefits of family planning and fertility decline. While this view acknowledges that the dividend can only be realized if associated with investments in human capital, its causal trigger is still seen in exogenous fertility decline. In contrast, unified growth theory has established human capital as a trigger of both demographic transition and economic growth. We assess the relative importance of changing age structure and increasing human capital for economic growth for a panel of 165 countries during the time period of 1980-2015. The results show a clear dominance of improving education over age structure and give evidence that the demographic dividend is driven by human capital. Declining youth dependency ratios even show negative impacts on income growth when combined with low education. Based on a multidimensional understanding of demography that considers education in addition to age, and with a view to the additional effects of education on health and general resilience, we conclude that the true demographic dividend is a human capital dividend. Global population policies should thus focus on strengthening the human resource base for sustainable development.


Changes in peripheral immune populations during pregnancy and modulation by probiotics and ω-3 fatty acids.
Allergic diseases have become a major health problem, partly due to reduced microbial stimulation and a decreased dietary ω-3/ω-6 long-chain polyunsaturated fatty acid ratio. Prenatal exposures have been reported to influence allergy development, possibly induced via changes in maternal immune regulation. In a randomized double-blind placebo-controlled multicenter allergy prevention trial (PROOM-3), pregnant women were recruited at gestational week 20, and randomized to four study groups, one receiving both L. reuteri oil drops and ω-3 PUFA capsules (n = 22), the second receiving ω-3 PUFA supplementation and placebo regarding L. reuteri (n = 21), the third receiving L. reuteri and placebo regarding ω-3 PUFA (n = 22) and the fourth group receiving placebo capsules and placebo oil drops (n = 23). In this substudy, supplemental and pregnancy-related effects on maternal peripheral immune cell populations during pregnancy were assessed by flow cytometry immune phenotyping at gestational week 20, 32 and 4 days after delivery. The numbers of activated and regulatory T (Treg) cells (CD45RA- Foxp3++/CD45RA+Foxp3+) were reduced after delivery, with the lowest count in the L. reuteri supplemented group compared with the placebo group 4 days after delivery, while the ω-3 PUFA group did not differ from the placebo group. Several treatment-independent changes were observed during and after pregnancy in lymphocytes (CD4+/8+/19+/56+/45RA+/-), CD14+16+/- monocytes, and in subpopulations of T helper cells (Th) CD4+CD45RA-Tbet+ (Th1) and CD4+CD45RA-RORC+ (Th17) cells. In conclusion, probiotic supplementation to the mother during the second half of pregnancy resulted in immunomodulatory effects among activated and resting Treg cells. Furthermore, several systemic immune modifying effects of pregnancy were observed.


Estrogen administered after cardiac arrest and cardiopulmonary resuscitation ameliorates acute kidney injury in a sex- and age-specific manner.
There is a sex difference in the risk of ischemic acute kidney injury (AKI), and estrogen mediates the protective effect of female sex. We previously demonstrated that preprocedural chronic restoration of physiologic estrogen to ovariectomized female mice ameliorated AKI after cardiac arrest and cardiopulmonary resuscitation (CA/CPR). In the present study, we hypothesized that male mice and aged female mice would benefit from estrogen administration after CA/CPR. We tested the effect of estrogen in a clinically relevant manner by administrating it after CA/CPR. CA/CPR was performed in young (10-15 weeks), middle-aged (43-48 weeks), and aged (78-87 weeks) C57BL/6 male and female mice. Mice received intravenous 17β-estradiol or vehicle 15 min after resuscitation. Serum chemistries and unbiased stereological assessment of renal injury were completed 24 h after CA. Regional renal cortical blood flow was measured by a laser Doppler, and renal levels of estrogen receptor alpha (ERα) and G protein-coupled estrogen receptor (GPER) were evaluated with immunoblotting. Post-arrest estrogen administration reduced injury in young males without significant changes in renal blood flow (percentage reduction compared with vehicle: serum urea nitrogen, 30 %; serum creatinine (sCr), 41 %; volume of necrotic tubules (VNT), 31 %; P < 0.05). In contrast, estrogen did not affect any outcomes in young females. In aged mice, estrogen significantly reduced sCr (80 %) and VNT (73 %) in males and VNT (51 %) in females. Serum estrogen levels in aged female mice after CA/CPR were the same as levels in male mice. With age, renal ERα was upregulated in females. Estrogen administration after resuscitation from CA ameliorates renal injury in young males and aged mice in both sexes. Because injury was small, young females were not affected. The protective effect of exogenous estrogen may be detectable with loss of endogenous estrogen in aged females and could be mediated by differences in renal ERs. Post-arrest estrogen administration is renoprotective in a sex- and age-dependent manner.


A multi-site, multi-disorder resting-state magnetic resonance image database.
Machine learning classifiers for psychiatric disorders using resting-state functional magnetic resonance imaging (rs-fMRI) have recently attracted attention as a method for directly examining relationships between neural circuits and psychiatric disorders. To develop accurate and generalizable classifiers, we compiled a large-scale, multi-site, multi-disorder neuroimaging database. The database comprises resting-state fMRI and structural images of the brain from 993 patients and 1,421 healthy individuals, as well as demographic information such as age, sex, and clinical rating scales. To harmonize the multi-site data, nine healthy participants ("traveling subjects") visited the sites from which the above datasets were obtained and underwent neuroimaging with 12 scanners. All participants consented to having their data shared and analyzed at multiple medical and research institutions participating in the project, and 706 patients and 1,122 healthy individuals consented to having their data disclosed. Finally, we have published four datasets: 1) the SRPBS Multi-disorder Connectivity Dataset 2), the SRPBS Multi-disorder MRI Dataset (restricted), 3) the SRPBS Multi-disorder MRI Dataset (unrestricted), and 4) the SRPBS Traveling Subject MRI Dataset.


RollFISH achieves robust quantification of single-molecule RNA biomarkers in paraffin-embedded tumor tissue samples.
Single-molecule RNA fluorescence in situ hybridization (smFISH) represents a promising approach to quantify the expression of clinically useful biomarkers in tumor samples. However, routine application of smFISH to formalin-fixed, paraffin-embedded (FFPE) samples is challenging due to the low signal intensity and high background noise. Here we present RollFISH, a method combining the specificity of smFISH with the signal boosting of rolling circle amplification. We apply RollFISH to quantify widely used breast cancer biomarkers in cell lines and FFPE samples. Thanks to the high signal-to-noise ratio, we can visualize selected biomarkers at low magnification (20 × ) across entire tissue sections, and thus assess their spatial heterogeneity. Lastly, we apply RollFISH to quantify HER2 mRNA in 150 samples on a single tissue microarray, achieving a sensitivity and specificity of detection of HER2-positive samples of ~90%. RollFISH is a robust method for quantifying the expression and intratumor heterogeneity of biomarkers in FFPE tissues.


Time does not cause forgetting in short-term serial recall.
Time-based theories expect memory performance to decline as the delay between study and recall of an item increases. The assumption of time-based forgetting, central to many models of serial recall, underpins their key behaviors. Here we compare the predictions of time-based and event-based models by simulation and test them in two experiments using a novel manipulation of the delay between study and retrieval. Participants were trained, via corrective feedback, to recall at different speeds, thus varying total recall time from 6 to 10 sec. In the first experiment, participants used the keyboard to enter their responses but had to repeat a word (called the suppressor) aloud during recall to prevent rehearsal. In the second experiment, articulation was again required, but recall was verbal and was paced by the number of repetitions of the suppressor in between retrieval of items. In both experiments, serial position curves for all retrieval speeds overlapped, and output time had little or no effect. Comparative evaluation of a time-based and an event-based model confirmed that these results present a particular challenge to time-based approaches. We conclude that output interference, rather than output time, is critical in serial recall.


MRI and laboratory features and the performance of international criteria in the diagnosis of multiple sclerosis in children and adolescents: a prospective cohort study.
MRI and laboratory features have been incorporated into international diagnostic criteria for multiple sclerosis. We assessed the pattern of MRI lesions and contributions of cerebrospinal fluid (CSF) and serum antibody findings that best identifies children with multiple sclerosis, and the applicability of international diagnostic criteria in the paediatric context. In this prospective cohort study, detailed clinical assessments, serum and CSF studies, and MRI scans were done in youth (aged 0·46-17·87 years) with incidental acquired demyelinating syndrome. Participants were examined prospectively to identify relapsing disease. All MRI scans were assessed using a validated scoring method. A random forest classifier identified imaging and laboratory features that best predicted a multiple sclerosis or monophasic outcome. Performance of the 2001, 2010, and 2017 international McDonald criteria for the diagnosis of multiple sclerosis, the 2016 MRI in multiple sclerosis (MAGNIMS) criteria, and our 2011 proposed (Verhey) criteria were determined; performance was adjudicated with generalised linear models. Between Sept 1, 2004, and June 30, 2017, we included 324 participants with median follow-up of 72 months (range 6-150), 71 (22%) participants with multiple sclerosis, 237 (73%) with monophasic acquired demyelinating syndrome, 14 (4%) with relapsing non-multiple sclerosis, and two (1%) with alternative diagnoses. We scored 2391 brain, 444 spinal, and 67 dedicated orbital MRI scans. One or more T1 hypointense lesions plus one or more periventricular lesions (Verhey criteria) best predicted multiple sclerosis outcome. Performance of the 2017 McDonald criteria was comparable to the 2010 McDonald criteria and was easier to adjudicate. The ability of CSF oligoclonal bands to substitute for the requirement for both enhancing and non-enhancing lesions in the 2017 McDonald criteria improved its performance compared with the 2010 criteria. Myelin oligodendrocyte testing at baseline did not improve performance of the 2017 McDonald criteria. The 2017 McDonald criteria for the diagnosis of multiple sclerosis, as applied at the time of incident attack, perform well in identifying children and youth with multiple sclerosis, indicating that the same diagnostic criteria for multiple sclerosis apply across the age span. The presence of so-called black holes on MRI and periventricular lesions at baseline (Verhey criteria) also effectively distinguish children with multiple sclerosis from children with monophasic demyelination. The presence of CSF oligoclonal bands improve diagnostic accuracy. Myelin oligodendrocyte glycoprotein antibodies identify children with acute disseminated encephalomyelitis, and those with relapsing non-multiple sclerosis, most of whom do not meet 2017 McDonald criteria at onset. The Multiple Sclerosis Scientific Research Foundation and The Children's Hospital of Philadelphia.


Reaction of nitric oxide with heme proteins: studies on metmyoglobin, opossum methemoglobin, and microperoxidase.
Kinetic and EPR studies show that the first step in the reaction of NO with ferric myoglobin, opossum hemoglobin, and microperoxidase is the reversible formation of the H-NO complex: H + NO in equilibrium H-NO (where H = Mb+, or Hb+ OP, or MP+). The NO-combination rates are markedly affected by the presence or absence of the distal histidine. The distal histidine significantly reduces the NO-combination rates, perhaps by interaction between the distal histidine and the ferric iron. Thus the beta-chains of Hb+ OP and metmyoglobin show similar combination rates. In the absence of a distal histidine, the NO-combination rates in the alpha-chains of Hb+ OP are much faster and similar to those observed for the five-coordinate heme in microperoxidase. The loss of a water molecule from the six-coordination site is assumed to be the rate-limiting step.


Femtosecond-resolution pulse-front distortion measurement by time-of-flight interferometry.
The pulse-front distortion occurring in lenses and lens systems has been measured by a Michelson interferometer. In this technique the plane pulse front from one arm of the interferometer is used as a temporal reference level to map contour lines of equal propagation time on the pulse-front surface. The experimental arrangement is capable of detecting pulse-front distortion with a resolution of 20 fsec, and this can be improved to approximately 1 fsec. The measured value of pulse-front distortion in a telescope (1.1 psec) is in good agreement with the calculated data.


[Pre-exposure prophylaxis for HIV transmission? No, unless].
Pre-exposure prophylaxis (PrEP) with tenofovir/emtricitabine (TDF/FTC) will soon be available in the Netherlands. Moderate evidence concerning practical efficacy, small absolute risk reduction (1-2%) and a high number needed to treat (50-75) are key figures. Prevention of one HIV infection will cost EUR 350,000 to 500,000. No information is available on long-term renal function and antiretroviral resistance. Guidelines are needed before treatment with PrEP is introduced in the Netherlands.


African droughts and dust transport to the Caribbean: climate change implications.
Great quantities of African dust are carried over large areas of the Atlantic and to the Caribbean during much of the year. Measurements made from 1965 to 1998 in Barbados trade winds show large interannual changes that are highly anticorrelated with rainfall in the Soudano-Sahel, a region that has suffered varying degrees of drought since 1970. Regression estimates based on long-term rainfall data suggest that dust concentrations were sharply lower during much of the 20th century before 1970, when rainfall was more normal. Because of the great sensitivity of dust emissions to climate, future changes in climate could result in large changes in emissions from African and other arid regions that, in turn, could lead to impacts on climate over large areas.


Experiences of dying, death and bereavement in motor neurone disease: a qualitative study.
to explore the experiences of people with Motor Neurone Disease (MND), current and bereaved carers in the final stages of the disease and bereavement period. a qualitative study using narrative interviews was used to elicit accounts from 24 people with MND and 18 current family carers and 10 former family carers. the needs of patients and carers are not being adequately met in the final stages of MND and there appears a need for increased, co-ordinated support from palliative care services. The use of advance care planning tools is regarded as beneficial for patients and carers, but health professionals demonstrate a limited understanding of them. Anxiety and distress in patients, carers and bereaved carers is heightened during this period. Carer burden is excessive and may exacerbate patient distress and desire for hastening death. this study has identified a number of issues people with MND and their carers face in the final stages of the illness, indicating some ways in which health, social and palliative care services could be improved or co-operate more effectively in order to better meet their needs.


Cellular DNA content as a predictor of response to chemotherapy in infants with unresectable neuroblastoma.
We studied the relation between the DNA content of neuroblastoma cells and the response to therapy in 35 infants under one year of age with a diagnosis of neuroblastoma. Using flow cytometric techniques, we found that in 27 cases the primary malignant stem line consisted of neuroblasts with hyperdiploid DNA content, ranging from 1.07 to 2.42 times the finding in normal diploid cells. All remaining cases had diploid stem lines. Diploidy was more common in infants with clinical Stage D neuroblastoma (metastases beyond regional lymph nodes) than in those with other, less advanced stages: 6 of 10 as compared with 2 of 25 (P = 0.003). Of 17 evaluable patients with unresectable hyperdiploid tumors, 15 had complete responses and two had partial responses to cyclophosphamide and doxorubicin; six others with diploid tumors did not respond (P = 0.00001). We also found that each of the four infants with Evans' Stage IV-S neuroblastoma, an unusual form of disseminated neuroblastoma with a relatively good prognosis, had hyperdiploid tumor cells of clonal origin. We conclude that in neuroblastoma of infants, hyperdiploidy of tumor cells is associated with a better response to chemotherapy than is diploidy.