Neural correlates of anticipation risk reflect risk preferences.
Individual risk preferences have a large influence on decisions, such as financial investments, career and health choices, or gambling. Decision making under risk has been studied both behaviorally and on a neural level. It remains unclear, however, how risk attitudes are encoded and integrated with choice. Here, we investigate how risk preferences are reflected in neural regions known to process risk. We collected functional magnetic resonance images of 56 human subjects during a gambling task (Preuschoff et al., 2006). Subjects were grouped into risk averters and risk seekers according to the risk preferences they revealed in a separate lottery task. We found that during the anticipation of high-risk gambles, risk averters show stronger responses in ventral striatum and anterior insula compared to risk seekers. In addition, risk prediction error signals in anterior insula, inferior frontal gyrus, and anterior cingulate indicate that risk averters do not dissociate properly between gambles that are more or less risky than expected. We suggest this may result in a general overestimation of prospective risk and lead to risk avoidance behavior. This is the first study to show that behavioral risk preferences are reflected in the passive evaluation of risky situations. The results have implications on public policies in the financial and health domain.


Oxytetracycline and penicillin-G residues in cattle slaughtered in south-western Nigeria: implications for livestock disease management and public health.
After the discovery of indiscriminate antibiotic use in ready-for-slaughter cattle in south-western Nigeria, 90 tissue samples from randomly selected slaughtered cattle were evaluated for oxytetracycline and penicillin-G residues using high performance liquid chromatography and the data analysed by one-way Analysis of variance (ANOVA). The findings revealed residues of oxytetracycline (kidney: 9.47 µ/kg ± 3.24 µ/kg; liver: 12.73 µ/kg ± 4.39 µ/kg; muscle: 16.17 µ/kg ± 5.52 µ/kg) and penicillin-G (kidney: 6.27 µ/kg ± 2.46 µ/kg; liver: 8.5 µ/kg ± 2.80 µ/kg; muscle: 11.67 µ/kg ± 2.94 µ/kg) in all tissues screened. Significantly high levels (oxytetracycline: F = 16.77; penicillin-G: F = 29.38) were, however, found in muscles, followed by liver and then kidney – findings confirming recent antibiotic administration to the animals before slaughter. The dietary intakes through the tissues screened were 0.024% (oxytetracycline) and 0.017% (penicillin-G) of the acceptable daily intake (ADI). Although the concentrations in the tissues screened were below the maximum residue limits despite recent administration of these antibiotics before slaughter, the lower concentrations are suggestive of the probable low dosages often administered by those involved in indiscriminate use of antibiotics. This therefore raises serious concerns for the livestock industry as well as human health, given the resultant emergence and spread of resistant strains of bacterial pathogens that could ensue from prolonged use of low dosages of antibiotics. Additionally, the lower concentrations of the daily intakes notwithstanding, the plausible exposure to these antibiotics from other food sources is a cause for concern. Since antimicrobial misuse and its consequent effects are not just a problem limited to Nigeria but also a concern in sub-Saharan Africa, the need for national and international stakeholder intervention is emphasised.


Technique for measuring visibility.
A technique for measuring atmospheric extinction of light, or visibility, from the backscattered signal of a modulated cw laser is presented. The extinction coefficient is contained in the amplitude and phase of the return signal and can be extracted in several ways from certain amplitude and/or phase measurements. No assumption about a relationship between the extinction coefficient and backscattering coefficient need be made.


Addressing NCDs: A unifying agenda for sustainable development.
Despite the mounting evidence that they impede social and economic development, increase inequalities, and perpetuate poverty, Noncommunicable diseases (NCDs) remain largely absent from the agendas of major development assistance initiatives. In addition, fundamental changes are developing in patterns of development assistance for health, and more of the burden for fighting NCDs is being placed on domestic budgets, thus increasing pressure on the most vulnerable countries. The paper argues, however, that a new day is coming. With the inclusion of NCDs and related targets in the 2030 Agenda for Sustainable Development, there is an unprecedented opportunity to explore linkages among the sustainable development goals, enhance policy coherence and advance the NCD agenda as part of sustainable development. International development partners (bilateral and multilateral) can help in this important effort to address NCDs and their shared risk factors by providing catalytic support to countries that are particularly vulnerable in terms of the disease burden but lack the resources (human, financial) and institutional arrangements to meet their commitments at national, regional, and global levels.


Sibling involvement in childhood chronic heart disease through a bead program.
In interviews with parents for the evaluation of a cardiac ward programme in a children's hospital, a number of parents mentioned the role of the Heart Beads Program in including siblings in the hospitalisation of the child with congenital heart condition (CHD). Inclusion of siblings in the events surrounding the child with the cardiac condition was of two kinds: (a) touching and explaining about the beads and the child's condition and (b) involvement in collecting and threading the beads. Discussion of the needs of siblings suggests that inclusion of siblings in activities related to the care and understanding of the CHD child as well as the creation and shaping of the family narrative is important. These cases illustrate the different ways in which siblings are involved and acknowledged and how involvement can be facilitated by a programme like Heart Beads.


Vocal fold fibroblasts immunoregulate activated macrophage phenotype.
Recent evidence suggests that fibroblasts play a critical role in regulating inflammation during wound healing because they express several inflammatory mediators in response to bacteria. The objective of this study was to analyze the effects of lipopolysaccharide (LPS) on the immunomodulatory properties of vocal fold fibroblasts (VFFs) derived from polyps, scar and normal tissue co-cultured with macrophages, to provide insight into their interactions during the inflammatory process. Fibroblasts were co-cultured with CD14+ monocytes and after 7 days, wells were treated with LPS for 24 and 72 h. Culture supernatants were collected and concentrations of TNF-α, IL-6, IL-8, IL-10, IL-12, IL-1β and MCP-1 were quantified by ELISA. Normal VFF and CD14+ monocultures were used as controls. Twenty-four hours after LPS activation, macrophages co-cultured with polyp VFF had significantly increased expression of TNF-α, IL-1β, IL-12 and IL-10 compared to controls (p<0.0001). In contrast, macrophages co-cultured with scar VFF had significantly lower expression of TNF-α, IL-1β and IL-12 with significantly higher IL-10 compared to control (p<0.0001). After 72 h, macrophages co-cultured with polyp VFF increased expression of TNF-α, IL-1β, IL-10, IL-6, IL-8, MCP-1 and TGF-β (p<0.01) and macrophages co-cultured with scar VFF significantly decreased their expression of IL-1β and IL-12 compared to control (p<0.0001). Scar VFF at both time points produced significantly lower levels of IL-8, MCP-1, IL-6 and TGF-β compared to controls (p<0.05). Based on our findings, VFF and macrophages secrete several inflammatory mediators that modify their diverse functions. Polyp and scar VFF may play a role in regulating abnormal inflammatory responses, which could result in excessive ECM deposition that disrupts the function of the vocal folds.


Pancreatic cancer: incidence, treatment and survival trends--1175 cases in Calvados (France) from 1978 to 2002.
To assess the trends in incidence, therapeutic modalities and survival of pancreatic cancer between 1978 and 2002 in a well-defined population, as recorded in the Calvados digestive cancer registry database. All patients living in Calvados with a diagnosis of pancreatic cancer were registered. Clinical data and treatment modalities were prospectively recorded. This 25-year database was divided into five 5-year periods. Data were compared using log-rank tests and the Cox model. A total of 1175 cases of pancreatic cancer (617 men, 558 women) were registered. Its incidence increased with an average annual coefficient of +2.8% in men and +5.1% in women. Therapeutic modalities changed over the five time periods: surgical resection increased from 6.8 to 13.4% (median survival 15 months) while radiation therapy and/or chemotherapy also increased from 5.5 to 13.2%. Palliative surgery decreased from 54.6 to 32.0% and favored interventional endoscopic techniques. Postoperative mortality decreased significantly. Survival increased significantly over the five time periods, although the median survival time remained stable (4 months). From 1978 to 2002, pancreatic cancer incidence increased in Calvados (France). Therapeutic modalities changed, with endoscopic treatments preferred over palliative surgery. The improvement in survival could be explained by the decrease in postoperative mortality.


Exploring the cellular activity of camptothecin-triple-helix-forming oligonucleotide conjugates.
Topoisomerase I is a ubiquitous DNA-cleaving enzyme and an important therapeutic target in cancer chemotherapy for camptothecins (CPTs). These drugs stimulate DNA cleavage by topoisomerase I but exhibit little sequence preference, inducing toxicity and side effects. A convenient strategy to confer sequence specificity consists of the linkage of topoisomerase poisons to DNA sequence recognition elements. In this context, triple-helix-forming oligonucleotides (TFOs) covalently linked to CPTs were investigated for the capacity to direct topoisomerase I-mediated DNA cleavage in cells. In the first part of our study, we showed that these optimized conjugates were able to regulate gene expression in cells upon the use of a Photinus pyralis luciferase reporter gene system. Furthermore, the formation of covalent topoisomerase I/DNA complexes by the TFO-CPT conjugates was detected in cell nuclei. In the second part, we elucidated the molecular specificity of topoisomerase I cleavage by the conjugates by using modified DNA targets and in vitro cleavage assays. Mutations either in the triplex site or in the DNA duplex receptor are not tolerated; such DNA modifications completely abolished conjugate-induced cleavage all along the DNA. These results indicate that these conjugates may be further developed to improve chemotherapeutic cancer treatments by targeting topoisomerase I-induced DNA cleavage to appropriately chosen genes.


Mammalian evolution may not be strictly bifurcating.
The massive amount of genomic sequence data that is now available for analyzing evolutionary relationships among 31 placental mammals reduces the stochastic error in phylogenetic analyses to virtually zero. One would expect that this would make it possible to finally resolve controversial branches in the placental mammalian tree. We analyzed a 2,863,797 nucleotide-long alignment (3,364 genes) from 31 placental mammals for reconstructing their evolution. Most placental mammalian relationships were resolved, and a consensus of their evolution is emerging. However, certain branches remain difficult or virtually impossible to resolve. These branches are characterized by short divergence times in the order of 1-4 million years. Computer simulations based on parameters from the real data show that as little as about 12,500 amino acid sites could be sufficient to confidently resolve short branches as old as about 90 million years ago (Ma). Thus, the amount of sequence data should no longer be a limiting factor in resolving the relationships among placental mammals. The timing of the early radiation of placental mammals coincides with a period of climate warming some 100-80 Ma and with continental fragmentation. These global processes may have triggered the rapid diversification of placental mammals. However, the rapid radiations of certain mammalian groups complicate phylogenetic analyses, possibly due to incomplete lineage sorting and introgression. These speciation-related processes led to a mosaic genome and conflicting phylogenetic signals. Split network methods are ideal for visualizing these problematic branches and can therefore depict data conflict and possibly the true evolutionary history better than strictly bifurcating trees. Given the timing of tectonics, of placental mammalian divergences, and the fossil record, a Laurasian rather than Gondwanan origin of placental mammals seems the most parsimonious explanation.


Different Muscle Action Training Protocols on Quadriceps-Hamstrings Neuromuscular Adaptations.
The aim of this study was to compare three specific concentric and eccentric muscle action training protocols on quadriceps-hamstrings neuromuscular adaptations. Forty male volunteers performed 6 weeks of training (two sessions/week) of their dominant and non-dominant legs on an isokinetic dynamometer. They were randomly assigned to one of four groups; concentric quadriceps and concentric hamstrings (CON/CON, n=10), eccentric quadriceps and eccentric hamstrings (ECC/ECC, n=10), concentric quadriceps and eccentric hamstrings (CON/ECC, n=10), or no training (CTRL, n=10). Intensity of training was increased every week by decreasing the angular velocity for concentric and increasing it for eccentric groups in 30°/s increments. Volume of training was increased by adding one set every week. Dominant leg quadriceps and hamstrings muscle thickness, muscle quality, muscle activation, muscle coactivation, and electromechanical delay were tested before and after training. Results revealed that all training groups similarly increased MT of quadriceps and hamstrings compared to control (p<0.05). However, CON/ECC and ECC/ECC training elicited a greater magnitude of change. There were no significant differences between groups for all other neuromuscular variables (p>0.05). These findings suggest that different short-term muscle action isokinetic training protocols elicit similar muscle size increases in hamstrings and quadriceps, but not for other neuromuscular variables. Nevertheless, effect sizes indicate that CON/ECC and ECC/ECC may elicit the greatest magnitude of change in muscle hypertrophy.


Atrial flutter and nonconducted bigeminy premature atrial contraction in a neonate with cardiac rhabdomyoma.
During the neonatal period the majority of cardiac tumors seen are rhabdomyomas, and the clinical manifestations are notably variable. Symptoms of rhabdomyoma depend on the presence of intracardiac obstructions, myocardial involvement, or rhythm disturbances. Most cardiac rhabdomyomas regress in follow-up, but some need medical/surgical intervention during the neonatal period as a result of resistant atrial or ventricular arrhythmia. The present case study is a description of an 8-day-old neonate with atrial bigeminy that caused nonconducted premature pulse-related bradycardia, and cardiac rhabdomyoma-related resistant atrial flutter that were detected and successfully treated.


Breast cancer recurrence in older women five to ten years after diagnosis.
Little is known about the risk of recurrence >5 years after diagnosis among older breast cancer survivors. A community-based population of women >or=65 years diagnosed with early-stage breast cancer who survived disease free for 5 years was followed for 5 additional years or until a diagnosis of breast cancer recurrence, second primary, death, or loss to follow-up. These 5-year disease-free survivors (N = 1,277) had primary breast cancers that were node negative (77%) and estrogen receptor positive or unknown (86%). Five percent (n = 61) developed a recurrence between 5 and 10 years after diagnosis: 25% local, 9.8% regional, and 66% distant. Women who were node positive [hazard ratio (HR), 3.9; 95% confidence interval (95% CI), 1.5-10], had poorly differentiated tumors (HR, 2.5; 95% CI, 0.9-6.6), or who received breast conserving surgery without radiation therapy (HR, 2.4; 95% CI, 1.0-5.8) had higher recurrence rates compared with node negative, well differentiated, and receipt of mastectomy, respectively. Not receiving adjuvant tamoxifen, compared with receiving adjuvant tamoxifen, was also positively associated with late recurrence among women with estrogen receptor-positive/unknown tumors. Although relatively few women experience a late recurrence, most recurrences present as advanced disease, which is difficult to treat in older women. This study of late recurrence emphasizes that the risk, although small, is not negligible even in this group at high risk of death due to competing causes.


Challenges and strategies in transcriptome assembly and differential gene expression quantification. A comprehensive in silico assessment of RNA-seq experiments.
Transcriptome Shotgun Sequencing (RNA-seq) has been readily embraced by geneticists and molecular ecologists alike. As with all high-throughput technologies, it is critical to understand which analytic strategies are best suited and which parameters may bias the interpretation of the data. Here we use a comprehensive simulation approach to explore how various features of the transcriptome (complexity, degree of polymorphism π, alternative splicing), technological processing (sequencing error ε, library normalization) and bioinformatic workflow (de novo vs. mapping assembly, reference genome quality) impact transcriptome quality and inference of differential gene expression (DE). We find that transcriptome assembly and gene expression profiling (EdgeR vs. BaySeq software) works well even in the absence of a reference genome and is robust across a broad range of parameters. We advise against library normalization and in most situations advocate mapping assemblies to an annotated genome of a divergent sister clade, which generally outperformed de novo assembly (Trans-Abyss, Trinity, Soapdenovo-Trans). Transcriptome complexity (size, paralogs, alternative splicing isoforms) negatively affected the assembly and DE profiling, whereas the effects of sequencing error and polymorphism were almost negligible. Finally, we highlight the challenge of gene name assignment for de novo assemblies, the importance of mapping strategies and raise awareness of challenges associated with the quality of reference genomes. Overall, our results have significant practical and methodological implications and can provide guidance in the design and analysis of RNA-seq experiments, particularly for organisms where genomic background information is lacking.


Review article: optimal preparation for surgery in Crohn's disease.
One-third of Crohn's disease (CD) patients will undergo abdominal surgery within the first 5 years of diagnosis. To review the available evidence on pre-operative optimisation of CD patients. The literature regarding psychological support, radiological imaging, abdominal abscess management, nutritional support, thromboembolic prophylaxis and immunosuppression in the perioperative setting was reviewed. For diagnosis of fistulas, abscesses and stenosis, ultrasonography (US), computed tomography (CT) and magnetic resonance imaging (MRI) have a high diagnostic accuracy. Under either CT or US guidance, it is possible to perform abscess percutaneous drainage (PD), which, with systemic antibiotic therapy, should be the first-line approach to intra-abdominal abscesses. CD patients with weight loss <10% within the last 3-6 months, body mass index < 18.5 kg/m(2) and/or albumin levels <30 g/L, are at an increased risk of post-operative complications. Pre-operative nutritional support should be used in these patients. IBD patients undergoing surgery have a higher risk of venous thromboembolic disease than patients with colorectal cancer, and current guidelines recommend that they should receive prophylaxis with heparin. Whether the use of anti-TNF agents before surgery increases the likelihood of post-operative complications, is the subject of much debate. To date, cumulative evidence from most studies (all retrospective) suggests that there is no such risk increment. Prospective studies are necessary to firmly establish this conclusion. Preparation for surgery requires close interaction between surgeons, gastroenterologist, radiologists, psychologists and the patient. Correct pre-operative planning of surgical treatment has a major impact on the outcome of such treatment.


Biotin in metabolism and molecular biology.
Biotin is a water-soluble vitamin required by all organisms by virtue of its essential role in carboxylation reactions. Although the metabolism and role of biotin in intermediary metabolism are well established, biotin remains one of the most poorly understood water-soluble vitamins in terms of nutritional requirements and responsiveness to physiological and pharmacological states. Significant advances in the understanding of biotin nutriture have been recently accomplished through the description of the kinetics and regulation of biotin transport and improved methods for biotin status assessment. Additionally, the potential role of biotin in the regulation of gene expression has been strengthened through description of altered gene expression during biotin deficiency and through newly described enzymatic activities of the enzyme biotinidase. Given mounting evidence of suboptimum biotin status, a more complete understanding of these aspects of biotin should lead to a greater appreciation of the ways in which biotin aids in the maintenance of health.


[Physicians´ insight about adverse drug reaction to frequently used medication groups in Bogotá (Colombia)].
Adverse drug reactions are a public health problem; however, still many prescribers do not seem to recognize the risk associated with the use of medications. To assess the perception of the risk of adverse reactions associated with the groups of drugs most frequently used in clinical practice. Descriptive study made in 200 physicians with at least 2 years of clinical experience in Bogota, Colombia. The risk of adverse drug reactions associated with the use of medications was assessed using a visual analog scale (0-10 points). The perception of risk was <5 points for 19 of the 31 (61%) therapeutic groups. The therapeutic groups that were related to increased perception of risk were chemotherapy for cancer (median, 8.5, interquartile range: 1.8), insulin (median, 8, interquartile range: 4.8) and anticoagulants (median, 7.5, interquartile range: 4). Although there is a relationship between the perception of risk and the frequency of adverse drug reactions associated with therapeutic groups of higher score, there is also a strong underestimation of the risk of medicines in common use at hospital and ambulatory level such as NSAID, antihypertensive drugs and oral contraceptives.


Electrophysiological Guidance of Epidural Electrode Array Implantation over the Human Lumbosacral Spinal Cord to Enable Motor Function after Chronic Paralysis.
Epidural electrical stimulation (EES) of the spinal cord has been shown to restore function after spinal cord injury (SCI). Characterization of EES-evoked motor responses has provided a basic understanding of spinal sensorimotor network activity related to EES-enabled motor activity of the lower extremities. However, the use of EES-evoked motor responses to guide EES system implantation over the spinal cord and their relation to post-operative EES-enabled function in humans with chronic paralysis attributed to SCI has yet to be described. Herein, we describe the surgical and intraoperative electrophysiological approach used, followed by initial EES-enabled results observed in 2 human subjects with motor complete paralysis who were enrolled in a clinical trial investigating the use of EES to enable motor functions after SCI. The 16-contact electrode array was initially positioned under fluoroscopic guidance. Then, EES-evoked motor responses were recorded from select leg muscles and displayed in real time to determine electrode array proximity to spinal cord regions associated with motor activity of the lower extremities. Acceptable array positioning was determined based on achievement of selective proximal or distal leg muscle activity, as well as bilateral muscle activation. Motor response latencies were not significantly different between intraoperative recordings and post-operative recordings, indicating that array positioning remained stable. Additionally, EES enabled intentional control of step-like activity in both subjects within the first 5 days of testing. These results suggest that the use of EES-evoked motor responses may guide intraoperative positioning of epidural electrodes to target spinal cord circuitry to enable motor functions after SCI.


In silico target predictions: defining a benchmarking data set and comparison of performance of the multiclass Naïve Bayes and Parzen-Rosenblatt window.
In this study, two probabilistic machine-learning algorithms were compared for in silico target prediction of bioactive molecules, namely the well-established Laplacian-modified Naïve Bayes classifier (NB) and the more recently introduced (to Cheminformatics) Parzen-Rosenblatt Window. Both classifiers were trained in conjunction with circular fingerprints on a large data set of bioactive compounds extracted from ChEMBL, covering 894 human protein targets with more than 155,000 ligand-protein pairs. This data set is also provided as a benchmark data set for future target prediction methods due to its size as well as the number of bioactivity classes it contains. In addition to evaluating the methods, different performance measures were explored. This is not as straightforward as in binary classification settings, due to the number of classes, the possibility of multiple class memberships, and the need to translate model scores into "yes/no" predictions for assessing model performance. Both algorithms achieved a recall of correct targets that exceeds 80% in the top 1% of predictions. Performance depends significantly on the underlying diversity and size of a given class of bioactive compounds, with small classes and low structural similarity affecting both algorithms to different degrees. When tested on an external test set extracted from WOMBAT covering more than 500 targets by excluding all compounds with Tanimoto similarity above 0.8 to compounds from the ChEMBL data set, the current methodologies achieved a recall of 63.3% and 66.6% among the top 1% for Naïve Bayes and Parzen-Rosenblatt Window, respectively. While those numbers seem to indicate lower performance, they are also more realistic for settings where protein targets need to be established for novel chemical substances.


Maternal diet, prenatal exposure to dioxin-like compounds and birth outcomes in a European prospective mother-child study (NewGeneris).
Maternal diet can result in exposure to environmental contaminants including dioxins which may influence foetal growth. We investigated the association between maternal diet and birth outcomes by defining a dioxin-rich diet. We used validated food frequency questionnaires to assess the diet of pregnant women from Greece, Spain, United Kingdom, Denmark and Norway and estimated plasma dioxin-like activity by the Dioxin-Responsive Chemically Activated LUciferase eXpression (DR-CALUX®) bioassay in 604 maternal blood samples collected at delivery. We applied reduced rank regression to identify a dioxin-rich dietary pattern based on dioxin-like activity (DR-CALUX®) levels in maternal plasma, and calculated a dioxin-diet score as an estimate of adherence to this dietary pattern. In the five country population, dioxin-diet score was characterised by high consumption of red and white meat, lean and fatty fish, low-fat dairy and low consumption of salty snacks and high-fat cheese, during pregnancy. The upper tertile of the dioxin-diet score was associated with a change in birth weight of -121g (95% confidence intervals: -232, -10g) compared to the lower tertile after adjustment for confounders. A small non-significant reduction in gestational age was also observed (-1.4days, 95% CI: -3.8, 1.0days). Our results suggest that maternal diet might contribute to the exposure of the foetus to dioxins and dioxin-like compounds and may be related to reduced birth weight. More studies are needed to develop updated dietary guidelines for women of reproductive age, aiming to the reduction of dietary exposure to persistent organic pollutants as dioxins and dioxin-like compounds.


Association between knowledge, risk behaviours, and testing for sexually transmitted infections among men who have sex with men: findings from a large online survey in the United Kingdom.
In the UK, men who have sex with men (MSM) bear a disproportionate sexually transmitted infection (STI) burden. We investigated MSM's STI knowledge; whether their STI testing behaviour met national guidelines (annually if sexually active; 3-monthly if engaging in STI risk behaviours); and the relationship between STI testing in the last 3 months, STI knowledge and STI risk behaviours by HIV status. Sexually active (in the last year) men aged > 15 years who were UK residents and were recruited from gay-orientated online dating platforms completed an anonymous online survey about STI knowledge, STI risk behaviours, and STI testing (March-May 2017). This included 11 true statements about STIs. Respondents scored 1 for each statement they 'knew', with those scoring < 6 overall treated as having 'poor' STI knowledge. Descriptive and multivariable analyses were conducted, separately by HIV status, to test our hypothesis and calculate adjusted odds ratios (AORs) with 95% confidence intervals (CIs). Compared to HIV-positive men (n = 489), the proportion of HIV-negative/unknown-status men (n = 3157) with 'poor' STI knowledge was significantly higher (46.4% versus 22.9% for HIV-positive men) and the proportion with STI testing in the last 12 months was lower (71.6% versus 87.2%, respectively). In the last 3 months, 56.9% of HIV-negative/unknown-status and 74.1% of HIV-positive men reported STI risk behaviours, of whom 45.8% and 55.1%, respectively, had been tested for STIs during this time. Among HIV-negative/unknown-status men, those reporting STI risk behaviours were more likely (AOR 1.52; 95% CI 1.26-1.84) and those with poor STI knowledge less likely (AOR 0.73; 95% CI 0.61-0.89) to have been tested during the last 3 months. However, neither factor was independently associated with 3-monthly testing among HIV-positive men. Improving STI knowledge, especially among HIV-negative/unknown-status men, and promoting frequent STI testing among men engaging in STI risk behaviours are vital to address the poor sexual health of MSM.


Molecular Imaging of Colorectal Tumors by Targeting Colon Cancer Secreted Protein-2 (CCSP-2).
A versatile biomarker for detecting colonic adenoma and colon cancer has yet to be developed. Colon cancer secreted protein-2 (CCSP-2) is a protein specifically expressed and secreted in colon adenomas and cancers. We developed a fluorescent imaging method based on CCSP-2 targeting for a more sensitive and specific detection of colorectal tumors. CCSP-2 expression was evaluated in human colon adenoma and colorectal specimens. Anti-CCSP-2 antibody was labeled with a near-infrared fluorescent dye, FPR-675, and molecular imaging of surgical human colorectal tumors was performed. Immunohistochemistry identified CCSP-2 expression in 87.0% of colorectal cancer specimens and 89.5% of colon adenoma specimens. Fluorescence imaging of surgical human colon specimens after spraying treatment with the probe permitted a clear distinction of cancer from paired normal colon tissue (target-to-background ratio, 4.09±0.42; P<.001). CCSP-2 targeting imaging was also evaluated in patient-derived colon cancer xenograft mouse and liver metastasis murine models. CCSP-2-positive colon cancer xenografts and liver metastases were visualized by near-infrared fluorescence imaging after intravenous injection of the probe, which showed significantly higher fluorescence. Our results show that CCSP-2 is a promising marker for colorectal tumor detection in clinical settings and that a CCSP-2-targeting molecular imaging strategy might improve the diagnosis of colorectal tumors in metastatic or recurrent cancers and aid in early colonoscopic detection of premalignant lesions.


Turner syndrome: diagnosis and management.
Turner syndrome occurs in one out of every 2,500 to 3,000 live female births. The syndrome is characterized by the partial or complete absence of one X chromosome (45,X karyotype). Patients with Turner syndrome are at risk of congenital heart defects (e.g., coarctation of aorta, bicuspid aortic valve) and may have progressive aortic root dilatation or dissection. These patients also are at risk of congenital lymphedema, renal malformation, sensorineural hearing loss, osteoporosis, obesity, diabetes, and atherogenic lipid profile. Patients usually have normal intelligence but may have problems with nonverbal, social, and psychomotor skills. Physical manifestations may be subtle but can include misshapen ears, a webbed neck, a broad chest with widely spaced nipples, and cubitus valgus. A Turner syndrome diagnosis should be considered in girls with short stature or primary amenorrhea. Patients are treated for short stature in early childhood with growth hormone therapy, and supplemental estrogen is initiated by adolescence for pubertal development and prevention of osteoporosis. Almost all women with Turner syndrome are infertile, although some conceive with assisted reproduction.


Childless Expectations and Childlessness Over the Life Course.
Using nineteen panels of the 1979 National Longitudinal Survey of Youth (NLSY-79), we construct life-lines characterizing women's childless expectations and fertility behavior. One-quarter of women in the NLSY-79 cohort ever reported an expectation for childlessness but only 14.8 percent of women remain childless. Childless women follow two predominant life course paths: (1) repeated postponement of childbearing and the subsequent adoption of a childless expectation at older ages or (2) indecision about parenthood signaled through vacillating reports of childless expectations across various ages. We also find that more than one in ten women became a mother after considering childlessness: an understudied group in research on childlessness and childbearing preferences. These findings reaffirm that it is problematic to assign expected and unexpected childlessness labels to the reproductive experience of childless women. In addition, despite their variability over time, childless expectations strongly predict permanent childlessness, regardless of the age when respondents offer them. Longitudinal logistic regression analysis of these childless expectations indicates a strong effect of childbearing postponement among the increasingly selective group of childless women. However, net of this postponement, few variables commonly associated with childlessness are associated with reports of a childless expectation. We thus conclude that the effects of socio-demographic and situational factors on childless expectations are channeled predominantly through repeated childbearing postponement.


Fowler's bacillus and its parasporal body.
Fowler's bacillus is one of several organisms which form a non-viable inclusion or parasporal body during the process of sporulation. This body is globular and may be as large as or larger than the spore. Its position in the cell is not random; the spore is terminal and the body paracentral, lying between the spore and the remaining vegetative cell chromatin bodies. On completion of sporulation both spore and body are contained within an exosporium. The sequence in the development of the cell structures was followed in ultrathin sections of material fixed in permanganate. When sporulation is well advanced the body begins to grow from a single crystal, then presumably as a result of some disorientation in the growth process it develops as a multicrystalline body with the lattices orientated at different angles. When the body approximates the spore in size, a lamella coat is formed and an exosporium develops which eventually encircles the body and the spore. Other lamella systems microscopically similar to those surrounding the parasporal body develop free in the cytoplasm outside the exosporium. In both of these systems the number of lamellae is variable. The spore coat of Fowler's bacillus, consisting of an outer lamella layer and an inner unresolved amorphous layer has been found microscopically identical to the spore coat of B. cereus. In both organisms the lamella layer of the spore coat consists, in contrast to the other lamella systems, of a regular number of lamellae. Physiological tests would indicate that Fowler's bacillus is a variety of B. cereus.


Parental Age in Relation to Offspring's Neurodevelopment.
Objective: Advanced parenthood increases the risk of severe neurodevelopmental disorders like autism, Down syndrome and schizophrenia. Does advanced parenthood also negatively impact offspring's general neurodevelopment?Method: We analyzed child-, father-, mother- and teacher-rated attention-problems (N = 38,024), and standardized measures of intelligence (N = 10,273) and educational achievement (N = 17,522) of children from four Dutch population-based cohorts. The mean age over cohorts varied from 9.73-13.03. Most participants were of Dutch origin, ranging from 58.7%-96.7% over cohorts. We analyzed 50% of the data to generate hypotheses and the other 50% to evaluate support for these hypotheses. We aggregated the results over cohorts with Bayesian research synthesis.Results: We mostly found negative linear relations between parental age and attention-problems, meaning that offspring of younger parents tended to have more attention problems. Maternal age was positively and linearly related to offspring's IQ and educational achievement. Paternal age showed an attenuating positive relation with educational achievement and an inverted U-shape relation with IQ, with offspring of younger and older fathers at a disadvantage. Only the associations with maternal age remained after including SES. The inclusion of child gender in the model did not affect the relation between parental age and the study outcomes.Conclusions: Effects were small but significant, with better outcomes for children born to older parents. Older parents tended to be of higher SES. Indeed, the positive relation between parental age and offspring neurodevelopmental outcomes was partly confounded by SES.


Telaprevir for HIV/hepatitis C virus-coinfected patients failing treatment with pegylated interferon/ribavirin (ANRS HC26 TelapreVIH): an open-label, single-arm, phase 2 trial.
Retreatment with pegylated interferon (peg-IFN) and ribavirin (RBV) results in poor sustained virological response (SVR) rates in human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients. There are limited data regarding the use of telaprevir plus peg-IFN/RBV in this population. HIV type 1-infected patients who previously failed ≥12 weeks of peg-IFN/RBV for HCV genotype 1 coinfection were enrolled in a single-arm, phase 2 trial. Patients with cirrhosis and previous null response were excluded. Authorized antiretrovirals were tenofovir, emtricitabine, efavirenz, atazanavir, and raltegravir. All patients received peg-IFN alfa-2a (180 µg/week) plus RBV (1000-1200 mg/day) for 4 weeks, followed by telaprevir (750 mg or 1125 mg every 8 hours with efavirenz) plus peg-IFN/RBV for 12 weeks and peg-IFN/RBV for 32-56 weeks according to virological response at week 8. The primary endpoint was the SVR rate at 24 weeks after the end of treatment (SVR24). Sixty-nine patients started treatment; SVR24 was achieved in 55 (80% [95% confidence interval, 68%-88%). SVR24 was not influenced by baseline fibrosis stage, IL28B genotype, antiretroviral regimen, HCV subtype, CD4 cell count, previous response to HCV treatment, HCV RNA level, or HCV RNA decline at week 4. HCV treatment was discontinued for adverse events (AEs) in 20% of patients, including cutaneous (4%), psychiatric (4%), hematological (6%), and other AEs (6%). Peg-IFN or RBV dose reduction was required in 23% and 43% of patients, respectively. Seventy percent of patients required erythropoietin, blood transfusions, or RBV dose reduction for anemia. Two patients died during the study. No HIV breakthrough was observed. Despite a high discontinuation rate related to toxicity, a substantial proportion of treatment-experienced HIV-coinfected patients achieved SVR24 with a telaprevir-based regimen. Clinical Trials Registration. NCT01332955.


Ringwoodite lamellae in olivine: Clues to olivine-ringwoodite phase transition mechanisms in shocked meteorites and subducting slabs.
The first natural occurrence of ringwoodite lamellae was found in the olivine grains inside and in areas adjacent to the shock veins of a chondritic meteorite, and these lamellae show distinct growth mechanism. Inside the veins where pressure and temperature were higher than elsewhere, ringwoodite lamellae formed parallel to the [101] planes of olivine, whereas outside they lie parallel to the (100) plane of olivine. The lamellae replaced the host olivine from a few percent to complete. Formation of these lamellae relates to a diffusion-controlled growth of ringwoodite along shear-induced planar defects in olivine. The planar defects and ringwoodite lamellae parallel to the [101] planes of olivine should have been produced in higher shear stress and temperature region than that parallel to the (100) plane of olivine. This study suggests that the time duration of high pressure and temperature for the growth of ringwoodite lamellae might have lasted at least for several seconds, and that an intracrystalline transformation mechanism of ringwoodite in olivine could favorably operate in the subducting lithospheric slabs in the deep Earth.


Contribution of the hepatic lipase gene to the atherogenic lipoprotein phenotype in familial combined hyperlipidemia.
Familial combined hyperlipidemia (FCH) is a common genetic lipid disorder with a frequency of 1-2% in the population. In addition to the hypercholesterolemia and/or hypertriglyceridemia that affected individuals exhibit, small, dense LDL particles and decreased HDL-cholesterol levels are traits frequently associated with FCH. Recently, we reported that families with FCH and families enriched for coronary artery disease (CAD) share genetic determinants for the atherogenic lipoprotein phenotype (ALP), a profile presenting with small, dense LDL particles, decreased HDL-cholesterol levels, and increased triglyceride levels. Other studies in normolipidemic populations have shown that the hepatic lipase (HL) gene is linked to HDL-cholesterol levels and that a polymorphism within the HL promoter (-514C-->T) is associated with increased HDL-cholesterol levels as well as larger, more buoyant LDL particles. In the present study, we tested whether the HL gene locus also contributes to ALP in a series of Dutch FCH families using nonparametric sibpair linkage analysis and association analysis. Evidence for linkage of LDL particle size (P < 0.019), HDL-cholesterol (P < 0.003), and triglyceride levels (P < 0.026) to the HL gene locus was observed. A genome scan in a subset of these families exhibited evidence for linkage of PPD (LOD = 2.2) and HDL-cholesterol levels (LOD = 1.2) to the HL gene locus as well. The -514C-->T promoter polymorphism was significantly associated (P < 0.0001) with higher HDL-cholesterol levels in the unrelated males of this population, but not in unrelated females. No association was observed between the polymorphism and LDL particle size or triglyceride levels. Our results provide support that ALP is a multigenic trait and suggest that the relationship between small, dense LDL particles, HDL-cholesterol, and triglyceride levels in FCH families is due, in part, to common genetic factors.


Fiddler on the tree--a bush-cricket species with unusual stridulatory organs and song.
Insects of the order Orthoptera are well-known for their acoustic communication. The structures used for this purpose show a high diversity which obviously relates to differences in song parameters and to the physics of sound production. Here we describe song and morphology of the sound producing organs of a tropical bush-cricket, Ectomoptera nepicauda, from East Africa. It has a very unusual calling song consisting of frequency-modulated, pure-tone sounds in the high ultrasonic range of 80 to 120 kHz and produced by extremely fast wing movements. Concerning morphology, it represents the most extreme state in the degree of left-right fore-wing differentiation found among Orthoptera: the acoustic parts of the left fore-wing consist exclusively of the stridulatory file, comparable in function to the bow of a violin, while the right wing carries only the plectrum ( = string) and mirror ( = soundbox).


Psychological and parental functioning of widowed fathers: The first two years.
Widowed parents play a critical role in promoting family adaptation and facilitating their children's adjustment to the loss of a parent; yet the psychological wellbeing of these parents has received scant attention. In this study we examined depressive symptoms and grief intensity in 252 spousally bereaved men with dependent-age children. Participants learned of the study and completed initial surveys at variable time points during their first 2 years of bereavement. Depressive and grief symptoms remained persistently high, with 45% of the sample exceeding screening thresholds for clinically significant depressive symptoms two years after the death of their spouses. In linear regression models, higher intensity or frequency of depression and grief symptoms were associated with poorer psychological adaptation, lower parenting self-efficacy, and lower parenting satisfaction scores. Relationships between fathers' distress and potentially modifiable end-of-life variables regarding their spouses were examined. Notably, those who reported that their wives were at peace with dying had lower depressive and grief scores at various intervals. Overall, the magnitude and duration of the depressive and grief symptoms suggests that widowed fathers' psychological distress does not quickly abate over the first 2 years of bereavement, which may be attributable to the unique set of bereavement challenges facing widowed parents such as facilitating their children's grief, assuming sole parenting responsibilities, and managing a household on their own. The findings underscore the need to further examine emotional distress in widowed parents and how their wellbeing impacts family functioning. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Accelerated changes in white matter microstructure during aging: a longitudinal diffusion tensor imaging study.
It is well established that human brain white matter structure changes with aging, but the timescale and spatial distribution of this change remain uncertain. Cross-sectional diffusion tensor imaging (DTI) studies indicate that, after a period of relative stability during adulthood, there is an accelerated decline in anisotropy and increase in diffusivity values during senescence; and, spatially, results have been discussed within the context of several anatomical frameworks. However, inferring trajectories of change from cross-sectional data can be challenging; and, as yet, there have been no longitudinal reports of the timescale and spatial distribution of age-related white matter change in healthy adults across the adult lifespan. In a longitudinal DTI study of 203 adults between 20 and 84 years of age, we used tract-based spatial statistics to characterize the pattern of annual change in fractional anisotropy, axial diffusivity, radial diffusivity, and mean diffusivity and examined whether there was an acceleration of change with age. We found extensive and overlapping significant annual decreases in fractional anisotropy, and increases in axial diffusivity, radial diffusivity, and mean diffusivity. Spatially, results were consistent with inferior-to-superior gradients of lesser-to-greater vulnerability. Annual change increased with age, particularly within superior regions, with age-related decline estimated to begin in the fifth decade. Charting white matter microstructural changes in healthy aging provides essential context to clinical studies, and future studies should compare age trajectories between healthy participants and at-risk populations and also explore the relationship between DTI rates of change and cognitive decline.


Biological activity of follistatin isoforms and follistatin-like-3 is dependent on differential cell surface binding and specificity for activin, myostatin, and bone morphogenetic proteins.
Follistatin (FST) and FST-like-3 (FSTL3) are activin-binding and neutralization proteins that also bind myostatin. Three FST isoforms have been described that differ in tissue distribution and cell-surface binding activity, suggesting that the FST isoforms and FSTL3 may have some nonoverlapping biological actions. We produced recombinant FST isoforms and FSTL3 and compared their biochemical and biological properties. Activin-binding affinities and kinetics were comparable between the isoforms and FSTL3, whereas cell-surface binding differed markedly (FST288 > FST303 > FST315 > FSTL3). Inhibition of endogenous activin bioactivity, whether the FST isoforms were administered endogenously or exogenously, correlated closely with surface binding activity, whereas neutralization of exogenous activin when FST and FSTL3 were also exogenous was consistent with their equivalent activin-binding affinities. This difference in activin inhibition was also evident in an in vitro bioassay because FST288 suppressed, whereas FST315 enhanced, activin-dependent TT cell proliferation. Moreover, when FSTL3, which does not associate with cell membranes, was expressed as a membrane-anchored protein, its endogenous activin inhibitory activity was dramatically increased. In competitive binding assays, myostatin was more potent than bone morphogenetic proteins (BMPs) 6 and 7, and BMPs 2 and 4 were inactive in binding to FST isoforms, whereas none of the BMPs tested competed with activin for binding to FSTL3. Neutralization of exogenous BMP or myostatin bioactivity correlated with the relative abilities of the isoforms to bind cell-surface proteoglycans. These results indicate that the differential biological actions among the FST isoforms and FSTL3 are primarily dependent on their relative cell-surface binding ability and ligand specificity.


Melittin ameliorates CVB3-induced myocarditis via activation of the HDAC2-mediated GSK-3β/Nrf2/ARE signaling pathway.
Viral myocarditis (VMC) is characterized as an inflammatory process of the myocardium and can be fatal in infants and children. Melittin is a major polypeptide in honey bee venom that has been traditionally used against inflammation. However, its effect on VMC and the underlying molecular mechanism has not been reported. In this study, BALB/c mice were intraperitoneally injected with CVB3 to build a VMC model and treated with melittin. The results showed that melittin increased the mice's body weight and inhibited CVB3 replication. HE staining also showed that melittin alleviated myocardial injury in the VMC model. Flow cytometry showed that melittin inhibited myocardial cell apoptosis; in addition, real-time PCR showed that melittin decreased the expression of bax and caspase-3, and increased the expression of bcl-2. The results of echocardiographic examination showed that melittin improved cardiac function. Moreover, melittin decreased the activity of AST, CK, HBDH and LDH, and decreased the production of IL-1β, IL-6, TNF-α and MCP-1 in CVB3-induced myocardial tissues. Finally, we also found that melittin increased the expression of HDAC2 and activated the GSK-3β/Nrf2/ARE signaling pathway, whereas these changes were reversed by inhibition of HDAC2 in VMC model mice. In conclusion, our results suggested that melittin ameliorates CVB3-induced myocarditis via activation of the HDAC2-mediated GSK-3β/Nrf2/ARE signaling pathway.


Combined off-pump coronary artery bypass grafting and thyroidectomy.
A 70-year-old Indian woman presented with an acute anterior wall myocardial infarction and a large multinodular goiter causing tracheal compression and dyspnea. Coronary artery angiography revealed severe triple-vessel disease, with an 80% occlusion of the left main stem, necessitating early coronary artery bypass grafting combined with total thyroidectomy. The procedure was performed successfully. At the 1-year follow-up, the patient remains euthyroid and in New York Heart Association functional class I. This case provides further evidence that combined coronary artery bypass grafting and total thyroidectomy is both feasible and safe.


Gene pathway development in human epicardial adipose tissue during early life.
Studies in rodents and newborn humans demonstrate the influence of brown adipose tissue (BAT) in temperature control and energy balance and a critical role in the regulation of body weight. Here, we obtained samples of epicardial adipose tissue (EAT) from neonates, infants, and children in order to evaluate changes in their transcriptional landscape by applying a systems biology approach. Surprisingly, these analyses revealed that the transition to infancy is a critical stage for changes in the morphology of EAT and is reflected in unique gene expression patterns of a substantial proportion of thermogenic gene transcripts (~10%). Our results also indicated that the pattern of gene expression represents a distinct developmental stage, even after the rebound in abundance of thermogenic genes in later childhood. Using weighted gene coexpression network analyses, we found precise anthropometric-specific correlations with changes in gene expression and the decline of thermogenic capacity within EAT. In addition, these results indicate a sequential order of transcriptional events affecting cellular pathways, which could potentially explain the variation in the amount, or activity, of BAT in adulthood. Together, these results provide a resource to elucidate gene regulatory mechanisms underlying the progressive development of BAT during early life.


ATP binding enables broad antibiotic selectivity of aminoglycoside phosphotransferase(3')-IIIa: an elastic network analysis.
The bacterial enzyme aminoglycoside phosphotransferase(3')-IIIa (APH) confers resistance against a wide range of aminoglycoside antibiotics. In this study, we use the Gaussian network model to investigate how the binding of nucleotides and antibiotics influences the dynamics and thereby the ligand binding properties of APH. Interestingly, in NMR experiments, the dynamics differ significantly in various APH complexes, although crystallographic studies indicate that no larger conformational changes occur upon ligand binding. Isothermal titration calorimetry also shows different thermodynamic contributions to ligand binding. Formation of aminoglycoside-APH complexes is enthalpically driven, while the enthalpic change upon aminoglycoside binding to the nucleotide-APH complex is much smaller. The differential effects of nucleotide binding and antibiotic binding to APH can be explained theoretically by single-residue fluctuations and correlated motions of the enzyme. The surprising destabilization of β-sheet residues upon nucleotide binding, as seen in hydrogen/deuterium exchange experiments, shows that the number of closest neighbors does not fully explain residue flexibility. Additionally, we must consider correlated motions of dynamic protein domains, which show that not only connectivity but also the overall protein architecture is important for protein dynamics.


[Health education as the principal element of prevention in cardiology: methods of intervention. Conclusions and operative suggestions].
In this symposium an extensive review of the basic role of health education for the prevention of cardiovascular diseases, has been made. Principles and methods have been analysed in the light of recent advances in primary and secondary prevention of rheumatic heart disease, ischemic heart disease and hypertension. The cardiologist's role in health education of individual subjects and of high-risk target groups or of the whole community, has been stressed. Recent trials have shown that it is possible to achieve behavioural changes and a reduction in the levels of risk factors in a good proportion of participants. It should be possible to bring up children virtually free from risk factors. Cardiologists on their own are unlikely to succeed in a program of prevention. They need the help of many others including public health workers, sociologists, nurses and above all, general practitioners. Cardiologists however have responsibility for leadership and for providing background knowledge. Cardiologists need to be educated and motivated. Health education should be founded on a scientific basis and should be organized in an efficient and planned fashion. Medical and post-graduated schools, hospital institutions and cardiological associations must be specifically involved in preparing the cardiologists for this specific task. On the other hand, dedicated teams or sections in the cardiological departments must be activated to promote, coordinate and carry out specific programs of health education for preventing cardiovascular diseases. The attention of governmental authorities should be drawn to the theoretical and practical importance of health education in preventive cardiology, especially in connection with the planning, organization and direction of health education at the regional and national level.


Dynamic ultrasound as a selection tool for reducing achilles tendon reruptures.
The optimal method of treatment for acute tendo-Achilles ruptures continues to be debated. The reported lower rerupture rate for operatively treated patients is an effect of tendon end apposition during the healing process, and patients in whom apposition can be demonstrated using ultrasound will have a similar rate of rerupture if treated nonoperatively. Cohort study; Level of evidence, 2. The authors reviewed all patients with an Achilles tendon rupture who were treated to a standard protocol during a 5-year period (2000-2005). Patients with a gap of 5 mm or more in equinus on ultrasound underwent surgery; those with a gap of less than 5 mm received nonoperative treatment. All patients were followed up to a minimum of 12 months. After exclusions, 125 patients were included: 67 treated operatively and 58 nonoperatively. There were 2 reruptures in the nonoperative group and 1 with surgery. There was no significant difference between the groups for any complication. Reduction of rerupture and surgery risks may be possible using dynamic ultrasound case selection. Further studies are needed to show whether functional results are the same with surgical and nonsurgical treatment when dynamic ultrasound criteria are used for case selection.


Biochar increases soil organic carbon, avocado yields and economic return over 4 years of cultivation.
The use of biochar in avocado orchard soils has not yet been investigated in rigorous scientific experiments. We determine the effect of wood biochar on avocado growth, fruit production and economic benefit. Biochar was applied at 0%, 5%, 10% and 20% volume by volume basis. Biochar significantly improved the growth of avocado seedlings and increased fruit yield in the first three years after planting. There was an overall increase in soil carbon, fruit yield, tree diameter and height in all biochar treatments relative to the control over the seasons. Trees planted with biochar had 18-26% greater growth rates (in terms of height and stem diameter) than the control. Tree diameter was significantly greater with biochar (145.4 ± 3.3 mm) relative to the control treatment (125.0 ± 2.7 mm). Tree height was also significantly greater with biochar (3.7 ± 0.1 m) relative to the control treatment (3.4 ± 0.1 m). The fruit count from the biochar row was significantly greater (97%) in 2018. Heavy bearing trees typically have a lower yield in the subsequent year but despite this, the 2019 fruit counts were higher in aggregate for the biochar amended trees (20%) relative to the control. A cost-benefit analysis indicated that if yield surplus of fruit trees continued for three years, and assuming avocado prices remain at similar levels, then the discounted net benefit over a hectare would amount to US$8581, or US$105 per metric tonne of biochar applied.


Interactions of doctors with the pharmaceutical industry.
To assess the opinions and practice patterns of obstetrician-gynaecologists on acceptance and use of free drug samples and other incentive items from pharmaceutical representatives. A questionnaire was mailed in March 2003 to 397 members of the American College of Obstetricians and Gynecologists who participate in the Collaborative Ambulatory Research Network. The response rate was 55%. Most respondents thought it proper to accept drug samples (92%), an informational lunch (77%), an anatomical model (75%) or a well-paid consultantship (53%) from pharmaceutical representatives. A third (33%) of the respondents thought that their own decision to prescribe a drug would probably be influenced by accepting drug samples. Respondents were more likely to think the average doctor's prescribing would be influenced by acceptance of the items than theirs would be (p<0.002). Respondents who distributed drug samples to patients indicated doing so because of patients' financial need (94%) and for their convenience (76%) and less so as a result of knowledge of the efficacy of the sample product (63%). A third (34%) of respondents agreed that interactions with industry should be more strictly regulated. Obstetrician-gynaecologists largely indicated that they would act in accordance with what they think is proper regarding accepting incentive items from pharmaceutical representatives. Although accepting free drug samples was considered to be appropriate more often than any other item, samples were most commonly judged to be influential on prescribing practices. The widely accepted practice of receiving and distributing free drug samples needs to be examined more carefully.


The relative importance of host characteristics and co-infection in generating variation in Heligmosomoides polygyrus fecundity.
We examined the relative importance of intrinsic host factors and microparasite co-infection in generating variation in Heligmosomoides polygyrus fecundity, a parameter that serves as a proxy for infectiousness. We undertook extensive trapping of Apodemus flavicollis, the yellow-necked mouse in the woodlands of the Italian Alps and recorded eggs in utero from the dominant nematode species H. polygyrus, and tested for the presence of five microparasite infections. The results showed that sex and breeding status interact, such that males in breeding condition harboured more fecund nematodes than other hosts; in particular, worms from breeding males had, on average, 52% more eggs in utero than worms from non-breeding males. In contrast, we found a weak relationship between intensity and body mass, and no relationship between intensity and sex or intensity and breeding condition. We did not find any evidence to support the hypothesis that co-infection with microparasites contributed to variation in worm fecundity in this system. The age-intensity profiles for mice singly-infected with H. polygyrus and those co-infected with the nematode and at least one microparasite were both convex and not statistically different from each other. We concluded that intrinsic differences between hosts, specifically with regard to sex and breeding condition, contribute relatively more to the variation in worm fecundity than parasite co-infection status.


Fluoride Alteration of [3H]Glucose Uptake in Wistar Rat Brain and Peripheral Tissues.
The present study was designed to investigate the role of postnatal fluoride intake on [3H]glucose uptake and transport in rat brain and peripheral tissues. Sodium fluoride (NaF) in a concentration of 10 or 50 ppm was added to the drinking water of adult Wistar rats. The control group received distilled water. After 4 weeks, respective plasma fluoride levels were 0.0541 ± 0.0135 μg/ml (control), 0.0596 ± 0.0202 μg/ml (10 ppm), and 0.0823 ± 0.0199 μg/ml (50 ppm). Although plasma glucose levels were not altered in any group, the plasma insulin level in the fluoride (50 ppm) group was elevated (0.72 ± 0.13 μg/ml) versus the control group (0.48 ± 0.24 μg/ml) and fluoride (10 ppm) group. In rats receiving fluoride for 4 weeks at 10 ppm in drinking water, [3H]glucose uptake was unaltered in all tested parts of the brain. However, in rats receiving fluoride at 50 ppm, [3H]glucose uptake in cerebral cortex, hippocampus, and thalamus with hypothalamus was elevated, versus the saline group. Fluoride intake had a negligible effect on [3H]glucose uptake by peripheral tissues (liver, pancreas, stomach, small intestine, atrium, aorta, kidney, visceral tissue, lung, skin, oral mucosa, tongue, salivary gland, incisor, molars, and jawbone). In neither fluoride group was glucose transporter proteins 1 (GLUT 1) or 3 (GLUT 3) altered in frontal cortex and striatum versus control. On the assumption that increased glucose uptake (by neural tissue) reasonably reflects neuronal activity, it appears that fluoride damage to the brain results in a compensatory increase in glucose uptake and utilization without changes in GLUT 1 and GLUT 3 expression.


Do bartonella infections cause agitation, panic disorder, and treatment-resistant depression?
Bartonella is an emerging infection found in cities, suburbs, and rural locations. Routine national labs offer testing for only 2 species, but at least 9 have been discovered as human infections within the last 15 years. Some authors discuss Bartonella cases having atypical presentations, with serious morbidity considered uncharacteristic of more routine Bartonella infections. Some atypical findings include distortion of vision, abdominal pain, severe liver and spleen tissue abnormalities, thrombocytopenic purpura, bone infection, arthritis, abscesses, heart tissue and heart valve problems. While some articles discuss Bartonella as a cause of neurologic illnesses, psychiatric illnesses have received limited attention. Case reports usually do not focus on psychiatric symptoms and typically only as incidental comorbid findings. In this article, we discuss patients exhibiting new-onset agitation, panic attacks, and treatment-resistant depression, all of which may be attributed to Bartonella. Three patients receiving care in an outpatient clinical setting developed acute onset personality changes and agitation, depression, and panic attacks. They were retrospectively examined for evidence of Bartonella infections. The medical and psychiatric treatment progress of each patient was tracked until both were significantly resolved and the Bartonella was cured. The patients generally seemed to require higher dosing of antidepressants, benzodiazepines, or antipsychotics in order to function normally. Doses were reduced following antibiotic treatment and as the presumed signs of Bartonella infection remitted. All patients improved significantly following treatment and returned to their previously healthy or near-normal baseline mental health status. New Bartonella species are emerging as human infections. Most do not have antibody or polymerase chain reaction (PCR) diagnostic testing at this time. Manual differential examinations are of unknown utility, due to many factors such as low numbers of infected red blood cells, the small size of the infecting bacteria, uncertainty of current techniques in viewing such small bacteria, and limited experience. As an emerging infection, it is unknown whether Bartonella occurrence in humans worldwide is rare or common, without further information from epidemiology, microbiology, pathology, and treatment outcomes research. Three patients presented with acute psychiatric disorders associated with Bartonella-like signs and symptoms. Each had clear exposure to ticks or fleas and presented with physical symptoms consistent with Bartonella, eg, an enlarged lymph node near an Ixodes tick bite and bacillary angiomatosis found only in Bartonella infections. Laboratory findings and the overall general course of the illnesses seemed consistent with Bartonella infection. The authors are not reporting that these patients offer certain proof of Bartonella infection, but we hope to raise the possibility that patients infected with Bartonella can have a variety of mental health symptoms. Since Bartonella can clearly cause neurologic disorders, we feel the presence of psychiatric disorders is a reasonable expectation.


DNA polymerase-beta from the nuclear fraction of sea urchin embryos: characterization of the purified enzyme.
Approximately 2,500-fold purifications of DNA polymerase-beta from the nuclear fraction of blastulae of the sea urchin, Hemicentrotus pulcherrimus, was performed. The enzyme preparation, which was devoid of DNase and terminal deoxynucleotidyl transferase as contaminants, showed a sedimentation constant of 3.0 S in a sucrose density gradient, a molecular weight of 50,000 by gel filtration, and an isoelectric point of pH 8.1. The enzyme activity was resistant to sulfhydryl group inhibitors. Its optimal pH was 9.0-9.5 in Tris-maleate buffer and 10.0 in glycine buffer. The optimal NaCl concentration for the activity was 30-60 mM and about half of the activity remained at 0.4 M NaCl. As a template-primer, the enzyme preferred synthetic homopolymers to activated DNA. The order of this preference was as follows; poly (dA)-oligo (dT)12-18 greater than poly (rA)-oligo (dT)12-18 greater than activated DNA. The above results indicate that the enzyme corresponds to DNA polymerase-beta from vertebrate cells.


Human lymphocytes: 5'-nucleotidase-positive and -negative subpopulations.
The enzyme, 5'-nucleotidase (5'N) (E.C.-188.8.131.52) is present in lymphocytes isolated from the blood of normal subjects. This activity is markedly decreased or not detectable in the cells from three-quarters of patients with chronic lymphocytic leukemia (CLL), while supranormal levels are found in less than 10% of the cases. To determine whether the decreased 5'N value in CLL represents a lower activity per cell or fewer enzyme-containing cells than in the normal, conditions were established for the histochemical measurement of 5'N in human lymphocytes. It was found that the cells isolated from the blood of normal subjects or patients with CLL consist of 5'N-positive and 5'N-negative subpopulations. Normal subjects who had high 5'N specific activity were shown to have a greater percentage of 5'N-positive cells than individuals with low 5'N activity. Patients with CLL who had no activity by standard chemical assay had no 5'N-positive cells, while the exceptional patient with CLL with a higher than normal specific activity showed an percentage of 5'N-positive cells. It is suggested that the selective proliferation of 5'N-positive and 5'N-negative populations may account for the heterogeneity of 5'N in CLL.


Saccharopolyspora maritima sp. nov., an actinomycete isolated from mangrove sediment.
A novel Saccharopolyspora strain, designated 3SS5-12T, isolated from mangrove sediment collected from Ranong Province is described. The strain was characterized by pale yellow branching aerial mycelium which differentiated into flexuous chains of spores covered with tufts of short curved hairs. The whole-cell hydrolysates of the strain contained meso-diaminopimelic acid as the diagnostic diamino acid, with arabinose, galactose and ribose as the main sugars. A major menaquinone of this strain was MK-9(H4). Mycolic acids were absent. The DNA G+C content of the genomic DNA was 69.4 mol%. The predominant cellular fatty acids were iso-C16 : 0 and anteiso-C17 : 0. Polar lipids consisted of diphosphatidylglycerol, hydroxy-phosphatidylethanolamine, hydroxy-phosphatidylmonomethylethanolamine, phosphatidylethanolamine, phosphatidylmonomethylethanolamine, phosphatidylcholine, phosphatidylglycerol, phosphatidylinositol, unidentified phospholipids and unidentified lipids. Phylogenetic determination based on 16S rRNA gene sequences indicated that the organism was classified in the genus Saccharopolyspora and highly similar to Saccharopolyspora jiangxiensis W12T (98.8 % sequence similarity), Saccharopolyspora hirsutasubsp. kobensis JCM 9109T (98.8 %), Saccharopolyspora antimicrobica I05-00074T (98.2 %) and Saccharopolyspora indica VRC122T (98.1 %). Evidence from the chemotaxonomic, phenotypic and molecular systematic data indicated that strain 3SS5-12T should be classified as a representing novel species of the genus Saccharopolyspora, for which the name Saccharopolyspora maritima sp. nov. is proposed. The type strain is 3SS5-12T (=TBRC 7048T=NBRC 112863T).


An Off-Grid Turbo Channel Estimation Algorithm for Millimeter Wave Communications.
The bandwidth shortage has motivated the exploration of the millimeter wave (mmWave) frequency spectrum for future communication networks. To compensate for the severe propagation attenuation in the mmWave band, massive antenna arrays can be adopted at both the transmitter and receiver to provide large array gains via directional beamforming. To achieve such array gains, channel estimation (CE) with high resolution and low latency is of great importance for mmWave communications. However, classic super-resolution subspace CE methods such as multiple signal classification (MUSIC) and estimation of signal parameters via rotation invariant technique (ESPRIT) cannot be applied here due to RF chain constraints. In this paper, an enhanced CE algorithm is developed for the off-grid problem when quantizing the angles of mmWave channel in the spatial domain where off-grid problem refers to the scenario that angles do not lie on the quantization grids with high probability, and it results in power leakage and severe reduction of the CE performance. A new model is first proposed to formulate the off-grid problem. The new model divides the continuously-distributed angle into a quantized discrete grid part, referred to as the integral grid angle, and an offset part, termed fractional off-grid angle. Accordingly, an iterative off-grid turbo CE (IOTCE) algorithm is proposed to renew and upgrade the CE between the integral grid part and the fractional off-grid part under the Turbo principle. By fully exploiting the sparse structure of mmWave channels, the integral grid part is estimated by a soft-decoding based compressed sensing (CS) method called improved turbo compressed channel sensing (ITCCS). It iteratively updates the soft information between the linear minimum mean square error (LMMSE) estimator and the sparsity combiner. Monte Carlo simulations are presented to evaluate the performance of the proposed method, and the results show that it enhances the angle detection resolution greatly.


Inflammation and resolution are associated with upregulation of fatty acid β-oxidation in Zymosan-induced peritonitis.
Inflammation is a fundamental defensive response to harmful stimuli. However, it can cause damage if it does not subside. To avoid such damage, organisms have developed a mechanism called resolution of inflammation. Here we applied an untargeted metabolomics approach to a sterile and self-resolving animal model of acute inflammation, namely zymosan-induced peritonitis in mice, to examine the effect of inflammation and resolution on the metabolomic profiles. Significant and time-dependent changes in metabolite profiles after zymosan administration were observed in both peritoneal wash fluid (PWF) and plasma. These metabolomic changes correlated well with inflammatory chemokine or cytokine production. In PWF, most of metabolites that could detected increased in zymosan-treated mice, which is suggestive of inflammation, oxidative stress and increased energy demands. In plasma, most metabolites in the central metabolic pathway (glycolysis and TCA cycle) were significantly downregulated after zymosan administration. The concentration of the ketone body 3-hydroxybutyric acid (3-HB) in plasma and PWF increased in zymosan-injected animals indicating upregulation of fatty acid β-oxidation. Increased 3-HB level was observed in the cells that infiltrated into the peritoneal cavity and these infiltrated cells might contribute, at least in part, to the production of 3-HB in the peritoneal cavity.


Cerebral folate deficiency: a neurometabolic syndrome?
Cerebral folate deficiency (CFD) is increasingly recognized in various neurological conditions, raising the question of whether it might represent a clear-cut clinical syndrome. Retrospective analysis of patients with low cerebral spinal fluid (CSF) 5-methyltetrahydrofolate (5MTHF) values was performed. 58 pediatric patients with low (-2nd to -3rd standard deviation) and 45 patients with very low 5MTHF values (<3rd standard deviation) were identified, including 22 patients with defined underlying neurological conditions. The leading symptoms were mental retardation (n=84), motor retardation (n=75), epilepsy (n=53), ataxia (n=44) and pyramidal tract signs (n=37). There was no relationship between 5MTHF levels and the severity of clinical disease, the duration of clinical disease, distinct neurological symptoms and antiepileptic drug treatment, respectively. Genetical analysis for mutations in the folate receptor 1 gene proved normal in all 16 children studied. For the majority of patients CFD is not a clear-cut neurometabolic syndrome but the common result of different genetic, metabolic or unknown processes. Nevertheless, CFD may represent a treatable disease-modifying factor which should therefore be addressed in prospective studies.


Serotyping and the Dienes reaction on Proteus mirabilis from hospital infections.
The serotype of 320 strains of Proteus mirabilis from clinical material was determined. Using 20 O antisera and four H antisera 61% of strains could be fully identified and 90% partially identified. A large number of serotypes were recognized but no difference was found between the serotype of organisms infecting the urinary tract and those from other infections. Biochemically identical organisms found in the same ward generally differed in serology. Proteus mirabilis was isolated from the faeces of 84.5% of 84 patients with urinary infection and from none of 20 normal controls. By serology and the Dienes test 61% of the organisms isolated from the urine and faeces of a single patient were identical, indicating that infection arose from the intestine. Most groups of serologically identical strains could, by the Dienes test, be further divided into a number of subtypes indicating that the strains were different and that cross infection had not been responsible for their spread. With three serological groups, however, the majority of strains belonged to a single Dienes type and it was concluded that these organisms had been spread from a common reservoir or carrier. Because of the unreliability of the Dienes test when carried out on random organisms it is suggested that reliable results can only be obtained by combining the Dienes test with serotyping.


Illumination performance and energy saving of a solar fiber optic lighting system.
The illumination performance and energy savings of a solar fiber optic lighting system have been verified in a study hall--corridor interior. The system provides intensive white light with a high luminous flux of 4500 lm under 130000 lx direct sun radiation at a 10 m fiber distance from the sun-tracking light collector. The color temperature that describes the light color perceived is 5800 ± 300 K, i.e. close to the direct sunlight outside, and the color rendering index (86), that describes how well colors are rendered under the light source, is higher for the solar lights than for the supplementary fluorescent lights (77). Thus this high quality solar lighting improves the visibility of all kinds of objects compared to the fluorescent lights. Annual lighting energy savings of 19% in Uppsala, Sweden and 46% in southern Europe were estimated for a study hall interior, as well as 27% and 55% respectively in an interior illuminated 16 h per day all days of a year.


Comparison of threshold of toxicological concern (TTC) values to oral reference dose (RfD) values.
Thousands of chemicals have limited, or no hazard data readily available to characterize human risk. The threshold of toxicological concern (TTC) constitutes a science-based tool for screening level risk-based prioritization of chemicals with low exposure. Herein we compare TTC values to more rigorously derived reference dose (RfD) values for 288 chemicals in the U.S. Environmental Protection Agency's (US EPA) Integrated Risk Information System (IRIS) database. Using the Cramer decision tree and the Kroes tiered decision tree approaches to determine TTC values, the TCC for the majority of these chemicals were determined to be lower than their corresponding RfD values. The ratio of log10(RfD/TCC) was used to measure the differences between these values and the mean ratio for the substances evaluated was ~0.74 and ~0.79 for the Cramer and Kroes approach, respectively, when considering the Cramer Classes only. These data indicate that the RfD values for Cramer Class III compounds were, on average, ~6-fold higher than their TTC value. These analyses indicate that provisional oral toxicity values might be estimated from TTCs in data-poor or emergency situations; moreover, RfD values that are well below TTC values (e.g., 2 standard deviations below the log10(Ratio)) might be overly conservative and targets for re-evaluation.


Host genotype-specific therapies can optimize the inflammatory response to mycobacterial infections.
Susceptibility to tuberculosis is historically ascribed to an inadequate immune response that fails to control infecting mycobacteria. In zebrafish, we find that susceptibility to Mycobacterium marinum can result from either inadequate or excessive acute inflammation. Modulation of the leukotriene A(4) hydrolase (LTA4H) locus, which controls the balance of pro- and anti-inflammatory eicosanoids, reveals two distinct molecular routes to mycobacterial susceptibility converging on dysregulated TNF levels: inadequate inflammation caused by excess lipoxins and hyperinflammation driven by excess leukotriene B(4). We identify therapies that specifically target each of these extremes. In humans, we identify a single nucleotide polymorphism in the LTA4H promoter that regulates its transcriptional activity. In tuberculous meningitis, the polymorphism is associated with inflammatory cell recruitment, patient survival and response to adjunctive anti-inflammatory therapy. Together, our findings suggest that host-directed therapies tailored to patient LTA4H genotypes may counter detrimental effects of either extreme of inflammation.


Relative Immaturity in Childhood and Attention-Deficit/Hyperactivity Disorder Symptoms From Childhood to Early Adulthood: Exploring Genetic and Environmental Overlap Across Development.
Attention-deficit/hyperactivity disorder (ADHD) has been linked to immaturity relative to peers in childhood, yet it is unclear how such immaturity is associated with ADHD across development. This longitudinal twin study examined the genetic and environmental contributions to the association between parents' perception of their child's immaturity relative to peers (RI) in childhood and ADHD symptoms across development. 1,302 twin pairs from the Swedish Twin Study of Child and Adolescent Development were followed prospectively from childhood to early adulthood. Parent ratings of RI were collected at 8 to 9 years and parent and self-ratings of ADHD symptoms were collected at 8 to 9, 13 to 14, 16 to 17, and 19 to 20 years using the Child Behavior Checklist Attention Problems scale. In addition, ADHD symptoms corresponding to DSM criteria were used for sensitivity analysis. Analyses were conducted using longitudinal structural equation modeling with multiple raters. RI-related etiologic factors, predominantly influenced by genes, explained 10-14% of the variance in ADHD symptoms from 8 to 9 up to 16 to 17 years. The influence of these RI-related factors on ADHD symptoms attenuated to 4% by 19 to 20 years of age. The remaining variance in ADHD symptoms was primarily explained by genetic factors independent of RI, which remained relatively stable across development, explaining 19% to 30% of the variance in ADHD symptoms from 13 to 14 up to 19 to 20 years. The results show that RI is significantly associated with ADHD symptoms, particularly during childhood and adolescence, and that the association is primarily explained by a shared genetic liability. Nevertheless, the magnitude of associations across development was modest, highlighting that RI is merely one aspect contributing to the complex etiology of ADHD symptoms.


Anesthetic management of the SRS™ Endoscopic Stapling System for gastro-esophageal reflux disease.
The SRS(TM) Endoscopic Stapling System (Medigus, Tel Aviv, Israel) is a new tool capable of creating a totally endoscopic fundoplication, combined with an endoscope, endoscopic ultrasound and a surgical stapler. SRS(TM) endoscopic stapling for gastro-esophageal reflux disease is a minimally invasive, outpatient procedure, which requires general anesthesia with positive-pressure ventilation. Keeping the patient on positive end-expiratory pressure (PEEP) may minimize the pressure gradient between the esophagus and the mediastinum, as well as help to prevent air from leaking around the screws and causing pneumomediastinum. In addition, in patients with hiatal hernia, higher PEEP levels may be required to increase intra-thoracic pressure and to force the stomach to slide into the abdomen for ease of endoscopy. We advise smoother emergence from anesthesia, taking precautions for retching, postoperative nausea and vomiting (PONV), while coughing and gagging during extubation and PONV may affect the success of the procedure. Total intravenous anesthesia with propofol and remifentanil seems to be a good choice for these reasons.


"MacCallum Plaque of the Heart": A Medicolegal Case.
Mural endocardial lesions can be seen as MacCallum plaques in rheumatic heart disease. These plaques appear as map-like areas of thickened, roughened, and wrinkled part of the endocardium in the left atrium. Perhaps they are caused by regurgitant jets of blood flow, due to incompetence of the mitral valve. Although MacCallum plaques are one of the characteristic features in rheumatic heart disease, they are very uncommon in recent times. We hereby report a case of an adolescent female with RHD, who was working as a housemaid in a doctor's house for a few months, and suddenly developed respiratory tract infection and cardiac failure. She died on the fourth day of admission. A medicolegal autopsy was conducted, as her relatives accused her master of sexual assault. On autopsy it was seen that the mitral valves were narrowed, showing multiple vegetations. MacCallum plaque was seen in the dilated left atrium. Hence, it is presented here for educative purposes.


Changes in food pricing and availability on the Navajo Nation following a 2% tax on unhealthy foods: The Healthy Diné Nation Act of 2014.
In 2014, the Navajo Nation Healthy Diné Nation Act (HDNA) was passed, combining a 2% tax on foods of 'minimal-to-no-nutritional value' and waiver of 5% sales tax on healthy foods, the first-ever such tax in the U.S. and globally among a sovereign tribal nation. The aim of this study was to measure changes in pricing and food availability in stores on the Navajo Nation following the implementation of the HDNA. Store observations were conducted in 2013 and 2019 using the Nutrition Environment Measurement Survey-Stores (NEMS-S) adapted for the Navajo Nation. Observations included store location, type, whether healthy foods or HDNA were promoted, and availability and pricing of fresh fruits and vegetables, canned items, beverages, water, snacks and traditional foods. Differences between 2013 and 2019 and by store type and location were tested. The matched sample included 71 stores (51 in the Navajo Nation and 20 in border towns). In 2019, fresh produce was available in the majority of Navajo stores, with 71% selling at least 3 types of fruit and 65% selling at least 3 types of vegetables. Compared with border town convenience stores, Navajo convenience stores had greater availability of fresh vegetables and comparable availability of fresh fruit in 2019. The average cost per item of fresh fruit decreased by 13% in Navajo stores (from $0.88 to $0.76) and increased in border stores (from $0.63 to $0.73), resulting in comparable prices in Navajo and border stores in 2019. While more Navajo stores offered mutton, blue corn and wild plants in 2019 compared to 2013, these changes were not statistically significant. The findings suggest modest improvements in the Navajo store environment and high availability of fruits and vegetables. Navajo stores play an important role in the local food system and provide access to local, healthy foods for individuals living in this rural, tribal community.


Data visualization optimization via computational modeling of perception.
We present a method for automatically evaluating and optimizing visualizations using a computational model of human vision. The method relies on a neural network simulation of early perceptual processing in the retina and primary visual cortex. The neural activity resulting from viewing flow visualizations is simulated and evaluated to produce a metric of visualization effectiveness. Visualization optimization is achieved by applying this effectiveness metric as the utility function in a hill-climbing algorithm. We apply this method to the evaluation and optimization of 2D flow visualizations, using two visualization parameterizations: streaklet-based and pixel-based. An emergent property of the streaklet-based optimization is head-to-tail streaklet alignment. It had been previously hypothesized the effectiveness of head-to-tail alignment results from the perceptual processing of the visual system, but this theory had not been computationally modeled. A second optimization using a pixel-based parameterization resulted in a LIC-like result. The implications in terms of the selection of primitives is discussed. We argue that computational models can be used for optimizing complex visualizations. In addition, we argue that they can provide a means of computationally evaluating perceptual theories of visualization, and as a method for quality control of display methods.


Dispersion and shape engineered plasmonic nanosensors.
Biosensors based on the localized surface plasmon resonance (LSPR) of individual metallic nanoparticles promise to deliver modular, low-cost sensing with high-detection thresholds. However, they continue to suffer from relatively low sensitivity and figures of merit (FOMs). Herein we introduce the idea of sensitivity enhancement of LSPR sensors through engineering of the material dispersion function. Employing dispersion and shape engineering of chiral nanoparticles leads to remarkable refractive index sensitivities (1,091 nm RIU(-1) at λ=921 nm) and FOMs (>2,800 RIU(-1)). A key feature is that the polarization-dependent extinction of the nanoparticles is now characterized by rich spectral features, including bipolar peaks and nulls, suitable for tracking refractive index changes. This sensing modality offers strong optical contrast even in the presence of highly absorbing media, an important consideration for use in complex biological media with limited transmission. The technique is sensitive to surface-specific binding events which we demonstrate through biotin-avidin surface coupling.


Intracerebral hemorrhage in pregnancy: frequency, risk factors, and outcome.
To describe the frequency, risk factors, and outcome of intracerebral hemorrhage (ICH) in pregnancy and the postpartum period using a large database of US inpatient hospitalizations. The authors obtained data from an administrative dataset, the Nationwide Inpatient Sample, which includes approximately 20% of all discharges from non-Federal hospitals, for the years 1993 through 2002. Women aged 15 to 44 years with a diagnosis of ICH were selected from the database for analysis, and within this group patients coded as pregnant or postpartum were identified. Using US Census data, estimates were made of the rates of ICH in pregnant/postpartum and non-pregnant women. Rates of various comorbidities in patients with pregnancy-related ICH were compared to the rates found in the general population of delivering patients using multivariate logistic regression to identify independent risk factors for pregnancy-related ICH. The authors identified 423 patients with pregnancy-related ICH, which corresponded to 6.1 pregnancy-related ICH per 100,000 deliveries and 7.1 pregnancy-related ICH per 100,000 at-risk person-years (compared to 5.0 per 100,000 person-years for non-pregnant women in the age range considered). The increased risk of ICH associated with pregnancy was largely attributable to ICH occurring in the postpartum period. The in-hospital mortality rate for pregnancy-related ICH was 20.3%. ICH accounted for 7.1% of all pregnancy-related mortality recorded in this database. Significant independent risk factors for pregnancy-related ICH included advanced maternal age (OR 2.11, 95% CI 1.69 to 2.64), African American race (OR 1.83, 95% CI 1.39 to 2.41), preexisting hypertension (OR 2.61, 95% CI 1.34 to 5.07), gestational hypertension (OR 2.41, 95% CI 1.62 to 3.59), preeclampsia/eclampsia (OR 10.39, 95% CI 8.32 to 12.98), preexisting hypertension with superimposed preeclampsia/eclampsia (OR 9.23, 95% CI 5.26 to 16.19), coagulopathy (OR 20.66, 95% CI 13.67 to 31.23), and tobacco abuse (OR 1.95, 95% CI 1.11 to 3.42). Intracerebral hemorrhage (ICH) accounts for a substantial portion of pregnancy-related mortality. The risk of ICH associated with pregnancy is greatest in the postpartum period. Advanced maternal age, African American race, hypertensive diseases, coagulopathy, and tobacco abuse were all independent risk factors for pregnancy-related ICH.


Development of microsatellite markers for Hancornia speciosa Gomes (Apocynaceae).
Herein, we describe 34 microsatellite loci developed using an enrichment genomic library for the tree species Hancornia speciosa Gomes (Apocynaceae). Thirty-five individuals were genotyped using 34 primers to analyze the polymorphisms at each locus. The number of alleles per locus ranged from 4 to 20. The average number of alleles was 8.11, and the expected heterozygosity ranged from 0.62 to 0.94. These microsatellite primers will be useful in population genetics studies for this species.


Generalized implicit fear associations in generalized anxiety disorder.
Cognitive schema theories of anxiety postulate that higher-level cognitive processes such as attention and memory are guided by underlying distorted fear associations. While numerous studies investigated these disorder-specific, biased processes, hardly any research addressed the underlying schemata themselves. In particular, no study has ever addressed implicit fear associations in Generalized Anxiety Disorder (GAD). In addition, no study has ever experimentally investigated the clinical observation that in GAD, patients' worry processes seem to be triggered by a broad range of materials, even by neutral or positive stimuli. We used a Single Target Implicit Association Task (STIAT) to investigate implicit associations and stimulus generalization with clearly negative worry-related words (e.g., cancer, bankruptcy) and neutral words that are only indirectly related to worry topics (e.g., doctor, bank). Participants were 39 GAD patients and 23 healthy controls. In line with our expectations, both groups showed negative implicit associations with negative target words, and only GAD patients also associated neutral words with negative attributes. These results support the hypothesis that GAD patients' fear associations generalize to stimuli that are only peripherally related to the core of their worries.