Adaptation during early childhood among mothers of children with disabilities.
This study documents the extent to which child-related and parenting stress vary during the early childhood period among mothers of children with developmental disabilities. The degree to which specific aspects of the family environment predict stress levels measured at age 3 years and 5 years, after controlling for child characteristics and family income, is also investigated. The Parenting Stress Index was completed by 79 mothers of children with developmental disabilities at three time points: (1) within 1 month of the child's entry into an early intervention program (T1); (2) within 1 month of the child's third birthday (T3); and (3) within 1 month of the child's fifth birthday (T5). Data on child characteristics and family income as well as measures of the family environment (i.e., negative life events, cohesion, and family support) were gathered at both T1 and T3. Repeated measures analysis of variance was used to assess whether there was significant change in the child-related and parenting stress scores across the three time points. Two sets of hierarchical regression equations were also analyzed. The first examined which child, family, and family environment characteristics assessed at T1 predicted stress at T3. The second identified the predictors of T5 stress based on independent variables measured at T3. Child-related stress increased significantly across the three time points, whereas parenting stress remained fairly stable. By age 5 years, one-third of the mothers had child-related stress scores above the clinical cutoff point. Regression analyses revealed the importance of the family environment in predicting both stress outcomes. The only statistically significant predictor of child-related stress at T3 was family cohesion, whereas parenting stress at T3 was predicted by income, cohesion, and family support. The predictors of both child-related and parenting stress at T5 were the same. Greater family cohesion and fewer negative life events predicted lower stress scores at T5. The significant increase in child-related stress during the early childhood period warrants attention by pediatricians, educators, and other professionals who must evaluate the needs of families of children with disabilities for supportive services. Aspects of the family environment were shown to be critical and consistent determinants of both child-related and parenting stress throughout the early childhood period. This finding suggests that pediatricians, in particular, must assess more than simply the diagnosis or the cognitive impairment of the child with a disability to make informed decisions about the frequency with which they should see particular families and whether referral to other services is necessary.


Synergistic roles of DYRK1A and GATA1 in trisomy 21 megakaryopoiesis.
Patients with Down syndrome (DS), or trisomy 21 (T21), are at increased risk of transient abnormal myelopoiesis (TAM) and acute megakaryoblastic leukemia (ML-DS). Both TAM and ML-DS require prenatal somatic mutations in GATA1, resulting in the truncated isoform GATA1s. The mechanism by which individual chromosome 21 (HSA21) genes synergize with GATA1s for leukemic transformation is challenging to study, in part due to limited human cell models with wild-type GATA1 (wtGATA1) or GATA1s. HSA21-encoded DYRK1A is overexpressed in ML-DS and may be a therapeutic target. To determine how DYRK1A influences hematopoiesis in concert with GATA1s, we used gene editing to disrupt all 3 alleles of DYRK1A in isogenic T21 induced pluripotent stem cells (iPSCs) with and without the GATA1s mutation. Unexpectedly, hematopoietic differentiation revealed that DYRK1A loss combined with GATA1s leads to increased megakaryocyte proliferation and decreased maturation. This proliferative phenotype was associated with upregulation of D-type cyclins and hyperphosphorylation of Rb to allow E2F release and derepression of its downstream targets. Notably, DYRK1A loss had no effect in T21 iPSCs or megakaryocytes with wtGATA1. These surprising results suggest that DYRK1A and GATA1 may synergistically restrain megakaryocyte proliferation in T21 and that DYRK1A inhibition may not be a therapeutic option for GATA1s-associated leukemias.


Reexpansion pulmonary edema following local anesthetic thoracoscopy: correlation and evolution of radiographic and ultrasonographic findings.
Local anesthetic (medical) thoracoscopy is used with increasing frequency by pulmonologists worldwide for both diagnostic and therapeutic purposes, notably in comorbid patients who may not be physiologically robust enough for general anesthesia. Understanding the complications that can arise and how to manage them is crucial for any physician performing this procedure. Reexpansion pulmonary edema is a rare but recognized complication of draining pleural effusions and pneumothoraces that has not been described previously in association with physician-led thoracoscopy. This case provides an opportunity for an overview of what is known about this unusual but potentially fatal condition. Data correlating ultrasonographic, radiographic, and clinical progression are also presented to highlight the potential usefulness of ultrasonography in identifying lung parenchymal abnormalities such as extravascular lung water.


A new species of Mysidobdella (Hirudinida: Piscicolidae) from mysids along the California coast.
Mysidobdella californiensis n. sp. is described from the mysid Holmesimysis sculpta from Bodega Bay on the central California coast and from Holmesimysis costata var. from San Pedro on the southern California coast. The internal anatomy of M. californiensis is similar to that of the only other species in the genus, Mysidobdella borealis from the north Atlantic Ocean, except that M. californiensis lacks the medial, unpaired seminal receptacle present in M. borealis. Externally, M. californiensis is slightly larger and more robust than M. borealis, with a much larger caudal sucker. The most striking difference between the species is the unusually large, trumpet-shaped, fluted oral sucker in M. californiensis. At Bodega Bay, the prevalence of M. californiensis on its host was 17% with an average intensity of 1.46 (range 1-3) leeches per host.


The neural bases of key competencies of emotional intelligence.
Emotional intelligence (EI) refers to a set of competencies that are essential features of human social life. Although the neural substrates of EI are virtually unknown, it is well established that the prefrontal cortex (PFC) plays a crucial role in human social-emotional behavior. We studied a unique sample of combat veterans from the Vietnam Head Injury Study, which is a prospective, long-term follow-up study of veterans with focal penetrating head injuries. We administered the Mayer-Salovey-Caruso Emotional Intelligence Test as a valid standardized psychometric measure of EI behavior to examine two key competencies of EI: (i) Strategic EI as the competency to understand emotional information and to apply it for the management of the self and of others and (ii) Experiential EI as the competency to perceive emotional information and to apply it for the integration into thinking. The results revealed that key competencies underlying EI depend on distinct neural PFC substrates. First, ventromedial PFC damage diminishes Strategic EI, and therefore, hinders the understanding and managing of emotional information. Second, dorsolateral PFC damage diminishes Experiential EI, and therefore, hinders the perception and integration of emotional information. In conclusion, EI should be viewed as complementary to cognitive intelligence and, when considered together, provide a more complete understanding of human intelligence.


Triglycerides in the human kidney cortex: relationship with body size.
Obesity is associated with increased risk for kidney disease and uric acid nephrolithiasis, but the pathophysiological mechanisms underpinning these associations are incompletely understood. Animal experiments have suggested that renal lipid accumulation and lipotoxicity may play a role, but whether lipid accumulation occurs in humans with increasing body mass index (BMI) is unknown. The association between obesity and abnormal triglyceride accumulation in non-adipose tissues (steatosis) has been described in the liver, heart, skeletal muscle and pancreas, but not in the human kidney. We used a quantitative biochemical assay to quantify triglyceride in normal kidney cortex samples from 54 patients undergoing nephrectomy for localized renal cell carcinoma. In subsets of the study population we evaluated the localization of lipid droplets by Oil Red O staining and measured 16 common ceramide species by mass spectrometry. There was a positive correlation between kidney cortex trigyceride content and BMI (Spearman R = 0.27, P = 0.04). Lipid droplets detectable by optical microscopy had a sporadic distribution but were generally more prevalent in individuals with higher BMI, with predominant localization in proximal tubule cells and to a lesser extent in glomeruli. Total ceramide content was inversely correlated with triglycerides. We postulate that obesity is associated with abnormal triglyceride accumulation (steatosis) in the human kidney. In turn, steatosis and lipotoxicity may contribute to the pathogenesis of obesity-associated kidney disease and nephrolithiasis.


Movement chunking during sequence learning is a dopamine-dependant process: a study conducted in Parkinson's disease.
Chunking of single movements into integrated sequences has been described during motor learning, and we have recently demonstrated that this process involves a dopamine-dependant mechanism in animal (Levesque et al. in Exp Brain Res 182:499-508, 2007; Tremblay et al. in Behav Brain Res 198:231-239, 2009). However, there is no such evidence in human. The aim of the present study was to assess this question in Parkinson's disease (PD), a neurological condition known for its dopamine depletion in the striatum. Eleven PD patients were tested under their usual levodopa medication (ON state), and following a 12-h levodopa withdrawal (OFF state). Patients were compared with 12 healthy participants on a motor learning sequencing task, requiring pressing fourteen buttons in the correct order, which was determined by visual stimuli presented on a computer screen. Learning was assessed from three blocks of 20 trials administered successively. Chunks of movements were intrinsically created by each participant during this learning period. Then, the sequence was shuffled according to the participant's own chunks, generating two new sequences, with either preserved or broken chunks. Those new motor sequences had to be performed separately in a fourth and fifth blocks of 20 trials. Results showed that execution time improved in every group during the learning period (from blocks 1 to 3). However, while motor chunking occurred in healthy controls and ON-PD patients, it did not in OFF-PD patients. In the shuffling conditions, a significant difference was seen between the preserved and the broken chunks conditions for both healthy participants and ON-PD patients, but not for OFF-PD patients. These results suggest that movement chunking during motor sequence learning is a dopamine-dependent process in human.


Effectiveness of the American Board of Orthodontics Discrepancy Index in predicting Treatment Time.
This study was aimed to explore the effect of pretreatment severity of malocclusion on the duration of the treatment using The American Board of Orthodontics discrepancy index (ABO-DI). This clinical retrospective study consisted of orthodontics records of 37 patients who were treated with comprehensive fixed orthodontic appliance from 2011 to 2013. The sample of the study was collected so as to exclude, to the maximum possible, the patient cooperation variability by reviewing all patient chart entries. The DI measurements were used to gather the information of the pretreatment and relate it to the time duration of the treatment. Statistical analyses were performed using the chi-square test and Pearson correlation coefficient. The average treatment time was 24.5 months. The DI scores mean for class I and II was 14.30 and 20.15 respectively. Age and sex did not significantly influence the treatment duration (p > 0.05). The results of this study showed that the ABO-DI could be a useful tool to predict orthodontic treatment time. The ABO-DI can significantly aid in orthodontic treatment time planning.


Liver receptor homolog 1 (LRH-1) regulates follicle vasculature during ovulation in mice.
It is well-established that liver receptor homolog 1 (LRH-1/NR5A2) regulates the ovarian function and is required for ovulation and luteinization in mice. In the present experiment, we showed that LRH-1 is required to control vascular changes during ovulation, a novel mechanism of action of this orphan nuclear receptor. Liver receptor homolog 1 (LRH-1/NR5A2) is a key regulator of ovarian function, and recently, it has been suggested that it may regulate changes in follicular angiogenesis, an important event during the ovulatory process and luteal development. In the present experiment, the objective was to determine whether conditional depletion of LRH-1 in mice granulosa cells modified vascular changes during the periovulatory period and to explore the possible mechanisms of this modification. We generated mice (22- to 25-day-old) with specific depletion of LRH-1 in granulosa cells by crossing Lrh1 floxed (Lrh1 f/f) mice with mice expressing Cre-recombinase driven by the anti-Müllerian type II receptor (Amhr2-cre; conditional knockout or cKO mice). We showed that preovulatory follicles of LRH-1 cKO mice had a reduced number of endothelial cells in the theca cell layer at 8 h after human chorionic gonadotropin treatment compared with control (CON) mice. Additionally, mRNA and protein expression of leptin receptor (LEPR), a protein that stimulates angiogenesis in a vascular endothelial growth factor-A (VEGFA)-dependent manner, and teratocarcinoma-derived growth factor-1 (TDGF1), which may directly stimulate endothelial cell function, were reduced in LRH-1 cKO mice as compared to CON after the LH surge. These results showed that LRH-1 is necessary for the correct vascular changes that accompany ovulation in mice and that this effect may be regulated through VEGFA-dependent and VEGFA-independent pathways mediated by LEPR and TDGF1.


Expression levels of Fv1: effects on retroviral restriction specificities.
The mouse protein Fv1 is a factor that can confer resistance to retroviral infection. The two major Fv1 alleles from laboratory mice, Fv1 (n) and Fv1 (b) , restrict infection by different murine leukaemia viruses (MLVs). Fv1(n) restricts B-tropic MLV, but not N-tropic MLV or NB-tropic MLV. In cells expressing Fv1(b) at natural levels, only N-MLV is restricted, however restriction of NB-MLV and partial restriction of B-MLV were observed when recombinant Fv1(b) was expressed from an MLV promoter in Fv1 null Mus dunni tail fibroblast cells. To investigate the relationship between expression level and restriction specificity we have developed new retroviral delivery vectors which allow inducible expression of Fv1, and yet allow sufficient production of fluorescent reporter proteins for analysis in our FACS-based restriction assay. We demonstrated that at concentrations close to the endogenous expression level, Fv1(b) specifically restricts only N-MLV, but restriction of NB-MLV, and to a lesser extent B-MLV, could be gained by increasing the protein level of Fv1(b). By contrast, we found that even when Fv1(n) is expressed at very high levels, no significant inhibition of N-MLV or NB-MLV could be observed. Study of Fv1 mutants using this assay led to the identification of determinants for N/B tropism at an expression level close to that of endogenous Fv1(n) and Fv1(b). We also compared the recently described restriction activities of wild mice Fv1 proteins directed against non-MLV retroviruses when expressed at different levels. Fv1 from M. spretus restricted N-MLV, B-MLV and equine infectious anaemia virus equally even at low concentrations, while Fv1 from M. macedonicus showed even stronger restriction against equine infectious anaemia virus than to N-MLV. Restriction of feline foamy virus by Fv1 of M. caroli occurred at levels equivalent to MLV restriction. Our data indicate that for some but not all Fv1 proteins, gain of restriction activities could be achieved by increasing the expression level of Fv1. However such a concentration dependent effect is not seen with most Fv1s and cannot explain the recently reported activities against non-MLVs. It will be interesting to examine whether overexpression of other capsid binding restriction factors such as TRIM5α or Mx2 result in novel restriction specificities.


Using a tailored web-based intervention to set goals to reduce unnecessary recall.
To examine whether an intervention strategy consisting of a tailored web-based intervention, which provides individualized audit data with peer comparisons and other data that can affect recall, can assist radiologists in setting goals for reducing unnecessary recall. In a multisite randomized controlled study, we used a tailored web-based intervention to assess radiologists' ability to set goals to improve interpretive performance. The intervention provided peer comparison audit data, profiled breast cancer risk in each radiologist's respective patient populations, and evaluated the possible impact of medical malpractice concerns. We calculated the percentage of radiologists who would consider changing their recall rates, and examined the specific goals they set to reduce recall rates. We describe characteristics of radiologists who developed realistic goals to reduce their recall rates, and their reactions to the importance of patient risk factors and medical malpractice concerns. Forty-one of 46 radiologists (89.1%) who started the intervention completed it. Thirty-one (72.1%) indicated they would like to change their recall rates and 30 (69.8%) entered a text response about changing their rates. Sixteen of the 30 (53.3%) radiologists who included a text response set realistic goals that would likely result in reducing unnecessary recall. The actual recall rates of those who set realistic goals were not statistically different from those who did not (13.8% vs. 15.1%, respectively). The majority of selected goals involved re-reviewing cases initially interpreted as Breast Imaging Reporting and Data System category 0. More than half of radiologists who commented on the influence of patient risk (56.3%) indicated that radiologists planned to pay more attention to risk factors, and 100% of participants commented on concerns radiologists have about malpractice with the primary concern (37.5%) being fear of lawsuits. Interventions designed to reduce unnecessary recall can succeed in assisting radiologists to develop goals that may ultimately reduce unnecessary recall.


Scaling of adult regional body mass and body composition as a whole to height: Relevance to body shape and body mass index.
Adult body mass (MB) empirically scales as height (Ht) squared (MB ∝ Ht(2) ), but does regional body mass and body composition as a whole also scale as Ht(2) ? This question is relevant to a wide range of biological topics, including interpretation of body mass index (BMI). Dual-energy X-ray absorptiometry (DXA) was used to quantify regional body mass [head (MH), trunk, arms, and legs] and whole-body composition [fat, lean soft tissue (LST), and bone mineral content (BMC)] in non-Hispanic (NH) white, NH black, Mexican American, and Korean adults participating in the National Health and Nutrition Examination Survey (NHANES; n = 17,126) and Korean NHANES (n = 8,942). Regression models were developed to establish Ht scaling powers for each measured component with adjustments for age and adiposity. Exploratory analyses revealed a consistent scaling pattern across men and women of the four population groups: regional mass powers, head (∼0.8-1) < arms and trunk (∼1.8-2.3) < legs (∼2.3-2.6); and body composition, LST (∼2.0-2.3) < BMC (∼2.1-2.4). Small sex and population differences in scaling powers were also observed. As body mass scaled uniformly across the eight sex and population groups as Ht(∼2) , tall and short subjects differed in body shape (e.g., MH/MB ∝ Ht(-∼1) ) and composition. Adult human body shape and relative composition are a function of body size as represented by stature, a finding that reveals a previously unrecognized phenotypic heterogeneity as defined by BMI. These observations provide new pathways for exploring mechanisms governing the interrelations between adult stature, body morphology, biomechanics, and metabolism.


First Report of Bacterial Leaf Spot Disease Caused by Pseudomonas syringae pv. syringae on Panax notoginseng.
Panax notoginseng is a species that produces a rare type of Chinese herbal medicine and is cultivated primarily in Yunnan Province. P. notoginseng has a 3-year-long crop cycle before harvest. A new bacterial disease was observed on P. notoginseng plants in the Wenshan Mountain area of Yunnan in 2012. The disease affected primarily leaves. Symptoms were circular or irregular brown leaf spots, surrounded by a yellow halo, located on the edges of the leaves. Eight creamy white pigmented, rounded strains were isolated consistently from leaf spots on Luria-Bertani agar (LB) medium, incubated at 28°C. Three strains (SQYB-1, SQYB-2, SQYB-3) of eight isolates were prepared for further study. Three isolates were purified and characterized: all were gram-negative, rod-shaped, motile, aerobic, non-spore forming, and negative for oxidase, potato soft rot, arginine dehydrolase, presence of tyrosinase and urease, nitrate, and fluorescent pigment production. Moreover, they were positive for levan production, presence of catalase, and for tobacco hypersensitivity. All three strains isolated were identified as Pseudomonas syringae pv. syringae (Pss) based on morphology, metabolic profile (Biolog Microbial ID System), and 16S rDNA sequence analysis (1). The metabolic similarity index between experiment strain SQYB-1 and a type of strain Pss was 0.619. The primers of 16S rDNA sequence amplification were 27F/1492R. Before sequencing, we cloned the PCR products. There was 99% homology in 16S rDNA sequences between one isolate, SQYB-1 (NCBI Accession No. JX876901) and Pss (HQ840766), supporting the identification of the P. notoginseng strains as Pss (3). For Koch's postulates, 10 surface-disinfected young leaves on three plants were inoculated with SQYB-1 isolates by spraying a phosphate-buffered saline cell suspension (3.0 × 108 CFU/ml) onto the leaves (4). Controls were inoculated similarly with sterile phosphate-buffered saline. Plants were covered with polyethylene bags for 24 h at 25°C and then transferred to a greenhouse. Circular or irregular brown spots were observed on all bacteria-inoculated leaves within 9 to 14 days after inoculation. No symptoms were observed on controls. Bacteria reisolated from inoculated leaves were identical to the original isolates as determined by the methods described above. The present study indicated that isolate SQYB-1 could independently infect P. notoginseng leaves, which was different from the finding of Luo et al. concerning involvement of Pss in root rot (2). To our knowledge, this is the first report of Pseudomonas syringae pv. syringae causing bacterial leaf spot on P. notoginseng in China. References: (1) M. R. Gillings et al. PNAS 12:102, 2005. (2) W. F. Luo et al. J. Yunnan Agric. Univ. 14:123, 1999 (in Chinese). (3) C. L. Oliver et al. Plant Dis. 4:96, 2012. (4) H. Ornek et al. New Dis. Rep. 13:40, 2006.


Return to play? Athletes with congenital long QT syndrome.
Competitive sports participation for athletes with congenital long QT syndrome (LQTS) is guided by the 2005 36th Bethesda Conference and the 2005 European Society of Cardiology (ESC) guidelines. The purpose of this study was to determine the prevalence and outcomes of patients with LQTS who chose to remain athletes following their diagnosis. Records of all patients between 6 and 40 years of age who were first evaluated in Mayo Clinic's LQTS Clinic from July 2000 to November 2010 were reviewed, for documentation of athletic participation after LQTS diagnosis and LQTS-related events during follow-up. Average follow-up was 5.5±3.4 years. The cohort included 353 patients with LQTS (199 females, mean age 17±11 years, mean QTc 472±42 ms), of whom 182 had LQT1, 130 had LQT2, 37 had LQT3 and 4 had multiple LQTS mutations. The majority of patients (223, 63%) were either not involved in sports (88%) or chose to discontinue sports (12%) following evaluation. 130 patients (37%, 60 females, mean age 11±7 years, mean QTc 471±46 ms) remained in competitive athletics, including 20 with implantable cardioverter defibrillators (ICDs). Of these 130, 70 (54%) were genotype-positive/phenotype-negative and competing contrary to ESC guidelines but within the Bethesda guidelines. None of these athletes had a sport-related event. Of the 60 LQTS athletes continuing in sports contrary to both the Bethesda and ESC guidelines (genotype-positive/phenotype-positive), only one had a sporting-related event with appropriate ICD shock. Athletes and their families are fully capable of self-disqualification. Among those athletes with LQTS who chose to remain in competitive sports, a low rate of cardiac events and no deaths were observed in over 650 athlete-years of follow-up. Current guideline-based recommendations for disqualification may be excessive for this disease.


Current management and perspectives in the treatment of ventricular assist device-specific infections.
Occurrence of ventricular assist device (VAD)-specific infections is a serious complication that can jeopardize on the long run the effectiveness of VAD therapy. In the light of ongoing shortage of organ available for heart transplantation there will be in the next future an increase necessity of conservative strategies. A multidisciplinary approach including cardiac surgeons, cardiologist, infectious disease (ID) consultant and nuclear medicine physicians should be the first step for the diagnosis and treatment of VAD-specific infections. Early detection of infections and consequently early treatment with innovative strategies may help physicians to improve outcomes.


Primary Care-Relevant Interventions for Tobacco and Nicotine Use Prevention and Cessation in Children and Adolescents: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.
Interventions to discourage the use of tobacco products (including electronic nicotine delivery systems or e-cigarettes) among children and adolescents may help decrease tobacco-related illness and injury. To update the 2013 review on primary care-relevant interventions for tobacco use prevention and cessation in children and adolescents to inform the US Preventive Services Task Force. The Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews, MEDLINE, PsyINFO, and EMBASE (September 1, 2012, to June 25, 2019), with surveillance through February 7, 2020. Primary care-relevant studies; randomized clinical trials and nonrandomized controlled intervention studies of children and adolescents up to age 18 years for cessation and age 25 years for prevention. Trials comparing behavioral or pharmacological interventions with no or a minimal tobacco use intervention control group (eg, usual care, attention control, wait list) were included. One investigator abstracted data and a second investigator checked data abstraction for accuracy. Two investigators independently assessed study quality. Studies were pooled using random-effects meta-analysis. Tobacco use initiation; tobacco use cessation; health outcomes; harms. Twenty-four randomized clinical trials (N = 44 521) met inclusion criteria. Behavioral interventions were associated with decreased likelihood of cigarette smoking initiation compared with control interventions at 7 to 36 months' follow-up (13 trials, n = 21 700; 7.4% vs 9.2%; relative risk [RR], 0.82 [95% CI, 0.73-0.92]). There was no statistically significant difference between behavioral interventions and controls in smoking cessation when trials were restricted to smokers (9 trials, n = 2516; 80.7% vs 84.1% continued smoking; RR, 0.97 [95% CI, 0.93-1.01]). There were no significant benefits of medication on likelihood of smoking cessation in 2 trials of bupropion at 26 weeks (n = 523; 17% [300 mg] and 6% [150 mg] vs 10% [placebo]; 24% [150 mg] vs 28% [placebo]) and 1 trial of nicotine replacement therapy at 12 months (n = 257; 8.1% vs 8.2%). One trial each (n = 2586 and n = 1645) found no beneficial intervention effect on health outcomes or on adult smoking. No trials of prevention in young adults were identified. Few trials addressed prevention or cessation of tobacco products other than cigarettes; no trials evaluated effects of interventions on e-cigarette use. There were few trials of pharmacotherapy, and they had small sample sizes. Behavioral interventions may reduce the likelihood of smoking initiation in nonsmoking children and adolescents. Research is needed to identify effective behavioral interventions for adolescents who smoke cigarettes or who use other tobacco products and to understand the effectiveness of pharmacotherapy.


Twenty-five years of violence: the epidemiology of terrorism in South America.
Terrorism is a global public health burden. South Americans have been victims of terrorism for many decades. While the causes vary, the results are the same: death, disability, and suffering. The objective of this study was to perform a comprehensive, epidemiological, descriptive study of terrorist incidents in South America. This is a cross-sectional, descriptive study. Data from January 1971 to July 2006 was selected using the RAND Terrorism Chronology 1968-1997 and RAND-Memorial Institute for Prevention of Terrorism (MIPT) Terrorism Incident database (1998-Present). Statistical significance was set at 0.05. The database reported a total of 2,997 incidents in South American countries that resulted in 3,435 victims with injuries (1.15 per incident) and 1,973 fatalities (0.66 per incident). The overall case fatality ratio (CFR) was 35.8%. Colombia had the majority of incidents with 57.9% (1,734 of 2,997), followed by Peru with 363 (12.1%), and Argentina with 267 (8.9%). The highest individual CFR occurred in Paraguay (83.3%), and the lowest in Chile with 4.8%. Of the total injuries and deaths, Colombia had 66.1% (2,269 of 2,997) of all injuries and 75.2% (1,443 out of 1,920) of all deaths. Living in the country of Colombia was associated with a 16 times greater likelihood of becoming a victim of terrorist violence [odds ratio (OR) 16.15; 95% CI 13.45 to 19.40; p < 0.0001]. The predominant method of choice for terrorist incidents was the use of conventional explosives with 2,543 of2,883 incidents (88.2%). Terrorist incidents in South America have accounted for nearly 2,000 deaths, with conventional explosive devices as the predominant method of choice. Understanding the nature of terrorist attacks and the medical consequences assist emergency preparedness and disaster management officials in allocating resources and preparing for potential future events.


Hypothalamic hamartoma: a paradigm/model for studying the onset of puberty.
This article discusses the potential mechanisms by which hypothalamic hamartomas (HHs) are formed and cause precocious puberty. The hypothesis is presented suggesting that HHs accelerate sexual development by producing bioactive substances that mimic - in an accelerated time-course - the cascade of events underlying the normal initiation of puberty. It is also proposed that because HHs contain key transcriptional and signaling networks required to initiate and sustain a pubertal mode of gonadotropin-releasing hormone (GnRH) release, they are able to trigger the pubertal process at an earlier age. The cellular components of this activating complex may include: (a) neurons able to produce GnRH within the HH: (b) controlling neurons synaptically connected to GnRH neurons in the HH itself and/or to neuronal networks (including GnRH neurons) in the patient's hypothalamus, and (c) signaling-competent astrocytic and ependymoglial cells. It is also possible that the developmental abnormalities leading to the formation of HHs result from sporadic defects affecting the same genes and hence the same morphogenic pathways involved in the embryonic development of the ventral hypothalamus and the floor of the third ventricle.


Inflammatory pseudotumor of the spleen associated with a clonal Epstein-Barr virus genome. Case report and review of the literature.
We report a case of an inflammatory pseudotumor (IPT) of the spleen occurring in an 81-year-old woman with a history of a monoclonal gammopathy of undetermined significance. Eighteen-month follow-up after splenectomy demonstrated no tumor recurrence or progression of underlying plasma cell disease. Histologic examination of the tumor demonstrated a polymorphic population of inflammatory and epithelioid and spindle cells. Immunophenotyping showed large numbers of T cells, B cells, and polyclonal plasma cells. The epithelioid and spindle cells were positive for vimentin and CD68 but lacked expression of follicular dendritic cell markers and actin. Epstein-Barr virus (EBV) genome was identified in the epithelioid and spindle cell population by in situ hybridization using probes specific for EBV-encoded RNAs (EBER1 and EBER2). Southern blot analysis of digested DNA extracted from the tumor using an EBV-specific probe (XhoI) demonstrated the presence of a single high-intensity band, indicative of EBV monoclonality. While there have been 2 previous reports of hepatic IPTs containing a monoclonal population of EBV-infected tumor cells, this is the first report of such an association occurring in the spleen. The presence of clonal EBV DNA suggests some splenic IPTs may be true neoplasms.


In vitro effects of a chemically modified titanium surface on ethanol-exposed osteoblasts.
No clinical evidence-based data on a possible negative influence of osteopenia and harmful lifestyles on implant osseointegration have been published to date. However, chronic alcohol abuse has been related to a progressive osteoporotic state. The continuous effort on developing better performing surfaces might offer improvement in osseointegration rates in conditions of poor bone quality. The aim of the present study was to investigate, in vitro, the behavior of osteoblasts obtained from rats exposed to ethanol vapor for 7 weeks and cultured on an innovative titanium surface achieved by a double anodic spark deposition. Ethanol-exposed and unexposed (control) osteoblasts were cultured on an anodic spark-deposited titanium surface and compared to those cultured on an acid-etched one. Cell proliferation and synthesis of alkaline phosphatase, osteocalcin, collagen I, transforming growth factor-β1, interleukin-6, and tumor necrosis factor-α were measured at 3, 7, and 14 days of culture. When cultured on the anodic spark-deposited titanium surface, ethanol-exposed osteoblasts recovered proliferation impairment. Anodic spark-deposited titanium surfaces significantly improved both ethanol-exposed and unexposed osteoblast bioactivity, particularly with regard to alkaline phosphatase and transforming growth factor-β1. Moreover, interleukin-6 release for ethanol-exposed osteoblasts was significantly reduced by the anodic spark-deposited titanium surface. Proliferative and synthetic cell processes altered by ethanol contact were positively and partially restored by contact with the tested innovative surface.


A Drosophila Tpr protein homolog is localized both in the extrachromosomal channel network and to nuclear pore complexes.
Here we report structural, molecular, and biochemical characterizations of Bx34, a Drosophila melanogaster nuclear coiled-coil protein which is localized to extrachromosomal and extranucleolar spaces in the nuclear interior and which is homologous to the mammalian nuclear pore complex protein Tpr. In the nuclear interior, Bx34 is excluded from chromosomes and the nucleolus and generally localizes to regions between these structures and the nuclear periphery. This distribution matches the 'extrachromosomal channel network' described previously. In the nuclear periphery, Bx34 localizes on or near nuclear pore complexes. Biochemically, Bx34 isolates exclusively with the nuclear matrix fraction. The Bx34 cDNA sequence predicts a large protein (262 kDa) with two distinct structural domains. The Bx34 N-terminal 70% (180 kDa) is predicted to form an extended region of coiled-coil, while the C-terminal 30% (82 kDa) is predicted to be unstructured and acidic. Bx34 shows moderate sequence identity over its entire length to the mammalian nuclear pore complex protein 'Tpr' (28% amino acid identity and 50% similarity). Furthermore, several of the sequence motifs and biochemical similarities between Bx34 and Tpr are sufficiently striking that it is likely that Bx34 and Tpr are functionally related. The Bx34 gene exists in a single copy in region 48C of chromosome 2R. The localization of coiled-coil Bx34 to both the nuclear interior and nuclear pore complexes and its sequence similarity to a known nuclear pore complex protein leads to speculations about a role for Bx34 in nucleo-cytoplasmic transport which we can test using molecular genetic approaches.


Human embryonic stem cells: potential tool for achieving immunotolerance?
The derivation of human embryonic stem cells (hESCs), whose in vitro differentiation might be directed toward different cell types, has raised the hope for cell replacement therapies. Despite the emerging reports to differentiate hESCs into specific lineages and then to distinct mature cell subsets, there are still several issues that need to be resolved before transplantation of these cells can be realized. In this context, immune rejection by the host immune system has been considered to be one of the greatest hurdles for cellular transplantation. However, recent data support the concept that hESCs and/or their differentiated derivatives possess immune-privileged properties, suggesting that cells derived from hESC may provide a potential tool for induction of immunetolerance. Currently, our understanding of the tolerogenic potential of hESCs is limited to assessment by in vitro assays or xenogenic transplantation approaches in vivo. Human ESCs express low levels of major histocompatability complex (MHC)-I antigens and lack expression of MHC-II antigens and costimulatory molecules, and are not recognized by natural killer cells and inhibit T-cell induced-stimulation by third-party antigen-presenting cells. Upon injection into immunocompetent mice, hESCs are unable to induce an immune response as demonstrated by their inability to induce an inflammatory response. Based on these initial observations, further studies in hESCs immunobiology are warranted and may reveal unique mechanisms that account for the immunological properties of hESCs. Here, we explore the prospect of using hESCs and their derivatives for immunomodulation and tolerance induction.


Maximal transcription of aur (aureolysin) and sspA (serine protease) in Staphylococcus aureus requires staphylococcal accessory regulator R (sarR) activity.
Previous studies have shown that expression of aur (metalloprotease; aureolysin) and sspA (V8 protease; serine protease) in Staphylococcus aureus strain 8325-4 is maximal in the postexponential phase of growth, when the agr (RNAIII) system is activated. Transcription of aur and sspA is mainly regulated through repression by sarA and rot, and RNAIII stimulates protease production by inhibiting translation of rot mRNA. As SarR is a repressor of sarA, inactivation of sarR would result in downregulation of aur and sspA transcription. This was confirmed by mRNA analysis using quantitative real-time PCR. However, we found that sarR acted as a direct stimulator, i.e. its positive effect on aur and sspA transcription did not require sarA (or rot) per se. In addition, aur and sspA were dependent on sarR for maximal transcription. This stimulating role of sarR was not restricted to the rsbU-deficient laboratory strain 8325-4 but was also demonstrated in S. aureus strain SH1000 (rsbU-complemented derivative of 8325-4) and in one clinical isolate.


Cold tolerance mechanisms of the free-living stages of Trichostrongylus colubriformis (Nematoda).
1. All free-living stages of the nematode parasite of sheep, Trichostrongylus colubriformis Giles, survived exposure to freezing temperatures in contact with water, with the exception of the first-stage juvenile (J1). The third-stage juvenile (J3) was the most resistant stage. The order of relative survival of the different stages was different from that of the lowest F50 (the temperature at which 50% froze), suggesting that an ability to supercool was not the only determinant of survival. 2. The F50 was shown to be a good measure of the degree of supercooling and to extend greatly the lower size limit of organisms that could be measured. 3. The J3 uses a freeze-avoiding strategy by supercooling when in air or covered by liquid paraffin. In water it uses a mixture of freeze-avoiding and freeze-tolerant strategies, with a proportion of the population surviving freezing caused by exogenous ice nucleation. 4. Removal of the J3 sheath results in a shift from freeze avoidance to freeze tolerance, with an overall reduction in survival. A major function of the sheath may be to reduce the probability of exogenous ice nucleation.


Design, synthesis, molecular-docking and antimycobacterial evaluation of some novel 1,2,3-triazolyl xanthenones.
As part of an ongoing effort to develop new antitubercular and antimicrobial agents, a series of substituted xanthenone derivatives (7a-p) were synthesized. Xanthenone derivatives (7a-p) were prepared via a one-pot three-component thermal cyclization reaction of β-naphthol (5), substituted 1-aryl-1H-[1,2,3]triazole-4-carbaldehydes (4a-h), and cyclic-1,3-diones (6a, b) in the presence of a catalytic amount of iodine. The newly synthesized compounds were characterized by IR, NMR, mass spectral data, and elemental analysis. These compounds (4a-h and 7a-p) were screened for in vitro antitubercular activity against the M. tuberculosis H37Rv (ATCC 27294) strain, for antibacterial activity against Gram-positive and Gram-negative strains, and for antifungal activity against a pathogenic strain of fungi. Among the compounds tested, most of them showed good to excellent antimicrobial and antitubercular activity. The active compounds displaying good potency in the MTB were further examined for toxicity in a HEK cell line. In addition, the structure and antitubercular activity relationship were further supported by in silico molecular-docking studies of the active compounds against the pantothenate synthetase (PS) enzyme of M. tuberculosis.


Fauna Europaea: Hymenoptera - Apocrita (excl. Ichneumonoidea).
Fauna Europaea provides a public web-service with an index of scientific names (including important synonyms) of all living European land and freshwater animals, their geographical distribution at country level (up to the Urals, excluding the Caucasus region), and some additional information. The Fauna Europaea project covers about 230,000 taxonomic names, including 130,000 accepted species and 14,000 accepted subspecies. This represents a huge effort by more than 400 contributing specialists throughout Europe and is a unique (standard) reference suitable for many users in science, government, industry, nature conservation and education. Hymenoptera is one of the four largest orders of insects, with about 130,000 described species. In the Fauna Europaea database, 'Hymenoptera - Apocrita (excluding Ichneumonoidea)' comprises 13 superfamilies, 52 families, 91 subfamilies, 38 tribes and 13,211 species. The paper includes a complete list of taxa dealt with, the number of species in each and the name of the specialist responsible for data acquisition. As a general conclusion about the European fauna of Hymenoptera, the best known countries in terms of recorded species are those from northwestern Europe, with the least known fauna probably in the more eastern and southeastern parts of Europe.


Role of virion-associated glycosylphosphatidylinositol-linked proteins CD55 and CD59 in complement resistance of cell line-derived and primary isolates of HIV-1.
This study investigates whether cell-derived glycosylphosphatidylinositol-linked complement control proteins CD55 and CD59 can be incorporated into HIV-1 virions and contribute to complement resistance. Virus was prepared by transfection of cell lines with pNL4-3, and primary isolates of HIV-1 were derived from patients' PBMCs. Virus was tested for sensitivity to complement-mediated virolysis in the presence of anti-gp160 antibody. Viral preparations from JY33 cells, which lack CD55 and CD59, were highly sensitive to complement. HIV-1 preparations from H9 and U937 cells, which express low levels of CD55 and CD59, had intermediate to high sensitivity while other cell line-derived viruses and primary isolates of HIV-1 were resistant to complement-mediated virolysis. Although the primary isolates were not lysed, they activated complement as measured by binding to a complement receptor positive cell line. While the primary isolates were resistant to lysis in the presence of HIV-specific antibody, antibody to CD59 induced lysis. Likewise, antibody to CD55 and CD59 induced lysis of cell line-derived virus. Western blot analysis of purified virus showed bands corresponding to CD55 and CD59. Phosphatidylinositol-specific phospholipase C treatment of either cell line-derived or primary isolates of HIV-1 increased sensitivity to complement while incubation of sensitive virus with purified CD55 and CD59 increased resistance to complement. These results show that CD55 and CD59 are incorporated into HIV-1 particles and function to protect virions from complement-mediated destruction, and they are the first report of host cell proteins functioning in protection of HIV-1 from immune effector mechanisms.


Molecular composition of the outermost capsular material of the tubercle bacillus.
To gain insight into the pathogenesis of tuberculosis, a molecular definition of the tubercle bacillus cell envelope, which is involved in the early stages of the infection, is required. The cell-surface-exposed material of the pathogen was isolated by mechanical means and chemically analysed. It was shown by scanning electron microscopy that the method used for extracting the surface-covering material preserves the integrity of the bacilli. Surprisingly, in view of the current opinion, only small amounts of lipids (1-6%) were present. Polysaccharides and proteins were the main components of the material. The polysaccharides were neutral and lipid-free D-glucan, D-arabino-D-mannan and D-mannan, which were eluted from gel-filtration columns in positions corresponding to molecular masses of 120, 13 and 4 kDa, respectively. Based on NMR spectroscopy and conventional chemical analyses, the major structural motifs of the purified polysaccharides were established as being identical to those of the polysaccharides we previously isolated from the culture filtrate of the tubercle bacillus. Immunocytochemical studies showed that these compounds were not only surface-located but were also present in the inner capsular compartment. The major protein constituents exhibited the same mobilities on SDS-PAGE as those of the culture filtrate on the tubercle bacillus and readily reacted with the monoclonal antibodies directed against these molecules. These proteins included the 19 and 38 kDa lipoproteins, the 30/31 kDa fibronectin-binding proteins and the 40 kDa L-alanine dehydrogenase. These findings suggest that the culture filtrate material represents part of the capsule which, in an in vivo context, could contribute to the electron transparent zone surrounding the tubercle bacillus. The 24 kDa (MPB/T64) protein was found to be a secreted protein, as it was detected almost exclusively in the culture filtrate. Taken together, the data give a new insight into the surface-exposed compounds of the tubercle bacillus and may explain part of the nature and limitation of the host immunity towards the pathogen.


Life table and consumption capacity of corn earworm, Helicoverpa armigera, fed asparagus, Asparagus officinalis.
The life table and consumption rate of Helicoverpa armigera (Hübner) (Lepidoptera: Noctuidae) reared on asparagus, Asparagus officinalis L. (Asparagales: Asparagaceae) were studied under laboratory conditions to assess their interaction. Development, survival, fecundity, and consumption data were analyzed by the age-stage, twosex life table. This study indicated that asparagus is a natural host of H. armigera. However, the poor nutritional content in asparagus foliage and the poor fitness of H. armigera that fed on asparagus indicated that asparagus is a suboptimal host in comparison to hybrid sweet corn. The uncertainty associated with life table parameters was estimated by using jackknife and bootstrap techniques, and the results were compared for statistical inference. The intrinsic rate of increase (r), finite rate of increase (λ), net reproductive rate (R0), and mean generation time (T) were estimated by the jackknife technique to be 0.0780 day(-1), 1.0811 day(-1), 67.4 offspring, and 54.8 days, respectively, while those estimated by the bootstrap technique were 0.0752 day(-1), 1.0781 day(-1), 68.0 offspring, and 55.3 days, respectively. The net consumption rate of H. armigera, as estimated by the jackknife and bootstrap technique, was 1183.02 and 1132.9 mg per individual, respectively. The frequency distribution of sample means obtained by the jackknife technique failed the normality test, while the bootstrap results fit the normal distribution well. By contrast, the relationship between the mean fecundity and the net reproductive rate, as estimated by the bootstrap technique, was slightly inconsistent with the relationship found by mathematical proof. The application of the jackknife and bootstrap techniques in estimating population parameters requires further examination.


Characterization of the alpha adrenergic receptor properties of rabbit ear artery and thoracic aorta.
The alpha adrenoceptor properties of the rabbit ear artery and thoracic aorta were assessed using isolated blood vessel rings mounted in tissue baths. ED50 values and dissociation constants for norepinephrine (NE), epinephrine (EPI), isoproterenol (ISO), methoxamine (MET) and clonidine (CLO) were determined by analysis of dose-response data with and without partial inactivation of alpha receptors by phenoxybenzamine. The order of affinity of these agonists for the alpha receptors of ear artery was CLO less than EPI = NE = MET much less than ISO, and that in aorta was EPI less than NE less than CLO less than MET less than ISO. Alpha receptor reserves were larger in ear artery than aorta by factors of 182, 17, 7, 3.8 and 2 for EPI, NE, ISO, MET and CLO, respectively. In contrast, the fraction of receptors occupied at threshold contractile response was larger in aorta than ear artery with every agonist studied except CLO. The maximal response to the partial agonist, CLO, expressed as a fraction of the maximal response to NE in each vessel, was nearly 1.8 times greater in ear artery than in aorta. It is concluded that the alpha receptors of rabbit ear artery are qualitatively different from those of the thoracic aorta. In addition, the larger receptor reserves, smaller fraction of receptors occupied at threshold and the larger maximal response of CLO in ear artery support the hypothesis that alpha receptor density in this vessel is greater than that in the aorta.


LACDIF, a new electron diffraction technique obtained with the LACBED configuration and a C(s) corrector: comparison with electron precession.
By combining the large-angle convergent-beam electron diffraction (LACBED) configuration together with a microscope equipped with a C(s) corrector it is possible to obtain good quality spot patterns in image mode and not in diffraction mode as it is usually the case. These patterns have two main advantages with respect to the conventional selected-area electron diffraction (SAED) or microdiffraction patterns. They display a much larger number of reflections and the diffracted intensity is the integrated intensity. These patterns have strong similarities with the electron precession patterns and they can be used for various applications like the identification of the possible space groups of a crystal from observations of the Laue zones or the ab-initio structure identifications. Since this is a defocused method, another important application concerns the analysis of electron beam-sensitive materials. Successful applications to polymers are given in the present paper to prove the validity of this method with regards to these materials.


E-mental health preferences of Veterans with and without probable posttraumatic stress disorder.
Mental health care practices supported by electronic communication, referred to as e-mental health, offer ways to increase access to mental health resources. In recent years, e-mental health interventions using clinical video teleconferencing, Internet-based interventions, social networking sites, and telephones have emerged as viable, cost-effective methods to augment traditional service delivery. Whereas some research evaluates attitudes about e-mental health, few studies have assessed interest in using these approaches in a contemporary sample of U.S. Veterans. This study sought to understand willingness to use e-mental health in a diverse group of Veterans residing in Hawaii. Mailed surveys were completed by 600 Operation Iraqi Freedom/Operation Enduring Freedom Veterans and National Guard members. Results suggest that overall willingness to use e-mental health ranged from 32.2% to 56.7% depending on modality type. Importantly, Veterans who screened positive for posttraumatic stress disorder (PTSD) were significantly less likely to report willingness to use each e-mental health modality than their peers without PTSD, despite their greater desire for mental health services. These results suggest that despite solutions to logistical barriers afforded via e-mental health services, certain barriers to mental health care may persist, especially among Veterans who screen positive for PTSD.


Dietary lipids modulate the expression of miR-107, an miRNA that regulates the circadian system.
The increased prevalence of cardiovascular diseases (CVDs) has been hypothesized to be the result of an increased exposure to a host of atherogenic environmental factors, paramount among them being unhealthy dietary habits. Long-chain n-3 polyunsaturated fatty acids have been shown to have cardio protective effects, partially due to their ability to regulate gene expression. In this regard, increasing attention has been devoted to the role of miRNAs as regulators of multiple metabolic pathways whose deregulation has been associated with CVD risk. In this work, we investigated whether miRNA expression was regulated by docosahexanoic acid, conjugated linoleic acid, and cholesterol in Caco-2 cells. The modulated miRNAs, miR-107 was differentially expressed by all treatments and this modulation was independent of its hosting gene, PANK1, possibly through its own promoter, which contains binding sites for metabolically relevant transcription factors. Among the putative target genes of miR-107, we found some genes with key roles in circadian rhythm. Specifically, we demonstrated that binding of miR-107 to the CLOCK gene results in the deregulation of the circadian rhythm of the cells. Since chronodisruption has been linked to metabolic disorders such as type 2 diabetes, atherosclerosis, obesity, and CVD, our findings suggests that miR-107 could represent a new approach for pharmacological treatment of these diseases.


High Performance of Ionic-Liquid-Based Materials to Remove Insecticides.
Neonicotinoids are systemic insecticides commonly used for pest control in agriculture and veterinary applications. Due to their widespread use, neonicotinoid insecticides (neonics) are found in different environmental compartments, including water, soils, and biota, in which their high toxicity towards non-target organisms is a matter of great concern. Given their widespread use and high toxicity, the development of strategies to remove neonics, while avoiding further environmental contamination is of high priority. In this work, ionic-liquid-based materials, comprising silica modified with tetraalkylammonium cations and the chloride anion, were explored as alternative adsorbent materials to remove four neonics insecticides, namely imidacloprid, acetamiprid, thiacloprid, and thiamethoxam, from aqueous media. These materials or supported ionic liquids (SILs) were first synthesized and chemically characterized and further applied in adsorption studies. It was found that the equilibrium concentration of the adsorbate in the solid phase decreases with the decrease in the SIL cation alkyl chain length, reinforcing the relevance of hydrophobic interactions between ionic liquids (ILs) and insecticides. The best-identified SIL for the adsorption of the studied insecticides corresponds to silica modified with propyltrioctylammonium chloride ([Si][N3888]Cl). The saturation of SILs was reached in 5 min or less, showing their fast adsorption rate towards all insecticides, in contrast with activated carbon (benchmark) that requires 40 to 60 min. The best fitting of the experimental kinetic data was achieved with the Pseudo Second-Order model, meaning that the adsorption process is controlled at the solid-liquid interface. On the other hand, the best fitting of the experimental isotherm data is given by the Freundlich isotherm model, revealing that multiple layers of insecticides onto the SIL surface may occur. The continuous removal efficiency of the best SIL ([Si][N3888]Cl) by solid-phase extraction was finally appraised, with the maximum adsorption capacity decreasing in the following sequence: imidacloprid > thiacloprid > thiamethoxam > acetamiprid. Based on real reported values, under ideal conditions, 1 g of [Si][N3888]Cl is able to treat at least 106 m3 of wastewater and water from wetland contaminated with the studied neonics. In summary, the enhanced adsorption capacity of SILs for a broad diversity of neonics was demonstrated, reinforcing the usefulness of these materials for their removal from aqueous matrices and thus contributing to preventing their introduction into the ecosystems and reducing their detrimental effects in the environment and human health.


Can basic risk research help in the prevention of childhood and adolescent depression? Examining a cognitive and emotional regulation approach.
This paper aims to highlight ways in which basic research findings in the field of childhood and adolescent depression can help to inform and refine preventive intervention efforts. We selectively review basic research evidence from community, clinical, and high-risk populations that identifies cognitive mechanisms (thought processes and reactions to negative affect) and emotional regulation as key processes involved in the onset and maintenance of depression. We focus on cognitive and emotional mechanisms in order to allow comparability with the majority of current preventive interventions. A range of basic research strategies and studies are then suggested that could be employed to help the development and refinement of prevention strategies. These include the need for prospective longitudinal studies to identify causal risk and protective factors, an integration of research approaches and methods, and a focus on understanding potential aetiological heterogeneity between childhood and adolescent depression.


Postprandial Metabolite Profiles and Risk of Prediabetes in Young People: A Longitudinal Multicohort Study.
Prediabetes in young people is an emerging epidemic that disproportionately impacts Hispanic populations. We aimed to develop a metabolite-based prediction model for prediabetes in young people with overweight/obesity at risk for type 2 diabetes. In independent, prospective cohorts of Hispanic youth (discovery; n = 143 without baseline prediabetes) and predominately Hispanic young adults (validation; n = 56 without baseline prediabetes), we assessed prediabetes via 2-h oral glucose tolerance tests. Baseline metabolite levels were measured in plasma from a 2-h postglucose challenge. In the discovery cohort, least absolute shrinkage and selection operator regression with a stability selection procedure was used to identify robust predictive metabolites for prediabetes. Predictive performance was evaluated in the discovery and validation cohorts using logistic regression. Two metabolites (allylphenol sulfate and caprylic acid) were found to predict prediabetes beyond known risk factors, including sex, BMI, age, ethnicity, fasting/2-h glucose, total cholesterol, and triglycerides. In the discovery cohort, the area under the receiver operator characteristic curve (AUC) of the model with metabolites and known risk factors was 0.80 (95% CI 0.72-0.87), which was higher than the risk factor-only model (AUC 0.63 [0.53-0.73]; P = 0.001). When the predictive models developed in the discovery cohort were applied to the replication cohort, the model with metabolites and risk factors predicted prediabetes more accurately (AUC 0.70 [95% CI 40.55-0.86]) than the same model without metabolites (AUC 0.62 [0.46-0.79]). Metabolite profiles may help improve prediabetes prediction compared with traditional risk factors. Findings suggest that medium-chain fatty acids and phytochemicals are early indicators of prediabetes in high-risk youth.


[Update on Current Care Guideline: Migraine].
Mild migraine attack can be treated with acetaminophen or NSAIDs either alone or combined with metoclopramide. In severe and devastating attacks triptans should be taken immediately, and not afterwards, when first line NSAIDs have proven ineffektive. No significant differences between triptans can be shown in clinical practice, when recommended doses are used. Opioid analgesics should not be used in the treatment of migraine. The recommended drugs for migraine attacks in children are acetaminophen or ibuprophen. Also intranasal sumatriptan can be used. The first line drugs for prophylactic treatment of migraine are non-ISA betablockers or candesartan and amitriptyline.


Experimental inhalation of chlorine gas produced with a different method; effects of N-acetyl cysteine on acute pulmonary damage.
ABSTRACT The two most common gas inhalation injuries encountered in emergency departments are carbon monoxide and chlorine inhalations. In this study, chlorine was produced through a method different to the previous experimental models. Rats were subjected to inhale chlorine, after which the effects of N-acetylcysteine on pulmonary damage were evaluated. A total of 50 rats were equally divided into five groups. Group 1 received nothing. Groups 2 and 3 were taken as 6 h, groups 4 and 5 as 24 h control and N-acetylcysteine groups, respectively. Firstly, 200 ppm chlorine gas was given for 20 min. Then, 40 mg/kg N-acetylcysteine was given intraperitoneally. The same procedure with the same dose was repeated 3 h later. The same procedures were applied to the control group but this time saline was used. Tissue samples of lungs were taken. Glutathione levels of the rats in the N-acetylcysteine group sacrificed at 24 h were significantly higher than those of the control group. Histopathological evaluation of the pulmonary tissues of the rats sacrificed at 6 and 24 h revealed mild-to-moderate degrees of tissue damage. The degree of tissue damage at 6 h and 24 h N-acetylcysteine group rats was lower than that in the control group. As a result, tissue damage resulting from experimental chlorine inhalation can be alleviated by N-acetylcysteine. This is mainly the result of the antioxidant effects of the N-acetylcysteine.


Oligonucleotide probes for the identification of three algal groups by dot blot and fluorescent whole-cell hybridization.
Photosynthetic pico- and nanoplankton dominate phytoplankton biomass and primary production in the oligotrophic open ocean. Species composition, community structure, and dynamics of the eukaryotic components of these size classes are poorly known primarily because of the difficulties associated with their preservation and identification. Molecular techniques utilizing 18S rRNA sequences offer a number of new and rapid means of identifying the picoplankton. From the available 18S rRNA sequence data for the algae, we designed new group-specific oligonucleotide probes for the division Chlorophyta, the division Haptophyta, and the class Pelagophyceae (division Heterokonta). Dot blot hybridization with polymerase chain reaction amplified target rDNA and whole-cell hybridization assays with fluorescence microscopy and flow cytometry were used to demonstrate probe specificity. Hybridization results with representatives from seven algal classes supported the phylogenetic affinities of the cells. Such group- or taxon-specific probes will be useful in examining community structure, for identifying new algal isolates, and for in situ detection of these three groups, which are thought to be the dominant algal taxa in the oligotrophic regions of the ocean.


Breast-feeding and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers.
Several studies have reported that the risk of breast cancer decreases with increasing duration of breast-feeding. Whether breast-feeding is associated with a reduced risk of hereditary breast cancer in women who carry deleterious BRCA1 and BRCA2 mutations is currently unknown. We conducted a case-control study of women with deleterious mutations in either the BRCA1 or the BRCA2 gene. Study participants, drawn from an international cohort, were matched on the basis of BRCA mutation (BRCA1 [n = 685] or BRCA2 [n = 280]), year of birth (+/-2 years), and country of residence. The study involved 965 case subjects diagnosed with breast cancer and 965 control subjects who had no history of breast or ovarian cancer. Information on pregnancies and breast-feeding practices was derived from a questionnaire administered to the women during the course of genetic counseling. Conditional logistic regression analyses were used to estimate odds ratios (ORs) for the risk of breast cancer. All statistical tests were two-sided. Among women with BRCA1 mutations, the mean total duration of breast-feeding was statistically significantly shorter for case subjects than for control subjects (6.0 versus 8.7 months, respectively; mean difference = 2.7 months, 95% confidence interval [CI] = 1.4 to 4.0; P<.001). The total duration of breast-feeding was associated with a reduced risk of breast cancer (for each month of breast-feeding, OR = 0.98, 95% CI = 0.97 to 0.99; P(trend)<.001). Women with BRCA1 mutations who breast-fed for more than 1 year were less likely to have breast cancer than those who never breast-fed (OR = 0.55, 95% CI = 0.38 to 0.80; P =.001), although no such association was seen for BRCA2 (OR = 0.95, 95% CI = 0.56 to 1.59; P =.83). Women with deleterious BRCA1 mutations who breast-fed for a cumulative total of more than 1 year had a statistically significantly reduced risk of breast cancer.


Reverse attenuation in interaction terms due to covariate measurement error.
Covariate measurement error may cause biases in parameters of regression coefficients in generalized linear models. The influence of measurement error on interaction parameters has, however, only rarely been investigated in depth, and if so, attenuation effects were reported. In this paper, we show that also reverse attenuation of interaction effects may emerge, namely when heteroscedastic measurement error or sampling variances of a mismeasured covariate are present, which are not unrealistic scenarios in practice. Theoretical findings are illustrated with simulations. A Bayesian approach employing integrated nested Laplace approximations is suggested to model the heteroscedastic measurement error and covariate variances, and an application shows that the method is able to reveal approximately correct parameter estimates.


Remembering object position in the absence of vision: egocentric, allocentric, and egocentric decentred frames of reference.
In three experiments we examined whether memory for object locations in the peri-personal space in the absence of vision is affected by the correspondence between encoding and test either of the body position or of the reference point. In particular, the study focuses on the distinction between different spatial representations, by using a paradigm in which participants are asked to relocate objects explored haptically. Three frames of reference were systematically compared. In experiment 1, participants relocated the objects either from the same position of learning by taking as reference their own body (centred egocentric condition) or from a 90 degrees decentred position (allocentric condition). Performance was measured in terms of linear distance errors and angular distance errors. Results revealed that the allocentric condition was more difficult than the centred egocentric condition. In experiment 2, participants performed either the centred egocentric condition or a decentred egocentric condition, in which the body position during the test was the same as at encoding (egocentric) but the frame of reference was based on a point decentred by 90 degrees. The decentred egocentric condition was found to be more difficult than the centred egocentric condition. Finally, in experiment 3, participants performed in the decentred egocentric condition or the allocentric condition. Here, the allocentric condition was found to be more difficult than the decentred egocentric condition. Taken together, the results suggest that also in the peripersonal space and in the absence of vision different frames of reference can be distinguished. In particular, the decentred egocentric condition involves a frame of reference which seems to be neither allocentric nor totally egocentric.


The effects of TAK-875, a selective G protein-coupled receptor 40/free fatty acid 1 agonist, on insulin and glucagon secretion in isolated rat and human islets.
G protein-coupled receptor 40 (GPR40)/free fatty acid 1 (FFA1) is a G protein-coupled receptor involved in free fatty acid-induced insulin secretion. To analyze the effect of our novel GPR40/FFA1-selective agonist, [(3S)-6-({2',6'-dimethyl-4'-[3-(methylsulfonyl)propoxy]biphenyl-3-yl}methoxy)-2,3-dihydro-1-benzofuran-3-yl]acetic acid hemi-hydrate (TAK-875), on insulin and glucagon secretion, we performed hormone secretion assays and measured intracellular Ca²⁺ concentration ([Ca²⁺](i)) in both human and rat islets. Insulin and glucagon secretion were measured in static and dynamic conditions by using groups of isolated rat and human pancreatic islets. [Ca²⁺](i) was recorded by using confocal microscopy. GPR40/FFA1 expression was measured by quantitative polymerase chain reaction. In both human and rat islets, TAK-875 enhanced glucose-induced insulin secretion in a glucose-dependent manner. The stimulatory effect of TAK-875 was similar to that produced by glucagon-like peptide-1 and correlated with the elevation of β-cell [Ca²⁺](i). TAK-875 was without effect on glucagon secretion at both 1 and 16 mM glucose in human islets. These data indicate that GPR40/FFA1 influences mainly insulin secretion in a glucose-dependent manner. The β-cell-specific action of TAK-875 in human islets may represent a therapeutically useful feature that allows plasma glucose control without compromising counter-regulation of glucagon secretion, thus minimizing the risk of hypoglycemia.


Optical characterization of cutaneous transilluminators for eye safety.
Cutaneous transilluminators are light-emitting devices used to localize blood vessels for various medical procedures. They are often used in populations that may be at increased risk for skin burns, such as neonates and the elderly. While there is a known potential for skin burns, little is known about the ophthalmic risk from the use of these devices. This paper will report on the laboratory evaluation of the potential ocular hazards from transilluminators (TIs). Our results indicate that transilluminators which incorporate white-light LEDs have emissions that have the potential for producing injury to the retina, especially in patients who may have a reduced aversion response.


Spike-timing-based computation in sound localization.
Spike timing is precise in the auditory system and it has been argued that it conveys information about auditory stimuli, in particular about the location of a sound source. However, beyond simple time differences, the way in which neurons might extract this information is unclear and the potential computational advantages are unknown. The computational difficulty of this task for an animal is to locate the source of an unexpected sound from two monaural signals that are highly dependent on the unknown source signal. In neuron models consisting of spectro-temporal filtering and spiking nonlinearity, we found that the binaural structure induced by spatialized sounds is mapped to synchrony patterns that depend on source location rather than on source signal. Location-specific synchrony patterns would then result in the activation of location-specific assemblies of postsynaptic neurons. We designed a spiking neuron model which exploited this principle to locate a variety of sound sources in a virtual acoustic environment using measured human head-related transfer functions. The model was able to accurately estimate the location of previously unknown sounds in both azimuth and elevation (including front/back discrimination) in a known acoustic environment. We found that multiple representations of different acoustic environments could coexist as sets of overlapping neural assemblies which could be associated with spatial locations by Hebbian learning. The model demonstrates the computational relevance of relative spike timing to extract spatial information about sources independently of the source signal.


Upward communication about cancer screening: adolescent daughter to mother.
Substantial breast and cervical cancer disparities exist in the United States, particularly among African American women with low socioeconomic status. There is considerable potential for discussions about cancer prevention between mothers and daughters. However, upward communication, from child to parent, remains a relatively novel research area, and it remains unclear how receptive mothers would be to messages from their daughter about cancer, a topic that may be considered culturally inappropriate for daughters to initiate. In this study, the authors simulated cancer message delivery to daughters and then conducted direct observation of daughters as they recalled and shared the message with their mother or female elder. The authors found that daughters were able to successfully recall and deliver a cancer appeal to their mother and mothers were generally receptive to this message. Not only did mothers listen to their daughters' appeals, but also daughters' knowledge of cancer was considerably improved by the opportunity to educate her female elder. Moreover, daughters' nonverbal communication suggested a surprisingly relaxed demeanor. The potential of young people to have an effect on the screening behavior of their female elders is very promising in terms of reducing cancer disparities.


Cyanotic breath-holding spells in children respond to adenotonsillectomy for sleep-disordered breathing.
Children with breath-holding (BH) spells may demonstrate sleep-disordered breathing (SDB) during polysomnography. We studied five young children with cyanotic spells retrospectively and found both SDB and a response to adenotonsillectomy. We therefore proceeded with a prospective investigation of treatment for SDB in children with comorbid cyanotic spells. Nineteen children with cyanotic BH spells were identified and enrolled in the prospective study. Parents chose either treatment or observation. Fourteen children underwent complete SDB evaluation and treatment trials while five selected observation only (control group). Sleep and sleep-surgery specialist evaluation and polysomnography revealed the presence of a narrow upper-airway and an abnormal respiratory disturbance index in all 14 children. Nasal CPAP was not successful, but adenotonsillectomy performed near 14 months of age eliminated SDB. BH spells were eliminated 1 month after surgery, while they persisted to the end of the study (24 months of age) in the control group. In conclusion, the presence of cyanotic BH should prompt investigation and polysomnography for possible SDB. Independent treatment of SDB may hasten resolution of BH spells in these cases.


A sensitivity metric and software to guide the analysis of soft films measured by a quartz crystal microbalance.
This article introduces a set of mathematical and computational tools for use with a quartz crystal microbalance (QCM) to aid in experimental planning and data interpretation. The optimisation tools are based on a metric we term the total parameter matrix sensitivity (TPM-sensitivity). TPM-sensitivity is defined mathematically as the Jacobian determinant of a QCM's responses (e.g., frequency change or dissipation/bandwidth change for a given harmonic) with respect to changes in the physical properties of a soft film and surrounding solution (e.g., density or viscosity). Large TPM-sensitivity values denote conditions where the sensor responses are not only large but also allow the selected unknown physical properties to be mathematically decoupled. In some cases, the viscoelastic properties of an adlayer can be determined using only frequency responses. We validated this method using experimentally obtained data of an ageing adlayer of the enzyme bilirubin oxidase from Myrothecium verrucaria. Fits to these measurements produced more realistic film parameters when responses, including frequency-only combinations, were selected to maximise TPM sensitivity. We provide documented MATLAB code with a graphical user interface to enable other QCM users to employ this analysis. The current software can be applied to any single, homogeneous adlayer that obeys a Kelvin-Voigt viscoelastic model and sits under a semi-infinite Newtonian fluid. Only initial estimates of the film values are required, with the analysis providing guidance and predictions, allowing users to create testable hypothesis and determine the physical changes on the surface rather than have pre-existing values for them.


Plasma levels of carotenoids, retinol and tocopherol and the risk of gastric cancer in Japan: a nested case-control study.
Fruits and vegetables have been suggested to confer protection against diseases such as cancer through the effects of antioxidants, often represented by carotenoids. We investigated the impact of carotenoids, retinol and tocopherol on gastric cancer development in a large nested case-control study among Japanese with known Helicobacter pylori infection status. A total of 36 745 subjects aged 40-69 in the Japan Public Health Center-based Prospective Study who responded to the baseline questionnaire and provided blood samples in 1990-1995 were followed until 2004. Plasma levels of carotenoids in 511 gastric cancer cases and 511 matched controls were measured by high-performance liquid chromatography. Odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were estimated using conditional logistic regression models. Plasma level of beta-carotene was inversely associated with the risk of gastric cancer (compared with the lowest quartile: OR = 0.63, 95% CI = 0.31-0.75; OR = 0.48, 95% CI = 0.31-0.75 and OR = 0.46, 95% CI = 0.28-0.75, for quartile 2, 3 and 4, respectively, P(trend) < 0.01). Inverse associations were evident in men for alpha-carotene (P(trend) = 0.04) and beta-carotene (P(trend) < 0.01), but not in women, who had relatively higher plasma levels compared with men. We found no statistically significant association between plasma levels of lutein/zeaxanthin, lycopene, retinol, alpha- or gamma-tocopherol and gastric cancer risk. Our findings suggest that those who have very low plasma levels of alpha-carotene and beta-carotene are at a higher risk of gastric cancer.


Learning to read and spell in Persian: a cross-sectional study from Grades 1 to 4.
We investigated the reading and spelling development of 140 Persian children attending Grades 1-4 in Iran. Persian has very consistent letter-sound correspondences, but it varies in transparency because 3 of its 6 vowel phonemes are not marked with letters. Persian also varies in spelling consistency because 6 phonemes have more than one orthographic representation. We tested whether lexicality effects-an advantage of words over nonwords-would be affected be reading transparency and spelling consistency. We found that children became more efficient readers and spellers across grades, with the greatest growth occurring between Grades 1 and 2. For reading, lexicality effects were present with transparent words starting in Grade 2, but lexicality effects with opaque words were not yet present in Grade 4. As expected, the size of transparency effects for reading decreased across grades. For spelling, however, there was no lexicality effect for either consistent or inconsistent words. Moreover, consistency effects were large and did not decrease systematically across grades. Most interesting from a developmental perspective was the finding that both reading transparency and spelling polygraphy affected reading as well as spelling in Grades 1 and 2, but the word characteristics had differential effects as a function of literacy task in Grades 3 and 4. This pattern highlights the vulnerability of children's representations and processes during the early phases of acquisition as well as the rapidity with which representations and processes become specialized as a function of the literacy task at hand.


What can comparative effectiveness research contribute to integrative health in international perspective?
The interest in Comparative Effectiveness Research (CER) in the international community is growing. A panel titled "What Can Comparative Effectiveness Research Contribute to Integrative Health in International Perspective?" took place at the 3rd International Research Congress on Integrative Medicine and Health in Portland, Oregon, in 2012. The presentations at this panel highlighted different perspectives on CER, including the funders' and the stakeholders' perspectives from the United States, as well as experiences with economic evaluations from Australia and pragmatic trials in Europe. The funders' perspective emphasized the need for innovation and controlling costs in large-scale studies. The stakeholder's perspective stressed the need to gather the input of stakeholders in shaping the framework for more informative, more decision-maker-driven research. Several examples of cost-effectiveness analyses were offered from Australia. The importance of balancing rigor and pragmatism was also discussed in a presentation of the efficacy-effectiveness continuum. A wide-ranging discussion explored additional questions concerning the translation of evidence into practice; the effect of pragmatic trials on funding or policy; evidentiary distinctions between and among pragmatic trials and traditional randomized clinical trials; and the multiple roles of stakeholders, particularly in generating new information and knowledge. The presentations and discussions showed that more development of methods is needed. This includes developments on study design and statistical approaches, as well as methods for stakeholder involvement and mechanisms to bring these results into practice.


Impact of calcium intake on body mass index in Venezuelan adolescents.
The prevalence of overweight and obesity is increasing worldwide, affecting approximately 15% of adolescents in Venezuela, 17% in United States, and more than 30% in Mexico and Puerto Rico. Recent studies have shown that dietary calcium and dairy intake are associated with body fat. These studies show that a high calcium intake results in low body mass index (BMI). Therefore, the objective of the present study is to relate calcium intake from foods rich in calcium-rich foods to body weight and BMI in a random sample of 100 adolescents, aged 13-18 years. Anthropometric measurements (weight and height) were obtained for each participant, who also completed a food frequency questionnaire (FFQ), modified with calcium-rich foods. Dietary calcium consumption was 1076+/-534 mg/d among the adolescents, which represented an adequacy of 90%. A negative and significant association was found between calcium intake and BMI in the boys aged 13-15 years (r=-0.39, p<0.05). This population subgroup exhibited the widest range of BMI values among all groups evaluated. This correlation was not found among the older boys (aged 16-18 years) or girls, in which BMI was in the normal range and with relatively high calcium intake. In conclusion, we found that high calcium intake in younger boys was related to a lower BMI. A high calcium intake, not only helps to maintain a healthy body weight, but also is essential for acquiring peak bone mass in this crucial stage of life.


Epidemiology of suicide in Austria during 2000-2010: potential years of life lost: time for the national suicide prevention program.
This article investigates suicide rates from 2000 to 2010 in Austria, a country with now average rates that had started to decline in the mid-80s. Rates declined in the observed period, to an average of 26.1 per 100,000 persons for men, 8.2 for women, and 16.9 in the general population. The decrease was found in all age-groups, but more marked in women, with a reduction by 26.3 % compared with the previous decade than in men (20.0 % reduction). Hanging still is the most common method, 49.1 % for men and 35.0 % for women, although also on the decline. Furthermore, person years of lost life were calculated, also reflecting a decrease from 40,702 years in 2000 to 29,883 in 2010. Altogether, 372,551 years of life were lost by suicide in Austria in the period 2000-2010, 277,998 years among men and 94,553 years among women. Concerning the still observed increase in old age-groups and the huge amount of lost life years, it is argued that implementation of the National Suicide Prevention Programme for Austria is strongly needed.


New evidence for self-medication in bonobos: Manniophyton fulvum leaf- and stemstrip-swallowing from LuiKotale, Salonga National Park, DR Congo.
The swallowing of entire leaves by apes across Africa without chewing has been observed for over 40 plant species. Here we add evidence for (a) a new site, LuiKotale where leaf-swallowing of Manniophyton fulvum (Euphorbiaceae) is observed in bonobos, (b) a so far unreported ingestion of unchewed stemstrips of M. fulvum, we name stemstrip-swallowing; and (c) a test of some of the requirements put forward by Huffman for the assessment of plants ingested for medical purpose. As ecological correlates we analyzed M. fulvum phenological data and examined 1,094 dung piles collected between 2002 and 2009. By that we assessed availability and choice of leaves. In addition, we provide the first full description of the behavior related to this plant species' use by chimpanzees or bonobos using 56 bouts of M. fulvum ingestion observed between October 2007 and February 2010. With these data we tested and met 4 of the 6 requirements given by Huffman, supporting ingestion of this species as self-medication. Despite species' year-round availability and abundance, M. fulvum was ingested only at specific times, in very small amounts, and by a small proportion of individuals per party. In the absence of our own parasitological data, we used M. fulvum swallowing as evidence for parasite infestation, and seasonality as a proxy for stressors underlying seasonal fluctuation and impacting immune responses. Using these indirect factors available, we investigated conditions for a parasite to develop to its infective stage as well as conditions for the host to cope with infections. Both rain and temperature were good predictors for M. fulvum ingestion. We discuss the use of M. fulvum with respect to its hispidity and subsequent purging properties and provide insight into its ethnomedicinal uses by humans, stimulating speculations about potentially additional pharmacological effects.


In Pursuit of Error: A Survey of Uncertainty Visualization Evaluation.
Understanding and accounting for uncertainty is critical to effectively reasoning about visualized data. However, evaluating the impact of an uncertainty visualization is complex due to the difficulties that people have interpreting uncertainty and the challenge of defining correct behavior with uncertainty information. Currently, evaluators of uncertainty visualization must rely on general purpose visualization evaluation frameworks which can be ill-equipped to provide guidance with the unique difficulties of assessing judgments under uncertainty. To help evaluators navigate these complexities, we present a taxonomy for characterizing decisions made in designing an evaluation of an uncertainty visualization. Our taxonomy differentiates six levels of decisions that comprise an uncertainty visualization evaluation: the behavioral targets of the study, expected effects from an uncertainty visualization, evaluation goals, measures, elicitation techniques, and analysis approaches. Applying our taxonomy to 86 user studies of uncertainty visualizations, we find that existing evaluation practice, particularly in visualization research, focuses on Performance and Satisfaction-based measures that assume more predictable and statistically-driven judgment behavior than is suggested by research on human judgment and decision making. We reflect on common themes in evaluation practice concerning the interpretation and semantics of uncertainty, the use of confidence reporting, and a bias toward evaluating performance as accuracy rather than decision quality. We conclude with a concrete set of recommendations for evaluators designed to reduce the mismatch between the conceptualization of uncertainty in visualization versus other fields.


A descriptive analysis of patients with an emergency department diagnosis of acute pericarditis.
To describe clinical characteristics, assessment and treatment of patients diagnosed in an emergency department (ED) with acute pericarditis. A medical record review of patients with an ED diagnosis of pericarditis conducted in an adult tertiary hospital over a 5-year period. Variables collected included pain characteristics, associated symptoms, physical examination findings, investigation results, ED treatment and disposition. 179 presentations were included, with 73.9% men and a mean age of 38.8 years. The majority of patients described pleuritic chest pain worse with inspiration with half characterising the pain as sharp or stabbing, with others describing tightness, dullness or cramping. Radiation to the left shoulder occurred in 2.8% and change of pain with posture occurred in 46.4%. A pericardial rub was documented in 19 presentations. All patients had an ECG recorded with ST segment elevation present in 69.3% and PR segment depression in 49.2%. Nearly 90% of patients had troponin testing but only 6.4% of these were positive. Only 8.1% of cases were treated with colchicine. No patients required pericardiocentesis. Patients with high-risk factors were more likely to have previous pericarditis, dyspnoea, nausea, abnormal investigation results, treatment with colchicine and admission to hospital. However, 16.9% of patients without risk factors were admitted, and 46.9% of patients with at least one risk factor were discharged. Pericarditis may not follow the classical clinical description. Admission and discharge decisions appear to relate to individual clinical characteristics rather than known risk factors. Use of colchicine for treatment in ED is infrequent.


The effect of non-insulin-dependent diabetes mellitus and obesity on glucose transport and phosphorylation in skeletal muscle.
Defects of glucose transport and phosphorylation may underlie insulin resistance in obesity and non-insulin-dependent diabetes mellitus (NIDDM). To test this hypothesis, dynamic imaging of 18F-2-deoxy-glucose uptake into midthigh muscle was performed using positron emission tomography during basal and insulin-stimulated conditions (40 mU/m2 per min), in eight lean nondiabetic, eight obese nondiabetic, and eight obese subjects with NIDDM. In additional studies, vastus lateralis muscle was obtained by percutaneous biopsy during basal and insulin-stimulated conditions for assay of hexokinase and citrate synthase, and for immunohistochemical labeling of Glut 4. Quantitative confocal laser scanning microscopy was used to ascertain Glut 4 at the sarcolemma as an index of insulin-regulated translocation. In lean individuals, insulin stimulated a 10-fold increase of 2-deoxy-2[18F]fluoro-D-glucose (FDG) clearance into muscle and significant increases in the rate constants for inward transport and phosphorylation of FDG. In obese individuals, the rate constant for inward transport of glucose was not increased by insulin infusion and did not differ from values in NIDDM. Insulin stimulation of the rate constant for glucose phosphorylation was similar in obese and lean subjects but reduced in NIDDM. Insulin increased by nearly twofold the number and area of sites labeling for Glut 4 at the sarcolemma in lean volunteers, but in obese and NIDDM subjects translocation of Glut 4 was attenuated. Activities of skeletal muscle HK I and II were similar in lean, obese and NIDDM subjects. These in vivo and ex vivo assessments indicate that impaired glucose transport plays a key role in insulin resistance of NIDDM and obesity and that an additional impairment of glucose phosphorylation is evident in the insulin resistance of NIDDM.


Denitrification at pH 4 by a soil-derived Rhodanobacter-dominated community.
Soil denitrification is a major source of nitrous oxide emission that causes ozone depletion and global warming. Low soil pH influences the relative amount of N₂O produced and consumed by denitrification. Furthermore, denitrification is strongly inhibited in pure cultures of denitrifying microorganisms below pH 5. Soils, however, have been shown to denitrify at pH values as low as pH 3. Here we used a continuous bioreactor to investigate the possibility of significant denitrification at low pH under controlled conditions with soil microorganisms and naturally available electron donors. Significant NO₃⁻ and N₂O reduction were observed for 3 months without the addition of any external electron donor. Batch incubations with the enriched biomass showed that low pH as well as low electron donor availability promoted the relative abundance of N₂O as denitrification end-product. Molecular analysis of the enriched biomass revealed that a Rhodanobacter-like bacterium dominated the community in 16S rRNA gene libraries as well as in FISH microscopy during the highest denitrification activity in the reactor. We conclude that denitrification at pH 4 with natural electron donors is possible and that a Rhodanobacter species may be one of the microorganisms involved in acidic denitrification in soils.


Health Care Transition in Young Adults With Type 1 Diabetes: Perspectives of Adult Endocrinologists in the U.S.
Young adults with type 1 diabetes transitioning from pediatric to adult care are at risk for adverse outcomes. Our objective was to describe experiences, resources, and barriers reported by a national sample of adult endocrinologists receiving and caring for young adults with type 1 diabetes. We fielded an electronic survey to adult endocrinologists with a valid e-mail address identified through the American Medical Association Physician Masterfile. We received responses from 536 of 4,214 endocrinologists (response rate 13%); 418 surveys met the eligibility criteria. Respondents (57% male, 79% Caucasian) represented 47 states; 64% had been practicing >10 years and 42% worked at an academic center. Only 36% of respondents reported often/always reviewing pediatric records and 11% reported receiving summaries for transitioning young adults with type 1 diabetes, although >70% felt that these activities were important for patient care. While most respondents reported easy access to diabetes educators (94%) and dietitians (95%), fewer (42%) reported access to mental health professionals, especially in nonacademic settings. Controlling for practice setting and experience, endocrinologists without easy access to mental health professionals were more likely to report barriers to diabetes management for young adults with depression (odds ratio [OR] 5.3; 95% CI 3.4, 8.2), substance abuse (OR 3.5; 95% CI 2.2, 5.6), and eating disorders (OR 2.5; 95% CI 1.6, 3.8). Our findings underscore the need for enhanced information transfer between pediatric and adult providers and increased mental health referral access for young adults with diabetes post-transition.