Ten Tips Based on Anatomy and Design to Refine Face and Neck Lift Surgery.
Any face/neck lift operation has a natural flow of slower and speedier portions; slower when dissecting under the superficial musculoaponeurotic system and around nerves while faster during opening, undermining, defatting, and closing. Surgeons can maximize efficiency with these simple maneuvers. We introduce and demonstrate ten reproducible surgical techniques based on anatomy, which span aspects of the entire face and neck lift procedure including markings, skin flap elevation, sub-superficial musculoaponeurotic system manipulation, preplatysmal fat management, skin re-draping, and post-operative dressings. As examples, altered scissors facilitate "push" undermining, scoops reduce time for fat removal in the neck, a non-inset method for lobule creation, and digital measurements for certain technical maneuvers are discussed. Moreover, a block and tackle method of facial nerve blocks is reviewed which permits local-only face and neck lifting as well as hematoma drainage without patient intolerance. Implementation of these surgical techniques in face and neck lift procedures allows the surgeon to potentially decrease operative time and work towards minimizing post-operative edema while attaining aesthetic and natural results.


Success factors of hospital information system implementation: what must go right?
Health care institutions are considering a variety of information technologies in the hope of increasing efficiency, reducing cost, re-engineering work processes, and improving quality of care. When we talk about any information system implementation, we need to keep in mind that there are actually three phases to such a project: pre-implementation, implementation and post-implementation. The aim of our contribution is to present the realities of successful implementation and our experience with such project.


Cutaneous accumulation of plasmacytoid dendritic cells associated with acute myeloid leukemia: a rare condition distinct from blastic plasmacytoid dendritic cell neoplasm.
A cutaneous infiltrate composed of plasmacytoid dendritic cells may occasionally occur in a patient suffering from a myeloid neoplasm. To date, the clinical and pathological features associated with this event remains poorly characterized. Herein, we report a patient with acute myeloid leukemia who developed pruritic papules or erythematous plaques scattered on the skin. Microscopic examination showed a dermal infiltrate rich in plasmacytoid dendritic cells expressing CD4, CD43, CD68, granzyme B, CD123, CD303 [blood dendritic cell antigen 2 (BDCA-2)], CD2-associated protein (CD2AP) and T-cell leukemia/lymphoma oncogene 1 (TCL1). Our observation illustrates further that cutaneous lesions associated with some myeloid neoplasms, especially those featuring a monocytic component, may be composed of plasmacytoid dendritic cells. Because of differences in clinical, pathological and genetic features, this rare condition should be distinguished from blastic plasmacytoid dendritic cell neoplasm.


Advances in the researches on the biological activities and inhibitors of phosphatidylinositol 3-kinase.
The PI3K/AKT/mTOR pathway is an intracellular signaling pathway, being important in apoptosis hence cancer such as breast cancer and non-small-cell lung cancer. It signaling axis controls cell proliferation and survival and has achieved major importance as a target for cancer therapy. The serine/threonine kinase Akt (also known as protein kinase B or PKB), since its initial discovery as a protooncogene, has become a major focus of attention because of its critical regulatory role in diverse cellular processes, including cancer progression and insulin metabolism. The Akt cascade is activated by receptor tyrosine kinases, integrins, B and T cell receptors, cytokine receptors, G protein coupled receptors and other stimuli that induce the production of phosphatidylinositol 3,4,5 triphosphates (PtdIns(3,4,5)P3) by phosphoinositide 3-kinase (PI3K). Therefore, PI3K plays an important role in in numerous cellular functions such as cell growth, proliferation, differentiation, motility, survival and intracellular trafficking. In this review, we introduced the structure of the PI3K, and then focused on its biological activities. In addition, we reviewed the advances in the researches of PI3K as well as related inhibitors over the last couple of decades. Finally, we also discussed the prospect and developmental trend of phosphatidylinositol 3-kinase as antitumor agents.


[The corn seedlings are affected by the heavy metal Pb2+].
The corn seedlings in hydroponic culture are treated with the lead acetate solutions of various concentrations, the content of Pb2+ in the roots, stems and leafs of the corns at 10th day, 20th day and 30th day is measured. The analyzing conclusions are that the contents of Pb2+ in the corns display a sequence of root>leaf>stem, the contains of chlorophyll in corns fall off, the raising of Pb2+ in solutions, the membrane penetrability of the corns increased along a sequence of root>leaf>stem, and the harmful rate of Pb2+ display a sequence of root>leaf>stem in corns. The data of the study gives some references for the further researches of the crops, relating the endurance and the distributing of corns with Pb2+.


Azathioprine in the treatment of chronic refractory steroid-dependent asthma.
We have described a patient with chronic, severe, steroid-dependent asthma resistant to all forms of anti-inflammatory therapy. Azathioprine alone effectively improved the patient's symptoms and decreased the daily steroid requirements. Further short- and long-term studies are needed to observe the effects of azathioprine in chronic asthma.


Dislocation-toughened ceramics.
Functional and structural ceramics have become irreplaceable in countless high-tech applications. However, their inherent brittleness tremendously limits the application range and, despite extensive research efforts, particularly short cracks are hard to combat. While local plasticity carried by mobile dislocations allows desirable toughness in metals, high bond strength is widely believed to hinder dislocation-based toughening of ceramics. Here, we demonstrate the possibility to induce and engineer a dislocation microstructure in ceramics that improves the crack tip toughness even though such toughening does not occur naturally after conventional processing. With modern microscopy and simulation techniques, we reveal key ingredients for successful engineering of dislocation-based toughness at ambient temperature. For many ceramics a dislocation-based plastic zone is not impossible due to some intrinsic property (e.g. bond strength) but limited by an engineerable quantity, i.e. the dislocation density. The impact of dislocation density is demonstrated in a surface near region and suggested to be transferrable to bulk ceramics. Unexpected potential in improving mechanical performance of ceramics could be realized with novel synthesis strategies.


Adverse clinical outcomes associated with elevated blood alcohol levels at the time of burn injury.
Elevated blood alcohol content (BAC) on admission is associated with poorer outcomes, larger burns and more inhalation injury. This study's purpose was to examine the effects of alcohol through a matched case-controlled study, measuring early and extended markers of clinical outcomes. The hypothesis was that patients with an elevated admission BAC would require more resuscitation and have a longer hospital stay. Admissions 16 to 75 years of age with 15 to 75% TBSA and admission BACs were identified. Patients with BAC >30 mg/dl (BAC+, cases) were matched with patients with undetectable BAC (BAC-, controls), according to age, sex, TBSA, inhalation injury and mechanism. Screening identified 258 patients, 146 with admission BACs. Twenty-seven had a BAC > or = 30 mg/dl. There were 24 matched pairs. At 24 hours, BAC+ group had larger acute physiology and chronic health evaluation II scores (23.33 vs 18.75, P < .05), fluid requirements (5.25 vs 3.82 L (cc/kg/TBSA), P < .05), and base deficit (11.15 vs 7.15, P < .05). The duration of mechanical ventilation (14.85 vs 4.23 days, P < .05), intensive care unit length of stay (22.85 vs 9.38, P < .05), hospital length of stay (28.95 vs 15.68, P < .05), and mean hospital charges ($239,507 vs $144,598, P < .05) were increased in the BAC+ patients. Despite matched baseline injury characteristics, elevated BAC was associated with poorer short term and extended clinical outcomes, illustrating the impact of alcohol intoxication on physiologic derangement after burn injury.


[Clinical results and pharmacokinetics of 6059-S in the field of pediatrics (author's transl)].
6059-S, a new injectable oxacephem antibiotic, has been investigated to give following results. 1. Clinical results Twenty patients were administrated intravenously 20 approximately 124 mg/kg/day of 6059-S for 2 approximately 14 days. Clinical effect was excellent in 5 cases, good in 7, fair in 3, poor in 1, unknown in 3 and except in 1, and efficacy rate was 75%. Side effect was observed only 1 case of discomfort and chill of hand and foot immediately after intravenous injection and no adverse value in laboratory findings was seen. 2. Pharmacokinetics Blood level and urinary excretion of 6059-S single administration were measured in 4 patients with normal renal function and a patient with renal failure. Half life was 1.27 approximately 1.76 hours in 4 patients with normal function and 4.33 hours in a patient with renal failure. Urinary excretion was 43.4 approximately 50.9% up to 4 hours in 2 patients with normal renal function, and it was delayed to 1.0% up to 12.5 hours in a patient with renal failure.


Size matters: When resource accessibility by ecosystem engineering elicits wood-boring beetle demographic responses.
Episodic natural disturbances play a key role in ecosystem renewal, and ecological engineering could do so by transforming resource accessibility. While such coupling creates nontrophic and lasting interactions between resource consumers and ecosystem engineers, it is unclear how large the disturbance must be to sustain such coupling. Natural disturbances that occur from the ecological engineering by the Canadian beaver (Castor canadensis) modulate deadwood dynamics in many forest ecosystems. Relying on such episodes of fresh woody debris, primary wood-boring beetles, organisms that dig tunnels into those debris for reproduction, act as important deadwood decomposers in the ecosystem. Here, we investigate how the age and size of beaver disturbances act as predictors for primary wood-boring beetle abundance and species richness around beaver-altered habitat patches. To do so, we sampled beetles around 16 beaver-disturbed and unaltered watercourses within the Kouchibouguac National Park (Canada) and modeled beetle demographic responses to site conditions and their physical characteristics, distance from the watercourse, deadwood biomass, and the geographical location of the sites. Our results indicate that the size of the disturbance is positively associated with beetle abundance, which highlights unique deadwood dynamics inherent to large beaver ponds. The role of beavers in forest ecosystems by reaching multiple taxa at multiple spatiotemporal scales further exemplifies the need to study nontrophic interactions and their complex consequences in ecosystem management.


Increasing the uptake of cervical smears: strategies implemented among general practitioners in Auckland.
To evaluate three strategies designed to increase the uptake of cervical smears among specified groups of women through a collaborative partnership between the Auckland Area Health Board and selected Auckland general practitioners. Using action-based research general practitioners and practice nurses were engaged to initiate ways of inviting women in their practices to have cervical smears. Both formative and process evaluations were made. Concurrently, outcomes were measured in terms of call/recall systems, uptake rates and cost barriers. Where financial incentives were given to establish call/recall systems for older women, overall uptake rates increased by 21%, and by 154% for women over 45 years. Over one third of a targeted group of women aged between 60 and 70 years responded to an invitation to have a free smear. Of these 109 women, fourteen, with a median age of 67 years, had their first smear. Almost two thirds indicated that cost had never been a barrier. The determining factor for women having a cervical smear in all three strategies was a personal invitation from their general practitioner or practice nurse. Invitations were dependent upon having accurate call/recall systems. This evaluation of the collaborative process between Auckland Area Health Board and local general practitioners demonstrated how manager and provider partnerships can benefit the consumer.


[An incomplete form of pachydermoperiostosis. Diagnosis of finger clubbing].
The finger clubbing is most of the time associated with cardiovascular and pulmonary diseases. Pachydermoperiostosis also known as osteodermopathic syndrome, an hereditary disorder, is a rare cause of finger clubbing which might be difficult to diagnose in an incomplete form. We report a 36 years old black man presenting over many years polyarthralgias, broadening of fingers and clubbing of the fingers and toes extremities. This was mentioned on other family members. The physical examination was otherwise unremarkable. There were no skin thickening, no psoriasis-like and cardio-pulmonary disease features. These following exams were normal; Hemogram, fibrinogen, C reactive protein, rheumatoïd factor, serum calcium and phosphorus, thyroid hormones, growth hormone, chest X-ray, gastroduodenoscopy, electrocardiogram. The skeletal X-ray documented a widespread bone formation, a sacro-iliac osteosclerosis and interosseous ossifications betwen tibias and fibulas. Pachydermoperiostosis diagnosis was set up on 3 out of the 4 Borochowitz criteria. The absence of pachyderma defines this incomplete form. The osteoarticular manifestations lead mainly to differential diagnosis with the secondary hypertrophic osteoarthropathy and chronic inflammatory rheumatisms. The underlying pathogenic mechanism of this disease remains still unclear.


Multiclass analysis of 23 veterinary drugs in milk by ultraperformance liquid chromatography-electrospray tandem mass spectrometry.
An ultraperformance liquid chromatography-electrospray tandem mass spectrometry (UPLC-MS/MS) method for the simultaneous detection and confirmation of 23 veterinary (multiclass) drugs in milk was developed and validated. The analytes were extracted by acetonitrile, evaporated and injected into the UPLC-MS/MS system on a Waters UPLC HSS T3 column in gradient mode. Data acquisition under MS/MS was achieved by applying multiple reaction monitoring (MRM) of two ion transitions per compound to provide a high degree of specificity. Results showed good repeatability, and recoveries for the 12 macrolide, 7 β-lactam and 2 lincosamide antibiotics and 2 other veterinary drugs (morantel, orbifloxacin) used in milk averaged 51.8-139.0%, 51.5-100.6%, 82.4-102.5% and 87.5-99.4%, respectively. The coefficients of variation (C.V.) of the recoveries were less than 15% for intraday and interday precisions. The limits of quantification (LOQs) were all lower than 5 ng/ml. This method was applied to 17 fresh milk samples and only lincomycin was found in milk samples under allowable levels. Overall, this method is a suitable and rapid tool to confirm the presence of 23 veterinary drug residues in milk.


Innovations in Medication Preparation Safety and Wastage Reduction: Use of a Workflow Management System in a Pediatric Hospital.
Background: USP <797> regulatory requirements have mandated that pharmacies improve aseptic techniques and cleanliness of the medication preparation areas. In addition, the Institute for Safe Medication Practices (ISMP) recommends that technology and automation be used as much as possible for preparing and verifying compounded sterile products. Objective: To determine the benefits associated with the implementation of the workflow management system, such as reducing medication preparation and delivery errors, reducing quantity and frequency of medication errors, avoiding costs, and enhancing the organization's decision to move toward positive patient identification (PPID). Methods: At Texas Children's Hospital, data were collected and analyzed from January 2014 through August 2014 in the pharmacy areas in which the workflow management system would be implemented. Data were excluded for September 2014 during the workflow management system oral liquid implementation phase. Data were collected and analyzed from October 2014 through June 2015 to determine whether the implementation of the workflow management system reduced the quantity and frequency of reported medication errors. Data collected and analyzed during the study period included the quantity of doses prepared, number of incorrect medication scans, number of doses discontinued from the workflow management system queue, and the number of doses rejected. Data were collected and analyzed to identify patterns of incorrect medication scans, to determine reasons for rejected medication doses, and to determine the reduction in wasted medications. Results: During the 17-month study period, the pharmacy department dispensed 1,506,220 oral liquid and injectable medication doses. From October 2014 through June 2015, the pharmacy department dispensed 826,220 medication doses that were prepared and checked via the workflow management system. Of those 826,220 medication doses, there were 16 reported incorrect volume errors. The error rate after the implementation of the workflow management system averaged 8.4%, which was a 1.6% reduction. After the implementation of the workflow management system, the average number of reported oral liquid medication and injectable medication errors decreased to 0.4 and 0.2 times per week, respectively. Conclusion: The organization was able to achieve its purpose and goal of improving the provision of quality pharmacy care through optimal medication use and safety by reducing medication preparation errors. Error rates decreased and the workflow processes were streamlined, which has led to seamless operations within the pharmacy department. There has been significant cost avoidance and waste reduction and enhanced interdepartmental satisfaction due to the reduction of reported medication errors.


[Effect of mechanical ventilation with different tidal volumes on the respiratory function during general anesthesia].
To determine the effect of mechanical ventilation with different tidal volumes on the respiratory function during general anesthesia and to seek optimum way and parameters of mechanical ventilation during general anesthesia. Forty ASA I-II patients scheduled for elective craniotomies in the supine position were included in this study. According to latin square design, the patients were randomly divided into 4 groups. Every group has its own tidal volume sequence. Each patient used 4 tidal volumes in turn. Every tidal volume maintained 30 minutes. The rate of mechanical ventilation was 15. But ECG, blood pressure, heart rate, SPO2, ETCO2, airway pressure, lung compliance, and blood gas analysis were continuously monitored. A-aDO2, P(a-ET)CO2, P(PEAK), P(MEAN), P(PLAT), C(DYN), and C(STAT) significantly increased as the tidal volume increased (P<0.05). But ETCO2 and PaCO2 decreased as the tidal volume increased (P<0.05). PaO2, SPO2, MAP and HR had no significant difference between the 4 tidal volume groups(P>0.05). The optimum tidal volume of mechanical ventilation is not 4 mL/kg at the rate of 15 respiratory rate during general anesthesia in the supine position because of a high arterial carbon dioxide tension. Yet 6-8 mL/kg is better for neurosurgical anesthesia. Increasing the tidal volume alone may not improve the respiratory function impairment during general anesthesia.


Association of vitamin B12 with obesity, overweight, insulin resistance and metabolic syndrome, and body fat composition; primary care-based study.
To investigate correlation of vitamin B12 with obesity insulin resistance, metabolic syndrome. The cross-sectional and primary care-based study was carried out. Anthropometric, blood pressure measurements and bioelectric impedance analysis (BIA) were recorded. Vitamin B12, folic acid, hemogram, insulin, ferritin, iron, total iron binding capacity and other biochemical tests were assayed. The subjects were grouped as obesity, overweight, control, metabolic syndrome (MetS) and insulin resistance (IR). Correlation of vitamin B12 with body mass index (BMI), IR, age, and BIA was evaluated. The study enrolled 976 patients (obesity: 414, overweight: 212, and control: 351). The mean age in groups of obesity, overweight and control were 35.9 ± 8.7, 28.9 ± 6.3 and 33.1 ± 8.7, respectively (p = 0.142). Vitamin B12 level was significantly lower in patients with obesity and overweight than healthy individuals (178.9 ± 25.2; 219.8 ± 78.5, and 328.5 ± 120.5, p less than 0.001, respectively). Vitamin B12 level was lower in patients with MetS (+/-) and IR (+/-), but insignificant (p = 0.075 and 0.058, respectively). Significant and negative correlation was observed between vitamin B12 and BMI (r =-0.221, p=0.001). No significant difference was observed between obese male and female patients (247.8 ± 89.1 versus 235.5 ± 89.3 pg/mL, respectively, p=0.090). Low Vitamin B12 level was associated with obesity and overweight, but not with insulin resistance, metabolic syndrome and gender. Vitamin B12 was negatively correlated only with body mass index.


Adipokines: a treasure trove for the discovery of biomarkers for metabolic disorders.
Adipose tissue is a major endocrine organ, releasing signaling and mediator proteins, termed adipokines, via which adipose tissue communicates with other organs. Expansion of adipose tissue in obesity alters adipokine secretion which may contribute to the development of metabolic diseases. Consequently, this correlation has emphasized the importance to further characterize the adipocyte secretion profile, and several attempts have been made to characterize the complex nature of the adipose tissue secretome by utilizing diverse proteomic profiling approaches. Although the entirety of human adipokines is still incompletely characterized, to date more than 600 potentially secretory proteins were identified providing a rich source to identify putative novel biomarkers associated with metabolic diseases.


Leaf age effects on the spectral predictability of leaf traits in Amazonian canopy trees.
Recent work has shown that leaf traits and spectral properties change through time and/or seasonally as leaves age. Current field and hyperspectral methods used to estimate canopy leaf traits could, therefore, be significantly biased by variation in leaf age. To explore the magnitude of this effect, we used a phenological dataset comprised of leaves of different leaf age groups -developmental, mature, senescent and mixed-age- from canopy and emergent tropical trees in southern Peru. We tested the performance of partial least squares regression models developed from these different age groups when predicting traits for leaves of different ages on both a mass and area basis. Overall, area-based models outperformed mass-based models with a striking improvement in prediction observed for area-based leaf carbon (Carea) estimates. We observed trait-specific age effects in all mass-based models while area-based models displayed age effects in mixed-age leaf groups for Parea and Narea. Spectral coefficients and variable importance in projection (VIPs) also reflected age effects. Both mass- and area-based models for all five leaf traits displayed age/temporal sensitivity when we tested their ability to predict the traits of leaves of other age groups. Importantly, mass-based mature models displayed the worst overall performance when predicting the traits of leaves from other age groups. These results indicate that the widely adopted approach of using fully expanded mature leaves to calibrate models that estimate remotely-sensed tree canopy traits introduces error that can bias results depending on the phenological stage of canopy leaves. To achieve temporally stable models, spectroscopic studies should consider producing area-based estimates as well as calibrating models with leaves of different age groups as they present themselves through the growing season. We discuss the implications of this for surveys of canopies with synchronised and unsynchronised leaf phenology.


Increasing the information content of STS-based genome maps: identifying polymorphisms in mapped STSs.
Physical maps of the human genome are being constructed by many groups using a mapping strategy that relies on the development of sequence-tagged sites (STSs). Thousands of physically mapped STSs, representing hundreds of kilobases (kb) of unique human DNA sequence, have been generated by these efforts. Since sequence variations are found every 1-2 kb in the genome, it is possible to extract additional information from mapped STSs by scanning them for variations. By screening 154 of the STSs published by the Whitehead Institute/MIT Genome Center, we have identified 47 new DNA sequence polymorphisms among the 37.2 kb of unique DNA sequence contained in these STSs. Using a sequence-based approach to estimate allele frequencies for these variations, 29 of the substitution polymorphisms (1 in 1.3 kb) were found to have heterozygosities exceeding 32%. Our study shows that the information content of STS-based genome maps can be increased with minimal additional effort by scanning for DNA polymorphisms, and that ambiguities and errors in the initial STS sequence can be resolved and corrected in the process.


Selective phase synthesis of a high luminescence Gd2O3:Eu nanocrystal phosphor through direct solution combustion.
A Gd(2)O(3):Eu nanocrystal phosphor has been directly synthesized by a mild solution combustion method with a single step approach while avoiding further thermal annealing. The as-combusted Gd(2)O(3):Eu powders have been characterized by x-ray diffraction, infrared spectroscopy, transmission electron microscopy and photoluminescence spectra. The ratio of citric acid to metal nitrate (C/M) has a critical impact on the phase composition and crystallization of as-combusted Gd(2)O(3):Eu. An optimal C/M ratio of 0.7 gave highly crystalline powders with a single cubic phase, and a high luminescence intensity comparable with that of a commercial Y(2)O(3):Eu phosphor, even without further thermal annealing. This direct solution combustion method can be used to prepare a variety of high quality oxide nanocrystals.


In vitro and in vivo antimicrobial potential of lithium complex against multi-drug resistant Acinetobacter baumannii.
Multi-drug resistance (MDR) by virtue of evolving resistance and virulence mechanisms among A. baumannii is a global concern which is responsible for lethal hospital-acquired infections. Therefore, it is crucial to develop new therapeutics against it. Metal complexes are compact structures with diverse mechanisms that the pathogens cannot evade easily which make them a strong drug candidate. In this study, we assessed the in vitro and in vivo efficacy of lithium complex {[Li(phen)2 sal]} against biofilm-forming MDR A. baumannii. The lithium complex displayed strong antimicrobial activity and reduced the pre-formed mature biofilm which is key barrier for antimicrobial action. Moreover, it employs oxidative stress as one of its mode of actions and causes cellular rupturing. Lithium complex was non-toxic and was significantly effective to overcome pneumonia in mice model. These results highlight the untapped potential of metal complexes that can be explored and utilized for combating notorious A. baumannii infections.


KOSMOS: An Open Source Underwater Video Lander for Monitoring Coastal Fishes and Habitats.
Monitoring the ecological status of coastal ecosystems is essential to track the consequences of anthropogenic pressures and assess conservation actions. Monitoring requires periodic measurements collected in situ, replicated over large areas and able to capture their spatial distribution over time. This means developing tools and protocols that are cost-effective and provide consistent and high-quality data, which is a major challenge. A new tool and protocol with these capabilities for non-extractively assessing the status of fishes and benthic habitats is presented here: the KOSMOS 3.0 underwater video system. The KOSMOS 3.0 was conceived based on the pre-existing and successful STAVIRO lander, and developed within a digital fabrication laboratory where collective intelligence was contributed mostly voluntarily within a managed project. Our suite of mechanical, electrical, and software engineering skills were combined with ecological knowledge and field work experience. Pool and aquarium tests of the KOSMOS 3.0 satisfied all the required technical specifications and operational testing. The prototype demonstrated high optical performance and high consistency with image data from the STAVIRO. The project's outcomes are shared under a Creative Commons Attribution CC-BY-SA license. The low cost of a KOSMOS unit (~1400 €) makes multiple units affordable to modest research or monitoring budgets.


Estimation of the probability of epidemic fade-out from multiple outbreak data.
Deterministic epidemic models that allow for replenishment of susceptibles typically display damped oscillatory behaviour. If the population is initially fully susceptible, once an epidemic takes off a distinct trough will exist between the first and second waves of infection. Epidemic dynamics are, however, influenced by stochastic effects, particularly when the prevalence is low. At the beginning of an epidemic, stochastic die-out is possible and well characterised through use of a branching process approximation. Conditional on an epidemic taking off, stochastic extinction is highly unlikely during the first epidemic wave, but the probability of extinction increases again as the wave declines. Extinction during this period, prior to a potential second wave of infection, is defined as 'epidemic fade-out'. We consider a set of observed epidemics, each distinct and having evolved independently, in which some display fade-out and some do not. While fade-out is necessarily a stochastic phenomenon, the probability of fade-out will depend on the model parameters associated with each epidemic. Accordingly, we ask whether time-series data for the epidemics contain sufficient information to identify the key driver(s) of different outcomes-fade-out or otherwise-across the sub-populations supporting each epidemic. We apply a Bayesian hierarchical modelling framework to synthetic data from an SIRS model of epidemic dynamics and demonstrate that we can (1) identify when the sub-population specific model parameters supporting each epidemic have significant variability and (2) estimate the probability of epidemic fade-out for each sub-population. We demonstrate that a hierarchical analysis can provide precise estimates of the probability of fade-out than is possible if considering each epidemic in isolation. Our methods may be applied to both epidemiological and other biological data to identify where differences in outcome-fade-out or recurrent infection/waves are purely due to chance or driven by underlying changes in the parameters driving the dynamics.


Optimization of cardiac resynchronization devices using acoustic cardiography: a comparison to echocardiography.
Optimization of pacemaker settings for cardiac resynchronization therapy (CRT) remains challenging and problematic. Several noninvasive methods are offered to customize the programmed parameters for individual patients, but so far only echocardiographic imaging has established itself as an accepted method. The authors examined the value of acoustic cardiography as a fast and more cost-efficient alternative to established echocardiographic imaging techniques for the optimization of CRT devices. The atrioventricular delay in 22 subjects with implanted CRT devices was independently optimized using echocardiography (Doppler transmitral flow) as well as acoustic cardiography, and the recommended settings from each method were later compared. Doppler echocardiography and acoustic cardiography recommendations matched within a mean value +/- SD of 17+/-16 milliseconds and gave a correlation coefficient of r=0.90 (p<0.001). In 17 of the 22 cases (77.3%), the difference between echocardiographic and acoustic cardiogram CRT optimization results was <or=20 milliseconds. Furthermore, the echocardiographic transmitral flow pattern was not significantly different for the setting independently chosen by the echocardiographic expert and the acoustic cardiographer for the cases with a difference of >20 milliseconds (22.7%). In addition, it took less time for the acoustic cardiogram to collect sufficient information to make a recommendation, and it was found that the acoustic cardiogram data trend is easier to interpret.


The Baker Biobank: Understanding Cardiovascular Outcomes.
Cardiovascular diseases (CVDs) and diabetes are two of the most important public health problems. Outcomes for patients with these disorders vary considerably, likely due to the added influence of a range of interacting clinical, metabolic, environmental, lifestyle, genetic and psychosocial risk factors associated with these diseases. The Baker Biobank study was designed to characterise these factors to inform better risk prediction, earlier diagnosis and better treatment of CVDs and diabetes. This paper describes the detailed methods for the establishment of the Baker Biobank. The study collected extensive phenotypic detail about the participants recruited from Victoria, Australia. Data and samples were collected at the Departments of Cardiology and Respiratory Medicine at the Alfred Hospital and Healthy Hearts Program at the Baker Institute. A total of 6,530 adults with age 18-69 years were recruited into the Biobank. The majority of these participants (63%) were male. The mean (standard deviation [SD]) age of the Biobank Cohort at the time of data collection was 57(15) years. The study collected data on socio-demographic characteristics, behavioural and lifestyle factors, anthropometric measurements, medical and medication history, and blood levels of various biomarkers. The study also collected and stored Guthrie cards, serum, plasma, buffy coat, whole blood collected in Tempus tubes (for RNA extraction). For some samples extracted DNA and RNA is stored. The Biobank data is also linked to echocardiogram, hospital admission, pathology and mortality datasets. The Baker Biobank data and samples are available for health researchers with approval of Biobank Steering Group and Human Research Ethics Committee. The Baker Biobank provides valuable data and samples into the study of the interplay among cardiovascular diseases risk factors and their impact on morbidity and mortality in Australia.


Complete genome sequence of a tobacco isolate of the tobacco vein banding mosaic virus strain prevailing in China.
Tobacco vein banding mosaic virus (TVBMV) is a species of the largest plant virus genus Potyvirus. Its incidence has been increasing in Chinese tobacco-growing area. TVBMV isolates can be clustered into three genetic groups that are corresponding with their geographical origin. We have reported the complete genomic sequence of TVBMV isolate YND with unique NIb/CP cleavage site. Here, we determined and analyzed the complete genomic sequence of isolate HN39, which was collected from tobacco in Henan Province and represented Chinese prevalent strain of TVBMV. HN39 has similar host range with YND, but induce mild vein banding symptom in Nicotiana tabacum cv. Samsun. The genome of TVBMV-HN39 is composed of 9,570 nucleotides, excluding the poly(A) tail. It contains a large ORF of 9,240 nucleotides and encode a polyprotein of 3,079 amino acids. The putative NIa-Pro cleavage site for NIb/CP is Q/G. The identities between the complete genomes of isolates HN39 and YND were 90.0% at nucleotide level and 95.4% at amino acid level. As for other potyviruses, HN39 shared the highest identity with wild tomato mosaic virus (WTMV) at complete genomic level, while different genes shared the highest identities with different potyviruses. This is the second complete genomic sequence of TVBMV reported.


Cardiovascular risk assessment of South Asian populations in religious and community settings: a qualitative study.
Cardiovascular disease (CVD) is a leading cause of mortality, and South Asian groups experience worse outcomes than the general population in the UK. Regular screening for CVD risk factors is recommended, but we do not know the best settings in which to deliver this for ethnically diverse populations. Health promotion in religious and community settings may reduce inequalities in access to cardiovascular preventative health care. To use stakeholders' and attendees' experiences to explore the feasibility and potential impact of cardiovascular risk assessment targeting South Asian groups at religious and community venues and how health checks in these settings might compare with general practice assessments. Qualitative semi-structured interviews were used. The settings were two Hindu temples, one mosque and one Bangladeshi community centre in central and north-west London. Twenty-four participants (12 stakeholders and 12 attendees) were purposively selected for interview. Interviews were recorded and transcribed verbatim. Themes from the data were generated using thematic framework analysis. All attendees reported positive experiences of the assessments. All reported making lifestyle changes after the check, particularly to diet and exercise. Barriers to lifestyle change, e.g. resistance to change from family members, were identified. Advantages of implementing assessments in religious and community settings compared with general practice included accessibility and community encouragement. Disadvantages included reduced privacy, organizational difficulties and lack of follow-up care. Cardiovascular risk assessment in religious and community settings has the potential to trigger lifestyle change in younger participants. These venues should be considered for future health promotional activities.


Epac signaling is required for hippocampus-dependent memory retrieval.
Previously we uncovered a critical role for norepinephrine and beta(1)-adrenergic signaling in hippocampus-dependent memory retrieval. Because the beta(1) receptor couples to G(s), we examine here whether cAMP is also required for contextual memory retrieval. Using pharmacologic and genetic approaches to manipulate cAMP and downstream signaling, we demonstrate that cAMP and two of its targets, protein kinase A (PKA) and exchange protein activated by cAMP (Epac), are both required for retrieval. These findings demonstrate that cAMP signaling through Epac (as well as PKA) plays an essential role in cognition.


Dromedary camels as a natural source of neutralizing nanobodies against SARS-CoV-2.
The development of prophylactic and therapeutic agents for coronavirus disease 2019 (COVID-19) is a current global health priority. Here, we investigated the presence of cross-neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in dromedary camels that were Middle East respiratory syndrome coronavirus (MERS-CoV) seropositive but MERS-CoV free. The tested 229 dromedaries had anti-MERS-CoV camel antibodies with variable cross-reactivity patterns against SARS-CoV-2 proteins, including the S trimer and M, N, and E proteins. Using SARS-CoV-2 competitive immunofluorescence immunoassays and pseudovirus neutralization assays, we found medium-to-high titers of cross-neutralizing antibodies against SARS-CoV-2 in these animals. Through linear B cell epitope mapping using phage immunoprecipitation sequencing and a SARS-CoV-2 peptide/proteome microarray, we identified a large repertoire of Betacoronavirus cross-reactive antibody specificities in these dromedaries and demonstrated that the SARS-CoV-2-specific VHH antibody repertoire is qualitatively diverse. This analysis revealed not only several SARS-CoV-2 epitopes that are highly immunogenic in humans, including a neutralizing epitope, but also epitopes exclusively targeted by camel antibodies. The identified SARS-CoV-2 cross-neutralizing camel antibodies are not proposed as a potential treatment for COVID-19. Rather, their presence in nonimmunized camels supports the development of SARS-CoV-2 hyperimmune camels, which could be a prominent source of therapeutic agents for the prevention and treatment of COVID-19.


Health Literacy in Context.
Health literacy has been defined and conceptualized in multiple ways, but almost all definitions have similar core elements describing the personal skills that enable individuals to obtain, understand, and use information to make decisions and take actions that will have an impact on their health. [...].


PATHOS: a screening instrument for adolescent overdose: a research note.
This author, in a previous study, devised post-hoc a five-question screening instrument, PATHOS, that identified a high-risk group within adolescent overdose. This study examines the concurrent validity of PATHOS, with measures of depression, hopelessness, premeditation and suicidal intent in adolescents presenting with an overdose. Strong correlations were found with the above features as well as problem duration and previous overdose history. The PATHOS was able also to identify a high-risk group with a sensitivity of 100%, a specificity of 57% and all misclassifications were false positive. It is suggested that this could be used as an aid for non-psychiatric assessors.


Lateral parabrachial afferent areas and serotonin mechanisms activated by volume expansion.
Recent evidence has shown that the serotonergic mechanism of the lateral parabrachial nucleus (LPBN) participates in the regulation of renal and hormonal responses to isotonic blood volume expansion (BVE). We investigated the BVE-induced Fos activation along forebrain and hindbrain nuclei and particularly within the serotonergic clusters of the raphé system that directly project to the LPBN. We also examined whether there are changes in the concentration of serotonin (5HT) within the raphé nucleus in response to the same stimulus. With this purpose, we analyzed the cells doubly labeled for Fos and Fluorogold (FG) following BVE (NaCl 0.15 M, 2 ml/100 g b.w., 1 min) 7 days after FG injection into the LPBN. Compared with the control group, blood volume-expanded rats showed a significant greater number of Fos-FG double-labeled cells along the nucleus of the solitary tract, locus coeruleus, hypothalamic paraventricular nucleus, central extended amygdala complex, and dorsal raphé nucleus (DRN) cells. Our study also showed an increase in the number of serotonergic DRN neurons activated in response to isotonic BVE. We also observed decreased levels of 5HT and its metabolite 5-hydroxyindoleacetic acid (measured by high-pressure liquid chromatography) within the raphé nucleus 15 min after BVE. Given our previous evidence on the role of the serotonergic system in the LPBN after BVE, the present morphofunctional findings suggest the existence of a key pathway (DRN-LPBN) that may control BVE response through the modulation of 5HT release.


Collective proton transfer in ordinary ice: local environments, temperature dependence and deuteration effects.
The transfer of multiple protons in hydrogen-bonded networks usually occurs one proton at a time. At sufficiently high temperatures, each proton transfers via thermally activated hopping along its hydrogen bond, thereby moving a charge defect through the network. At low temperatures, quantum-mechanical tunnelling might set in instead, thus avoiding hopping over the energy barriers. In the case of several transferring protons, independent thermal hopping or quantum tunnelling of the individual protons becomes less favourable because of a significant creation of charge defects. In individual molecules or hydrogen-bonded molecular complexes, for instance, double proton transfer is often found to be concerted. Multiple proton transfer that avoids charge defects can occur in cyclic topologies built from several hydrogen bonds that allow for directional chains of proton transfer. This requires perfect proton order within these rings, which imposes handedness and thus chirality, and changes parity upon transfer of all protons. Ordinary ice, which is hexagonal ice Ih, is the most stable form of crystalline ice obtained upon freezing liquid water at ambient pressure and consists of interconnected six rings of oxygen atoms that host six protons each. These hexagonal rings remain proton disordered even down to low temperatures, as heralded by the residual entropy of ice Ih. However, owing to combinatorics, a certain number of these six rings is proton ordered in macroscopic crystals. These chiral hexameric rings might support coherent tunnelling of the hosted protons. Indeed, there is some evidence in the recent literature, both experimental and simulational, that correlated tunnelling of all six protons might be possible in proton-ordered six rings in ice Ih if temperatures are low enough. In this Perspective, the key ideas and previous findings will be reviewed in the light of relevant experiments with a focus on available ab initio path integral simulation work supplemented with additional data provided herein.


ATF2, a paradigm of the multifaceted regulation of transcription factors in biology and disease.
Stringent transcriptional regulation is crucial for normal cellular biology and organismal development. Perturbations in the proper regulation of transcription factors can result in numerous pathologies, including cancer. Thus, understanding how transcription factors are regulated and how they are dysregulated in disease states is key to the therapeutic targeting of these factors and/or the pathways that they regulate. Activating transcription factor 2 (ATF2) has been studied in a number of developmental and pathological conditions. Recent findings have shed light on the transcriptional, post-transcriptional, and post-translational regulatory mechanisms that influence ATF2 function, and thus, the transcriptional programs coordinated by ATF2. Given our current knowledge of its multiple levels of regulation and function, ATF2 represents a paradigm for the mechanistic complexity that can regulate transcription factor function. Thus, increasing our understanding of the regulation and function of ATF2 will provide insights into fundamental regulatory mechanisms that influence how cells integrate extracellular and intracellular signals into a genomic response through transcription factors. Characterization of ATF2 dysfunction in the context of pathological conditions, particularly in cancer biology and response to therapy, will be important in understanding how pathways controlled by ATF2 or other transcription factors might be therapeutically exploited. In this review, we provide an overview of the currently known upstream regulators and downstream targets of ATF2.


Aerobic training with a self-selected or predetermined intensity on sleep parameters in adolescents with obesity: a randomized clinical trial.
To compare the effects of self-selected and predetermined intensity on sleep quality and duration, daytime sleepiness, and sleep efficiency of adolescents with obesity after 12 weeks of aerobic training. Thirty-seven adolescents (12 girls), 13-18 years old, with obesity (BMI = 95th) were randomized into a predetermined intensity group (PIG), exercise intensity around 60-70% of heart rate reserve; or self-selected intensity group (SIG), the adolescents chose the speed/intensity at the beginning of each session and were able to change it every 5 minutes. The Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) were used to assess sleep outcomes. No differences were observed for PSQI [0.00 ± 2.00 vs 1.38 ± 2.7; p=0.195; d=0.60 (moderate effect)], sleep duration [-0.95 ± 1.2 vs -0.35 ± 1.6; p=0.358; d=0.41 (small effect)], ESS [(2.10 ± 3.9 vs 1.15 ± 4.5; p=0.195; d=0.23 (small effect)], and sleep efficiency [(81.5 ± 24.0 vs 79.4 ± 17.0; p=0.8.14; d=0.10 (trivial effect)] for the PIG and SIG groups, respectively. Aerobic training at a self- selected or predetermined intensity does not modulate sleep quality, sleep duration and efficiency, and daytime sleepiness, independent of intensity.


Field observations of stratification in stormwater wet ponds.
Stratification is one of the fundamental physical processes that may have a significant impact on water quality in stormwater wet ponds. However, the role of thermal and chemical stratifications in governing water quality processes is not fully understood. This is in part due to the lack of detailed field measurements of sufficient governing parameters over time periods that span a wide range of environmental conditions. To fill this gap, a comprehensive 2-year field program was undertaken in two stormwater wet ponds in Calgary, Alberta, Canada, during the ice-free season from May to November in 2018 and 2019. At different locations in each pond, thermal and chemical stratifications were observed, thermocline depth and strength were determined, and continuous water velocity profiles were measured. In addition, the effect of local weather conditions on stratification, thermocline, and hydrodynamics was investigated. The results showed that the ponds had vertical water temperature differences >1 °C for 99% of the time, May to August. In addition, salt-laden inflows from road deicing salts led to strong chemical stratification up to five times stronger in the sediment forebays than in the main cells in spring. Wind-induced surface currents were insignificant, scaling at 0.3% of the wind speed with negligible impact on vertical mixing in the ponds. Our results demonstrate that the ponds' strong and prolonged stratification decreased pollutant retention capacity and caused the water at depth to become anoxic, degrading the quality of the water discharged downstream. Hence, additional consideration of stratification is required when designing new stormwater ponds.


Sensor Fusion to Estimate the Depth and Width of the Weld Bead in Real Time in GMAW Processes.
The arc welding process is widely used in industry but its automatic control is limited by the difficulty in measuring the weld bead geometry and closing the control loop on the arc, which has adverse environmental conditions. To address this problem, this work proposes a system to capture the welding variables and send stimuli to the Gas Metal Arc Welding (GMAW) conventional process with a constant voltage power source, which allows weld bead geometry estimation with an open-loop control. Dynamic models of depth and width estimators of the weld bead are implemented based on the fusion of thermographic data, welding current and welding voltage in a multilayer perceptron neural network. The estimators were trained and validated off-line with data from a novel algorithm developed to extract the features of the infrared image, a laser profilometer was implemented to measure the bead dimensions and an image processing algorithm that measures depth by making a longitudinal cut in the weld bead. These estimators are optimized for embedded devices and real-time processing and were implemented on a Field-Programmable Gate Array (FPGA) device. Experiments to collect data, train and validate the estimators are presented and discussed. The results show that the proposed method is useful in industrial and research environments.


Critical care management of verapamil and diltiazem overdose with a focus on vasopressors: a 25-year experience at a single center.
Verapamil or diltiazem overdose can cause severe morbidity and death, and there exist limited human data describing management and outcome of a large number of such patients. This article describes the management and outcome of patients with nondihydropyridine calcium-channel blocker overdose, with an emphasis on vasopressor dosing, at a single center. This study is a retrospective chart review of patients older than 14 years and admitted to the inpatient toxicology service of a single tertiary care medical center for treatment of verapamil or diltiazem overdose from 1987 through 2012, and who had the presence of either drug confirmed by urine drug screening. Patients were identified by review of patient encounter logs. Data abstracted from medical records included demographics, laboratory results, drugs used to support blood pressure, complications, and outcomes. A second group included patients with a reported calcium channel blocker ingestion but for whom results of the urine drug testing were no longer available. In an effort to assess selection bias, this group was included to determine whether patients who were excluded from the primary group only because of unavailability of urine drug screen results had different outcomes. During the study period, 48 patients met inclusion criteria. The median age was 45 years, with a range of 15 to 76 years, and 52% were male patients. Verapamil accounted for 24 of 48 (50%) ingestions. Vasopressors were administered to 33 of 48 (69%) patients. Maximal vasopressor infusion doses were epinephrine 150 μg/minute, dopamine 100 μg/kg per minute, dobutamine 245 μg/kg per minute, isoproterenol 60 μg/minute, phenylephrine 250 μg/minute, and norepinephrine 100 μg/minute. The use of multiple vasopressors was common. Hyperinsulinemic euglycemia was used in 3 patients who also received multiple vasopressors. Eight probable or possible ischemic complications were noted in 5 of 48 (10%) patients. Gastrointestinal bleeding occurred in 3 of 48 (6%) patients; a brain magnetic resonance imaging in 1 patient suggested mild ischemia, without clinical evidence of infarction; 1 patient had ischemic bowel; and 3 patients developed renal failure from acute tubular necrosis, which resolved in each case. Six of the 8 ischemic complications were evident before use of vasopressor therapy. Three patients sustained inhospital cardiac arrest before admission and were successfully resuscitated. Each of these arrests occurred before instituting vasopressor infusions. One patient experienced a late cardiac arrest from primary respiratory arrest from administration of sedatives, and multiple organ system failure followed resuscitation, with death occurring during manipulation of a pulmonary artery catheter. The remaining 47 patients recovered. There were 12 patients in the group of additional poisoned patients for whom results of urine drug screening were unavailable. Four patients were treated with vasopressors, 2 experienced acute tubular necrosis that was present before vasopressor use, and all recovered. In our series of patients admitted with verapamil or diltiazem overdose, hypotension was common and managed with the use of multiple vasopressors and without hyperinsulinemic euglycemia in all but 3 cases. Despite high doses of vasopressors, ischemic complications were the exception and were usually present before use of vasopressors. Death occurred in a single patient whose death was not attributed directly to calcium-channel blocker toxicity. Vasopressor use after verapamil or diltiazem overdose was associated with good clinical outcomes without permanent sequelae.


Analysis of paternity. The use of HLA and red cell antigens.
Over a 6-year period, 866 cases were analyzed for disputed parentage. In 194 cases (22%), the alleged father was excluded as the biological father. One hundred and eight-one cases (93%) were direct exclusions, and 13 cases (7%) were indirect exclusions. Ninety-two percent of falsely accused men were identified by typing for HLA antigens alone. Exclusions based solely on red cell data occurred in 8 percent of the cases. When only HLA testing was performed, 177 of 362 (43%) cases had a probability of paternity of greater than or equal to 95 percent. When both HLA and red cell typings were performed, 110 of 160 (69%) cases had a probability of paternity of greater than or equal to 95 percent. No significant differences in the proportion of exclusions or proportion of alleged fathers with a probability of paternity of greater than or equal to 95 percent were observed between Caucasians or blacks. We conclude that typing for HLA antigens provides the most powerful data for excluding or including an alleged father. However, typing for red cell antigens adds significant data in excluding a falsely accused man and in determining the probability of paternity at a critical level (greater than or equal to 95%). In addition, the current study suggests that additional assays are needed to identify genetic characteristics of cases with probability of paternity less than 95 percent.


[Mixed culture of sperm and lymphocyte in infertility with unexplained cause and its clinical implications (author's transl)].
Mixed culture of sperm and lymphocytes were performed in the samples of 32 infertile couples with unexplained cause, 16 couples with proven fertility and 47 virginal women in order to investigate the role of cellular-immunologic factors in infertility. 1) The means of stimulation index (S.I.) and the standard deviation in mixed cultures with donor's sperm were, 2.51 +/- 1.08 in infertile, 2.25 +/- 0.79 in fertile and 1.96 +/- 0.71 in virgin group. The S.I. of the virgin group was significantly lower (p less than 0.01) than that of the other two groups. 2) The means of S.I. in mixed cultures with husband's sperm were, 2.96 +/- 1.43 in infertile and 2.44 +/- 1.24 in fertile women. There was no significance in the S.I. of these two groups. 3) It was found during two years' prospective observation that 14 of 32 unexplainedly infertile couples achieved pregnancy. Retrospective analysis disclosed that there was no significant difference between pregnant and non-pregnant groups, when S.I. with husband's sperm were compared. Neither, no difference between S.I. with husband's sperm and donor's sperm was revealed in non-pregnant group. In conclusion, no evidence was obtained that unexplainedly infertile women, as a group, were suffered from immunologic factors.


Sites of disruption of the blood-aqueous barrier after application of prostaglandin E2 in pigmented rabbits.
We examined the disruption of the blood-aqueous barrier following prostaglandin (PG)-E2 application in rabbits. Vehicle or PGE2 in 10, 50 or 250 microg/ml concentration was applied to the cornea of pigmented rabbit with the use of a glass cylinder. After PGE2 administration, horseradish peroxidase (HRP) was injected intravenously. Then the eyes were enucleated, and distribution of HRP in the anterior segments was examined by electron microscopy. In control eyes, diffusion of HRP was blocked by vascular endothelial cells in the iris and by nonpigmented epithelial cells in the iridial and ciliary processes. In the iridial and ciliary processes of the eyes treated with 10 microg/ml PGE2, no HRP reaction product was seen in intercellular spaces of the nonpigmented epithelial cells, but it was found in pinocytotic vesicles. In the eyes treated with 50 microg/ml PGE2 HRP reaction product was found in intercellular spaces of the nonpigmented cells in the iridial processes. In the eyes treated with 250 microg/ml PGE2 HRP reaction product was further distributed in the iris stroma. The present study demonstrated that the sites of breakdown of the blood-aqueous barrier depended upon the doses of exogenous PGE2.


Spatio-temporal analysis of cortical activity evoked by gustatory stimulation in humans.
Gustatory activated regions in the cerebral cortex have not been identified precisely in humans. In this study we recorded the magnetic fields from the brain in response to two tastants, 1 M NaCl and 3 mM saccharin. We estimated the location of areas activated sequentially after the onset of stimulation with magnetic source imaging. We investigated the primary gustatory area (area G) precisely, and found it at the transition between the parietal operculum and the insular cortex. The central sulcus was activated less frequently than area G but with almost the same latency in cases of NaCl stimulation. Following area G, we found activation in several cortical regions, e.g. both the frontal operculum and the anterior part of the insula, the hippocampus, the parahippocampal gyrus and the superior temporal sulcus.


Idiopathic giant right atrial aneurysm.
A 2-year-old boy with an incidental finding of massive cardiomegaly on a chest X-ray was diagnosed with a giant right atrial aneurysm upon further investigation with echocardiography. The patient underwent successful surgical reduction of the right atrium and closure of the patent foramen ovale to prevent thromboembolic complications and to lower the risk of atrial arrhythmias. The resected atrium had paper-thin walls and pathological features of interstitial fibrosis with endocardial thickening.


Connectivity dependence of Fano resonances in single molecules.
Using a first principles approach combined with analysis of heuristic tight-binding models, we examine the connectivity dependence of two forms of quantum interference in single molecules. Based on general arguments, Fano resonances are shown to be insensitive to connectivity, while Mach-Zehnder-type interference features are shown to be connectivity dependent. This behaviour is found to occur in molecular wires containing anthraquinone units, in which the pendant carbonyl groups create Fano resonances, which coexist with multiple-path quantum interference features.


[Prolonged contrast infusion echocardiography with hydrogen peroxide].
A new method of prolonged C-echo-CG with HP implies intravenous administration of 0.3% HP solution for continuous contrasting of right heart chambers for 5-20 minutes. A new technique of C-echo-CG was introduced in 277 patients with innocent cardiac murmur (93), interventricular septal defects (19), interatrial septal defects (26), open oval foramen (42), tricuspid regurgitation (56), pulmonary artery regurgitation (41). Prolonged C-echo-CG with HP was combined with respiratory stress tests. The technique is simple, more effective than short-term C-echo-CG, free of severe side effects and complications.


Evaluation of certain veterinary drug residues in food.
This report represents the conclusions of a Joint FAO/WHO Expert Committee convened to evaluate the safety of residues of certain veterinary drugs in food and to recommend maximum levels for such residues in food. The first part of the report considers general principles regarding the evaluation of veterinary drugs within the terms of reference of the Joint FAO/WHO Expert Committee on Food Additives (JECFA), including a hypothesis-driven decision tree approach for the safety evaluation of residues of veterinary drugs; comments on the Committee for Veterinary Products for Medicinal Use reflection paper on the new approach developed by JECFA for exposure and maximum residue limit (MRL) assessment of residues; residues of veterinary drugs in honey and possible approaches to derive MRLs for this commodity; comments on a paper entitled "Risk-assessment policies: Differences among jurisdictions"; and the use of no-observed-effect level (NOEL) and no-observed-adverse-effect level (NOAEL) in JECFA assessments. Summaries follow of the Committee's evaluations of toxicological and residue data on a variety of veterinary drugs: three antimicrobial agents (avilamycin, tilmicosin, tylosin), one anthelminthic (triclabendazole), one production aid (melengestrol acetate), two antimicrobial agents and production aids (monensin and narasin), a glucocarticosteroid (dexamethasone) and an antimicrobial agent and contaminant (malachite green). Annexed to the report is a summary of the Committee's recommendations on these drugs, including acceptable daily intakes (ADIs) and proposed MRLs.


Hollow poly(MPC-g-PEG-b-PLA) graft copolymer microcapsule as a potential drug carrier.
In this article, an amphiphilic graft copolymer composed of poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) as the hydrophilic backbone, poly(L-lactic acid) (PLA) as the hydrophobic side-chains and polyethylene glycol (PEG) as the spacer was synthesized. Transmission electron microscopy revealed that the graft copolymer could self-assemble into hollow microcapsules when dialyzed in aqueous solution and particle sizes ranged from 200 to 300 nm, while the graft copolymer formed core-shell microspheres with the absence of PEG spacer. X-ray photoelectron microscope showed that MPC polymers were located at the surface of the microcapsules. The amounts of adsorbed bovine serum albumin and Fg on the microcapsules were significantly decreased than that on the conventional PLA particles (74% and 60%, respectively), well indicating the anti-adhesive property of the microcapsules. Paclitaxel was chosen as a prototype anticancer drug for the encapsulation and release studies, the results showed that the drug encapsulation efficiency was 89.3 ± 1.2% and the microcapsules exhibited controlled release behaviour.


Effects of clenbuterol on body stores of polychlorinated dibenzofurans (PCDF) and dibenzo-p-dioxins (PCDD) in rats.
Polychlorinated dibenzo-p-dioxins (PCDD) and polychlorinated dibenzofurans (PCDF), persistent pollutants that accumulate in the food chain, pose a risk to humans through consumption of tainted livestock. Clenbuterol, a leanness-enhancing agent, was tested for usefulness in PCDD/F body store reduction through body fat reduction (the predominant site of accumulation). To mimic the situation of contaminated animals, rats were given feed with or without a mixture of PCDD/F (0.6 to 2.7 ng/congener per day) for 10 d, followed by 16 d of feed with or without dietary clenbuterol (2 mg/kg feed). Clenbuterol reduced body fat by 28% (P < 0.05), increased muscle mass by 25% (P < 0.02), and decreased liver mass by 7% (P < 0.02). Although the concentrations of most PCDD/F per gram of fat were slightly increased after clenbuterol treatment, the total amount of PCDD/F that remained in fat was reduced by approximately 30%. Muscle PCDD/F concentrations and total burden were decreased by clenbuterol. In contrast, clenbuterol tended to increase concentration, but not total burden of PCDD/F in livers. One congener known to be rapidly metabolized and excreted, 2,3,7,8-TCDF, was the exception to this increase, decreasing 40% with clenbuterol treatment. This was also the congener that showed the greatest reduction in both fat and muscle. Examination of the ratio of PCDD/F in liver and fat revealed that clenbuterol increased the liver's share of the body burden of PCDD/F, from 38 to 75%. In a remediation/disposal context, these findings would be beneficial if clenbuterol lowered the meat and carcass burden of PCDD/F to safe levels, requiring only livers to be disposed of as hazardous waste.


Role of Neisseria gonorrhoeae and Chlamydia trachomatis in intraabdominal abscess formation in the rat.
Our concept of the pathogenesis of acute salpingitis and advanced pelvic infection, such as tuboovarian abscess, is evolving. Although Neisseria gonorrhoeae and Chlamydia trachomatis are thought to play a significant role in acute pelvic inflammatory disease, other microorganisms, such as aerobes and anaerobes, have repeatedly been reported to play a significant role, also, particularly in the patient with advanced disease. A study was designed to evaluate the pathogenesis, and particularly any synergistic role, of some aerobes and anaerobes with N gonorrhoeae and C trachomatis abscess formation. Using the rat model developed by Weinstein and Onderdonk, the study demonstrated that N gonorrhoeae and C trachomatis alone do not produce abscesses. However, when combined with facultative or anaerobic bacteria, synergism with abscess formation is noted frequently. The data support the hypothesis that N gonorrhoeae and C trachomatis initiate infection and that aerobic and anaerobic bacteria act synergistically to produce abscesses. In addition, microorganisms not inoculated were found to be recruited into the infectious process. The organisms may gain access to the peritoneal cavity via the lower genital tract or from transmucosal migration from the intestinal flora.


Effect of transgenic expression of human alpha 1-acid glycoprotein (AGP) on the glycosylation of human and mouse AGP in various transgenic mouse sera.
The occurrence and the glycosylation of human alpha 1-acid glycoprotein (AGP) was studied in two classes of transgenic mice expressing either the A, B and B' genes (ABB'-mice) or only the A gene of human AGP (A-mice). The glycosylation of the human AGP molecules in the transgenic mouse sera was compared with the glycosylation of mouse AGP in the same animal and with human AGP in normal human serum by studying their heterogeneity in binding to concanavalin A (Con A), using crossed affino immunoelectrophoresis (CAIE) with Con A as the affinocomponent in the first dimension gel. Three to four different glycosylated fractions of human as well as mouse AGP were revealed by this method in all the transgenic mouse sera. A close relationship was apparent between the heterogeneities in Con A binding of human and mouse AGP in the same transgenic mouse. The magnitude of this so-called Con A reactivity was, however, strongly dependent on the transgenic mouse studied. Especially within the group of ABB'-mice dramatic changes in Con A reactivity were found when the human AGP genes were expressed. This indicates in the first place that the oligosaccharide chains of the human AGP molecules expressed also mouse-specific features. Secondly, and more importantly, these findings indicate that the expression of the human AGP genes affected the glycosylation process of the transgenic mouse liver. This organ is the source of the AGP forms occurring in serum. We do not know whether this effect has been caused by the introduction or the expression of the human gene(s) or by the presence of human AGP in the Golgi system or in serum.(ABSTRACT TRUNCATED AT 250 WORDS)


[Abnormal reaction for anaesthetics in a critically ill child with acute myeloid leukemia--case report].
The authors present a case report of an abnormal reaction for anaesthetics correlated with cytostatic therapy in the course of preparation time for bone marrow transplantation due to acute myeloid leukemia. Problems of pharmacological interaction of ketamine and benzodiazepines are emphasized. Special attention was paid to the risk of abnormal drug reactions during general anaesthesia in children with leukemia.


Ubiquitin-specific proteases UBP12 and UBP13 act in circadian clock and photoperiodic flowering regulation in Arabidopsis.
Protein ubiquitination is involved in most cellular processes. In Arabidopsis (Arabidopsis thaliana), ubiquitin-mediated protein degradation regulates the stability of key components of the circadian clock feedback loops and the photoperiodic flowering pathway. Here, we identified two ubiquitin-specific proteases, UBP12 and UBP13, involved in circadian clock and photoperiodic flowering regulation. Double mutants of ubp12 and ubp13 display pleiotropic phenotypes, including early flowering and short periodicity of circadian rhythms. In ubp12 ubp13 double mutants, CONSTANS (CO) transcript rises earlier than that of wild-type plants during the day, which leads to increased expression of FLOWERING LOCUS T. This, and analysis of ubp12 co mutants, indicates that UBP12 and UBP13 regulate photoperiodic flowering through a CO-dependent pathway. In addition, UBP12 and UBP13 regulate the circadian rhythm of clock genes, including LATE ELONGATED HYPOCOTYL, CIRCADIAN CLOCK ASSOCIATED1, and TIMING OF CAB EXPRESSION1. Furthermore, UBP12 and UBP13 are circadian controlled. Therefore, our work reveals a role for two deubiquitinases, UBP12 and UBP13, in the control of the circadian clock and photoperiodic flowering, which extends our understanding of ubiquitin in daylength measurement in higher plants.


Clinical utility of liver biopsy in children with acquired immunodeficiency syndrome.
Little is known about hepatic histology in children with AIDS, although the liver is frequently involved in the course of HIV infection. The clinical utility of liver biopsy in these patients is not well-defined. We reviewed retrospectively the results of this procedure in a group of infected children better to delineate its indications. Eighteen children with AIDS underwent liver biopsy in our institution. The indications were unexplained fever in eight children, six of whom had an elevated erythrocyte sedimentation rate and clinical suspicion of mycobacterial infection; jaundice in four; suspicion of drug toxicity (dideoxyinosine) in two; discussion of treatment for chronic hepatitis B in three; suspicion of cytomegalovirus infection in one who had also AIDS cholangiopathy. Of the six children thought to have mycobacterial infection, two had the disease on biopsy, both of whom had abnormal liver enzymes. The children with unexplained fever had nonspecific findings, except for one with lymphoid interstitial pneumonitis who had a dense lymphoid infiltrate. Of the four with jaundice two had extensive necrosis caused by adenovirus infection in one and suspected herpes simplex infection in the other. The other two with jaundice had unexplained findings, severe necrosis and fibrosis in one case and hemophagocytosis in the other one; both improved clinically. Both children with suspected dideoxyinosine hepatotoxicity had nonspecific findings. The three children with chronic hepatitis B had mild lesions that were not an indication for treatment. Liver biopsy appeared to be useful in two groups of selected children with AIDS: when there is strong clinical suspicion of mycobacterial infection; and when the child is jaundiced.


Modeling velocity in gradient flows with coupled-map lattices with advection.
We introduce a simple model to investigate large scale behavior of gradient flows based on a lattice of coupled maps which, in addition to the usual diffusive term, incorporates advection, as an asymmetry in the coupling between nearest neighbors. This diffusive-advective model predicts traveling patterns to have velocities obeying the same scaling as wind velocities in the atmosphere, regarding the advective parameter as a sort of geostrophic wind. In addition, the velocity and wavelength of traveling wave solutions are studied. In general, due to the presence of advection, two regimes are identified: for strong diffusion the velocity varies linearly with advection, while for weak diffusion a power law is found with a characteristic exponent proportional to the diffusion.


Intracranial dislocation of the mandibular condyle: report of two cases and review of the literature.
Fractures of the mandibular condylar process are common and account for up to 40% of all mandibular fractures. Penetration of the condylar head into the middle cranial fossa is, however, rare. We have found reports of only 43 cases since 1834. The diagnosis of intracranial condylar dislocation is difficult, there are usually no particular symptoms or neurological signs. As a result, detailed radiological studies are necessary. In the absence of clear radiographic images of the condylar structures, computed tomography (CT) is essential to locate the fragments and to investigate and monitor intracranial lesions. This paper describes the diagnostic and surgical procedures used in two cases of condylar dislocation and discusses them with reference to previous cases. The use of a titanium screw, which was positioned intracranially in the first case, has not, to our knowledge, been described previously.


Insights into β-lactamases from Burkholderia species, two phylogenetically related yet distinct resistance determinants.
Burkholderia cepacia complex and Burkholderia pseudomallei are opportunistic human pathogens. Resistance to β-lactams among Burkholderia spp. is attributable to expression of β-lactamases (e.g. PenA in B. cepacia complex and PenI in B. pseudomallei). Phylogenetic comparisons reveal that PenA and PenI are highly related. However, the analyses presented here reveal that PenA is an inhibitor-resistant carbapenemase, most similar to KPC-2 (the most clinically significant serine carbapenemase), whereas PenI is an extended spectrum β-lactamase. PenA hydrolyzes β-lactams with k(cat) values ranging from 0.38 ± 0.04 to 460 ± 46 s(-1) and possesses high k(cat)/k(inact) values of 2000, 1500, and 75 for β-lactamase inhibitors. PenI demonstrates the highest kcat value for cefotaxime of 9.0 ± 0.9 s(-1). Crystal structure determination of PenA and PenI reveals important differences that aid in understanding their contrasting phenotypes. Changes in the positioning of conserved catalytic residues (e.g. Lys-73, Ser-130, and Tyr-105) as well as altered anchoring and decreased occupancy of the deacylation water explain the lower k(cat) values of PenI. The crystal structure of PenA with imipenem docked into the active site suggests why this carbapenem is hydrolyzed and the important role of Arg-220, which was functionally confirmed by mutagenesis and biochemical characterization. Conversely, the conformation of Tyr-105 hindered docking of imipenem into the active site of PenI. The structural and biochemical analyses of PenA and PenI provide key insights into the hydrolytic mechanisms of β-lactamases, which can lead to the rational design of novel agents against these pathogens.


Integration of animal health and public health surveillance sources to exhaustively inform the risk of zoonosis: An application to echinococcosis in Rio Negro, Argentina.
The analysis of zoonotic disease risk requires the consideration of both human and animal geo-referenced disease incidence data. Here we show an application of joint Bayesian analyses to the study of echinococcosis granulosus (EG) in the province of Rio Negro, Argentina. We focus on merging passive and active surveillance data sources of animal and human EG cases using joint Bayesian spatial and spatio-temporal models. While similar spatial clustering and temporal trending was apparent, there appears to be limited lagged dependence between animal and human outcomes. Beyond the data quality issues relating to missingness at different times, we were able to identify relations between dog and human data and the highest 'at risk' areas for echinococcosis within the province.


Insulin-like growth factor-I inhibits lysosomal and proteasome-dependent proteolysis in skeletal muscle after burn injury.
Previous studies suggest that insulin-like growth factor-I (IGF-I) inhibits burn-induced muscle wasting mainly by reducing muscle protein degradation. The intracellular mechanisms of this effect of IGF-I are not known. In the present study, we examined the influence of IGF-I on individual proteolytic pathways in muscles from burned rats. Extensor digitorum longus muscles from burned rats were incubated with specific blockers of lysosomal, calcium-calpain-dependent, and ubiquitin-proteasome-dependent proteolytic pathways in the absence or presence of IGF-I. In addition, cathepsin B and L activities and 20S proteasome activity were determined. IGF-I inhibited lysosomal and ubiquitin-proteasome-dependent protein breakdown in skeletal muscle from burned rats by 70 and 90%, respectively, but did not influence calcium-calpain-dependent protein breakdown. The hormone blocked the burn-induced increase in cathepsin B and L activities but did not reduce 20S proteasome activity. Results are important because they provide novel information about intracellular mechanisms by which IGF-I inhibits the catabolic response to burn injury in skeletal muscle.


Suppression of MHD fluctuations leading to improved confinement in a gun-driven spheromak.
Magnetic fluctuations have been reduced to approximately 1% during discharges on the Sustained Spheromak Physics Experiment by shaping the spatial distribution of the bias magnetic flux in the device. In the resulting quiescent regime, the safety factor profile is nearly flat in the plasma and the dominant ideal and resistive MHD modes are greatly reduced. During this period, the temperature profile is peaked at the magnetic axis and maps onto magnetic flux contours. Energy confinement time is improved over previous reports in a driven spheromak.


Cytotoxicity of titanium carbonitride coatings for prostodontic alloys with different amounts of carbon and nitrogen.
The aim of our work was to examine the cytotoxicity of NiCr alloys coated with Ti(C,N) with different amounts of C and N in the layer on human gingival fibroblasts. Cells were cultured for 24 hours in the alloy extracts or on the surface of tested materials. The viability of the cells exposed to 1-, 3-, 5- and 7-day extracts did not change in comparison to the viability of cells cultured in a control medium assayed by an MTT test. Moreover, the flow cytometry analysis of fibroblasts cultured in direct contact with tested alloys revealed that all coatings except TiC did not induce apoptosis or necrosis. Interestingly, 24 hour fibroblast culture on alloys with Ti(C,N) coatings showed that the number of fibroblasts adhered to these alloys, evaluated by scanning electron microscope, increased with an increase in the content of nitrogen in the layer. The present study demonstrates that Ti(C,N) coatings were not cytotoxic and did not induce apoptosis in Ti(C,N) extracts, nor in direct contact with gingival fibroblasts, and can be considered for biomedical applications in the future.


Active traffic management on road networks: a macroscopic approach.
Active traffic management (ATM) is the ability to dynamically manage recurrent and non-recurrent congestion based on prevailing traffic conditions in order to maximize the effectiveness and efficiency of road networks. It is a continuous process of (i) obtaining and analysing traffic measurement data, (ii) operations planning, i.e. simulating various scenarios and control strategies, (iii) implementing the most promising control strategies in the field, and (iv) maintaining a real-time decision support system that filters current traffic measurements to predict the traffic state in the near future, and to suggest the best available control strategy for the predicted situation. ATM relies on a fast and trusted traffic simulator for the rapid quantitative assessment of a large number of control strategies for the road network under various scenarios, in a matter of minutes. The open-source macrosimulation tool Aurora ROAD NETWORK MODELER is a good candidate for this purpose. The paper describes the underlying dynamical traffic model and what it takes to prepare the model for simulation; covers the traffic performance measures and evaluation of scenarios as part of operations planning; introduces the framework within which the control strategies are modelled and evaluated; and presents the algorithm for real-time traffic state estimation and short-term prediction.


Dihydrotanshinone I inhibits human glioma cell proliferation via the activation of ferroptosis.
The aim of the present study was to investigate the effect of dihydrotanshinone I (DHI) on the survival of human glioma cells and the expression levels of ferroptosis-associated proteins. Human U251 and U87 glioma cells were cultured in vitro and treated with different concentrations of DHI and/or the ferroptosis inhibitor ferrostatin-1. A Cell Counting Kit-8 assay was used to determine the cell survival rate. The cells were further analyzed to determine their 5-, 12- and 15-hydroxyeicosatetraenoic acid (HETE), lactate dehydrogenase (LDH) and malondialdehyde (MDA) levels, and reduced glutathione (GSH)/oxidized glutathione (GSSG) ratios. Western blotting was used to detect ferroptosis-associated glutathione peroxidase 4 (GPX4) and long-chain acyl-CoA synthetase 4 (ACSL-4). Changes in the mitochondrial membrane potential (MMP) were also observed using tetramethylrhodamine methyl ester staining and confocal fluorescence microscopy. The results revealed that DHI inhibited the proliferation of human glioma cells. Following treatment of the U251 and U87 cells with DHI, changes in the expression levels of ferroptosis-associated proteins were observed; the expression level of GPX4 decreased and that of ACSL-4 increased. DHI also increased the levels of LDH and MDA in the human glioma cells and reduced the GSH/GSSG ratio. The DHI-treated cells also exhibited a marked reduction in MMP. Furthermore, ferrostatin-1 blocked the DHI-induced effects in human glioma cells. From these results, it may be concluded that DHI inhibits the proliferation of human glioma cells via the induction of ferroptosis.


Twin-free GaAs nanosheets by selective area growth: implications for defect-free nanostructures.
Highly perfect, twin-free GaAs nanosheets grown on (111)B surfaces by selective area growth (SAG) are demonstrated. In contrast to GaAs nanowires grown by (SAG) in which rotational twins and stacking faults are almost universally observed, twin formation is either suppressed or eliminated within properly oriented nanosheets are grown under a range of growth conditions. A morphology transition in the nanosheets due to twinning results in surface energy reduction, which may also explain the high twin-defect density that occurs within some III–V semiconductor nanostructures, such as GaAs nanowires. Calculations suggest that the surface energy is significantly reduced by the formation of {111}-plane bounded tetrahedra after the morphology transition of nanowire structures. By contrast, owing to the formation of two vertical {11[overline]0} planes which comprise the majority of the total surface energy of nanosheet structures, the energy reduction effect due to the morphology transition is not as dramatic as that for nanowire structures. Furthermore, the surface energy reduction effect is mitigated in longer nanosheets which, in turn, suppresses twinning.


Assessment of brachial artery blood flow across the cardiac cycle: retrograde flows during cycle ergometry.
We describe a novel software system that utilizes automated algorithms to perform edge detection and wall tracking of high-resolution B-mode arterial ultrasound images, combined with synchronized Doppler waveform envelope analysis, to calculate conduit arterial blood flow (BF) across the cardiac cycle. Furthermore, we describe changes in brachial arterial BF to the resting forearm during incremental cycle ergometry in eight subjects. During exercise, peak BF during the cardiac cycle increased at each workload (P < 0.001), because of increased velocity in the presence of unaltered cross-sectional area. In contrast, mean BF calculated across each cardiac cycle decreased at lower workloads before increasing at 100 and 160 W (P < 0.001). Differences in the pattern of peak and mean cardiac cycle flows were due to the influence of retrograde diastolic flow, which had a larger impact on mean flows at lower workloads. In conclusion, BF can be measured with high temporal resolution across the cardiac cycle in humans. Resting brachial arterial flow, including retrograde flow, increases during lower limb exercise.


G-quadruplex DNA structures--variations on a theme.
To be functional, nucleic acids need to adopt particular three-dimensional structures. For a long time DNA was regarded as a rigid and passive molecule with the sole purpose to store genetic information, but experimental data has now accumulated that indicates the full dynamic repertoire of this macromolecule. During the last decade, four-stranded DNA structures known as G-quadruplexes, or DNA tetraplexes, have emerged as a three-dimensional structure of special interest. Motifs for the formation of G-quadruplex DNA structures are widely dispersed in eukaryotic genomes, and are abundant in regions of biological significance, for example, at telomeres, in the promoters of many important genes, and at recombination hotspots, to name but a few in man. Here I explore the plethora of G-quadruplex DNA structures, and discuss their possible biological functions as well as the proteins that interact with them.


Associations between reproductive performance and seropositivity for bovine leukemia virus, bovine viral-diarrhea virus, Mycobacterium avium subspecies paratuberculosis, and Neospora caninum in Canadian dairy cows.
Our objective was to investigate effects of seropositivity for bovine leukemia virus (BLV), Type 1 bovine viral-diarrhea virus (BVDV), Mycobacterium avium subspecies paratuberculosis (MAP), and Neospora caninum (NC), and their possible interactions, on reproductive efficiency (specifically, first-service conception [FSC], and calving interval [CI]) in dairy cows. The sample population included up to 30 randomly selected animals from 179 randomly selected farms in five provinces in Canada, from which 23 farms did not meet the inclusion criteria for the final dataset. Serum samples were tested for antibodies against the stated pathogens using commercially available diagnostic tests. A Cox proportional hazards model with shared (herd-level) frailty was utilized to analyze the CI data. In this model, BLV-seropositive cows had a 7% lower rate of conception compared to seronegative cows (P=0.06). Mixed logistic regression models of CI>484 days, CI>534 days, and CI>584 days were built to explore factors of long CIs. These cut-offs were selected to represent calving-to-conception intervals of >200 days, >250 days, and >300 days. BLV-seropositive cows had higher odds of having a CI>484 days compared to BLV-seronegative cows, and BLV serostatus interacted with lactation number in this model, with 1st lactation seropositive cows being more likely to have a CI>484 days than older seropositive cows. NC-seropositive cows had a 1.27 times higher odds of exhibiting a CI>484 days, a 1.37 times higher odds of a CI>534 days, and a 1.54 times higher odds of a CI>584 days, compared to NC-seronegative cows. Neither BVDV nor MAP seropositivity showed any significant effect in these models. For the FSC models, a first service was classified successful (pregnancy=1) if it was the cow's last service and she calved 270-290 days later. A mixed logistic regression model of FSC revealed an interaction between NC and BVDV-seropositivity at the herd level, with odds ratios of 0.64, 1.06 and 0.85 for NC-seropositive cows (compared to NC-seronegative cows) in BVDV-seronegative, BVDV-seropositive and BVDV-missing herds, respectively. BLV and MAP seropositivity had no significant impact on FSC. All models controlled for herd-clustering effects, and included parity, linear score of somatic cell counts, peak milk, and province to control for confounding. The overall FSC was 51%, the average CI was 393 days, and 18%, 9% and 5% of lactations had CI>484 days, >534 days, and >584 days, respectively.


Highly Enhanced Force Generation of Ionic Polymer-Metal Composite Actuators via Thickness Manipulation.
On purpose to enhance the generating force of ionic polymer-metal composite (IPMC) actuators, the thickness of the ion-exchange membrane is manipulated in two different ways. One is grafting poly(styrenesulfonic acid) onto poly(vinylidene fluoride-co-hexafluoropropylene) films with varying thickness, and the other is stacking pre-extruded Nafion films to thicker films by pressing at high temperatures. For both groups of the membranes, ionic properties including ion-exchange capacity and ionic conductivity are maintained similarly inside the groups regardless of the thickness. The actuation tests clearly show the increase in generating force with increasing thickness of the IPMCs prepared. It is due to a larger bending stiffness of thicker IPMCs, which is consistent with the predicted result from the cantilever beam model. The increase in force is more remarkable in Nafion-stacked IPMCs, and a thick IPMC lifts a weight of 100 g, which far exceeds the reported values for IPMCs.


Quercetin regulates growth of Ishikawa cells through the suppression of EGF and cyclin D1.
Quercetin and other polyphenols have anti-carcinogenic and anti-tumorigenic activity in various organs, however, studies of this activity are lacking in endometrial cancer. We hypothesize that quercetin has anti-proliferative activity and the mechanisms of quercetin action may be through modulation of cell cycle and cell growth regulatory genes. To test this hypothesis, we treated endometrial cancer cells (Ishikawa cell line) with quercetin, and cell proliferation, expression of growth signal genes (EGF, VEGF, and TGF-alpha), cell cycle genes (p53, p21, p73, and cyclin D1), and apoptosis-related genes (bcl-2 and bax) were analyzed. Results of these experiments demonstrate that after a 7-day exposure to 1, 10 and 100 micro M of quercetin, growth of Ishikawa cells was inhibited by 3, 51 and 87%, respectively. The gene and protein expression data suggest that quercetin treatment (100 micro M) significantly decreased EGF and cyclin D1, whereas VEGF was up-regulated in Ishiwaka cell lines. Other genes such as TGF-alpha, p53, p21, p73, bcl-2 and bax were not significantly changed with quercetin treatment in Ishiwaka cell lines. The present study suggests that quercetin can suppress proliferation of Ishikawa cells through down-regulation of EGF and cyclin D1.


Fine mapping of the clubroot resistance gene CRb and development of a useful selectable marker in Brassica rapa.
In Chinese cabbage (Brassica rapa), the clubroot resistance (CR) gene CRb is effective against Plasmodiophora brassicae isolate No. 14, which is classified as pathotype group 3. Although markers linked to CRb have been reported, an accurate position in the genome and the gene structure are unknown. To determine the genomic location and estimate the structure of CRb, we developed 28 markers (average distance, 20.4 kb) around CRb and constructed a high-density partial map. The precise position of CRb was determined by using a population of 2,032 F2 plants generated by selfing B. rapa 'CR Shinki.' We determined that CRb is located in the 140-kb genomic region between markers KB59N07 and B1005 and found candidate resistance genes. Among other CR genes on chromosome R3, a genotype of CRa closest marker clearly matched those of CRb and Crr3 did not confer resistance to isolate No. 14. Based on the genotypes of 11 markers developed near CRb and resistance to isolate No. 14, 82 of 108 cultivars showed a strong correlation between genotypes and phenotypes. The results of this study will be useful for isolating CRb and breeding cultivars with resistance to pathotype group 3 by introducing CRb into susceptible cultivars through marker-assisted selection.


Molecular biology of pituitary development and disease.
The major endocrine cell types of the anterior and intermediate pituitary arise in sequential order during development. Our laboratory seeks to understand the molecular basis for different lineages among these cell types. Previous data from our group and others have shown that the POU-domain factor, Pit-1, and the orphan nuclear receptor, SF-1, are critical in the specification and maintenance of these cell types. The analysis of naturally occurring mutations revealed that Pit-1 is needed for development of three cell types, the thyrotropes (thyroid-stimulating hormone), somatotropes (growth hormone), and lactotropes (prolactin). Recently, a genetically engineered mouse mutant demonstrated that SF-1 is required for the maintenance of the gonadotrope (luteinizing hormone/follicle-stimulating hormone) cellular phenotype. To date, a similar factor for the corticotrope and melanotrope lineages expressing propiomelanocortin (POMC) has not been identified. Surprisingly, the serotonin (5-HT) neurotransmitter receptor 5-HT3 was found to be expressed in the anterior and intermediate lobes of the developing rodent pituitary. We are using this new marker to examine the molecular basis of the POMC lineages.


Enduring effects of Preventive Cognitive Therapy in adults remitted from recurrent depression: A 10 year follow-up of a randomized controlled trial.
Prevention of recurrence is a challenge in the management of major depressive disorder (MDD). The long-term effects of Preventive Cognitive Therapy (PCT) in preventing recurrence in MDD are not known. A RCT comparing the addition of PCT to Treatment As Usual (TAU), versus TAU including patients with recurrent depression who were in remission at entry (N=172). PCT consisted of eight weekly group sessions. TAU involved standard treatment. Primary outcome is time to first recurrence of a depressive episode as assessed by blinded interviewers over 10 years based on DSM-IV-TR criteria. Also over 10 years, the protective effect of PCT was dependent on the number of previous episodes a patient experienced. The protective effect intensified with the number of previous depressive episodes (Cox regression; p=.004, Hazard ratio=.576, 95% CI=.396-.837) and is mainly established within the first half of the 10 year follow-up period. For patients with more than three previous episodes (52% of the sample), PCT significantly increased the median survival time (713.0 days) versus patients that received TAU (205.0 days). No enduring effects were found on secondary outcomes. Dropout rates were relatively high for secondary outcomes, but relatively low for the primary outcome. Results were comparable after multiple imputation. PCT in remitted patients with multiple prior episodes has long-term preventive effects on time to recurrence. To reduce recurrence rates, booster sessions might be necessary. A personalized medicine approach might be necessary to reduce recurrence rates even further.