Structure of an intermediate state in protein folding and aggregation.
Protein-folding intermediates have been implicated in amyloid fibril formation involved in neurodegenerative disorders. However, the structural mechanisms by which intermediates initiate fibrillar aggregation have remained largely elusive. To gain insight, we used relaxation dispersion nuclear magnetic resonance spectroscopy to determine the structure of a low-populated, on-pathway folding intermediate of the A39V/N53P/V55L (A, Ala; V, Val; N, Asn; P, Pro; L, Leu) Fyn SH3 domain. The carboxyl terminus remains disordered in this intermediate, thereby exposing the aggregation-prone amino-terminal β strand. Accordingly, mutants lacking the carboxyl terminus and thus mimicking the intermediate fail to safeguard the folding route and spontaneously form fibrillar aggregates. The structure provides a detailed characterization of the non-native interactions stabilizing an aggregation-prone intermediate under native conditions and insight into how such an intermediate can derail folding and initiate fibrillation.


Endoscopic ultrasound-guided fine needle aspiration cytology of solid liver lesions: a large single-center experience.
The aim of this study was to report the sensitivity, cytological diagnoses, endoscopic ultrasound (EUS) features, complications, clinical impact, and long term follow-up of a large single-center experience with endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) of benign and malignant solid liver lesions. A database of cytologic specimens from EUS-FNA was reviewed to identify all hepatic lesions aspirated between January, 1997, and July, 2002. Procedural indications, prior radiographic data, patient demographics, EUS examination results, complications, and follow-up data were obtained and recorded. EUS-FNA of 77 liver lesions in 77 patients was performed without complications. Of these 77 lesions, 45 (58%) were diagnostic for malignancy, 25 (33%) were benign, and seven (9%) were nondiagnostic. A total of 22 lesions were confirmed as negative for malignancy by follow-up (mean 762 days, range 512-1556 days) or intraoperative examination; however, seven lesions could not be classified as benign or malignant. Depending on the status of the seven unclassified lesions, sensitivity of EUS-FNA for the diagnosis of malignancy ranged from 82 to 94%. When compared with benign lesions, EUS features predictive of malignant hepatic masses were the presence of regular outer margins (60% vs 27%; p = 0.02) and the detection of two or more lesions (38% vs 9%; p = 0.03). Of the 42 patients with malignancy identified by EUS-FNA and other available imaging records, EUS detected the malignancy in 41% of patients with previously negative examinations. For the 45 subjects with cytology positive for malignancy, EUS-FNA changed management in 86% of subjects. EUS-FNA of the liver is a safe and sensitive procedure that can have a significant impact on patient management. Prospective studies comparing the accuracy and complication rate of EUS-FNA and percutaneous fine needle aspiration (P-FNA) for the diagnosis of liver tumors are needed.


Foliar-applied glyphosate substantially reduced uptake and transport of iron and manganese in sunflower (Helianthus annuus L.) plants.
Evidence clearly shows that cationic micronutrients in spray solutions reduce the herbicidal effectiveness of glyphosate for weed control due to the formation of metal-glyphosate complexes. The formation of these glyphosate-metal complexes in plant tissue may also impair micronutrient nutrition of nontarget plants when exposed to glyphosate drift or glyphosate residues in soil. In the present study, the effects of simulated glyphosate drift on plant growth and uptake, translocation, and accumulation (tissue concentration) of iron (Fe), manganese (Mn), zinc (Zn), and copper (Cu) were investigated in sunflower (Helianthus annuus L.) plants grown in nutrient solution under controlled environmental conditions. Glyphosate was sprayed on plant shoots at different rates between 1.25 and 6.0% of the recommended dosage (i.e., 0.39 and 1.89 mM glyphosate isopropylamine salt). Glyphosate applications significantly decreased root and shoot dry matter production and chlorophyll concentrations of young leaves and shoot tips. The basal parts of the youngest leaves and shoot tips were severely chlorotic. These effects became apparent within 48 h after the glyphosate spray. Glyphosate also caused substantial decreases in leaf concentration of Fe and Mn while the concentration of Zn and Cu was less affected. In short-term uptake experiments with radiolabeled Fe (59Fe), Mn (54Mn), and Zn (65Zn), root uptake of 59Fe and 54Mn was significantly reduced in 12 and 24 h after application of 6% of the recommended dosage of glyphosate, respectively. Glyphosate resulted in almost complete inhibition of root-to-shoot translocation of 59Fe within 12 h and 54Mn within 24 h after application. These results suggest that glyphosate residues or drift may result in severe impairments in Fe and Mn nutrition of nontarget plants, possibly due to the formation of poorly soluble glyphosate-metal complexes in plant tissues and/or rhizosphere interactions.


Rathke cleft cysts in pediatric patients: presentation, surgical management, and postoperative outcomes.
Rathke cleft cysts (RCC) are benign sellar lesions most often found in adults, and more infrequently in children. They are generally asymptomatic but sometimes require surgical treatment through a transsphenoidal corridor. The purpose of this study was to compare adult versus pediatric cases of RCC. The authors retrospectively reviewed presenting symptoms, MR imaging findings, laboratory study results, and pathological findings in 147 adult and 14 pediatric patients who underwent surgery for treatment of RCCs at the University of Californial at San Francisco between 1996 and 2008. In both the adult and pediatric groups, most patients were female (78% of adults, 79% of pediatric patients, p = 0.9). Headache was the most common symptom in both groups (reported by 50% of pediatric patients and 33% of adults, p = 0.2). Preoperative hypopituitarism occurred in 41% of adults and 45% of pediatric patients (p = 0.8). Growth delay, a uniquely pediatric finding, was a presenting sign in 29% of pediatric patients. Visual complaints were a presenting symptom in 16% of adult and 7% of pediatric patients (p = 0.4). There was no difference between median cyst size in adults versus pediatric patients (1.2 cm in both, p = 0.7). Temporary or permanent postoperative diabetes insipidus occurred in 12% of adults and 21% of pediatric patients (p = 0.4). Kaplan-Meier analysis revealed an 8% RCC recurrence rate at 2 years for each group (p = 0.5). The incidence of RCCs is much lower in the pediatric population; however, symptoms, imaging findings, and outcomes are similar, suggesting that pediatric RCCs arise from growth of remnants of the embryonic Rathke pouch earlier in life than adult RCCs but do not differ in any other way. It is important to consider RCCs in the differential diagnosis when pediatric patients present with visual impairment, unexplained headache, or hypopituitarism including growth delay. Although the average RCC size was similar in our pediatric and adult patient groups, the smaller size of the pituitary gland in pediatric patients suggests an increased relative RCC size.


Long-term dynamics of Mycoplasma conjunctivae at the wildlife-livestock interface in the Pyrenees.
Functional roles of domestic and wild host populations in infectious keratoconjunctivitis (IKC) epidemiology have been extensively discussed claiming a domestic reservoir for the more susceptible wild hosts, however, based on limited data. With the aim to better assess IKC epidemiology in complex host-pathogen alpine systems, the long-term infectious dynamics and molecular epidemiology of Mycoplasma conjunctivae was investigated in all host populations from six study areas in the Pyrenees and one in the Cantabrian Mountains (Northern Spain). Detection of M. conjunctivae was performed by qPCR on 3600 eye swabs collected during seven years from hunted wild ungulates and sympatric domestic sheep (n = 1800 animals), and cluster analyses of the strains were performed including previous reported local strains. Mycoplasma conjunctivae was consistently detected in three Pyrenean chamois (Rupicapra p. pyrenaica) populations, as well as in sheep flocks (17.0% of sheep) and occasionally in mouflon (Ovis aries musimon) from the Pyrenees (22.2% in one year/area); statistically associated with ocular clinical signs only in chamois. Chamois populations showed different infection dynamics with low but steady prevalence (4.9%) and significant yearly fluctuations (0.0%- 40.0%). Persistence of specific M. conjunctivae strain clusters in wild host populations is demonstrated for six and nine years. Cross-species transmission between chamois and sheep and chamois and mouflon were also sporadically evidenced. Overall, independent M. conjunctivae sylvatic and domestic cycles occurred at the wildlife-livestock interface in the alpine ecosystems from the Pyrenees with sheep and chamois as the key host species for each cycle, and mouflon as a spill-over host. Host population characteristics and M. conjunctivae strains resulted in different epidemiological scenarios in chamois, ranging from the fading out of the mycoplasma to the epidemic and endemic long-term persistence. These findings highlight the capacity of M. conjunctivae to establish diverse interactions and persist in host populations, also with different transmission conditions.


Clustering of HCV coinfections on HIV phylogeny indicates domestic and sexual transmission of HCV.
HCV coinfection remains a major cause of morbidity and mortality among HIV-infected individuals and its incidence has increased dramatically in HIV-infected men who have sex with men(MSM). Hepatitis C virus (HCV) coinfection in the Swiss HIV Cohort Study(SHCS) was studied by combining clinical data with HIV-1 pol-sequences from the SHCS Drug Resistance Database(DRDB). We inferred maximum-likelihood phylogenetic trees, determined Swiss HIV-transmission pairs as monophyletic patient pairs, and then considered the distribution of HCV on those pairs. Among the 9748 patients in the SHCS-DRDB with known HCV status, 2768(28%) were HCV-positive. Focusing on subtype B(7644 patients), we identified 1555 potential HIV-1 transmission pairs. There, we found that, even after controlling for transmission group, calendar year, age and sex, the odds for an HCV coinfection were increased by an odds ratio (OR) of 3.2 [95% confidence interval (CI) 2.2, 4.7) if a patient clustered with another HCV-positive case. This strong association persisted if transmission groups of intravenous drug users (IDUs), MSMs and heterosexuals (HETs) were considered separately(in all cases OR>2). Finally we found that HCV incidence was increased by a hazard ratio of 2.1 (1.1, 3.8) for individuals paired with an HCV-positive partner. Patients whose HIV virus is closely related to the HIV virus of HIV/HCV-coinfected patients have a higher risk for carrying or acquiring HCV themselves. This indicates the occurrence of domestic and sexual HCV transmission and allows the identification of patients with a high HCV-infection risk.


Programmable disorder in random DNA tilings.
Scaling up the complexity and diversity of synthetic molecular structures will require strategies that exploit the inherent stochasticity of molecular systems in a controlled fashion. Here we demonstrate a framework for programming random DNA tilings and show how to control the properties of global patterns through simple, local rules. We constructed three general forms of planar network-random loops, mazes and trees-on the surface of self-assembled DNA origami arrays on the micrometre scale with nanometre resolution. Using simple molecular building blocks and robust experimental conditions, we demonstrate control of a wide range of properties of the random networks, including the branching rules, the growth directions, the proximity between adjacent networks and the size distribution. Much as combinatorial approaches for generating random one-dimensional chains of polymers have been used to revolutionize chemical synthesis and the selection of functional nucleic acids, our strategy extends these principles to random two-dimensional networks of molecules and creates new opportunities for fabricating more complex molecular devices that are organized by DNA nanostructures.


Prevalence and associated factors of female genital mutilation among Somali refugees in eastern Ethiopia: a cross-sectional study.
Eastern Ethiopia hosts a substantial number of refugees originated from Somalia. Female genital mutilation (FGM) is a common practice in the area, despite the campaigns to eliminate it. A cross-sectional study was conducted among 492 respondents sampled from three refugee camps in Somali Regional State, Eastern Ethiopia, to determine the prevalence and associated factors of FGM. Data were collected using pre-tested structured questionnaires. Although the intention of the parents to circumcise their daughters was high (84%), 42.4% of 288 < or = 12 girls were reported being undergone FGM. The prevalence increased with age, and about 52% and 95% were circumcised at the age of 7-8 and 11-12 years, respectively. Almost all operations were performed by traditional circumcisers (81%) and birth attendants (18%). Clitoral cutting (64%) and narrowing of the vaginal opening through stitching (36%) were the two common forms of FGM reported by the respondents. Participation of the parents in anti-FGM interventions is statistically associated with lower practice and intention of the procedures. FGM is widely practised among the Somali refugee community in Eastern Ethiopia, and there was a considerable support for the continuation of the practice particularly among women. The findings indicate a reported shift of FGM from its severe form to milder clitoral cutting. More men than women positively viewed anti-FGM interventions, and fewer men than women had the intention to let their daughters undergo FGM, indicating the need to involve men in anti-FGM activities.


Reverse Electrodialysis Chemical Cell for Energy Harvesting from Controlled Acid-Base Neutralization.
We report a novel reverse electrodialysis (RED) chemical cell that integrates RED with acid/base neutralization. This RED neutralization process (REDn) approximately doubled the power density compared to a conventional RED stack (REDc), thanks to the additional salinity gradients established by H+ and OH- ions as a result of the neutralization reaction. Detailed analysis shows that the power performance, i.e., the open circuit voltage and power density, of the REDn cell was greatly limited by concentration polarization and uphill transport of ions. Addressing these issues could potentially lead to an order of magnitude improvement in power density as predicted by the Nernst equation. The current study provides a simple strategy for effectively extracting energy from the neutralization of waste acid and base solutions. Future studies shall further explore the treatment of acid mine drainage and landfill leachate with the RED chemical cell as well as its extension to a wider range of reactions.


Vesicular stomatitis virus-based vaccine protects hamsters against lethal challenge with Andes virus.
Andes virus (ANDV) is a highly pathogenic South American hantavirus that causes hantavirus pulmonary syndrome (HPS). A high case fatality rate, the potential for human-to-human transmission, the capacity to infect via aerosolization, and the absence of effective therapies make it imperative that a safe, fast-acting, and effective ANDV vaccine be developed. We generated and characterized a recombinant vesicular stomatitis virus (VSV) vector expressing the ANDV surface glycoprotein precursor (VSVΔG/ANDVGPC) as a possible vaccine candidate and tested its efficacy in the only lethal-disease animal model of HPS. Syrian hamsters immunized with a single injection of VSVΔG/ANDVGPC were fully protected against disease when challenged at 28, 14, 7, or 3 days postimmunization with a lethal dose of ANDV; however, the mechanism of protection seems to differ depending on when the immunization occurs. At 28 days postimmunization, a lack of detectable ANDV RNA in lung, liver, and blood tissue samples, as well as a lack of seroconversion to the ANDV nucleocapsidprotein in nearly all animals, suggested largely sterile immunity. The vaccine was able to generate high levels of neutralizing anti-ANDV G(N)/G(C) antibodies, which seem to play a role as a mechanism of vaccine protection. Administration of the vaccine at 7 or 3 days before challenge also resulted in full protection but with no specific neutralizing humoral immune response, suggesting a possible role of innate responses in protection against challenge virus replication. Administration of the vaccine 24 h postchallenge was successful in protecting 90% of hamsters and again suggested the induction of a potent antiviral state by the recombinant vector as a potential mechanism. Overall, our data suggest the potential for the use of the VSV platform as a fast-acting and effective prophylaxis/postexposure treatment against lethal hantavirus infections.


Perceptions of family styles by adolescents with eating disorders and their parents.
The traditional view has been that there is a great deal of rigidity and enmeshment in the families of adolescents with eating disorders, with poor communication and satisfaction among family members. We used the Family Adaptability and Cohesion Evaluation Scales IV (FACES-IV) to study whether this traditional view remains true or whether family styles among those with eating disorders have changed over time to include a wider range of families. Forty-four patients (aged 14-18 years; mean, 15.4 years; 38 females and 6 males) being treated for an eating disorder in a Division of Adolescent Medicine completed the FACES-IV questionnaire, along with the Beck Depression Inventory (BDI). Patients were diagnosed with anorexia nervosa (38.6%), eating disorders not otherwise specified (59.5%), and bulimia nervosa (2.3%) according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. They had a mean BMI of 19.6 at the time of questionnaire completion, which was an average of 175 days from first visit. Parents (38 mothers and 6 fathers) completed the FACES-IV and the BDI at the same visit without conferring with their children. A great majority of patients and parents reported their families as being connected/very connected (93% of patients and 98% of parents) and flexible/very flexible (80% and 93%), with low/very low enmeshment (89% and 89%), moderate/low/very low rigidity (77% and 95%), low/very low chaos (84% and 86%), and moderate/high/very high communication (85% and 50%). Despite these scores, all well within the normal range for families with teenagers, 70% of patients and 64% of parents reported low/very low satisfaction with their families, well below the normal range. Depression scores were moderate/severe for 44% of patients and 14% of parents. Analysis of variance and t-tests showed no differences between FACES-IV scores and age, gender, ethnicity, diagnosis, and time from first visit for patients, whereas patients and parents who were more depressed were each more likely (p<0.05) to report greater dissatisfaction with their families. A great majority of patients with eating disorders and their parents reported their family styles to be in the healthy range. However, many patients and parents, especially those with depression, expressed dissatisfaction with their families. These data demonstrate that older concepts of the families of adolescents with eating disorders need to be reconsidered.


Pigeon perception of letters of the alphabet.
In a three-choice discrimination task three pigeons learned to distinguish each letter of the alphabet from all other letters. Errors during learning were based on 54 presentations of each target letter with every other letter. The errors were used to scale letters in a multidimensional similarity space and to associate them in hierarchical clusters. The results resembled those generated from similarity judgments by humans, suggesting cross-task and cross-species generality in processes of letter discrimination.


Training in vascular medicine for vascular surgeons--what is it and how will we accomplish it?
The goal of vascular surgery training program should be the training of a complete vascular surgeon proficient not only in the management of established peripheral vascular disease but also in the prevention of the atherosclerotic process through management of risk factors. In addition, vascular surgeons should develop expertise in the treatment of nonatherosclerotic arterial disease, nonoperative management of acute and chronic venous disease, lymphedema, and the treatment of various coagulation disorders. To accomplish these goals, we should establish a comprehensive, patient-centered vascular medicine curriculum and appropriate methods for its implementation.


Prevalence and Impact of SDHI Fungicide Resistance in Alternaria solani.
Early blight, caused by Alternaria solani, is an important chronic foliar disease of potato (Solanum tuberosum) present every growing season in the Midwestern United States. Most currently grown potato cultivars lack resistance to early blight; therefore, foliar fungicides are relied upon for disease management. Foliar fungicides with high efficacy against the pathogen, such as boscalid, frequently are used under high disease pressure situations, such as potatoes grown under overhead irrigation. Boscalid is a member of the succinate dehydrogenase inhibiting (SDHI) fungicide group and was registered for use on potato in 2005. Baseline sensitivity of A. solani to the SDHI fungicides boscalid, penthiopyrad, and fluopyram using a spore germination assay demonstrated similar intrinsic activity against A. solani with mean EC50 values of 0.33, 0.38, and 0.31 μg/ml, respectively. However, isolates varied in their sensitivity to each of these fungicides, resulting in very low correlations (r) among isolate sensitivity to each fungicide. Resistance to boscalid in A. solani was detected in the states of North Dakota, Minnesota, Nebraska, Texas, Idaho, Wisconsin, and Florida from early blight samples collected in 2010 and 2011. Two phenotypes of boscalid resistance were detected. Approximately 80% of all A. solani assayed were found to have some level of resistance to boscalid with about 5 and 75% of the population moderately resistant (5 to 20 μg/ml) and highly resistant (>20 μg/ml), respectively, to the fungicide. Nearly 99% of all boscalid resistant isolates possessed the F129L mutation in the cytrochrome b gene, indicating that an A. solani population with dual fungicide resistance predominates in the states surveyed. However, A. solani isolates resistant to boscalid remained sensitive to fluopyram, and a large proportion of moderately resistant and resistant isolates were sensitive to penthiopyrad. Disease control data from in vivo trials demonstrated a significant loss of fungicide efficacy when boscalid and fluxapyroxad were used to control moderately and highly resistant isolates of A. solani relative to the control these fungicides provided wild-type isolates. Fluopyram, however, controlled boscalid resistant isolates as well as it controlled wild-type isolates of A. solani. These data will assist potato growers in regions where boscalid resistance is prevalent by assisting them in avoiding fungicides that do not effectively control early blight and in selecting SDHI fungicide molecules that remain efficacious.


Roles of Infected Seed Tubers and Soilborne Inoculum on Verticillium Wilt of 'Russet Burbank' Potato.
Verticillium dahliae, causal agent of Verticillium wilt of potato, persists in soil as microsclerotia and can be found in infected tubers used for seed. The effects of naturally infected tubers and soilborne inoculum on Verticillium wilt symptoms were compared in the greenhouse. Infected and noninfected tubers were grown in infested and noninfested potting soil. Chlorosis and necrosis were measured and converted to area under senescence progress curves (AUSPC). Aboveground stems and progeny tubers were assayed for V. dahliae. Plants from infested soils exhibited significantly greater AUSPC than plants from noninfested soil. Plants grown from infected and noninfected tubers had similar AUSPC and interactions between infected tubers and infested soil were not observed. The pathogen was isolated from the vascular system of 94% of plants grown in infested soils and 8% of plants grown from infected tubers in noninfested soil. Plants grown in infested soil contained microsclerotia on 46% of stems while plants grown from infected tubers in noninfested soils exhibited microsclerotia on <1% of stems. Infected progeny tubers were only recovered from plants grown in infested soil. Seed tuber infection did not contribute to premature senescence or potential inoculum production, indicating that management efforts should focus on reducing soilborne inoculum.


The shadow of the future promotes cooperation in a repeated prisoner's dilemma for children.
Cooperation among genetically unrelated individuals can be supported by direct reciprocity. Theoretical models and experiments with adults show that the possibility of future interactions with the same partner can promote cooperation via conditionally cooperative strategies such as tit-for-tat (TFT). Here, we introduce a novel implementation of the repeated Prisoner's Dilemma (PD) designed for children to examine whether repeated interactions can successfully promote cooperation in 10 and 11 year olds. We find that children cooperate substantially more in repeated PDs than in one-shot PDs. We also find that girls cooperate more than boys, and that children with more conduct problems cooperate less. Finally, we find that children use conditional cooperation strategies but that these strategies vary by gender and conduct problem rating. Specifically, girls and children with few conduct problems appear to follow an altruistic version of win-stay, lose-shift (WSLS), attempting to re-establish cooperation after they had defected. Boys and children with more conduct problems appear to follow a Grim strategy, defecting for the duration after the partner defects. Thus we provide evidence that children utilize the power of direct reciprocity to promote cooperation in strategic interactions and that, by late elementary school, distinct strategies of conditional cooperation have emerged.


Hospital Evaluations by Social Media: A Comparative Analysis of Facebook Ratings among Performance Outliers.
An increasing number of hospitals and health systems utilize social media to allow users to provide feedback and ratings. The correlation between ratings on social media and more conventional hospital quality metrics remains largely unclear, raising concern that healthcare consumers may make decisions on inaccurate or inappropriate information regarding quality. The purpose of this study was to examine the extent to which hospitals utilize social media and whether user-generated metrics on Facebook(®) correlate with a Hospital Compare(®) metric, specifically 30-day all cause unplanned hospital readmission rates. This was a retrospective cross-sectional study conducted among all U.S. hospitals performing outside the confidence interval for the national average on 30-day hospital readmission rates as reported on Hospital Compare. Participants were 315 hospitals performing better than U.S. national rate on 30-day readmissions and 364 hospitals performing worse than the U.S. national rate. The study analyzed ratings of hospitals on Facebook's five-star rating scale, 30-day readmission rates, and hospital characteristics including beds, teaching status, urban vs. rural location, and ownership type. Hospitals performing better than the national average on 30-day readmissions were more likely to use Facebook than lower-performing hospitals (93.3 % vs. 83.5 %; p < 0.01). The average rating for hospitals with low readmission rates (4.15 ± 0.31) was higher than that for hospitals with higher readmission rates (4.05 ± 0.41, p < 0.01). Major teaching hospitals were 14.3 times more likely to be in the high readmission rate group. A one-star increase in Facebook rating was associated with increased odds of the hospital belonging to the low readmission rate group by a factor of 5.0 (CI: 2.6-10.3, p < 0.01), when controlling for hospital characteristics and Facebook-related variables. Hospitals with lower rates of 30-day hospital-wide unplanned readmissions have higher ratings on Facebook than hospitals with higher readmission rates. These findings add strength to the concept that aggregate measures of patient satisfaction on social media correlate with more traditionally accepted measures of hospital quality.


Morphological and functional evaluation of intrapericardial cyst as a cause of severe right heart failure: dual source computed tomography and magnetic resonance imaging.
A case of an intrapericardial cyst causing heart failure due to right ventricular compression is presented. Characterization of the lesion and its repercussion on right ventricular function by means of state-of-the-art dual source computed tomography (DSCT) and magnetic resonance imaging (MRI) is shown. The diagnosis of intrapericardial cyst was confirmed after surgical excision and biopsy. Usefulness of these noninvasive techniques for the diagnosis of this rare entity is emphasized.


DeepFall: Non-Invasive Fall Detection with Deep Spatio-Temporal Convolutional Autoencoders.
Human falls rarely occur; however, detecting falls is very important from the health and safety perspective. Due to the rarity of falls, it is difficult to employ supervised classification techniques to detect them. Moreover, in these highly skewed situations, it is also difficult to extract domain-specific features to identify falls. In this paper, we present a novel framework, DeepFall, which formulates the fall detection problem as an anomaly detection problem. The DeepFall framework presents the novel use of deep spatio-temporal convolutional autoencoders to learn spatial and temporal features from normal activities using non-invasive sensing modalities. We also present a new anomaly scoring method that combines the reconstruction score of frames across a temporal window to detect unseen falls. We tested the DeepFall framework on three publicly available datasets collected through non-invasive sensing modalities, thermal camera and depth cameras, and show superior results in comparison with traditional autoencoder methods to identify unseen falls.


Development of Canadian screening tools for fetal alcohol spectrum disorder.
Fetal alcohol spectrum disorder (FASD) is the most common cause of neurobehavioural handicap in North America. Screening for FASD may facilitate diagnosis and hence management of these children. We present a variety of screening tools for the identification of children at risk for FASD. We critically reviewed and evaluated published and practiced methods for their potential of screening suspected cases, their epidemiological characteristics (sensitivity, specificity, positive and negative predictive values) [Phase I], as well as their feasibility [Phase II]. The following five tools were selected for the FASD screening toolkit: screening fatty acid ethyl esters in neonatal meconium, the modified Child Behaviour Checklist, Medicine Wheel tool, Asante Centre Probation Officer Tool, and maternal history of drinking and drug use. The toolkit for FASD screening aims at screening different populations, from the newborns to youth and at-risk mothers. It is anticipated that the toolkit will facilitate diagnosis of FASD.


Mitochondrial membrane permeabilization and cell death during myocardial infarction: roles of calcium and reactive oxygen species.
Excess generation of reactive oxygen species (ROS) and cytosolic calcium accumulation play major roles in the initiation of programmed cell death during acute myocardial infarction. Cell death may include necrosis, apoptosis and autophagy, and combinations thereof. During ischemia, calcium handling between the sarcoplasmic reticulum and myofilament is disrupted and calcium is diverted to the mitochondria causing swelling. Reperfusion, while essential for survival, reactivates energy transduction and contractility and causes the release of ROS and additional ionic imbalance. During acute ischemia-reperfusion, the principal death pathways are programmed necrosis and apoptosis through the intrinsic pathway, initiated by the opening of the mitochondrial permeability transition pore and outer mitochondrial membrane permeabilization, respectively. Despite intense investigation, the mechanisms of action and modes of regulation of mitochondrial membrane permeabilization are incompletely understood. Extrinsic apoptosis, necroptosis and autophagy may also contribute to ischemia-reperfusion injury. In this review, the roles of dysregulated calcium and ROS and the contributions of Bcl-2 proteins, as well as mitochondrial morphology in promoting mitochondrial membrane permeability change and the ensuing cell death during myocardial infarction are discussed.


Physical Activity Levels Among Adolescent and Young Adult Women and Men with and without Intellectual Disability.
As physical activity can prevent overweight and promote general health, the aim was to investigate the amount of physical activity among adolescent and young adult women and men with intellectual disability (ID), compared to age-matched control groups without intellectual disability. A further aim was to examine whether physical activity level was associated with the body mass index (BMI). Fifty-two adolescent and young adult women and men with intellectual disability and 48 without intellectual disability, between the ages 16 and 20 years, BMIs ranging from 16.3 to 50.3 kg/m(2) , were measured for number of steps taken with a pedometer for five consecutive days (Sunday-Thursday). The only group to meet recommendations regarding number of steps (10 000-12 000/day) was women without intellectual disability. No significant associations were found between total number of steps taken and BMI. As the majority of adolescents and young adults with intellectual disability, especially women, did not reach recommended activity levels regardless of their BMIs, this call for broad measures to increase physical activity.


Reliable discrimination of 10 ungulate species using high resolution melting analysis of faecal DNA.
Identifying species occupying an area is essential for many ecological and conservation studies. Faecal DNA is a potentially powerful method for identifying cryptic mammalian species. In New Zealand, 10 species of ungulate (Order: Artiodactyla) have established wild populations and are managed as pests because of their impacts on native ecosystems. However, identifying the ungulate species present within a management area based on pellet morphology is unreliable. We present a method that enables reliable identification of 10 ungulate species (red deer, sika deer, rusa deer, fallow deer, sambar deer, white-tailed deer, Himalayan tahr, Alpine chamois, feral sheep, and feral goat) from swabs of faecal pellets. A high resolution melting (HRM) assay, targeting a fragment of the 12S rRNA gene, was developed. Species-specific primers were designed and combined in a multiplex PCR resulting in fragments of different length and therefore different melting behaviour for each species. The method was developed using tissue from each of the 10 species, and was validated in blind trials. Our protocol enabled species to be determined for 94% of faecal pellet swabs collected during routine monitoring by the New Zealand Department of Conservation. Our HRM method enables high-throughput and cost-effective species identification from low DNA template samples, and could readily be adapted to discriminate other mammalian species from faecal DNA.


Risk versus benefit: Should not audiologists assess this in the context of occupational noise-induced hearing loss in the mining industry?
Hearing conservation programmes (HCPs) are an important aspect of occupational health efforts to prevent occupational noise-induced hearing loss (ONIHL). In low- and middle income (LAMI) countries, where the incidence of ONIHL is significant, it is important to deliberate on the risk or benefit of HCPs. This article is an attempt at highlighting important strategic indicators as well as important variables that the occupational health and audiology community need to consider to plan efficacious HCPs within the South African mining context. The current arguments are presented in the form of a viewpoint publication. Occupational audiology vigilance in the form of engagement with HCPs in the mining industry has been limited within the South African research and clinical communities. When occupational audiology occurs, it is conducted by mid-level workers and paraprofessionals; and it is non-systematic, non-comprehensive and non-strategic. This is compounded by the current, unclear externally enforced accountability by several bodies, including the mining industry regulating body, with silent and/or peripheral regulation by the Health Professions Council of South Africa and the Department of Health. The lack of involvement of audiologists in the risk or benefit evaluation of HCPs during their development and monitoring process, as well as their limited involvement in the development of policies and regulations concerning ear health and safety within this population are probable reasons for this. Increased functioning of the regulatory body towards making the employers accountable for the elimination of ONIHL, and a more central and prominent role for audiologists in HCPs, are strongly argued for.


Fractional proliferation: a method to deconvolve cell population dynamics from single-cell data.
We present an integrated method that uses extended time-lapse automated imaging to quantify the dynamics of cell proliferation. Cell counts are fit with a quiescence-growth model that estimates rates of cell division, entry into quiescence and death. The model is constrained with rates extracted experimentally from the behavior of tracked single cells over time. We visualize the output of the analysis in fractional proliferation graphs, which deconvolve dynamic proliferative responses to perturbations into the relative contributions of dividing, quiescent (nondividing) and dead cells. The method reveals that the response of 'oncogene-addicted' human cancer cells to tyrosine kinase inhibitors is a composite of altered rates of division, death and entry into quiescence, a finding that challenges the notion that such cells simply die in response to oncogene-targeted therapy.


Combined analysis of r-1,t-2,3,c-4-tetrahydroxy-1,2,3,4-tetrahydrophenanthrene and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol in smokers' plasma.
Polycyclic aromatic hydrocarbons (PAH) and tobacco-specific nitrosamines, such as 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), are widely accepted to be two important types of lung carcinogens in cigarette smoke. In this study, we have developed a method to estimate individual uptake of these compounds by quantifying r-1,t-2,3,c-4-tetrahydroxy-1,2,3,4-tetrahydrophenanthrene (PheT) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) in 1 mL of smokers' plasma. PheT and NNAL are biomarkers of PAH and NNK uptake, respectively. [D10]PheT and [pyridine-D4]NNAL were added to plasma as internal standards. The plasma was treated with beta-glucuronidase to release any conjugated PheT and NNAL. The analytes were enriched by solid-phase extraction on a mixed mode cation exchange cartridge and the PheT fraction was further purified by high-performance liquid chromatography. The appropriate fractions were analyzed by gas chromatography-negative ion chemical ionization-mass spectrometry for PheT and liquid chromatography-electrospray ionization-mass spectrometry for NNAL. The method was sensitive (limits of quantitation: PheT, 13 fmol/mL; NNAL, 3 fmol/mL), accurate, and precise. Levels of PheT and NNAL in plasma from 16 smokers averaged 95 +/- 71 and 36 +/- 21 fmol/mL, respectively, which are approximately 1% to 2% of the amounts found in urine. This method should be useful in molecular epidemiology studies of carcinogen uptake and lung cancer in smokers.


The PhytoClust tool for metabolic gene clusters discovery in plant genomes.
The existence of Metabolic Gene Clusters (MGCs) in plant genomes has recently raised increased interest. Thus far, MGCs were commonly identified for pathways of specialized metabolism, mostly those associated with terpene type products. For efficient identification of novel MGCs, computational approaches are essential. Here, we present PhytoClust; a tool for the detection of candidate MGCs in plant genomes. The algorithm employs a collection of enzyme families related to plant specialized metabolism, translated into hidden Markov models, to mine given genome sequences for physically co-localized metabolic enzymes. Our tool accurately identifies previously characterized plant MGCs. An exhaustive search of 31 plant genomes detected 1232 and 5531 putative gene cluster types and candidates, respectively. Clustering analysis of putative MGCs types by species reflected plant taxonomy. Furthermore, enrichment analysis revealed taxa- and species-specific enrichment of certain enzyme families in MGCs. When operating through our web-interface, PhytoClust users can mine a genome either based on a list of known cluster types or by defining new cluster rules. Moreover, for selected plant species, the output can be complemented by co-expression analysis. Altogether, we envisage PhytoClust to enhance novel MGCs discovery which will in turn impact the exploration of plant metabolism.


Computational fluid dynamics with stents: quantitative comparison with particle image velocimetry for three commercial off the shelf intracranial stents.
Validation of computational fluid dynamics (CFD) in stented intracranial aneurysms (IAs) is still lacking, to reliably predict prone to occlusion hemodynamics, probing, in particular, velocity reduction, and flow pattern changes. This study compares CFD outcome with particle imaging velocimetry (PIV) for three commercial off the shelf (COTS) stents of different material densities. The recently developed uniform and high precision multi-time lag PIV method was applied to a sidewall aneurysm before and after implantation of three COTS stents with high, intermediate, and low material densities. The measured laser sheet flow patterns and velocity reductions were compared with CFD results and correlated with stent material density. Velocity reduction was in good agreement for unstented high and low porosity stented IA, while flow pattern change was fully matched for unstented and high porosity stented IA. Poor CFD-PIV matching in IA was found for intermediate porosity stents. CFD reproduced fully PIV measurements in unstented and high porosity stented IAs. With low porosity stents, CFD reproduced velocity reduction and high velocities close to the neck, while a marked mismatch on sluggish flow was found at the dome. CFD was unable to match PIV with intermediate porosity stents for which hemodynamic transition occurred.


Management of the older person with atrial fibrillation.
Atrial fibrillation (AF) is associated with a higher incidence of mortality, stroke, and coronary events than is sinus rhythm. AF with a rapid ventricular rate may cause a tachycardia-related cardiomyopathy. Immediate direct-current (DC) cardioversion should be performed in patients with AF and acute myocardial infarction, chest pain due to myocardial ischemia, hypotension, severe heart failure, or syncope. Intravenous beta blockers, verapamil, or diltiazem may be given to slow immediately a very rapid ventricular rate in AF. An oral beta blocker, verapamil, or diltiazem should be used in persons with AF if a fast ventricular rate occurs at rest or during exercise despite digoxin. Amiodarone may be used in selected patients with symptomatic life-threatening AF refractory to other drugs. Nondrug therapies should be performed in patients with symptomatic AF in whom a rapid ventricular rate cannot be slowed by drugs. Paroxysmal AF associated with the tachycardia-bradycardia syndrome should be treated with a permanent pacemaker in combination with drugs. A permanent pacemaker should be implanted in patients with AF and with symptoms such as dizziness or syncope associated with ventricular pauses greater than 3 seconds that are not drug-induced. Elective DC cardioversion has a higher success rate and a lower incidence of cardiac adverse effects than does medical cardioversion in converting AF to sinus rhythm. Unless transesophageal echocardiography has shown no thrombus in the left atrial appendage before cardioversion, oral warfarin should be given for 3 weeks before elective DC or drug cardioversion of AF and should be continued for at least 4 weeks after maintenance of sinus rhythm. Many cardiologists prefer, especially in older persons, ventricular rate control plus warfarin rather than maintaining sinus rhythm with antiarrhythmic drugs. Digoxin should not be used to treat patients with paroxysmal AF. Patients with chronic or paroxysmal AF at high risk for stroke should be treated with long-term warfarin to achieve an International Normalized Ratio of 2.0 to 3.0. Patients with AF at low risk for stroke or with contraindications to warfarin should receive 325 mg of aspirin daily.


Perioperative Efficiency vs. Quality of Care - Do We Always Have to Choose?
Introduction: ATTEMPTS to enforce optimization practices for operating room (OR) efficiency are often interpreted as a "pressure for production" which threatens patient safety. The aim of this study is to assess if and how improvements in OR efficiency affect patient safety and thus the quality of care. Methods: In an attempt to optimize OR efficiency, a new OR management approach "Integrated Practice Improvement Solutions" (IPIS) was developed at the Weiler Division of Montefiore Medical Center in 2011. IPIS is a flexible managerial system based on elements of multiple practice improvement methodologies incorporated into an open source framework. It was implemented in 2012. The data presented covers the period from 2012 through 2014 when the system was temporarily discontinued due to administrative restructuring. Data from 2011 was used as a baseline. The impact of IPIS on patient safety and quality of care was assessed based on quality improvement and patient safety (QIPS) Committee reports covering the same period of time. Results: IPIS implementation resulted in an increase in surgical workload by an average of 10.7%, an increase in OR and anesthesia revenues by 18.5% and 6.9%, respectively, and decreases in turnover time by 15% and overtime for the anesthesia staff by 26%. Based on QIPS reports, the total number of complications potentially attributable to "production pressure" was 0.25%, 0.2% and 0.16% in 2012, 2013 and 2014, respectively compared to 0.21% in 2011 (p = 0.56). Conclusions: Gradual implementation of a methodologically structured improvement in OR efficiency has no negative impact on patient safety and quality of care.


Cranberries: ripe for more cancer research?
Berries have been recognized as a functional food with potential to protect against a variety of health conditions, including some cancers. Cranberry (Vaccinium macrocarpon) production and consumption have grown in recent years, warranting further evaluation of potential health benefits. Extracts and isolated constituents from cranberry fruit inhibit growth and proliferation of tumor cells in vitro, and recent data from animal studies lend further support to cranberry's reputation as a cancer fighter. Several likely mechanisms of action for cranberry against prostate and other cancers have been identified, including induction of apoptosis and inhibition of events linked to cellular invasion and migration. This article attempts to put into perspective what is known about cranberry's potential chemopreventive properties, what is yet to be determined, and some factors to consider as research moves forward.


Compact and blinking-suppressed quantum dots for single-particle tracking in live cells.
Quantum dots (QDs) offer distinct advantages over organic dyes and fluorescent proteins for biological imaging applications because of their brightness, photostability, and tunability. However, a major limitation is that single QDs emit fluorescent light in an intermittent on-and-off fashion called "blinking". Here we report the development of blinking-suppressed, relatively compact QDs that are able to maintain their favorable optical properties in aqueous solution. Specifically, we show that a linearly graded alloy shell can be grown on a small CdSe core via a precisely controlled layer-by-layer process, and that this graded shell leads to a dramatic suppression of QD blinking in both organic solvents and water. A substantial portion (>25%) of the resulting QDs does not blink (more than 99% of the time in the bright or "on" state). Theoretical modeling studies indicate that this type of linearly graded shell not only can minimize charge carrier access to surface traps but also can reduce lattice defects, both of which are believed to be responsible for carrier trapping and QD blinking. Further, we have evaluated the biological utility of blinking-suppressed QDs coated with polyethylene glycol (PEG)-based ligands and multidentate ligands. The results demonstrate that their optical properties are largely independent of surface coatings and solvating media, and that the blinking-suppressed QDs can provide continuous trajectories in live-cell receptor tracking studies.


Information efficiency of line-scan imaging mechanisms.
Information theory is used to formulate a single figure of merit for assessing the performance of line-scan imaging systems as a function of their spatial response (PSF or MTF), sensitivity, and sampling and quantization intervals and of the statistical properties of a random radiance field. Information density and efficiency (i.e., the ratio of information density to data density) tend to be optimum when the MTF and sampling passband of the imaging system are matched to the Wiener spectrum of the radiance field. Computational results for the statistical properties of natural radiance fields and the responses of common line-scan imaging mechanisms indicate that information density and efficiency are not strongly sensitive to variations in typical statistical properties of the radiance field and that the best practically realizable performance is approached when the sampling intervals are ~0.5-0.7 times the equivalent diameter of the PSF.


The ACE gene and human performance: 12 years on.
Some 12 years ago, a polymorphism of the angiotensin I-converting enzyme (ACE) gene became the first genetic element shown to impact substantially on human physical performance. The renin-angiotensin system (RAS) exists not just as an endocrine regulator, but also within local tissue and cells, where it serves a variety of functions. Functional genetic polymorphic variants have been identified for most components of RAS, of which the best known and studied is a polymorphism of the ACE gene. The ACE insertion/deletion (I/D) polymorphism has been associated with improvements in performance and exercise duration in a variety of populations. The I allele has been consistently demonstrated to be associated with endurance-orientated events, notably, in triathlons. Meanwhile, the D allele is associated with strength- and power-orientated performance, and has been found in significant excess among elite swimmers. Exceptions to these associations do exist, and are discussed. In theory, associations with ACE genotype may be due to functional variants in nearby loci, and/or related genetic polymorphism such as the angiotensin receptor, growth hormone and bradykinin genes. Studies of growth hormone gene variants have not shown significant associations with performance in studies involving both triathletes and military recruits. The angiotensin type-1 receptor has two functional polymorphisms that have not been shown to be associated with performance, although studies of hypoxic ascent have yielded conflicting results. ACE genotype influences bradykinin levels, and a common gene variant in the bradykinin 2 receptor exists. The high kinin activity haplotye has been associated with increased endurance performance at an Olympic level, and similar results of metabolic efficiency have been demonstrated in triathletes. Whilst the ACE genotype is associated with overall performance ability, at a single organ level, the ACE genotype and related polymorphism have significant associations. In cardiac muscle, ACE genotype has associations with left ventricular mass changes in response to stimulus, in both the health and diseased states. The D allele is associated with an exaggerated response to training, and the I allele with the lowest cardiac growth response. In light of the I-allele association with endurance performance, it seems likely that other regulatory mechanisms exist. Similarly in skeletal muscle, the D allele is associated with greater strength gains in response to training, in both healthy individuals and chronic disease states. As in overall performance, those genetic polymorphisms related to the ACE genotype, such as the bradykinin 2 gene, also influence skeletal muscle strength. Finally, the ACE genotype may influence metabolic efficiency, and elite mountaineers have demonstrated an excess of I alleles and I/I genotype frequency in comparison to controls. Interestingly, this was not seen in amateur climbers. Corroboratory evidence exists among high-altitude settlements in both South America and India, where the I allele exists in greater frequency in those who migrated from the lowlands. Unfortunately, if the ACE genotype does influence metabolic efficiency, associations with peak maximal oxygen consumption have yet to be rigorously demonstrated. The ACE genotype is an important but single factor in the determinant of sporting phenotype. Much of the mechanisms underlying this remain unexplored despite 12 years of research.


Development and initial validation of a Parkinson's disease caregiver strain risk screen.
Family caregivers face potential strain in caring for persons with Parkinson's disease because of the unpredictability of symptom presentation. The Caregiver Strain Risk Screen (CSRS) was developed and tested for initial validation. Instrument item development was guided by focus-group and interview data and a theoretical conceptualization of caregiver strain risk in caregivers of persons with Parkinson's disease. Caregivers of persons with Parkinson's disease (N = 217) provided data. Principal components analysis supported a 28-item instrument with 4 factors: self-preservation, nursing home consideration, coping through spirituality, and coping through formal support. The 28-item CSRS demonstrated acceptable validity and reliability in measuring the construct. Research using a new sample is underway to further psychometrically test and validate the CSRS through confirmatory factor analysis.


Aggregation and stability in metapopulation models.
We analyze a metapopulation model of the interactions between Lotka-Volterra-type prey and predators that occur in two environmentally distinguishable patches and are linked by migration. Environmental differences between the patches tend to stabilize the otherwise neutrally stable model by causing the per capita immigration rate on a patch to be temporally density-dependent, partly as a consequence of out-of-phase fluctuations in density. However, the environmental differences can also lead to indirect effects on the temporal dependence of per capita prey death rate on prey density in each patch and on temporal dependence of per capita predator birthrate on predator density in each patch. Spatially density-dependent movement by the prey can be either uniformly destabilizing or initially stabilizing and then destabilizing as the degree of density dependence increases, depending on the overall rate of prey movement. Aggregation by the predator to the patch with more prey modifies one or more of the three processes listed above. Typically, weak aggregation is stabilizing, and strong aggregation is destabilizing. Aggregation can also render unstable an initially stable model. We conclude that metapopulation and single-population models are not good analogues of each other and that predator aggregation affects the two types of models via different mechanisms.


Comparing antiviral strategies against COVID-19 via multiscale within-host modelling.
Within-host models of COVID-19 infection dynamics enable the merits of different forms of antiviral therapy to be assessed in individual patients. A stochastic agent-based model of COVID-19 intracellular dynamics is introduced here, that incorporates essential steps of the viral life cycle targeted by treatment options. Integration of model predictions with an intercellular ODE model of within-host infection dynamics, fitted to patient data, generates a generic profile of disease progression in patients that have recovered in the absence of treatment. This is contrasted with the profiles obtained after variation of model parameters pertinent to the immune response, such as effector cell and antibody proliferation rates, mimicking disease progression in immunocompromised patients. These profiles are then compared with disease progression in the presence of antiviral and convalescent plasma therapy against COVID-19 infections. The model reveals that using both therapies in combination can be very effective in reducing the length of infection, but these synergistic effects decline with a delayed treatment start. Conversely, early treatment with either therapy alone can actually increase the duration of infection, with infectious virions still present after the decline of other markers of infection. This suggests that usage of these treatments should remain carefully controlled in a clinical environment.


Development of a quality-of-movement measure for children with cerebral palsy.
Development of a suitable measure of quality of movement, or gross motor performance, for children with cerebral palsy is a complex undertaking. A variety of conceptual, methodological, and practical issues inherent in such a project are discussed in this article. We report on the methodology used in the planning and construction of the Gross Motor Performance Measure. The measure has been developed by a multicenter, interdisciplinary group of therapists, methodologists, research staff, and international experts. Five attributes of gross motor performance have been defined, scaled, and operationalized. Results of content validity studies demonstrate that the measure has adequate completeness, clarity, and potential for evaluating change in quality of movement in children who have cerebral palsy. The measure is currently undergoing extensive testing to determine the reliability, validity, and responsiveness of the obtained scores. [Boyce WF, Gowland C, Hardy S, et al. Development of a quality-of-movement measure for children with cerebral palsy.


Increased gut microbiota diversity and abundance of Faecalibacterium prausnitzii and Akkermansia after fasting: a pilot study.
An impaired gut microbiota has been reported as an important factor in the pathogenesis of obesity. Weight reduction has already been mentioned to improve gut microbial subpopulations involved in inflammatory processes, though other subpopulations still need further investigation. Thus, weight reduction in the context of a fasting program together with a probiotic intervention may improve the abundance and diversity of gut microbiota. In this pilot study, overweight people underwent a fasting program with laxative treatment for 1 week followed by a 6 week intervention with a probiotic formula. Gut microbiota were analyzed on the basis of 16s rDNA with a quantitative real time polymerase chain reaction. Additionally, a food frequency questionnaire with questions about nutritional behavior, lifestyle, and physical activity was administered before and after the intervention. We observed an increase in microbial diversity over the study period. No significant changes in abundance of total bacteria, or of Bacteroidetes, Prevotella, Clostridium cluster XIVa, or Clostridium cluster IV were found, although Faecalibacterium prausnitzii showed an increase over the study period. In addition, Akkermanisa and Bifidobacteria increased in abundance due to intervention. The inflammation-associated gut microbes Enterobacteria and Lactobacilli increased during the first week and then declined by the end of the intervention. Two-thirds of the study participants harbored Archaea. No significant improvements of eating habits were reported, although physical activity improved due to the intervention. Our results show that caloric restriction affects gut microbiota by proliferating mucin-degrading microbial subpopulations. An additional intervention with a probiotic formula increased probiotic-administered gut microbial populations.


The cylindrical or tubiliform glands of Nephila clavipes.
The cylindrical or tubiliform glands of the spider Nephila clavipes have been studied and compared to the large ampullates on which we have previously reported. The three pairs of cylindrical or tubiliform glands secrete the fibroin for the organism's egg case. Their solubilized luminar contents migrate as a homogeneous band in Sodium dodecyl sulfate polyacrylamide gel electrophoresis and turn out to be a larger protein than that produced by the large ampullates. The excised cylindrical glands remain metabolically active for several hours in a simple culture medium, where fibroin synthesis can be monitored through the incorporation of 14C alanine. The glands' response to a fibroin production stimulus does not reach the magnitude displayed by the large ampullates, but this is to be expected since their products supply different functions in this organism. This fibroin also seems to be elongated discontinuously. Translational pauses have been detected in the secretory epithelium of cylindrical and large ampullate glands of Nephila as well as in the silk glands of Bombyx mori. Since these glands produce the fibroin for the females egg case, they should prove to be an interesting model system.


Search for gluinos in events with an isolated lepton, jets and missing transverse momentum at [Formula: see text] = 13 Te V with the ATLAS detector.
The results of a search for gluinos in final states with an isolated electron or muon, multiple jets and large missing transverse momentum using proton-proton collision data at a centre-of-mass energy of [Formula: see text] are presented. The dataset used was recorded in 2015 by the ATLAS experiment at the Large Hadron Collider and corresponds to an integrated luminosity of 3.2 fb[Formula: see text]. Six signal selections are defined that best exploit the signal characteristics. The data agree with the Standard Model background expectation in all six signal selections, and the largest deviation is a 2.1 standard deviation excess. The results are interpreted in a simplified model where pair-produced gluinos decay via the lightest chargino to the lightest neutralino. In this model, gluinos are excluded up to masses of approximately 1.6 Te V depending on the mass spectrum of the simplified model, thus surpassing the limits of previous searches.


Estrogen alone and joint symptoms in the Women's Health Initiative randomized trial.
Although joint symptoms are commonly reported after menopause, observational studies examining exogenous estrogen's influence on joint symptoms provide mixed results. Against this background, estrogen-alone effects on joint symptoms were examined in post hoc analyses in the Women's Health Initiative randomized, placebo-controlled, clinical trial. A total of 10,739 postmenopausal women who have had a hysterectomy were randomized to receive daily oral conjugated equine estrogens (0.625 mg/d) or a matching placebo. The frequency and severity of joint pain and joint swelling were assessed by questionnaire in all participants at entry and on year 1, and in a 9.9% random subsample (n = 1,062) after years 3 and 6. Logistic regression models were used to compare the frequency and severity of symptoms by randomization group. Sensitivity analyses evaluated adherence influence on symptoms. At baseline, joint pain and joint swelling were closely comparable in the randomization groups (about 77% with joint pain and 40% with joint swelling). After 1 year, joint pain frequency was significantly lower in the estrogen-alone group compared with the placebo group (76.3% vs 79.2%, P = 0.001), as was joint pain severity, and the difference in pain between randomization groups persisted through year 3. However, joint swelling frequency was higher in the estrogen-alone group (42.1% vs 39.7%, P = 0.02). Adherence-adjusted analyses strengthen estrogen's association with reduced joint pain but attenuate estrogen's association with increased joint swelling. The current findings suggest that estrogen-alone use in postmenopausal women results in a modest but sustained reduction in the frequency of joint pain.


[Isolation and characteristics of Chinese hamster cells resistant to colchicine].
Several ClchR clones of CHO-K1 have been isolated by a single- and multistep selection. They are distinct from each other both in the level of colchicine resistance and in the phenotypic stability of this feature. Fluctuation tests showed that the generation of drug resistant variants in the wild type population was random and did not depend on the action of selective agent. The rate of spontaneous occurrence of these variants was approximatley 1.79 x 10(-6) per cell per generation. Treatment with MNNG enhanced the frequency of ClchR variants by 100 fold. Cytotoxic effect of Clch on resistant cells has been potentiated by non-ionic detergent Tween 80. All the stable resistant clones appeared to be cross resistant to unrelated drugs such as actinomycin D, ethydium bromide and aminopterine . These two observations allow to suggest the alteration of membrane permeability as a mechanism of resistance to Clch . Genetical mechanisms of Clch -resistance of cells are discussed.


National Partnership for Maternal Safety Recommended Maternal Early Warning Criteria Are Associated With Maternal Morbidity.
Many cases of maternal mortality and morbidity are preventable. A delayed response to clinical warning signs contributes to preventability. Therefore, the National Partnership for Maternal Safety devised maternal early warning criteria (MEWC), composed of abnormal vital signs that trigger bedside evaluation by a provider with the capacity to escalate care. The relationship of the MEWC to maternal morbidity has not been studied. We evaluated the correlation between the MEWC and maternal morbidity. We retrospectively reviewed the first 400 deliveries at the University of Chicago in 2016. We analyzed the electronic medical record to determine whether vital signs triggered the MEWC during the admission to labor and delivery and whether patients experienced morbidity during their delivery hospitalization. The association between MEWC and morbidity was tested using χ analysis. We calculated the sensitivity, specificity, and positive and negative predictive values of the MEWC. Two hundred eighty-one (70%) of 400 patients triggered the MEWC at least once, and 198 (50%) of 400 patients had multiple or recurrent triggers. Ninety-nine (25%) of 400 patients experienced morbidity. The most common causes of morbidity were hemorrhage, suspected infection, and preeclampsia with severe features. The relative risk of maternal morbidity with at least a single trigger was 13.55 (95% confidence interval [CI], 4.38-41.91) and with recurrent or multiple triggers was 5.29 (95% CI, 3.22-8.71). The sensitivity of the MEWC in predicting morbidity was 0.97 (95% CI, 0.92-0.99) and the specificity was 0.39 (95% CI, 0.33-0.44) when patients with at least a single trigger were included. When including only patients with multiple or recurrent triggers, the sensitivity was 0.84 (95% CI, 0.75-0.90) and the specificity was 0.62 (95% CI, 0.56-0.67). The positive predictive value of the MEWC in our population was 0.34 (95% CI, 0.29-0.40), and the negative predictive value was 0.97 (95% CI, 0.93-0.99). When considering only patients with multiple or recurrent triggers, the positive predictive value was 0.42 (95% CI, 0.38-0.46) and the negative predictive value was 0.92 (95% CI, 0.88-0.95). The MEWC are associated with maternal morbidity. As a screening tool, they appropriately prioritize sensitivity and have an excellent negative predictive value. The criteria demonstrate low specificity, which is slightly improved by considering only patients with recurrent or multiple triggers. Additional efforts to improve the specificity of MEWC, with a focus on identifying sustained or recurrent patterns of abnormal vital signs, may be necessary before their widespread implementation.


Optimizing conditions for utilization of an H2 oxidation catalyst with outer coordination sphere functionalities.
As a starting point for evaluating a broader range of conditions for H2 oxidation complexes, in this work we investigate an efficient and reversible Ni-based H2 oxidation and production complex with an arginine in the outer coordination sphere, [Ni(P(Cy)2N(Arginine)2)2](7+) (CyArg). We tested this complex under a wide range of pressures and temperatures, in two different solvents (methanol and water), to determine if simultaneous improvements in rate and overpotential could be achieved. We found that the optimal conditions combined both high temperature (72 °C) and pressure (100 atm H2) in acidic aqueous solution (pH = 1), resulting in the fastest H2 oxidation reported for any homogeneous electrocatalyst to date (TOF 1.1 × 10(6) s(-1)) operating at 240 mV overpotential. The activation free energy in water was determined to be 10 kcal mol(-1) at all pressures studied. Surprisingly, in methanol under the same temperature and pressure, CyArg had a TOF for H2 oxidation of only 280 s(-1) at an overpotential of 750 mV. Comparisons to the data in water, and to a control complex, [Ni(P(Cy)2N(Benzyl)2)2](2+) (CyBn; Bn = benzyl), suggest that this substantial difference is likely due to a change in rate limiting step from H2 addition to deprotonation. Importantly, the optimal conditions we identified for CyArg (elevated temperature and acidic aqueous solutions), are amenable to fuel cell technologies and provide an important advancement in implementing homogeneous synthetic catalysts for renewable energy.


Expression of the 3' terminal region of human T-cell leukemia viruses.
Human T-cell leukemia viruses (HTLV) are closely associated with some human T-cell leukemias and lymphomas. A unique 3' region of the HTLV genome is believed to be involved in HTLV-induced cellular transformation, although the function of this region has yet to be determined. A subgenomic messenger RNA transcribed from this region of HTLV has now been characterized. These results provide direct evidence for the expression of a novel gene in HTLV.


Measuring color differences in automotive samples with lightness flop: a test of the AUDI2000 color-difference formula.
From a set of gonioapparent automotive samples from different manufacturers we selected 28 low-chroma color pairs with relatively small color differences predominantly in lightness. These color pairs were visually assessed with a gray scale at six different viewing angles by a panel of 10 observers. Using the Standardized Residual Sum of Squares (STRESS) index, the results of our visual experiment were tested against predictions made by 12 modern color-difference formulas. From a weighted STRESS index accounting for the uncertainty in visual assessments, the best prediction of our whole experiment was achieved using AUDI2000, CAM02-SCD, CAM02-UCS and OSA-GP-Euclidean color-difference formulas, which were no statistically significant different among them. A two-step optimization of the original AUDI2000 color-difference formula resulted in a modified AUDI2000 formula which performed both, significantly better than the original formula and below the experimental inter-observer variability. Nevertheless the proposal of a new revised AUDI2000 color-difference formula requires additional experimental data.


Mouse SmI cortex: qualitative and quantitative classification of golgi-impregnated barrel neurons.
The neurons in layer IV of the mouse somatosensory cortex are arranged in a remarkably consistent pattern of multicellular cytoarchitectonic units called "barrels." Each barrel is known to be related, in a one to one manner, to a contralateral whisker or vibrissa on the animal's face. In this study we have examined Golgi-impregnated neurons that comprise the "barrels." Several criteria, some being quantitative measures of dendritic arbors and somal sizes which were obtained with a computer-microscope system, suggest that all barrel neurons can be placed in two classes, the members of which are present in approximately equal numbers. The cells in the two classes can be further subdivided on the basis of the relationship of their processes to the barrels: 85% of them have processes restricted to a single barrel; 15% of them distribute their processes to two or more barrels. From these observations it is possible to suggest that a majority of neurons comprising the barrels would respond initially to movements of only one whisker while the remainder would respond to movements of two or more whiskers. In addition it has been shown that the quantitation of neuronal structure can provide a numerical basis for the classification of neurons in the central nervous system.


Surgical training in Guyana: the next generation.
The pioneering surgical training partnership between the Canadian Association of General Surgeons (CAGS) and the University of Guyana has successfully graduated 14 surgeons since 2006. The association has recruited 29 surgeons who have made 75 teaching visits to Guyana, and CAGS involvement has been critical to providing local credibility to the program, organizing the curriculum structure and developing rigorous examinations. The program is now locally sustained, with graduates leading a number of clinical hospital programs. The initial diploma qualification is being reassessed, as other specialties have introduced postgraduate Master of Medicine degree programs. Many graduates are pursuing additional training opportunities overseas, and almost all of those remaining in Guyana have returned to the tertiary centre from the regional hospitals. The program has succeeded in training surgeons and raising the standards of surgical care in Guyana, but broader health system efforts are necessary to retain surgeons in outlying regional hospitals.


90Y radioembolization of metastatic breast cancer to the liver: toxicity, imaging response, survival.
To present data from patients with breast cancer liver metastases who underwent radioembolization with yttrium (90Y) microspheres. Using standard 90Y lobar treatment protocol, 27 female patients with progressing liver metastases on standard of care polychemotherapy were treated under an open-label phase 2 protocol. After treatment, we assessed (a) tumor response using computed tomography and/or positron emission tomography, (b) biochemical toxicity, and (c) survival. The mean age of the patients was 52. Seventeen (63%) patients received 20 left lobe treatments (median radiation dose, 123 Gy; mean, 119 Gy), and 20 (74%) patients received 22 right lobe treatments (median radiation dose, 121 Gy; mean, 109 Gy) to the treatment site. No significant dose-difference was noted between the two lobes (P=.69). Tumor response on 90-day follow-up computed tomography showed (a) complete and partial response in nine (39.1%) patients, (b) stable disease in 12 (52.1%) patients, and (c) progressive disease in 2 (8.8%) patients. Positive tumor response on positron emission tomography was noted in 17 (63%) patients. Three of 27 (11%) patients (Eastern Cooperation Oncology Group 1, 2, or 3) showed bilirubin toxicity of grade 3, all of which were attributed to disease progression. Median survival for Eastern Cooperation Oncology Group 0 versus 1, 2, or 3 patients was 6.8 months and 2.6 months, respectively (P=.24) and for patients with tumor burden<25% versus >25% was 9.4 and 2.0 months, respectively (P=.46). Radioembolization with 90Y brachytherapy device may be a viable therapeutic option for the treatment of breast cancer liver metastases in patients who have progressed or failed on standard of care polychemotherapy.


The morphology and function of healing cat corneal endothelium.
We mechanically damaged the entire corneal endothelium of one eye of each of ten cats and then examined both eyes by fluorophotometry and specular microscopy for 5 months. Six weeks after damage, when the corneas had cleared sufficiently to make accurate measurements, the mean endothelial permeability to carboxyfluorescein was increased 11% (P = 0.02) and the mean central corneal thickness was increased 11% (P = 0.05) in the damaged eyes. The mean endothelial pump rate was decreased 29% (P = 0.05), indicating that the increase in permeability was insufficient to explain the increase in thickness. The permeability returned to normal by 3 months and the pump rate by 5 months. Six weeks after damage, the mean endothelial cell size was increased 89% (P less than 0.01), the mean coefficient of variation of cell size was increased 200% (P less than 0.01), and the mean percentage of hexagonal cells was decreased 34% (P less than 0.01). By 5 months, the mean cell size had changed very little, and none of the three morphologic measurements had returned to normal. As in rabbits, the endothelial barrier in cats recovers before the pump after wounding. Unlike in rabbits, functional recovery in cats requires at least several months. Such prolonged functional recovery after endothelial trauma might also be expected in humans who, like cats and unlike rabbits, have little capacity for endothelial mitosis during healing.


Low-Dose Daily Intake of Vitamin K(2) (Menaquinone-7) Improves Osteocalcin γ-Carboxylation: A Double-Blind, Randomized Controlled Trials.
Vitamin K is essential for bone health, but the effects of low-dose vitamin K intake in Japanese subjects remain unclear. We investigated the effective minimum daily menaquinone-7 dose for improving osteocalcin γ-carboxylation. Study 1 was a double-blind, randomized controlled dose-finding trial; 60 postmenopausal women aged 50-69 y were allocated to one of four dosage group and consumed 0, 50, 100, or 200 μg menaquinone-7 daily for 4 wk, respectively, with a controlled diet in accordance with recommended daily intakes for 2010 in Japan. Study 2 was a double-blind, randomized placebo-controlled trial based on the results of Study 1; 120 subjects aged 20-69 y were allocated to the placebo or MK-7 group and consumed 0 or 100 μg menaquinone-7 daily for 12 wk, respectively. In both studies, circulating carboxylated osteocalcin and undercarboxylated osteocalcin were measured. The carboxylated osteocalcin/undercarboxylated osteocalcin ratio decreased significantly from baseline in the 0 μg menaquinone-7 group, in which subjects consumed the recommended daily intake of vitamin K with vitamin K1 and menaquinone-4 (Study 1). Menaquinone-7 increased the carboxylated osteocalcin/undercarboxylated osteocalcin ratio dose dependently, and significant effects were observed in both the 100 and 200 μg groups compared with the 0 μg group. Undercarboxylated osteocalcin concentrations decreased significantly, and the carboxylated osteocalcin/undercarboxylated osteocalcin ratio increased significantly in the 100 μg menaquinone-7 group compared with the placebo group (Study 2). Daily menaquinone-7 intake ≥100 μg was suggested to improve osteocalcin γ-carboxylation.


First Report of Calonectria hongkongensis Causing Fruit Rot of Rambutan (Nephelium lappaceum).
Fruit rot of rambutan is a pre- and post-harvest disease problem of rambutan orchards. In 2011, fruit rot was observed at USDA-ARS orchards in Mayaguez, Puerto Rico. Infected fruit were collected and 1 mm2 tissue sections were surface disinfested with 70% ethanol followed by 0.5% sodium hypochlorite. Infected fruit were rinsed with sterile, deionized, double-distilled water and transferred to acidified potato dextrose agar (APDA). Plates were incubated at 25 ± 1°C for 6 days. Three isolates of Calonectria hongkongensis (Cah), CBS134083, CBS134084, and CBS134085, were identified morphologically using taxonomic keys (2,3). In APDA, colonies of Cah produced raw sienna to rust-colored aerial mycelial growth. Conidiophores of Cah had a penicillate arrangement of primary to quaternary branches of 2 to 6 phialides. Conidia (n = 50) were cylindrical, hyaline, 1-septate, rounded at both ends, and 44 to 52 μm × 3.5 to 4.5 μm. Conidiophores produced terminal and lateral stipe extensions with terminal sphaeropedunculate vesicles that were 8 to 12 μm wide. Subglobose to ovoid perithecia, 300 to 500 μm × 200 to 350 μm and orange to red-brown, were produced in groups of 3. Asci were clavate and contained 8 ascospores aggregated at the top of the ascus. Ascospores (n = 50) were hyaline, guttulate, fusoid with rounded ends, straight to curved, 1-septate with constriction at the septum, and 28 to 36 μm × 4 to 7 μm. For molecular identification, the ITS rDNA, fragments of β-tubulin (BT), histone H3 (HIS3), and elongation factor (EF1-α) genes were amplified by PCR, sequenced, and compared using BLASTn with Calonectria spp. submitted to the NCBI GenBank. The sequences of Cah submitted to GenBank include accessions KC342208, KC342206, and KC342207 for ITS; KC342217, KC342215, and KC342216 for BT; KC342211, KC342209, and KC342210 for HIS3; and KC342214, KC342212, and KC342213 for EF1α. The sequences were >99% or identical with the ex-type specimen of Cah CBS 114828 for all genes used. Pathogenicity tests were conducted on 5 healthy superficially sterilized fruits per isolate. Both scalpel-wounded and unwounded fruit tissues were inoculated with 5-mm mycelial disks from 8-day-old pure cultures grown in APDA. Untreated controls were inoculated with APDA disks only. Fruits were kept in a humid chamber for 8 days at 25°C under 12 h of fluorescent light. The test was repeated once. Three days after inoculation (DAI), white mycelial growth was observed on the fruit. Five DAI, the fruit changed color from red to brown and yellowish mycelia colonized 50 to 62% of the fruit surface. Eight DAI, all the fruit turned brown, the mycelium growth covered the entire fruit, and conidiophores were produced on spinterns (hairlike appendages). Fruit rot of spinterns, exocarp (skin), endocarp (aril), and light brown discoloration were observed inside the fruit. Untreated controls showed no symptoms of fruit rot and no fungi were reisolated from tissue. Cah was reisolated from diseased tissue, fulfilling Koch's postulates. Calonectria spp. (or their Cylindrocladium asexual states) have been associated with lychee decline syndrome in North Vietnam (1). Both fruits belong to the Sapindaceae family. To our knowledge, this is the first report of Cah causing fruit rot of rambutan. References: (1) L. M. Coates et al. Diseases of Longan, Lychee and Rambutan. Pages 307-325 in: Diseases of Tropical Fruit Crops. R. C. Ploetz, ed. CABI Publishing, Cambridge, MA, 2003. (2) P. W. Crous. Taxonomy and Pathology of Cylindrocladium (Calonectria) and Allied Genera. APS Press, St Paul, MN, 2002. (3) P. W. Crous, et al. Stud. Mycol. 50:415, 2004.


Safety of efavirenz in the first trimester of pregnancy: an updated systematic review and meta-analysis.
Evidence of the risk of birth defects with efavirenz use is limited. We updated a meta-analysis of birth defects in infants with first trimester efavirenz exposure up to July 2011. In 21 studies, there were 39 defects among live births in 1437 women receiving first trimester efavirenz [2.0%, 95% confidence interval (CI) 0.82-3.18]. The relative risk of defects comparing women on efavirenz-based (1290 live births) and nonefavirenz-based regimens (8122 live births) was 0.85 (95% CI 0.61-1.20). One neural tube defect was observed (myelomeningocele), giving an incidence of 0.07% (95% CI 0.002-0.39).


Formyl peptide receptors and the regulation of ACTH secretion: targets for annexin A1, lipoxins, and bacterial peptides.
The N-formyl peptide receptors (FPRs) are a family of G-protein coupled receptors that respond to proinflammatory N-formylated bacterial peptides (e.g., formyl-Met-Leu-Phe, fMLF) and, thus, contribute to the host response to bacterial infection. Paradoxically, a growing body of evidence suggests that some members of this receptor family may also be targets for certain anti-inflammatory molecules, including annexin A1 (ANXA1), which is an important mediator of glucocorticoid (GC) action. To explore further the potential role of FPRs in mediating ANXA1 actions, we have focused on the pituitary gland, where ANXA1 has a well-defined role as a cell-cell mediator of the inhibitory effects of GCs on the secretion of corticotrophin (ACTH), and used molecular, genetic, and pharmacological approaches to address the question in well-established rodent models. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis identified mRNAs for four FPR family members in the mouse anterior pituitary gland, Fpr-rs1, Fpr-rs2, Fpr-rs6, and Fpr-rs7. Functional studies confirmed that, like dexamethasone, ANXA1 and two ANXA1-derived peptides (ANXA1(1-188) and ANXA1(Ac2-26)) inhibit the evoked release of ACTH from rodent anterior pituitary tissue in vitro. Fpr1 gene deletion failed to modify the pituitary responses to dexamethasone or ANXA1(Ac2-26). However, lipoxin A4 (LXA4, 0.02-2 microM, a lipid mediator with high affinity for Fpr-rs1) mimicked the inhibitory effects of ANXA1 on ACTH release as also did fMLF in high (1-100 microM) but not lower (10-100 nM) concentrations. Additionally, a nonselective FPR antagonist (Boc1, 100 microM) overcame the effects of dexamethasone, ANXA1(1-188), ANXA1(Ac2-26), fMLF, and LXA4 on ACTH release, although at a lower concentration (50 microM), it was without effect. Together, the results suggest that the actions of ANXA1 in the pituitary gland are independent of Fpr1 but may involve other FPR family members, in particular, Fpr-rs1 or a closely related receptor. They thus provide the first evidence for a role of the FPR family in the regulation of neuroendocrine function.


Assessment of potential atmospheric transport and deposition patterns due to Russian Pacific Fleet operations.
A probabilistic analysis of atmospheric transport and deposition patterns from two nuclear risk sites-Kamchatka and Vladivostok-situated in the Russian Far East to countries and geographical regions of interest (Japan, China, North and South Koreas, territories of the Russian Far East, State of Alaska, and Aleutian Chain Islands, US) was performed. The main questions addressed were the following: Which geographical territories are at the highest risk from hypothetical releases at these sites? What are the probabilities for radionuclide atmospheric transport and deposition on different neighboring countries in case of accidents at the sites? For analysis, several research tools developed within the Arctic Risk Project were applied: (1) isentropic trajectory model to calculate a multiyear dataset of 5-day forward trajectories that originated over the site locations at various altitudes; (2) DERMA long-range transport model to simulate 5-day atmospheric transport, dispersion, and deposition of 137Cs for 1-day release (at the rate of 10(10) Bq/s); and (3) a set of statistical methods (including exploratory, cluster, and probability fields analyses) for evaluation of trajectory and dispersion modeling results. The possible impact (on annual, seasonal, and monthly basis) of selected risk sites on neighboring geographical regions is evaluated using a set of various indicators. For trajectory modeling, the indicators examined are: (1) atmospheric transport pathways, (2) airflow probability fields, (3) fast transport probability fields, (4) maximum possible impact zone, (5) maximum reaching distance, and (6) typical transport time fields. For dispersion modeling, the indicators examined are: (1) time integrated air concentration, (2) dry deposition, and (3) wet deposition. It was found for both sites that within the boundary layer the westerly flows are dominant throughout the year (more than 60% of the time), increasing with altitude of free troposphere up to 85% of the time. For the Kamchatka site, the US regions are at the highest risk with the average times of atmospheric transport ranging from 3 to 5.1 days and depositions of 10(-1) Bq/m2 and lower. For the Vladivostok site, the northern China and Japan regions are at the highest risk with the average times of atmospheric transport of 0.5 and 1.6 days, respectively, and depositions ranging from 10(0) to 10(+2) Bq/m2. The areas of maximum potentially impacted zones are 30 x 10(4) km2 and 25 x 10(4) km2 for the Kamchatka and Vladivostok sites, respectively.


Dry Eye Disease: A Review of Epidemiology in Taiwan, and its Clinical Treatment and Merits.
Dry eye disease (DED) has become common on a global scale in recent years. There is a wide prevalence of DED in different countries based on various ethnicities and environment. DED is a multifactorial ocular disorder. In addition to advanced age and gender, such factors as living at high altitude, smoking, pterygium, prolonged use of consumer electronics or overingesting of caffeine or multivitamins are considered to be the major risk factors of DED. We report the DED epidemiology in Taiwan firstly in this article. According to the pathophysiological factors and changes inthe composition of the tear film in DED, it can be categorized into several subtypes, including lipid anomaly dry eye, aqueous tear deficiency, allergic and toxic dry eye among others. Each subtype has its own cause and disease management; therefore, it is important for ophthalmologists to identify the type through literature review and investigation. The management of DED, relies not only on traditional medications such as artificial tears, gels and ointments, but also newer treatment options such as acupuncture, SYL1001, and nanomedicine therapy. We also conducted a comprehensive literature review including common subtypes and treatment of DED. Clearly, more clinical trials are needed to assess the efficacy and safety of the various treatments and common subtypes of DED.


Prognostic Significance of Diffuse Large B-Cell Lymphoma Cell of Origin Determined by Digital Gene Expression in Formalin-Fixed Paraffin-Embedded Tissue Biopsies.
To evaluate the prognostic impact of cell-of-origin (COO) subgroups, assigned using the recently described gene expression-based Lymph2Cx assay in comparison with International Prognostic Index (IPI) score and MYC/BCL2 coexpression status (dual expressers). Reproducibility of COO assignment using the Lymph2Cx assay was tested employing repeated sampling within tumor biopsies and changes in reagent lots. The assay was then applied to pretreatment formalin-fixed paraffin-embedded tissue (FFPET) biopsies from 344 patients with de novo diffuse large B-cell lymphoma (DLBCL) uniformly treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) at the British Columbia Cancer Agency. MYC and BCL2 protein expression was assessed using immunohistochemistry on tissue microarrays. The Lymph2Cx assay provided concordant COO calls in 96% of 49 repeatedly sampled tumor biopsies and in 100% of 83 FFPET biopsies tested across reagent lots. Critically, no frank misclassification (activated B-cell-like DLBCL to germinal center B-cell-like DLBCL or vice versa) was observed. Patients with activated B-cell-like DLBCL had significantly inferior outcomes compared with patients with germinal center B-cell-like DLBCL (log-rank P < .001 for time to progression, progression-free survival, disease-specific survival, and overall survival). In pairwise multivariable analyses, COO was associated with outcomes independent of IPI score and MYC/BCL2 immunohistochemistry. The prognostic significance of COO was particularly evident in patients with intermediate IPI scores and the non-MYC-positive/BCL2-positive subgroup (log-rank P < .001 for time to progression). Assignment of DLBCL COO by the Lymph2Cx assay using FFPET biopsies identifies patient groups with significantly different outcomes after R-CHOP, independent of IPI score and MYC/BCL2 dual expression.


The MUC5B mucin polymer is dominated by repeating structural motifs and its topology is regulated by calcium and pH.
The polymeric mucin MUC5B provides the structural and functional framework of respiratory mucus, conferring both viscoelastic and antimicrobial properties onto this vital protective barrier. Whilst it is established that MUC5B forms disulfide-linked linear polymers, how this relates to their packaging in secretory granules, and their molecular form in mucus remain to be fully elucidated. Moreover, the role of the central heavily O-glycosylated mucin domains in MUC5B conformation is incompletely described. Here we have completed a detailed structural analysis on native MUC5B polymers purified from saliva and subsequently investigated how MUC5B conformation is affected by changes in calcium concentration and pH, factors important for mucin intragranular packaging and post-secretory expansion. The results identify that MUC5B has a beaded structure repeating along the polymer axis and suggest that these repeating motifs arise from distinct glycosylation patterns. Moreover, we demonstrate that the conformation of these highly entangled linear polymers is sensitive to calcium concentration and changes in pH. In the presence of calcium (Ca2+, 10 mM) at pH 5.0, MUC5B adopted a compact conformation which was lost either upon removal of calcium with EGTA, or by increasing the pH to 7.4. These results suggest a pathway of mucin collapse to enable intracellular packaging and mechanisms driving mucin expansion following secretion. They also point to the importance of the tight control of calcium and pH during different stages of mucin biosynthesis and secretion, and in the generation of correct mucus barrier properties.


Dispersion and stability of titanium dioxide nanoparticles in aqueous suspension: effects of ultrasonication and concentration.
The increasing applications of titanium dioxide (TiO(2)) nanoparticles raise concerns about their potential environmental impacts. To investigate the fate and transport of TiO(2) nanoparticles in aqueous suspension, ultrasonication is widely used for the dispersion of TiO(2) nanoparticles in laboratory-scale studies. There is a pressing need for detailed information on the dispersion and stability of TiO(2) nanoparticles. This study investigated the change of size, zeta potential, and pH of TiO(2) nanoparticles aqueous suspension under different conditions of ultrasonication and concentrations. It was found that the hydrodynamic diameter of TiO(2) nanoparticles decreased with increasing suspension concentration and remained stable for more than 1 hour after sonication, which is enough for experimental research. The pH decreased with increasing nanoparticles concentration. Ultrasonication remarkably improved zeta potential to be above 15 mV for all the samples. Therefore, 20 minutes of ultrasonication (180 W) is sufficient for the dispersion of this rutile TiO(2) nanoparticles suspension, which can remain stable for more than 1 hour. However, the optimum sonication time for TiO(2) nanoparticles dispersion is influenced by many factors, such as TiO(2) nanoparticles concentration, solution chemistry, and sonicator parameters.


Edge detection revisited.
The present manuscript aims at solving four problems of edge detection: the simultaneous detection of all step edges from a fine to a coarse scale; the detection of thin bars with a width of very few pixels; the detection of trihedral junctions; the development of an algorithm with image-independent parameters. The proposed solution of these problems combines an extensive spatial filtering with classical methods of computer vision and newly developed algorithms. Step edges are computed by extracting local maxima from the energy summed over a large bank of directional odd filters with a different scale. Thin roof edges are computed by considering maxima of the energy summed over narrow odd and even filters along the direction providing maximal response. Junctions are precisely detected and recovered using the output of directional filters. The proposed algorithm has a threshold for the minimum contrast of detected edges: for the large number of tested images this threshold was fixed equal to three times the standard deviation of the noise present in usual acquisition system (estimated to be between 1 and 1.3 gray levels out of 256), therefore, the proposed scheme is in fact parameter free. This scheme for edge detection performs better than the classical Canny edge detector in two quantitative comparisons: the recovery of the original image from the edge map and the structure from motion task. As the Canny detector in previous comparisons was shown to be the best or among the best detectors, the proposed scheme represents a significant improvement over previous approaches.