Associations of collectivism with relationship commitment, passion, and mate preferences: opposing roles of parental influence and family allocentrism.
In collectivist cultures, families tend to be characterized by respect for parental authority and strong, interdependent ties. Do these aspects of collectivism exert countervailing pressures on mate choices and relationship quality? In the present research, we found that collectivism was associated with greater acceptance of parental influence over mate choice, thereby driving relationship commitment down (Studies 1 and 2), but collectivism was also associated with stronger family ties (referred to as family allocentrism), which drove commitment up (Study 2). Along similar lines, Study 1 found that collectivists' greater acceptance of parental influence on mate choice contributed to their reduced relationship passion, whereas Study 2 found that their greater family allocentrism may have enhanced their passion. Study 2 also revealed that collectivists may have reported a smaller discrepancy between their own preferences for mates high in warmth and trustworthiness and their perception of their parents' preferences for these qualities because of their stronger family allocentrism. However, their higher tolerance of parental influence may have also contributed to a smaller discrepancy in their mate preferences versus their perceptions of their parents' preferences for qualities signifying status and resources. Implications for the roles of collectivism, parental influence, and family allocentrism in relationship quality and mate selection will be discussed.


Decision-to-incision times and maternal and infant outcomes.
To measure decision-to-incision intervals and related maternal and neonatal outcomes in a cohort of women undergoing emergency cesarean deliveries at multiple university-based hospitals comprising the National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. All women undergoing a primary cesarean delivery at a Network center during a 2-year time span were prospectively ascertained. Emergency procedures were defined as those performed for umbilical cord prolapse, placental abruption, placenta previa with hemorrhage, nonreassuring fetal heart rate pattern, or uterine rupture. Detailed information regarding maternal and neonatal outcomes, including the interval from the decision time to perform cesarean delivery to the actual skin incision, was collected. Of the 11,481 primary cesarean deliveries, 2,808 were performed for an emergency indication. Of these, 1,814 (65%) began within 30 minutes of the decision to operate. Maternal complication rates, including endometritis, wound infection, and operative injury, were not related to the decision-to-incision interval. Measures of newborn compromise including umbilical artery pH less than 7 and intubation in the delivery room were significantly greater when the cesarean delivery was commenced within 30 minutes, likely attesting to the need for expedited delivery. Of the infants with indications for an emergency cesarean delivery who were delivered more than 30 minutes after the decision to operate, 95% did not experience a measure of newborn compromise. Approximately one third of primary cesarean deliveries performed for emergency indications are commenced more than 30 minutes after the decision to operate, and the majority were for nonreassuring heart rate tracings. In these cases, adverse neonatal outcomes were not increased. II-2.


Behavior of 11 Foodborne Bacteria on Whole and Cut Mangoes var. Ataulfo and Kent and Antibacterial Activities of Hibiscus sabdariffa Extracts and Chemical Sanitizers Directly onto Mangoes Contaminated with Foodborne Bacteria.
The behavior of foodborne bacteria on whole and cut mangoes and the antibacterial effect of Hibiscus sabdariffa calyx extracts and chemical sanitizers against foodborne bacteria on contaminated mangoes were investigated. Mangoes var. Ataulfo and Kent were used in the study. Mangoes were inoculated with Listeria monocytogenes, Shigella flexneri, Salmonella Typhimurium, Salmonella Typhi, Salmonella Montevideo, Escherichia coli strains (O157:H7, non-O157:H7 Shiga toxin-producing, enteropathogenic, enterotoxigenic, enteroinvasive, and enteroaggregative). The antibacterial effect of five roselle calyx extracts (water, ethanol, methanol, acetone, and ethyl acetate), sodium hypochlorite, colloidal silver, and acetic acid against foodborne bacteria were evaluated on contaminated mangoes. The dry extracts obtained with ethanol, methanol, acetone, and ethyl acetate were analyzed by nuclear magnetic resonance spectroscopy to determine solvent residues. Separately, contaminated whole mangoes were immersed in five hibiscus extracts and in sanitizers for 5 min. All foodborne bacteria attached to mangoes. After 20 days at 25 ± 2°C, all foodborne bacterial strains on whole Ataulfo mangoes had decreased by approximately 2.5 log, and on Kent mangoes by approximately 2 log; at 3 ± 2°C, they had decreased to approximately 1.9 and 1.5 log, respectively, on Ataulfo and Kent. All foodborne bacterial strains grew on cut mangoes at 25 ± 2°C; however, at 3 ± 2°C, bacterial growth was inhibited. Residual solvents were not detected in any of the dry extracts by nuclear magnetic resonance. Acetonic, ethanolic, and methanolic roselle calyx extracts caused a greater reduction in concentration (2 to 2.6 log CFU/g) of all foodborne bacteria on contaminated whole mangoes than the sodium hypochlorite, colloidal silver, and acetic acid. Dry roselle calyx extracts may be a potentially useful addition to disinfection procedures of mangoes.


Relaxant effect of Crocus sativus (saffron) on guinea-pig tracheal chains and its possible mechanisms.
As indicated in ancient Iranian medical books, Crocus sativus has therapeutic effects on respiratory diseases. The relaxant effect of this plant has been observed also on smooth muscles in previous studies. Therefore, in this study the relaxant effects of aqueous-ethanolic extracts of C. sativus and one of its main constituents, safranal, were examined on guinea-pig tracheal chains. The relaxant effects of four cumulative concentrations of aqueous-ethanolic extract (0.15, 0.3, 0.45, and 0.60 g %) and safranal (0.15, 0.30, 0.45, and 0.60 mL 0.2 mg mL(-1) solution) in comparison with saline, as negative control, and four cumulative concentrations of theophylline (0.15, 0.30, 0.45, and 0.60 mM), as positive control, were examined using guinea-pig precontracted tracheal chains. The tracheal chains had been precontracted by three different methods. Group 1 had been precontracted using 10 microM methacholine. The other two groups had been precontracted using 60 mM KCl at two different conditions: non-incubated tissues (group 2) and tissues incubated with 1 microM propranolol, 1 microM chlorpheniramine and 1 microM atropine (group 3) (for each group, n = 6). In group 1 all concentrations of theophylline, extract and safranal showed significant relaxant effects compared with saline (P < 0.05 to P < 0.001). In group 2 theophylline, extract and safranal showed concentration-dependent relaxant effects also compared with saline (P < 0.05 to P < 0.001 for different concentrations except two low concentrations of safranal). However, in group 3 the extracts of C. sativus showed a weak relaxant effect (P < 0.05 only for the highest concentration). The effects of the last concentration of safranal (0.60 mL 0.2 mg mL(-1) solution) in group 1, and all its concentrations in group 2 were significantly lower than those of theophylline (P < 0.05 to P < 0.001). In addition, the effects of safranal 0.45 and 0.60 mL 0.2 mg mL(-1) solution in groups 1 and 2 were significantly lower than that of C. sativus extract. There were significant correlations between the relaxant effects and concentrations for extract, safranal and theophylline in all experimental groups (P < 0.001 for all cases). These results showed a potent relaxant effect of C. sativus on tracheal chains of guinea-pigs that was comparable to or even higher than that of theophylline at the concentrations used. The results indicated that safranal was, at least in part, responsible for the relaxant effect of C. sativus.


Clinical features and outcome of pulmonary embolism in children.
Pulmonary embolism (PE) is rare in childhood but evidence suggests it is under-recognised. Children diagnosed with PE at a large tertiary centre over an 8-year period were retrospectively reviewed. Fifty-six children with radiologically proven PE were identified, 31 males and 25 females, median age 12 years. Eighty-four per cent had symptoms of PE. Risk factors for thromboembolism were present in 54 patients (96.4%); most commonly immobility (58.9%), central venous line (35.7%) and recent surgery (28.6%). Investigation revealed a thrombophilic abnormality in 14/40 patients (35%). Concurrent deep vein thrombosis was confirmed in 31 patients (55.4%), predominantly lower limb. D dimer was elevated at presentation in 26/30 patients (86.7%). Eight patients underwent systemic thrombolysis. An inferior vena cava filter was placed in five patients. Therapy was complicated by major haemorrhage in 12 patients (21.4%). The majority (82.1%) had complete or partial resolution of PE following a median of 3 months anticoagulation. Seven patients had a recurrent thromboembolic event and 12 patients died (mortality 21.4%); five due to thromboembolism (8.9%) and two due to haemorrhage. Risk factors for PE in children are distinct from adults and morbidity and mortality is significant. Multicentre prospective studies are required to determine optimal treatment and long-term outcome of childhood PE.


Phylogenomics resolves the deep phylogeny of seed plants and indicates partial convergent or homoplastic evolution between Gnetales and angiosperms.
After decades of molecular phylogenetic studies, the deep phylogeny of gymnosperms has not been resolved, and the phylogenetic placement of Gnetales remains one of the most controversial issues in seed plant evolution. To resolve the deep phylogeny of seed plants and to address the sources of phylogenetic conflict, we conducted a phylotranscriptomic study with a sampling of all 13 families of gymnosperms and main lineages of angiosperms. Multiple datasets containing up to 1 296 042 sites across 1308 loci were analysed, using concatenation and coalescence approaches. Our study generated a consistent and well-resolved phylogeny of seed plants, which places Gnetales as sister to Pinaceae and thus supports the Gnepine hypothesis. Cycads plus Ginkgo is sister to the remaining gymnosperms. We also found that Gnetales and angiosperms have similar molecular evolutionary rates, which are much higher than those of other gymnosperms. This implies that Gnetales and angiosperms might have experienced similar selective pressures in evolutionary histories. Convergent molecular evolution or homoplasy is partially responsible for the phylogenetic conflicts in seed plants. Our study provides a robustly reconstructed backbone phylogeny that is important for future molecular and morphological studies of seed plants, in particular gymnosperms, in the light of evolution.


Telangiectasia and venous reflux in the Edinburgh Vein Study.
The purpose of this study was to correlate the clinical findings in the Edinburgh Vein Study with the results of duplex scanning of the deep and superficial venous systems. An age-stratified random sample of 1566 people (699 men and 867 women) aged 16-64 were selected from computerized age-sex registers of participating practices (twelve general practices with catchment areas geographically and socioeconomically distributed throughout Edinburgh). Screening included clinical examination, photography and duplex ultrasonography of the superficial veins and the deep veins down to popliteal level. Telangiectasia and varicose veins were graded 1-3 according to severity. Since there was good agreement between the duplex findings of the right versus left legs, the current analyses are based on 1092 subjects (486 men and 606 women) with complete duplex scan data in their left legs. There was no significant trend of increasing incompetence in either the deep veins only (P = 0.214) or in the combined deep and superficial veins (P = 0.111) with increasing severity of the telangiectasia. There was a statistically significant trend for increasing incompetence in (a) the superficial veins (P = 0.006) and (b) either the superficial or deep veins (P < 0.001) to be associated with advancing grade of telangiectasia. When stratified by gender, significant trends were maintained for male superficial vein incompetence and for either superficial or deep incompetence in both genders. Examination of incompetence in individual venous segments showed that increasing severity of telangiectasia was significantly associated with an increasing proportion of reflux in the upper and lower great saphenous and femoral vein segments. There was no significant association between small saphenous incompetence and increasing grade of telangiectasia. There is a significant, but not wholly consistent, association between grade of telangiectasia and reflux in both the deep and superficial systems. This association does not apply to the small saphenous system.


Plasticity during childhood and adolescence: innovative approaches to investigating neurocognitive development.
Adolescence is a period of profound change, which holds substantial developmental milestones, but also unique challenges to the individual. In this opinion paper, we highlight the potential of combining two recently developed behavioural and neural training techniques (cognitive bias modification and functional magnetic neuroimaging-based neurofeedback) into a research approach that could help make the most of increased levels of plasticity during childhood and adolescence. We discuss how this powerful combination could be used to explore changing brain-behaviour relationships throughout development in the context of emotion processing, a cognitive domain that exhibits continuous development throughout the second decade of life. By targeting both behaviour and brain response, we would also be in an excellent position to define sensible time windows for enhancing plasticity, thereby allowing for targeted intervention approaches that can help improve emotion processing in both typically and atypically developing populations.


Surgical Management of Primary Hyperparathyroidism in the Era of Focused Parathyroidectomy: A Study in Tertiary Referral Centre of North India.
Despite the benefits of focused parathyroidectomy (FPTx), few studies have questioned its durability with lower long-term cure rates than bilateral or conventional parathyroidectomy (CPTx). The objective of this study is to bring out the information on the type of surgical management versus cure rate, recurrence, and role of intra-operative parathyroid hormone (IOPTH) level monitoring of PHPT patients. This was a retrospective study of all PHPT patients treated at our center based on operative approach (CPTx vs FPTx) or use of IOPTH. Treatment failure was divided into persistent or recurrent disease, based on documentation of hypercalcemia in combination with an inappropriate PTH within 6 months or more of surgery, respectively. Overall, 50.78% patients underwent CPTx and 49.32% FPTx. 29 FPTx were converted to CPTx. Intention to treat analysis between CPTx and FPTx showed that the persistence rate was not statistically different at 2.54% and 4%, respectively (P = 0.98). Furthermore, when the persistence rate was scrutinized by a treatment received (TR) instead of ITT analysis, the persistence rate was higher for the patients who underwent TR-CPTX than for the patients subjected to TR-FPTX (3.22% vs 1.08%) but not significant statistically. We further analyzed the outcome of FPTx with IOPTH (n = 213) and FPTx without IOPTH (n = 28). The outcome did not differ between two groups statistically. FPTx yields a similar success rate as compared to CPTx even in symptomatic PHPT patients and can be performed safely even without intra-opeartive adjunct IOPTH in selected patients.


Do Dog Behavioral Characteristics Predict the Quality of the Relationship between Dogs and Their Owners?
This paper explores whether dog behavioral characteristics predict the quality of the relationship between dogs and their owners (i.e., owner attachment to dog), and whether relations between dog behavior and owner attachment are moderated by demographic characteristics. In this study, N = 92 children and N = 60 adults from 60 dog-owning families completed questionnaires about their attachment to their pet dog, their level of responsibility for that dog, and their general attitudes toward pets. They also rated their dogs on observable behavioral characteristics. Individuals who held positive attitudes about pets and who provided much of their dog's care reported stronger attachments to their dogs. The strength of owners' attachments to their dogs was associated with dog trainability and separation problems. Relationships between owner attachment and both dog excitability and attention-seeking behavior were further moderated by demographic characteristics: for Caucasians but not for non-Caucasians, dog excitability was negatively associated with owner attachment to dog; and for adults, dog attention-seeking behavior was positively associated with owner attachment, but children tended to be highly attached to their dogs, regardless of their dogs' attention-seeking behaviors. This study demonstrates that certain dog behavioral traits are indeed associated with the strength of owners' attachments to their dogs.


Peptide nucleic acid - an opportunity for bio-nanotechnology.
DNA is a major player in the field of bio-nanotechnology and many interesting applications have been realized using this oligonucleotide. In contrast, the use of peptide nucleic acid (PNA), which is a non-natural, neutral analogue of DNA with superior hybridization strengths compared to DNA, is still in its infancy in bio-nanotechnology. However, as demonstrated in this short review using selected studies, promising examples demonstrating the tremendous opportunities that PNA can offer for bio-nanotechnology were recently described.


Effect of explosive versus slow contractions and exercise intensity on energy expenditure.
The primary purpose of this study was to compare the effects of explosive versus slow contractions on the rate of energy expenditure during and after resistance exercise. Nine men (20 +/- 2.5 yr) performed three exercise protocols using a plate-loaded squat machine, and a no-exercise (CONTROL) session in a randomly assigned, counterbalanced order. Subjects performed squats using either two second (SLOW) or explosive concentric contractions (EXPL), but identical repetitions (8), sets (4), and loads (60% 1RM). A secondary objective was to compare high- versus moderate-intensity exercise. Thus, a third protocol was performed that also used explosive contractions, with heavier loads (80% 1RM) and six sets of four reps (HEAVYEXPL). Eccentric reps (2 s), work (reps x sets x load), range of motion, and rest intervals between sets (90 s) were identical among all three protocols. Expired air was collected continuously for 20 min before, during, and 1 h after exercise and for about 1.5 h during CONTROL. Blood samples (25 microL) were collected before, immediately after, and 15, 30, 45, and 60 min after each protocol, and these samples were analyzed for blood lactate (mM). Average rates of energy expenditure (kcal.min) were significantly greater (P <or= 0.05) during (7.27 +/- 2.00 > 6.43 +/- 1.64 and 6.25 +/- 1.55, respectively) and after (2.54 +/- 1.44 > 2.38 +/- 1.31 and 2.21 +/- 1.08, respectively) EXPL compared with SLOW and HEAVYEXPL, despite significantly (P <or= 0.05) greater blood lactate after SLOW. Squat exercise using explosive contractions and moderate intensity induced a greater increase in the rate of energy expenditure than squats using slow contractions or high intensity in all subjects tested. Thus, by using explosive contractions and moderate exercise intensity, experienced recreational exercisers can increase their energy expenditure during and after resistance exercise, and this could enhance weight-loss adaptations.


Using an Interaction Parameter in Model-Based Phase I Trials for Combination Treatments? A Simulation Study.
There is growing interest in Phase I dose-finding studies studying several doses of more than one agent simultaneously. A number of combination dose-finding designs were recently proposed to guide escalation/de-escalation decisions during the trials. The majority of these proposals are model-based: a parametric combination-toxicity relationship is fitted as data accumulates. Various parameter shapes were considered but the unifying theme for many of these is that typically between 4 and 6 parameters are to be estimated. While more parameters allow for more flexible modelling of the combination-toxicity relationship, this is a challenging estimation problem given the typically small sample size in Phase I trials of between 20 and 60 patients. These concerns gave raise to an ongoing debate whether including more parameters into combination-toxicity model leads to more accurate combination selection. In this work, we extensively study two variants of a 4-parameter logistic model with reduced number of parameters to investigate the effect of modelling assumptions. A framework to calibrate the prior distributions for a given parametric model is proposed to allow for fair comparisons. Via a comprehensive simulation study, we have found that the inclusion of the interaction parameter between two compounds does not provide any benefit in terms of the accuracy of selection, on average, but is found to result in fewer patients allocated to the target combination during the trial.


An experimental comparison of min-cut/max-flow algorithms for energy minimization in vision.
After [15], [31], [19], [8], [25], [5], minimum cut/maximum flow algorithms on graphs emerged as an increasingly useful tool for exact or approximate energy minimization in low-level vision. The combinatorial optimization literature provides many min-cut/max-flow algorithms with different polynomial time complexity. Their practical efficiency, however, has to date been studied mainly outside the scope of computer vision. The goal of this paper is to provide an experimental comparison of the efficiency of min-cut/max flow algorithms for applications in vision. We compare the running times of several standard algorithms, as well as a new algorithm that we have recently developed. The algorithms we study include both Goldberg-Tarjan style "push-relabel" methods and algorithms based on Ford-Fulkerson style "augmenting paths." We benchmark these algorithms on a number of typical graphs in the contexts of image restoration, stereo, and segmentation. In many cases, our new algorithm works several times faster than any of the other methods, making near real-time performance possible. An implementation of our max-flow/min-cut algorithm is available upon request for research purposes.


Gankyrin plays an essential role in Ras-induced tumorigenesis through regulation of the RhoA/ROCK pathway in mammalian cells.
Activating mutations in Ras proteins are present in about 30% of human cancers. Despite tremendous progress in the study of Ras oncogenes, many aspects of the molecular mechanisms underlying Ras-induced tumorigenesis remain unknown. Through proteomics analysis, we previously found that the protein Gankyrin, a known oncoprotein in hepatocellular carcinoma, was upregulated during Ras-mediated transformation, although the functional consequences of this were not clear. Here we present evidence that Gankyrin plays an essential role in Ras-initiated tumorigenesis in mouse and human cells. We found that the increased Gankyrin present following Ras activation increased the interaction between the RhoA GTPase and its GDP dissociation inhibitor RhoGDI, which resulted in inhibition of the RhoA effector kinase Rho-associated coiled coil-containing protein kinase (ROCK). Importantly, Gankyrin-mediated ROCK inhibition led to prolonged Akt activation, a critical step in activated Ras-induced transformation and tumorigenesis. In addition, we found that Gankyrin is highly expressed in human lung cancers that have Ras mutations and that increased Gankyrin expression is required for the constitutive activation of Akt and tumorigenesis in these lung cancers. Our findings suggest that Gankyrin is a key regulator of Ras-mediated activation of Akt through inhibition of the downstream RhoA/ROCK pathway and thus plays an essential role in Ras-induced tumorigenesis.


Distinctive Feature of Microbial Communities and Bacterial Functional Profiles in Tricholoma matsutake Dominant Soil.
Tricholoma matsutake, the pine mushroom, is a valuable forest product with high economic value in Asia, and plays an important ecological role as an ectomycorrhizal fungus. Around the host tree, T. matsutake hyphae generate a distinctive soil aggregating environment called a fairy ring, where fruiting bodies form. Because T. matsutake hyphae dominate the soil near the fairy ring, this species has the potential to influence the microbial community. To explore the influence of T. matsutake on the microbial communities, we compared the microbial community and predicted bacterial function between two different soil types-T. matsutake dominant and T. matsutake minor. DNA sequence analyses showed that fungal and bacterial diversity were lower in the T. matsutake dominant soil compared to T. matsutake minor soil. Some microbial taxa were significantly more common in the T. matsutake dominant soil across geographic locations, many of which were previously identified as mycophillic or mycorrhiza helper bacteria. Between the two soil types, the predicted bacterial functional profiles (using PICRUSt) had significantly distinct KEGG modules. Modules for amino acid uptake, carbohydrate metabolism, and the type III secretion system were higher in the T. matsutake dominant soil than in the T. matsutake minor soil. Overall, similar microbial diversity, community structure, and bacterial functional profiles of the T. matsutake dominant soil across geographic locations suggest that T. matsutake may generate a dominance effect.


Repressors NFI and NFY participate in organ-specific regulation of von Willebrand factor promoter activity in transgenic mice.
To determine the role of repressors in cell type and organ-specific activation of von Willebrand factor (VWF) promoter sequences -487 to 247 in vivo. Activation patterns of wild-type and mutant VWF promoters (sequences -487 to 247) containing mutations in repressors nuclear factor-I (NFI)- and nuclear factor Y (NFY)-binding sites were analyzed in transgenic mice. Mutation of the NFI-binding site activated the promoter in heart and lung endothelial cells, whereas mutation of the NFY-binding site activated the promoter in kidney vasculature. Immunofluorescence analyses showed that NFIB was predominant in heart and lung endothelial cells, whereas NFIX was predominantly detected in kidney endothelial cell nuclei. By using chromatin immunoprecipitation, we demonstrated that the distal lung-specific enhancer (containing a YY1 site) of the VWF gene is brought in proximity to the NFI binding site. The NFI and NFY repressors contribute differentially to organ-specific regulation of the VWF promoter, and the organ-specific action of NFI may reflect its organ-specific isoform distribution. In addition, the lung-specific enhancer region of the endogenous VWF gene may inhibit NFI repressor function through chromatin looping, which can approximate the 2 regions.


Intestinal lipid absorption in the nephrotic rat.
There is limited data on intestinal lipid absorption in the nephrotic syndrome. This study investigated whether the efficiency of intestinal lipid absorption is altered in nephrotic lymph-fistula rats. The nephrotic syndrome was induced in nine Sprague-Dawley rats by an i.v. injection of puromycin aminonucleoside in saline; seven control rats received saline only. At 10 to 14 days after injection, the main intestinal lymph duct was cannulated for collection of lymph. The duodenum was also cannulated and a fasting saline-glucose solution was infused overnight at 3 mL/h. The next day, the infusate was changed to a lipid emulsion that contained (14C) cholesterol and (3H)triglyceride (triolein) that was infused at 3 mL/h for 8 h. During the last hour of fasting and during the lipid infusion, lymph flow in the Nephrotic group averaged 0.6 mL/h higher than the Control group (P = 0.02). No significant differences were found between the two groups in recovery of infused radioactive cholesterol (P = 0.37) or triglyceride (P = 0.38) from the gastrointestinal lumen, small intestinal mucosa, or lymph. Lymphatic output of chemically measured cholesterol was also similar (P = 0.96). These results suggest that mucosal uptake and lymphatic output of cholesterol and triglyceride are not altered in the nephrotic syndrome.


Bayesian nonparametric discovery of isoforms and individual specific quantification.
Most human protein-coding genes can be transcribed into multiple distinct mRNA isoforms. These alternative splicing patterns encourage molecular diversity, and dysregulation of isoform expression plays an important role in disease etiology. However, isoforms are difficult to characterize from short-read RNA-seq data because they share identical subsequences and occur in different frequencies across tissues and samples. Here, we develop BIISQ, a Bayesian nonparametric model for isoform discovery and individual specific quantification from short-read RNA-seq data. BIISQ does not require isoform reference sequences but instead estimates an isoform catalog shared across samples. We use stochastic variational inference for efficient posterior estimates and demonstrate superior precision and recall for simulations compared to state-of-the-art isoform reconstruction methods. BIISQ shows the most gains for low abundance isoforms, with 36% more isoforms correctly inferred at low coverage versus a multi-sample method and 170% more versus single-sample methods. We estimate isoforms in the GEUVADIS RNA-seq data and validate inferred isoforms by associating genetic variants with isoform ratios.


Antimicrobial and Antibiofilm Activities of the Fungal Metabolites Isolated from the Marine Endophytes Epicoccum nigrum M13 and Alternaria alternata 13A.
Epicotripeptin (1), a new cyclic tripeptide along with four known cyclic dipeptides (2-5) and one acetamide derivative (6) were isolated from seagrass-associated endophytic fungus Epicoccum nigrum M13 recovered from the Red Sea. Additionally, two new compounds, cyclodidepsipeptide phragamide A (7) and trioxobutanamide derivative phragamide B (8), together with eight known compounds (9-16), were isolated from plant-derived endophyte Alternaria alternata 13A collected from a saline lake of Wadi El Natrun depression in the Sahara Desert. The structures of the isolated compounds were determined based on the 1D and 2D NMR spectroscopic data, HRESIMS data, and a comparison with the reported literature. The absolute configurations of 1 and 7 were established by advanced Marfey's and Mosher's ester analyses. The antimicrobial screening indicated that seven of the tested compounds exhibited considerable (MIC range of 2.5-5 µg/mL) to moderate (10-20 µg/mL) antibacterial effect against the tested Gram-positive strains and moderate to weak (10-30 µg/mL) antibacterial effect against Gram-negative strains. Most of the compounds exhibited weak or no activity against the tested Gram-negative strains. On the other hand, four of the tested compounds showed considerable antibiofilm effects against biofilm forming Gram-positive and Gram-negative strains.


Evolution and diversification of Pseudomonas aeruginosa in the paranasal sinuses of cystic fibrosis children have implications for chronic lung infection.
The opportunistic pathogen Pseudomonas aeruginosa is a frequent colonizer of the airways of patients suffering from cystic fibrosis (CF). Depending on early treatment regimens, the colonization will, with high probability, develop into chronic infections sooner or later, and it is important to establish under which conditions the switch to chronic infection takes place. In association with a recently established sinus surgery treatment program for CF patients at the Copenhagen CF Center, colonization of the paranasal sinuses with P. aeruginosa has been investigated, paralleled by sampling of sputum from the same patients. On the basis of genotyping and phenotypic characterization including transcription profiling, the diversity of the P. aeruginosa populations in the sinuses and the lower airways was investigated and compared. The observations made from several children show that the paranasal sinuses constitute an important niche for the colonizing bacteria in many patients. The paranasal sinuses often harbor distinct bacterial subpopulations, and in the early colonization phases there seems to be a migration from the sinuses to the lower airways, suggesting that independent adaptation and evolution take place in the sinuses. Importantly, before the onset of chronic lung infection, lineages with mutations conferring a large fitness benefit in CF airways such as mucA and lasR as well as small colony variants and antibiotic-resistant clones are part of the sinus populations. Thus, the paranasal sinuses potentially constitute a protected niche of adapted clones of P. aeruginosa, which can intermittently seed the lungs and pave the way for subsequent chronic lung infections.


Graph edit distance from spectral seriation.
This paper is concerned with computing graph edit distance. One of the criticisms that can be leveled at existing methods for computing graph edit distance is that they lack some of the formality and rigor of the computation of string edit distance. Hence, our aim is to convert graphs to string sequences so that string matching techniques can be used. To do this, we use a graph spectral seriation method to convert the adjacency matrix into a string or sequence order. We show how the serial ordering can be established using the leading eigenvector of the graph adjacency matrix. We pose the problem of graph-matching as a maximum a posteriori probability (MAP) alignment of the seriation sequences for pairs of graphs. This treatment leads to an expression in which the edit cost is the negative logarithm of the a posteriori sequence alignment probability. We compute the edit distance by finding the sequence of string edit operations which minimizes the cost of the path traversing the edit lattice. The edit costs are determined by the components of the leading eigenvectors of the adjacency matrix and by the edge densities of the graphs being matched. We demonstrate the utility of the edit distance on a number of graph clustering problems.


Longitudinal propagation of contraction in the isolated conduit coronary arteries of humans and pigs.
We examined the longitudinal propagation of contraction in isolated human and pig coronary arteries. Epicardial coronary arteries of about 2 cm were cut open longitudinally, and the tension development of circular muscles was measured simultaneously at three sites (both cut ends and the midportion of the segment). Cyclic tension changes arising at one site of human coronary artery propagated smoothly to the other sites, and the whole length of segment worked as a single unit. Contraction induced by locally applied prostaglandin F2 alpha or histamine also propagated in four of seven preparations. The remaining three human and all seven pig coronary arteries showed propagation of such drug-induced contraction after treatment with 10 mM tetraethylammonium (TEA). In pig coronary arteries treated with TEA, electrical stimulation evoked a reproducible local contraction and its propagation. Propagation velocity was 9.0 +/- 0.7 at 0.8 mM calcium concentration and increased to 11.1 +/- 0.9 and 13.1 +/- 1.4 mm/sec as calcium concentration rose to 1.8 mM and 7.2 mM, respectively. Local contraction did not propagate at calcium concentrations of 0.2 mM or less. The calcium antagonist diltiazem decreased the propagation velocity dose dependently and blocked propagation of contraction at 0.3 microM without significant effects on the magnitude of local contraction. We conclude that smooth propagation of contraction develops in epicardial coronary arteries of humans and pigs and that the propagation may depend on calcium influx.


Workplace risk factors for anxiety and depression in male-dominated industries: a systematic review.
Background and Aims: Working conditions are an important health determinant. Employment factors can negatively affect mental health (MH), but there is little research on MH risk factors in male-dominated industries (MDI). Method: A systematic review of risk factors for anxiety and depression disorders in MDI was undertaken. MDI comprised ≥ 70% male workers and included agriculture, construction, mining, manufacturing, transport and utilities. Major electronic databases (CINAHL, Cochrane Library, Informit, PsycINFO, PubMed and Scopus) were searched. Each study was categorised according to National Health and Medical Research Council's hierarchy of evidence and study quality was assessed according to six methodological criteria. Results: Nineteen studies met the inclusion criteria. Four categories of risk were identified: individual factors, team environment, work conditions and work-home interference. The main risk factors associated with anxiety and depression in MDI were poor health and lifestyles, unsupportive workplace relationships, job overload and job demands. Some studies indicated a higher risk of anxiety and depression for blue-collar workers. Conclusion: Substantial gaps exist in the evidence. Studies with stronger methodologies are required. Available evidence suggests that comprehensive primary, secondary and tertiary prevention approaches to address MH risk factors in MDI are necessary. There is a need for organisationally focused workplace MH policies and interventions.


Trauma in pregnancy. Predicting pregnancy outcome.
A multicenter study involving three American College of Surgeons Level 1 trauma centers was undertaken to assess parameters that may predict fetal outcome. The records of 93 injured pregnant patients admitted from April 1, 1985, to March 31, 1990, were reviewed. There were three maternal deaths (3%) (mean Injury Severity Score, 43). Fourteen fetal/neonatal deaths (15%) occurred during the acute care admission period. Of these, eight were fetal deaths (two associated with maternal death), four were cases of elective abortions, and two were neonatal deaths. In general, the maternal physiologic and laboratory parameters assessed failed to accurately predict pregnancy outcome, while Injury Severity Score did differ significantly between patients whose pregnancies were viable (Injury Severity Score = 6.2) and those whose pregnancies were nonviable (Injury Severity Score = 21.6). Unique to this study were the findings that the Glasgow Coma Score also differed significantly in patients with viable (Glasgow Coma Score, 14.5) and nonviable (Glasgow Coma Score, 12.0) pregnancies, while fetal heart rate at admission to the emergency department did not. In this study, the incidence of fetal death was increased following direct uteroplacental fetal injury (100% of cases), maternal shock (67%), pelvic fracture (57%), severe head injury (56%), and hypoxia (33%). The adequacy of noninvasive maternal monitoring in assessing fetal well-being is challenged, and a discussion of diagnostic modalities for assessment for the injured gravida is set forth.


How to prevent endophthalmitis in cataract surgeries?
Postoperative endophthalmitis is a very devastating complication and every step should be taken to reduce its occurrence. Unattended air conditioning filter systems are often the culprits and regular maintenance of the filters is of paramount importance. Shedders of pathogenic organisms amongst the theater personnel should be identified by regular screening and should be promptly treated. In addition to the use of Povidone iodine 5% solution in the conjunctival sac few minutes prior to surgery, proper construction of wound, injectable intraocular lenses, use of prophylactic intracameral antibiotics or prophylactic subconjunctival antibiotic injection at the conclusion of cataract surgery, placing a patch after the surgery for at least 4 h and initiating topical antibiotics from the same day of surgery helps to lower the frequency of postoperative endophthalmitis. Intraoperative posterior capsule rupture and anterior vitrectomy are risk factors for acute endophthalmitis, and utmost care to prevent posterior capsular rent should be taken while performing cataract surgery. Also, in case of such complication, these patients should be closely monitored for early signs of endophthalmitis in the postoperative period. In the unfortunate event of endophthalmitis the diagnosis should be prompt and treatment must be initiated as early as possible.


Fungal colonization in soils with different management histories: modeling growth in three-dimensional pore volumes.
Despite the importance of fungi in soil functioning they have received comparatively little attention, and our understanding of fungal interactions and communities is lacking. This study aims to combine a physiologically based model of fungal growth with digitized images of internal pore volume of samples of undisturbed soil from contrasting management practices to determine the effect of physical structure on fungal growth dynamics. We quantified pore geometries of the undisturbed-soil samples from two contrasting agricultural practices, conventionally plowed (chisel plow) (CT) and no till (NT), and from native-species vegetation land use on land that was taken out of production in 1989 (NS). Then we modeled invasion of a fungal species within the soil samples and evaluated the role of soil structure on the progress of fungal colonization of the soil pore space. The size of the studied pores was > or =110 microm. The dynamics of fungal invasion was quantified through parameters of a mathematical model fitted to the fungal invasion curves. Results indicated that NT had substantially lower porosity and connectivity than CT and NS soils. For example, the largest connected pore volume occupied 79% and 88% of pore space in CT and NS treatments, respectively, while it only occupied 45% in NT. Likewise, the proportion of pore space available to fungal colonization was much greater in NS and CT than in NT treatment, and the dynamics of the fungal invasion differed among the treatments. The relative rate of fungal invasion at the onset of simulation was higher in NT samples, while the invasion followed a more sigmoidal pattern with relatively slow invasion rates at the initial time steps in NS and CT samples. Simulations allowed us to elucidate the contribution of physical structure to the rates and magnitudes of fungal invasion processes. It appeared that fragmented pore space disadvantaged fungal invasion in soils under long-term no-till, while large connected pores in soils under native vegetation or in tilled agriculture promoted the invasion.


Hydronephrosis of pregnancy associated with torsion of the fallopian tube: a case report.
Isolated tubal torsion accompanying pregnancy is an extremely rare condition. Preoperative diagnosis is generally difficult; most of the cases can be diagnosed intraoperatively. Here, we reported a 36-week pregnant with a complaint of acute pain in right lower quadrant that emanating to right lomber region. Abdominal utrasonography showed grade 3 hydronephrosis in right kidney, other findings were normal. A cesarean section was carried out and a twisted right tube were diagnosed. Right ovary was normal in appearance. The torsioned tube compressed the right ureter and caused ureteral dilatation. Right salpingectomy was performed. Postoperative follow-up of the patient was uneventful.


The effect of menaquinone-7 (vitamin K2) supplementation on osteocalcin carboxylation in healthy prepubertal children.
Vitamin K contributes to bone health, probably through its role as cofactor in the carboxylation of osteocalcin. Intervention studies in adults have demonstrated that markedly higher osteocalcin carboxylation is obtained by intakes of vitamin K well above the current recommended dietary intake. However, the relationship between increased vitamin K2 intake and enhanced osteocalcin carboxylation has never been shown in healthy children. The objective was to study the effect of 45 microg menaquinone-7 (MK-7; one of the vitamin K2 species) on the circulating levels of undercarboxylated osteocalcin (ucOC) and carboxylated osteocalcin (cOC) in healthy prepubertal children. We hypothesised that MK-7 supplementation will reduce the ucOC:cOC ratio (UCR), indicating an improved vitamin K status. The present study is a double-blind randomised placebo-controlled trial examining the effect of 8 weeks MK-7 supplementation on the carboxylation of osteocalcin in healthy children (n 55). Serum levels of ucOC, cOC and MK-7 were measured at baseline and after 8 weeks, together with bone markers and coagulation parameters. The UCR was used as an indicator of vitamin K status. In the MK-7-supplemented group (n 28), the circulating concentration of inactive ucOC reduced and the UCR improved whereas the concentration of MK-7 increased. Within the placebo group, ucOC, cOC, UCR and MK-7 did not significantly change over time. In both groups, bone markers and coagulation parameters remained constant over time. These findings demonstrate that in healthy, prepubertal children, modest supplementation with MK-7 increases circulating concentrations of MK-7 and increases osteocalcin carboxylation.


Thiazolidinediones, peripheral oedema and congestive heart failure: what is the evidence?
Cardiovascular disease is the most common complication of type 2 diabetes mellitus (type 2 DM), accounting for approximately 80% of deaths. While atherosclerotic vascular disease accounts for much of the cardiovascular morbidity and mortality among diabetic patients, congestive heart failure (CHF) is another key complication associated with diabetes, with an incidence three to five times greater in diabetic patients than in those without diabetes. One of the most promising developments in the treatment of type 2 DM has been the introduction of the thiazolidinedione (TZD) class of drugs, which appear to have pleiotropic effects beyond glycaemic control. Enthusiasm has been tempered, however, by concerns for safety in patients with CHF, given reports of worsening heart failure symptoms and peripheral oedema. With the growing epidemic of type 2 DM and the increasing use of TZDs, such concern has important therapeutic implications for a population of patients with a high prevalence of often subclinical systolic and diastolic dysfunction. This review provides an overview of the currently available data regarding the effects of TZDs on fluid retention and cardiac function. Particular emphasis is placed on the mechanisms of development of peripheral oedema and its significance in patients with impaired left ventricular function. TZDs are well known to cause an expansion in plasma volume; there has also been concern that TZDs may have direct toxic effects on the myocardium, leading to impaired cardiac function. Studies to date do not support this hypothesis and in fact there is growing evidence from animal models and human trials that treatment with TZDs actually improves cardiac function. There are also preclinical data to suggest TZDs may protect the myocardium in the setting of ischaemic insult or the toxic effects of myocardial lipid deposition. Ongoing clinical trials examining the use of these agents in patients at risk for heart failure will probably provide further insight into the aggregate cardiovascular effects of this promising class of medications.


DNA Origami-Anthraquinone Hybrid Nanostructures for In Vivo Quantitative Monitoring of the Progression of Tumor Hypoxia Affected by Chemotherapy.
Hypoxia is a well-known feature of malignant solid tumors. To explain the misinterpretation of tumor hypoxia variation during chemotherapy, we developed a DNA origami-based theranostic nanoplatform with an intercalated anticancer anthraquinone as both the chemotherapeutic drug and the photoacoustic contrast agent. The size distribution of the DNA origami nanostructure is 44.5 ± 2.3 nm, whereas the encapsulation efficiency of the drug is 90.7 ± 1.0%, and the drug loading content is 92.2 ± 0.1%. The controlled cumulative release rates were measured in vitro, showing an acidic environment induced rapid drug release. The values of free energy of binding between the drugs and the DNA double helix were calculated through molecular simulations. The cell viability assay was used to characterize cytotoxicity, and fluorescence confocal cell imaging illustrates the biodistribution of the probe in vitro. Photoacoustic and fluorescence imaging were used to indicate drug delivery, release, and biodistribution to predict the drug's chemotherapeutic effect in vivo, whereas the photoacoustic signals were compared with those of deoxygenated/oxygenated hemoglobin to represent the tissue hypoxia/normoxia maps during the chemotherapeutic process and indicate alleviated tumor hypoxia. Staining of tissue sections taken from organs and tumors was used to verify the results of photoacoustic imaging. Our results suggest that photoacoustic imaging can visualize this DNA origami-based theranostic nanoplatform and reveal the mechanisms of chemotherapy on tumor hypoxia.


Osseous abnormalities associated with collateral desmopathy of the distal interphalangeal joint: part 1.
Osseous abnormalities associated with collateral ligament (CL) injury of the distal interphalangeal (DIP) joint have been documented using magnetic resonance imaging (MRI) but there is currently limited information about the frequency of osseous pathology associated with CL injury. To determine the frequency of occurrence of osseous abnormality coexistent with CL injury of the DIP joint and describe the distribution and character of osseous lesions; and to establish if there was an association between osseous abnormality and increased radiopharmaceutical uptake (IRU). There would be a higher incidence of osseous abnormality at the insertion of an injured CL than at the origin; and a relationship between the presence of osseous abnormality and duration of lameness. Magnetic resonance images of 313 feet of 289 horses with foot pain and a definitive diagnosis of collateral desmopathy of the DIP joint were analysed retrospectively for presence and type of osseous abnormality in the middle and distal phalanges. Scintigraphic images were examined and the presence of IRU in the middle or distal phalanges recorded. Osseous abnormalities were detected in 143 (45.7%) feet, 27 (18.8%) of which had osseous and CL injury alone, while the remaining 116 had CL related osseous injury and multiple injuries within the hoof capsule. Entheseous new bone and endosteal irregularity of the middle and distal phalanges were the most frequent types of osseous abnormality. There was a higher incidence of osseous abnormalities medially than laterally and at the ligament insertion than at the origin. There was a significant association between presence of IRU and osseous injury. A variety of osseous lesions of differing severity are associated with CL injury. Normal radiopharmaceutical uptake does not preclude significant osseous pathology associated with CL injury. Further studies are necessary in order to determine if osseous abnormalities associated with CL injury influence prognosis for return to performance.


Criminal manifestations of dementia patients: report from the national forensic hospital.
Some dementia patients have profound behavioral and psychological symptoms which might cause legal violation. We illustrate clinical and criminal characteristics of dementia patients who had been incarcerated because of criminal activity. The National Forensic Hospital is the only hospital-based correctional facility in the Republic of Korea which incarcerates criminals with psychiatric or neurological disease. Between May 2008 and April 2009, those patients who had been diagnosed with dementia in the National Forensic Hospital were included in the study. We reviewed their medical and legal reports. There were 7 dementia patients out of 752 patients, including 2 Alzheimer's disease (AD) patients, 1 vascular dementia patient, and 4 patients with alcohol-related dementia. Criminal behavior included simple larceny by the 2 AD patients, and multiple violent crimes in a drunken state by the other 5 patients. This study reported diverse criminal behaviors among dementia patients. Inebriation may be related to violent criminal behavior among some dementia patients.


Effects of tannic acid on gluten protein structure, dough properties and bread quality of Chinese wheat.
The effects of tannic acid, which is present in many plants, on the structure of gluten proteins and the properties of dough and bread were studied. Tannic acid was added at levels of 0.01, 0.02 and 0.03 g kg(-1) during the dough-making process. The added tannic acid acted negatively on disulfide bond formation but interacted with gluten proteins via other covalent bonds, as detected by UV spectroscopy and dynamic rheometry. Rheological properties and texture of the bread were measured by farinograph, extensograph and texture profile analyser. Texture analysis indicated little change in adhesiveness and resilience of the bread at all three levels of tannic acid compared with the control, but changes in hardness and chewiness of the bread made with added tannic acid indicated that tannic acid could delay bread staling. The effect of tannic acid on flour and dough is different from that of other flour redox agents. It breaks down disulfide bonds but also has positive effects on dough properties and bread quality. Disulfide bonds are commonly considered to be the most important factor affecting changes in the quality of bread. However, this study presents the new concept that other covalent bonds can also improve the quality of flour and bread and uses this property to investigate new, safe and efficient flour additives.


Selective apoptotic effects of piceatannol and myricetin in human cancer cells.
Numerous studies have shown the potential of dietary polyphenols as anticarcinogenic agents. The aim of the present study was to evaluate the apoptotic effects of piceatannol and myricetin, naturally occurring polyphenols in red wine, alone or in combination, in two human cell lines: HL-60 (leukemia) and HepG2 (hepatoma). Apoptotic cells were identified by chromatin condensation, poly(ADP-ribose) polymerase cleavage and flow cytometry analysis. Results from TUNEL assay showed that piceatannol or myricetin alone induced apoptotic cell death in a concentration- and time-dependent manners in HL-60 cells. Furthermore, in combined treatment the percentage of apoptotic HL-60 cells was significantly higher. Nevertheless, the percentage of TUNEL positive HepG2 cells only was significant after piceatannol treatment and in combined treatment was even lower than in cells treated with piceatannol alone. Moreover, we also studied the relative reactive oxygen species (ROS) production. Our results indicate that apoptosis induced by piceatannol or myricetin occurs through an ROS-independent cell death pathway. In conclusion, piceatannol and myricetin synergistically induced apoptosis in HL-60 cells but not in HepG2 cells. These findings suggest that the potential anticarcinogenic properties of dietary polyphenols depend largely on the cell line used. The relevance of these data needs to be verified in human epidemiological studies.


Bidirectional influence of sodium channel activation on NMDA receptor-dependent cerebrocortical neuron structural plasticity.
Neuronal activity regulates brain development and synaptic plasticity through N-methyl-D-aspartate receptors (NMDARs) and calcium-dependent signaling pathways. Intracellular sodium ([Na(+)](i)) also exerts a regulatory influence on NMDAR channel activity, and [Na(+)](i) may, therefore, function as a signaling molecule. In an attempt to mimic the influence of neuronal activity on synaptic plasticity, we used brevetoxin-2 (PbTx-2), a voltage-gated sodium channel (VGSC) gating modifier, to manipulate [Na(+)](i) in cerebrocortical neurons. The acute application of PbTx-2 produced concentration-dependent increments in both intracellular [Na(+)] and [Ca(2+)]. Pharmacological evaluation showed that PbTx-2-induced Ca(2+) influx primarily involved VGSC activation and NMDAR-mediated entry. Additionally, PbTx-2 robustly potentiated NMDA-induced Ca(2+) influx. PbTx-2-exposed neurons showed enhanced neurite outgrowth, increased dendritic arbor complexity, and increased dendritic filopodia density. The appearance of spontaneous calcium oscillations, reflecting synchronous neuronal activity, was accelerated by PbTx-2 treatment. Parallel to this response, PbTx-2 increased cerebrocortical neuron synaptic density. PbTx-2 stimulation of neurite outgrowth, dendritic arborization, and synaptogenesis all exhibited bidirectional concentration-response profiles. This profile paralleled that of NMDA, which also produced bidirectional concentration-response profiles for neurite outgrowth and synaptogenesis. These data are consistent with the hypothesis that PbTx-2-enhanced neuronal plasticity involves NMDAR-dependent signaling. Our results demonstrate that PbTx-2 mimics activity-dependent neuronal structural plasticity in cerebrocortical neurons through an increase in [Na(+)](i), up-regulation of NMDAR function, and engagement of downstream Ca(2+)-dependent signaling pathways. These data suggest that VGSC gating modifiers may represent a pharmacologic strategy to regulate neuronal plasticity through NMDAR-dependent mechanisms.


Natural history of disease in the YAC128 mouse reveals a discrete signature of pathology in Huntington disease.
Models of Huntington disease (HD) recapitulate some neuropathological features of the disease. However, a global natural history of neuroanatomy in a mouse expressing full-length huntingtin has not been conducted. We investigated neuropathological changes in the YAC128 murine model of HD using magnetic resonance imaging (MRI). Structures affected in human HD are reduced in the YAC128 mice both in absolute terms and in terms of percentage of brain volume. Structures resistant to degeneration in HD, including the cerebellum and hippocampus, are spared in the YAC128 mice. Segmentation of major white matter structures confirms specific, progressive, loss of white matter in HD. In parallel with their specific volume loss, the YAC128 mice also show progressive increases in total ventricular volume, similarly to human HD patients. Cortical atrophy in the YAC128 mice is layer specific, which is the observed pattern of cortical loss in human HD patients. Finally, we have used a classification tree analysis to maximize separation of genotypes using all 62 structure volumes in an objective manner. This analysis demonstrates that sub-cortical gray matter structures (striatum, globus pallidus, thalamus) and cerebral white matter structures (corpus callosum, anterior commisure, fimbria) are the most discriminatory. The high resolution of the current study enables robust measurement of subtle early pathological changes. The use of mice furthermore enables us to address questions difficult to address in humans, including the sequential changes of HD from baseline and the relation between MRI and stereological measures.


Complementary surgical/interventional techniques for nonresective management of "inoperable" aneurysms: a second look.
Induced thrombosis ("nonresective" therapy) of aortic aneurysms by distal arterial ligation, coil/wire embolization, and extraanatomic bypass was devalued by anecdotal reports emerging during the mid-1980s. Nevertheless, we have recently found the technique to be life-saving in occasional cases and worth revisiting. Since 1990, standard aortic aneurysm repair has been performed in 231 patients (99.1% survival), endovascular aortic aneurysm repair in 6 patients (83.3% survival), and combined surgical/interventional "nonresective" repair of a variety of aneurysms in 10 patients (100% survival). Mean age of the group was 67.9 years. Repair was performed for aortoiliac aneurysms (4), common iliac aneurysms (3), internal iliac aneurysms (2), and a large proximal subclavian artery pseudoaneurysm (1). Four of the patients had been explored and declared to be "inoperable" (retroperitoneal fibrosis) prior to transfer to the Columbia-Presbyterian Medical Center. All patients survived. Aneurysm rupture has not occurred in any patient, but one patient with a presumably thrombosed subclavian pseudoaneurysm presented 26 months postcoil-induced thrombosis with progressive aneurysm enlargement due to incomplete aneurysm thrombosis and required repair using circulatory arrest. Eight of the patients remain alive (80%) at a mean follow-up of 40.3 months (range 14-88 months). Two patients died of malignancy (30 months) and cardiac disease (15 months). It is concluded that combined surgical/interventional techniques can be life-saving in the rare instances when conventional or endovascular aneurysm repair is not advisable but that complete aneurysm thrombosis is essential and occasionally difficult to achieve. Since small proximal portions of the aneurysm may remain patent and not be visualized on magnetic resonance imaging (MRI) or computed tomography (CT) scans, contrast angiographic documentation of complete aneurysm thrombosis is essential prior to hospital discharge and close follow-up is necessary to ascertain long-term adequacy of the repair. Incomplete thrombosis is suspected as a major factor in earlier reports of aneurysm rupture after seemingly successful nonresective therapy.


Azathioprine-induced liver injury in a patient with multiple autoimmune syndrome.
Extraintestinal manifestations are frequent in patients with ulcerative colitis. They are most commonly associated with active bowel disease but can also occur prior to bowel disease or during a period of remission. The disease often requires long-term therapy. The tolerability of drugs is essential for the comprehensive management of patients. Azathioprine is considered an indispensable drug for the treatment of severe ulcerative colitis patients. It is used to prevent relapse or to treat patients who are refractory to corticosteroids. We report a patient who had alopecia areata, vitiligo, recurrent episcleritis, ulcerative colitis and azathioprine-induced liver injury, and review the related literature.


Anhidrosis and absence of sweat glands in mice hemizygous for the Tabby gene: supportive evidence for the hypothesis of homology between Tabby and human anhidrotic (hypohidrotic) ectodermal dysplasia (Christ-Siemens-Touraine syndrome).
I have suggested that the X-linked gene Tabby (Ta) and its autosomal mimics in the mouse may be homologous with the genes for sex-linked anhidrotic (hypohidrotic) ectodermal dysplasia (Christ-Siemens-Touraine syndrome, CST) and its apparent autosomal mimics in the human. In the present study, I examined whether anhidrosis, a cardinal feature of CST, is present in the putative mouse sex-linked model, Tabby. The results demonstrate that whereas normal mice perspire on the volar and plantar surfaces of their paws, hemizygous Ta/Y male mice show anhidrosis and absence of sweat glands, as do human hemizygous male sufferers of CST. This result is strongly supportive of the hypothesis that Ta is homologous to the gene for CST.


Anti-tumor necrosis factor-alpha therapy-induced vasculitis: case series.
As experience with anti-tumor necrosis factor (TNF-alpha) therapy increases, there has been the expected emergence of reports on uncommon side effects. Large clinical trials identified the development of autoantibodies and postmarketing surveillance has identified problems including tuberculosis. There have been several case reports of drug-induced systemic lupus erythematosus. We describe eight patients with rheumatoid arthritis treated with anti-TNF therapies who developed presumed vasculitis, with different pathophysiologic causes. We discuss the literature and potential causal mechanisms, including disease activity, the role of autoantibodies, and shifts in T cell responses.


Measuring growth and gene expression dynamics of tumor-targeted S. typhimurium bacteria.
The goal of these experiments is to generate quantitative time-course data on the growth and gene expression dynamics of attenuated S. typhimurium bacterial colonies growing inside tumors. We generated model xenograft tumors in mice by subcutaneous injection of a human ovarian cancer cell line, OVCAR-8 (NCI DCTD Tumor Repository, Frederick, MD). We transformed attenuated strains of S. typhimurium bacteria (ELH430:SL1344 phoPQ- (1)) with a constitutively expressed luciferase (luxCDABE) plasmid for visualization(2). These strains specifically colonize tumors while remaining essentially non-virulent to the mouse(1). Once measurable tumors were established, bacteria were injected intravenously via the tail vein with varying dosage. Tumor-localized, bacterial gene expression was monitored in real time over the course of 60 hours using an in vivo imaging system (IVIS). At each time point, tumors were excised, homogenized, and plated to quantitate bacterial colonies for correlation with gene expression data. Together, this data yields a quantitative measure of the in vivo growth and gene expression dynamics of bacteria growing inside tumors.


Usefulness of the CHADS2 Score for Determining Risk of Seizure in Patients With Atrial Fibrillation.
Atrial fibrillation (AF) secondary to seizure has been described in case reports, but the association between AF and risk of seizure has never been evaluated in longitudinal studies. The objectives of this study were to investigate the role of AF on the risk of development of seizure and the usefulness of CHADS2 score for predicting the risk of seizure. Our analyses were conducted using information from a random sample of 1 million subjects enrolled in Taiwan National Health Insurance Research Database. A total of 11,552 subjects aged ≥18 years, comprising 5,776 subjects diagnosed with AF during the study period and 5,776 age and sex-matched subjects without AF were enrolled in our study. During the mean follow-up of 6.7 ± 3.3 years, seizure events occurred in 235 patients. In comparison, the AF group had a higher incidence rate of seizure occurrence (4.17 vs 1.90 per 1,000 person-years). Cox proportional hazard regression model analysis showed that development of AF was independently associated with a higher risk of developing future seizure (adjusted HR 2.30; 95% confidence interval 1.73 to 3.05). In multivariate Cox regression analysis adjusted for potentially confounding variables, a higher CHADS2 score was associated with a higher risk of seizure in a dose-dependent manner. AF may cause an ischemic stroke that subsequently leads to seizure, and present study further demonstrates that AF patients are associated with higher rate of subsequent seizure, even after adjusting for stroke. The CHADS2 score was found to be a useful scheme for predicting the risk of seizure occurrence.


Isolation, cloning, and expression mapping of a gene encoding an antidiuretic hormone and other CAPA-related peptides in the disease vector, Rhodnius prolixus.
After a blood meal, Rhodnius prolixus undergoes a rapid diuresis to eliminate excess water and salts. During the voiding of this primary urine, R. prolixus acts as a vector of Chagas' disease, with the causative agent, Trypanosoma cruzi, infecting the human host via the urine. Diuresis in R. prolixus is under the neurohormonal control of serotonin and peptidergic diuretic hormones, and thus, diuretic hormones play an important role in the transmission of Chagas' disease. Although diuretic hormones may be degraded or excreted, resulting in the termination of diuresis, it would also seem appropriate, given the high rates of secretion, that a potent antidiuretic factor could be present and act to prevent excessive loss of water and salts after the postgorging diuresis. Despite the medical importance of R. prolixus, no genes for any neuropeptides have been cloned, including obviously, those that control diuresis. Here, using molecular biology in combination with matrix-assisted laser desorption ionization-time of flight-tandem mass spectrometry, we determined the sequence of the CAPA gene and CAPA-related peptides in R. prolixus, which includes a peptide with anti-diuretic activity. We have characterized the expression of mRNA encoding these peptides in various developmental stage and also examined the tissue-specific distribution in fifth-instars. The expression is localized to numerous bilaterally paired cell bodies within the central nervous system. In addition, our results show that RhoprCAPA gene expression is also associated with the testes, suggesting a novel role for this family of peptides in reproduction.


Meeting the information needs of adult daughters of women with early breast cancer. Patients and health care professionals as information providers.
This study explored the information needs of adult daughters whose mothers had early breast cancer and illustrated the information flows between the daughters and two information providers: patients and health care professionals (HCPs). Participants were 97 daughters, who completed a 30-time self-administered questionnaire, a tool designed to identify the information needs of daughters and their communication channels. Daughters also completed the Miller Behavioral Style Scale, a scale used to determine the information-seeking behavior of individuals under threat. Descriptive statistics revealed that the information flows between women with breast cancer and daughters participating in this study were good. Most of the daughters received information from their mothers and asked their mothers questions. Few daughters thought their mothers avoided giving them information. The vast majority of the daughters, however, sought information from sources other than their mothers, indicating that the mothers alone did not satisfy their information needs. More than half of the daughters participating in this study accompanied their mothers to their medical consultations and received information from HCPs. Logistic regression indicated that the communication flows between patients, HCPs, and adult daughters of women with breast cancer depended on a number of factors, in particular, on the amount of communication desired by women with breast cancer.


Glutamine Metabolism Drives Growth in Advanced Hormone Receptor Positive Breast Cancer.
Dependence on the glutamine pathway is increased in advanced breast cancer cell models and tumors regardless of hormone receptor status or function. While 70% of breast cancers are estrogen receptor positive (ER+) and depend on estrogen signaling for growth, advanced ER+ breast cancers grow independent of estrogen. Cellular changes in amino acids such as glutamine are sensed by the mammalian target of rapamycin (mTOR) complex, mTORC1, which is often deregulated in ER+ advanced breast cancer. Inhibitor of mTOR, such as everolimus, has shown modest clinical activity in ER+ breast cancers when given with an antiestrogen. Here we show that breast cancer cell models that are estrogen independent and antiestrogen resistant are more dependent on glutamine for growth compared with their sensitive parental cell lines. Co-treatment of CB-839, an inhibitor of GLS, an enzyme that converts glutamine to glutamate, and everolimus interrupts the growth of these endocrine resistant xenografts. Using human tumor microarrays, we show that GLS is significantly higher in human breast cancer tumors with increased tumor grade, stage, ER-negative and progesterone receptor (PR) negative status. Moreover, GLS levels were significantly higher in breast tumors from African-American women compared with Caucasian women regardless of ER or PR status. Among patients treated with endocrine therapy, high GLS expression was associated with decreased disease free survival (DFS) from a multivariable model with GLS expression treated as dichotomous. Collectively, these findings suggest a complex biology for glutamine metabolism in driving breast cancer growth. Moreover, targeting GLS and mTOR in advanced breast cancer may be a novel therapeutic approach in advanced ER+ breast cancer.


Using a 2-stage strategy with respondent-driven sampling to recruit a hard-to-reach population for a placebo microbicide gel clinical trial in Nellore, Andhra Pradesh (India).
Traditional recruitment methods for microbicide efficacy trials are labor intensive and may fail to reach high-risk hard-to-reach populations. We report duration of recruitment and lessons learned from a two-stage process to recruit female sex workers (FSWs) into a placebo microbicide trial, and examined characteristics associated with successful recruitment of peers who screened for and enrolled in the trial. FSWs were first recruited via respondent-driven sampling (RDS) to complete a survey and subsequently invited to screen for enrollment into a placebo microbicide trial taking place at a local clinic. It took 6 months to enroll 267 participants into the trial. Successful recruiters of peers who enrolled were more likely to have enrolled themselves (AOR 2.0, CI 1.3-2.9) and less likely to visit Nellore city (AOR 0.5, CI 0.3-0.9). Recruitment of FSWs via a two-stage recruitment strategy with RDS can be a good option for future clinical trials.


Promoting the Quality of Teacher-Toddler Interactions: A Randomized Controlled Trial of "Thrive by Three" In-Service Professional Development in 187 Norwegian Toddler Classrooms.
The effectiveness of the Thrive by Three intervention, a 10-month, multicomponent, in-service professional development model to promote the quality of caregiver-toddler interactions (i.e., process quality), was tested utilizing a clustered randomized controlled design. Eighty childcare centers with 187 toddler classrooms in Norway were randomly assigned to either the Thrive by Three intervention group (n=87) or a usual-activity wait list control group (n=100). Interactional quality was assessed with the Toddler version of the Classroom Assessment Scoring System (CLASS-Toddler) at three timepoints: pre-, mid-, and post-intervention. There were significant group differences in change in quality during the intervention period in both CLASS domains, Emotional and Behavioral Support (EBS), and Engaged Support for Learning (ESL), with greater overall differences in the ESL domain. Quality increased in the intervention groups, but quality decreased in the control group from baseline to post-intervention. There were significant group differences in quality at baseline. The Thrive by Three intervention had a positive effect on teacher-toddler interactions in both the EBS and ESL domains. Results need to be replicated preferably in more diverse samples. Clinical Trial Registration: ClinicalTrials.gov #NCT03879733.


Cardiopulmonary exercise testing for identification of patients with hyperventilation syndrome.
Measurement of ventilatory efficiency, defined as minute ventilation per unit carbon dioxide production (VE/VCO2), by cardiopulmonary exercise testing (CPET) has been proposed as a screen for hyperventilation syndrome (HVS). However, increased VE/VCO2 may be associated with other disorders which need to be distinguished from HVS. A more specific marker of HVS by CPET would be clinically useful. We hypothesized ventilatory control during exercise is abnormal in patients with HVS. Patients who underwent CPET from years 2015 through 2017 were retrospectively identified and formed the study group. HVS was defined as dyspnea with respiratory alkalosis (pH >7.45) at peak exercise with absence of acute or chronic respiratory, heart or psychiatric disease. Healthy patients were selected as controls. For comparison the Student t-test or Mann-Whitney U test were used. Data are summarized as mean ± SD or median (IQR); p<0.05 was considered significant. Twenty-nine patients with HVS were identified and 29 control subjects were selected. At rest, end-tidal carbon dioxide (PETCO2) was 27 mmHg (25-30) for HVS patients vs. 30 mmHg (28-32); in controls (p = 0.05). At peak exercise PETCO2 was also significantly lower (27 ± 4 mmHg vs. 35 ± 4 mmHg; p<0.01) and VE/VCO2 higher ((38 (35-43) vs. 31 (27-34); p<0.01)) in patients with HVS. In contrast to controls, there were minimal changes of PETCO2 (0.50 ± 5.26 mmHg vs. 6.2 ± 4.6 mmHg; p<0.01) and VE/VCO2 ((0.17 (-4.24-6.02) vs. -6.6 (-11.4-(-2.8)); p<0.01)) during exercise in patients with HVS. The absence of VE/VCO2 and PETCO2 change during exercise was specific for HVS (83% and 93%, respectively). Absence of VE/VCO2 and PETCO2 change during exercise may identify patients with HVS.


A Chimeric Antibody against ACKR3/CXCR7 in Combination with TMZ Activates Immune Responses and Extends Survival in Mouse GBM Models.
Glioblastoma (GBM) is the least treatable type of brain tumor, afflicting over 15,000 people per year in the United States. Patients have a median survival of 16 months, and over 95% die within 5 years. The chemokine receptor ACKR3 is selectively expressed on both GBM cells and tumor-associated blood vessels. High tumor expression of ACKR3 correlates with poor prognosis and potential treatment resistance, making it an attractive therapeutic target. We engineered a single chain FV-human FC-immunoglobulin G1 (IgG1) antibody, X7Ab, to target ACKR3 in human and mouse GBM cells. We used hydrodynamic gene transfer to overexpress the antibody, with efficacy in vivo. X7Ab kills GBM tumor cells and ACKR3-expressing vascular endothelial cells by engaging the cytotoxic activity of natural killer (NK) cells and complement and the phagocytic activity of macrophages. Combining X7Ab with TMZ allows the TMZ dosage to be lowered, without compromising therapeutic efficacy. Mice treated with X7Ab and in combination with TMZ showed significant tumor reduction by MRI and longer survival overall. Brain-tumor-infiltrating leukocyte analysis revealed that X7Ab enhances the activation of M1 macrophages to support anti-tumor immune response in vivo. Targeting ACKR3 with immunotherapeutic monoclonal antibodies (mAbs) in combination with standard of care therapies may prove effective in treating GBM.


Death associated protein 1 is correlated with the clinical outcome of patients with colorectal cancer and has a role in the regulation of cell death.
Death-associated protein 1 (DAP1) is a member of the DAP family and has been implicated in the regulation of cell growth and death including that of cancer cells. However, the roles of DAP1 in clinical cancer and in the regulation of colorectal cancer cells are largely unknown. The present study investigated the expression profile of DAP1 in human colorectal cancer and the impact of DAP1 on apoptosis and the cellular response to 5-FU. Human colorectal cancer specimens (n=94) and human colorectal cancer cell lines HRT18 and HT115 were used. DAP1 transcript and protein were evaluated using quantitative transcript analysis and immunohistochemistry. DAP1-knockdown cells were generated using anti-DAP1 transgene. The results revealed that human colorectal cancer tissues had lower levels of DAP1 when compared with the normal tissues. The reduced levels were associated with higher Dukes' stage and lymph node metastasis. Patients with low DAP1 expression had a markedly reduced survival. Loss of DAP1 in colorectal cancer cells resulted in a gain in cellular migration and loss of their sensitivity of apoptosis to chemotherapeutic agent, 5-FU. DAP1 was found to be correlated with disease progression and long-term survival of the colorectal patients. DAP1 is also a pivotal regulator of the growth and apoptosis and cellular response to chemotherapy agents.


Differences in energy absorption between heads of adults and children in the near field of sources.
This paper was motivated by a recent article in which the levels of electromagnetic energy absorbed in the heads of mobile phone users were compared for children and adults at the frequencies of 835 MHz and 1,900 MHz. Significant differences were found, in particular substantially greater absorption in children's heads at 835 MHz. These findings contradict other studies in which no significant changes had been postulated. The clarification of this issue is crucial to the mobile communications industry since current SAR evaluations as required by the FCC are only performed with phantoms based on the heads of adults. In order to investigate the differences in absorption between adults and children due to their differing anatomies, simulations have been performed using head phantoms based on MRI scans of an adult (voxel size 2 x 2 x 1 mm3) and two children (voxel size 2 x 2 x 1.1 mm3) of the ages of 3 and 7 y. Ten different tissue types were distinguished. The differences in absorption were investigated for the frequencies of 900 MHz and 1,800 MHz using 0.45 lambda dipoles instead of actual mobile phones. These well-defined sources simplified the investigation and facilitated the comparison to previously published data obtained from several numerical and experimental studies on phantoms based on adults. All simulations were performed using a commercial code based on the finite integration technique. The results revealed no significant differences in the absorption of electromagnetic radiation in the near field of sources between adults and children. The same conclusion holds when children are approximated as scaled adults.


Inferring hypotheses on functional relationships of genes: Analysis of the Arabidopsis thaliana subtilase gene family.
The gene family of subtilisin-like serine proteases (subtilases) in Arabidopsis thaliana comprises 56 members, divided into six distinct subfamilies. Whereas the members of five subfamilies are similar to pyrolysins, two genes share stronger similarity to animal kexins. Mutant screens confirmed 144 T-DNA insertion lines with knockouts for 55 out of the 56 subtilases. Apart from SDD1, none of the confirmed homozygous mutants revealed any obvious visible phenotypic alteration during growth under standard conditions. Apart from this specific case, forward genetics gave us no hints about the function of the individual 54 non-characterized subtilase genes. Therefore, the main objective of our work was to overcome the shortcomings of the forward genetic approach and to infer alternative experimental approaches by using an integrative bioinformatics and biological approach. Computational analyses based on transcriptional co-expression and co-response pattern revealed at least two expression networks, suggesting that functional redundancy may exist among subtilases with limited similarity. Furthermore, two hubs were identified, which may be involved in signalling or may represent higher-order regulatory factors involved in responses to environmental cues. A particular enrichment of co-regulated genes with metabolic functions was observed for four subtilases possibly representing late responsive elements of environmental stress. The kexin homologs show stronger associations with genes of transcriptional regulation context. Based on the analyses presented here and in accordance with previously characterized subtilases, we propose three main functions of subtilases: involvement in (i) control of development, (ii) protein turnover, and (iii) action as downstream components of signalling cascades. Supplemental material is available in the Plant Subtilase Database (PSDB) (http://csbdb.mpimp-golm.mpg.de/psdb.html), as well as from the CSB.DB (http://csbdb.mpimp-golm.mpg.de).


Integrating in-situ, Landsat, and MODIS data for mapping in Southern African savannas: experiences of LCCS-based land-cover mapping in the Kalahari in Namibia.
Integrated ecosystem assessment initiatives are important steps towards a global biodiversity observing system. Reliable earth observation data are key information for tracking biodiversity change on various scales. Regarding the establishment of standardized environmental observation systems, a key question is: What can be observed on each scale and how can land cover information be transferred? In this study, a land cover map from a dry semi-arid savanna ecosystem in Namibia was obtained based on the UN LCCS, in-situ data, and MODIS and Landsat satellite imagery. In situ botanical relevé samples were used as baseline data for the definition of a standardized LCCS legend. A standard LCCS code for savanna vegetation types is introduced. An object-oriented segmentation of Landsat imagery was used as intermediate stage for downscaling in-situ training data on a coarse MODIS resolution. MODIS time series metrics of the growing season 2004/2005 were used to classify Kalahari vegetation types using a tree-based ensemble classifier (Random Forest). The prevailing Kalahari vegetation types based on LCCS was open broadleaved deciduous shrubland with an herbaceous layer which differs from the class assignments of the global and regional land-cover maps. The separability analysis based on Bhattacharya distance measurements applied on two LCCS levels indicated a relationship of spectral mapping dependencies of annual MODIS time series features due to the thematic detail of the classification scheme. The analysis of LCCS classifiers showed an increased significance of life-form composition and soil conditions to the mapping accuracy. An overall accuracy of 92.48% was achieved. Woody plant associations proved to be most stable due to small omission and commission errors. The case study comprised a first suitability assessment of the LCCS classifier approach for a southern African savanna ecosystem.


Chronoregulation by asparagine deamidation.
Every asparagine in every protein undergoes nonenzymatic deamidation to aspartate or isoaspartate at a rate determined by the surrounding protein structure and cellular environment. Under physiologic conditions, the deamidation half-life of individual asparagines in proteins is proposed to range from less than a day to several centuries. More than 200 proteins have been shown to undergo deamidation to a meaningful degree, and modeling predicts that hundreds more undergo deamidation at rates that have the potential to be of biological consequence. Because deamidation converts an asparagine into an aspartate or isoaspartate, it introduces a negative charge into a protein and results in the isomerization of a residue. Therefore, deamidation has the potential to change protein function. Additionally, deamidation is thought to render some proteins more susceptible to degradation. In most instances in which asparagine deamidation has been identified in vivo, it is involved in pathology. Hence, deamidation has been viewed primarily as a form of protein damage. However, the pervasiveness and evolutionary persistence of these unstable asparagines suggest that they may have a beneficial role. Notably, the change of even a single neighboring amino acid can have a marked effect on the rate of deamidation of an asparagine. Therefore, the underlying rate of deamidation of any asparagine is genetically programmable. This characteristic, combined with the wide range of deamidation rates that can be programmed, imparts to asparagines the potential to serve as molecular timers that regulate protein function and stability.


Psychosocial predictors of post-natal anxiety and depression: Using Structural Equation Modelling to investigate the relationship between pressure to breastfeed, health care professional support, post-natal guilt and shame, and post-natal anxiety and depression within an infant feeding context.
High perceived pressure to breastfeed and poor perceived quality of health care professional support have been associated with early breastfeeding cessation, guilt, and shame. This is problematic because guilt and shame significantly predict post-natal anxiety and depression. No previous attempts have been made to provide quantitative evidence for relationships mapped between the post-natal social context, infant feeding method and post-natal emotional well-being. The current study aimed to empirically investigate aforementioned pathways. Structural equation modelling was applied to survey data provided online by 876 mothers. Guilt and shame both significantly predicted anxiety and depression. Poor health care professional support and high pressure to breastfeed increased anxiety and depression, and these effects were explained by indirect pathways through increases in guilt and shame. Formula feeding exclusivity was negatively correlated with post-natal anxiety symptoms. This finding may be explained by feelings of relief associated with observed infant weight gain and being able to share infant feeding responsibilities others e.g., with one's partner. This relationship was counterbalanced by an indirect pathway where greater formula feeding exclusivity positively predicted guilt, which increased post-natal anxiety score. While guilt acted as mediator of infant feeding method to increase post-natal depression and anxiety, shame acted independently of infant feeding method. These identified differences provide empirical support for the transferability of general definitions of guilt (i.e., as remorse for having committed a moral transgression) and shame (i.e., internalisation of transgressive remorse to the self), to an infant feeding context. Recommendations for health care practitioners and the maternal social support network are discussed.


Interactive Apps Promote Learning of Basic Mathematics in Children With Special Educational Needs and Disabilities.
Interactive apps delivered on touch-screen tablets can be effective at supporting the acquisition of basic skills in mainstream primary school children. This technology may also be beneficial for children with Special Educational Needs and Disabilities (SEND) as it can promote high levels of engagement with the learning task and an inclusive learning environment. However, few studies have measured extent of learning for SEND pupils when using interactive apps, so it has yet to be determined if this technology is effective at raising attainment for these pupils. We report the first observational study of a group of 33 pupils with SEND from two primary schools in Malawi that are implementing a new digital technology intervention which uses touch-screen tablets to deliver interactive apps designed to teach basic mathematical skills. The apps contain topics that align to the national curriculum. To assess learning gains, rate of progress (minutes per topic) for each pupil was determined by calculating the average time taken to complete a topic. Progress rate was then correlated with teacher ratings of extent of disability and independent ratings of pupil engagement with the apps. Results showed SEND pupils could interact with the apps and all pupils passed at least one topic. Average progress rate for SEND pupils was twice as long as mainstream peers. Stepwise regression revealed extent of disability significantly predicted progress rate. Further exploratory correlations revealed pupils with moderate to severe difficulties with hearing and/or language made slower progress through the apps than those with greater functionality in these two domains because the use of verbal instructions within the apps limited their capacity to learn. This original quantitative analysis demonstrates that interactive apps can raise learning standards in pupils with SEND but may have limited utility for pupils with severe difficulties. Software modifications are needed to address specific areas of difficulty preventing pupils from progressing.


Laboratory assessment of Beauveria bassiana (Hypocreales: Clavicipitaceae) strain GHA for control of Listronotus maculicollis (Coleoptera: Curculionidae) adults.
Bioassays were designed to evaluate Beauveria bassiana (Balsamo) Vuillemin strain GHA against Listronotus maculicollis (Kirby) adults. B. bassiana and its "inert" carrier oil in the product BotaniGard and the inert carrier oil alone provided 99 and 96% mortality, respectively, in petri dish assays 1 d after treatment when applied in 1 ml water. When the same treatments were applied in 0.5 ml of carrier water, mortality was only 1.4 and 0.7%, respectively, 1 d after treatment. After 10 d in petri dishes, B. bassiana and its inert carrier oil and the inert carrier oil alone applied in 0.5 ml water showed 77 and 9% mortality, respectively. When one-tenth the label dosage of B. bassiana and inert carrier oil was combined with neonicotinoids applied in 1 ml water, there were significant increases in weevil mortality over the neonicotinoids alone 1 d after treatment. When 88.7% of one-tenth the label dosage of inert carrier oil alone was combined with neonicotinoids clothianidin, imidacloprid, and dinotefuran applied in 1 ml water, there was also a significant increases (38%) with clothianidin in weevil mortality over clothianidin alone 1 d after treatment. B. bassiana and its inert carrier oil provided 28, 50, and 78% mortality at the highest label dosage and 47, 76, and 89% mortality at 4x the highest label dosage in turf plug assays at 7, 10, and 14 d after treatment. Addition of 5 or 20% MycoMax (a nutrient source for B. bassiana) did not significantly increase mortality.


State-dependent network connectivity determines gating in a K+ channel.
X-ray crystallography has provided tremendous insight into the different structural states of membrane proteins and, in particular, of ion channels. However, the molecular forces that determine the thermodynamic stability of a particular state are poorly understood. Here we analyze the different X-ray structures of an inwardly rectifying potassium channel (Kir1.1) in relation to functional data we obtained for over 190 mutants in Kir1.1. This mutagenic perturbation analysis uncovered an extensive, state-dependent network of physically interacting residues that stabilizes the pre-open and open states of the channel, but fragments upon channel closure. We demonstrate that this gating network is an important structural determinant of the thermodynamic stability of these different gating states and determines the impact of individual mutations on channel function. These results have important implications for our understanding of not only K+ channel gating but also the more general nature of conformational transitions that occur in other allosteric proteins.


Population genetic analysis of Plasmodium falciparum parasites using a customized Illumina GoldenGate genotyping assay.
The diversity in the Plasmodium falciparum genome can be used to explore parasite population dynamics, with practical applications to malaria control. The ability to identify the geographic origin and trace the migratory patterns of parasites with clinically important phenotypes such as drug resistance is particularly relevant. With increasing single-nucleotide polymorphism (SNP) discovery from ongoing Plasmodium genome sequencing projects, a demand for high SNP and sample throughput genotyping platforms for large-scale population genetic studies is required. Low parasitaemias and multiple clone infections present a number of challenges to genotyping P. falciparum. We addressed some of these issues using a custom 384-SNP Illumina GoldenGate assay on P. falciparum DNA from laboratory clones (long-term cultured adapted parasite clones), short-term cultured parasite isolates and clinical (non-cultured isolates) samples from East and West Africa, Southeast Asia and Oceania. Eighty percent of the SNPs (n = 306) produced reliable genotype calls on samples containing as little as 2 ng of total genomic DNA and on whole genome amplified DNA. Analysis of artificial mixtures of laboratory clones demonstrated high genotype calling specificity and moderate sensitivity to call minor frequency alleles. Clear resolution of geographically distinct populations was demonstrated using Principal Components Analysis (PCA), and global patterns of population genetic diversity were consistent with previous reports. These results validate the utility of the platform in performing population genetic studies of P. falciparum.


P53 gene mutations: case study of a clinical marker for solid tumors.
P53 is a tumor-suppressor gene that codes for a multifunctional DNA-binding protein involved in cell cycle arrest, DNA repair, differentiation, and apoptosis. The P53 gene is mutated in approximately 50% of human cancers and in germline DNA of families with inherited cancer syndromes. The role of P53 mutations in the program of carcinogenic genetic alterations differs among tumor sites ranging from the earliest mutations that can be detected in premalignant cells to mutations that trigger malignant transformation of a benign neoplasm. P53 mutations can cause expression of abnormal proteins or result in complete absence of P53 expression. For these reasons the role of P53 genetic disruption has different implications in different tumor types and may vary depending on the effect of the mutation on P53 protein function. Immunohistochemical detection of P53, commonly used as a surrogate for identification of a mutant gene, has imperfect sensitivity and specificity, further complicating correlations between P53 gene status and clinical outcomes. The presence of P53 mutations has been shown to affect prognosis of some cancers. The identity of P53 mutations can be used to determine tumor clonality. The detection of P53 mutations suggests the severity of premalignant lesions. Evolving technology for more accurate identification of P53 mutations, better understanding of the function of mutant P53 protein, and more detailed analysis of individual tumor types may expand the relevance of P53 gene analysis for clinical outcomes and therapeutic response.