OBJECT
The purpose of this study was to identify risk factors for surgical site infection after spine surgery, noting the amount of saline used for intraoperative irrigation to minimize wound contamination.

METHODS
The authors studied 223 consecutive spine operations from January 2006 through December 2006 at our institute. For a case to meet inclusion criteria as a site infection, it needed to require surgical incision and drainage and show positive intraoperative cultures. Preoperative and intraoperative data regarding each patient were collected. Patient characteristics recorded included age, sex, and body mass index (BMI). Preoperative risk factors included preoperative hospital stay, history of smoking, presence of diabetes, and an operation for a traumatized spine. Intraoperative factors that might have been risk factors for infection were collected and analyzed; these included type of procedure, estimated blood loss, duration of operation, and mean amount of saline used for irrigation per hour. Data were subjected to univariate and multivariate logistic regression analyses.

RESULTS
The incidence of surgical site infection in this population was 6.3%. According to the univariate analysis, there was a significant difference in the mean duration of operation and intraoperative blood loss, but not in patient age, BMI, or preoperative hospital stay. The mean amount of saline used for irrigation in the infected group was less than in the noninfected group, but was not significantly different. In the multivariate analysis, sex, advanced age (> 60 years), smoking history, and obesity (BMI > 25 kg/m(2)) did not show significant differences. In the analysis of patient characteristics, only diabetes (patients receiving any medications or insulin therapy at the time of surgery) was independently associated with an increased risk of surgical site infection (OR 4.88). In the comparison of trauma and elective surgery, trauma showed a significant association with surgical site infection (OR 9.42). In the analysis of surgical factors, a sufficient amount of saline for irrigation (mean > 2000 ml/hour) showed a strong association with the prevention of surgical site infection (OR 0.08), but prolonged operation time (> 3 hours), high blood loss (> 300 g), and instrumentation were not associated with surgical site infection.

CONCLUSIONS
Diabetes, trauma, and insufficient intraoperative irrigation of the surgical wound were independent and direct risk factors for surgical site infection following spine surgery. To prevent surgical site infection in spine surgery, it is important to control the perioperative serum glucose levels in patients with diabetes, avoid any delay of surgery in patients with trauma, and decrease intraoperative contamination by irrigating > 2000 ml/hour of saline in all patients.


AIMS
To assess the pharmacokinetic and pharmacodynamic effects of co-administration of a combined oral contraceptive (ethinyloestradiol plus levonorgestrel) and lamotrigine.

METHODS
Over a period of 130 days, healthy female subjects took lamotrigine (titrated up to 300 mg day(-1)) and the combined oral contraceptive, either individually or as co-therapy. Plasma ethinyloestradiol and levonorgestrel concentrations were measured in the presence and absence of lamotrigine, and serum lamotrigine concentrations were measured in the presence and absence of the combined oral contraceptive. Serum concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), progesterone, oestradiol and sex hormone binding globulin were also determined.

RESULTS
Of the 22 enrolled subjects, 16 had evaluable pharmacokinetic data. The mean (90% CI) ratios of lamotrigine area under the concentration-time curve from 0 to 24 h (AUC(0,24 h)) and maximum observed concentration (C(max)) of lamotrigine when it was given with the combined oral contraceptive and during monotherapy were 0.48 (0.44, 0.53) and 0.61 (0.57, 0.66), respectively. Ethinyloestradiol pharmacokinetics were unchanged by lamotrigine, the mean combined oral contraceptive + lamotrigine : combined oral contraceptive alone ratios (90% CI) of the AUC(0,24 h) and C(max) of levonorgestrel were 0.81 (0.76, 0.86) and 0.88 (0.82, 0.93), respectively. FSH and LH concentrations were increased (by 4.7-fold and 3.4-fold, respectively) in the presence of lamotrigine, but the low serum progesterone concentrations suggested that suppression of ovulation was maintained. Intermenstrual bleeding was reported by 7/22 (32%) of subjects during co-administration of lamotrigine and combined oral contraceptive.

CONCLUSIONS
A clinically relevant pharmacokinetic interaction was observed during co-administration of a combined oral contraceptive and lamotrigine. A dosage adjustment for lamotrigine may need to be considered when these agents are co-administered. A modest decrease in the plasma concentration of levonorgestrel was also observed but there was no corresponding hormonal evidence of ovulation.


An ERP component called the Sustained Posterior Negativity (SPN) indexes the brain response to regularity in visual patterns (e.g. vertical reflectional symmetry, horizontal reflectional symmetry or rotational symmetry). However it is unclear if different regularities are coded by independent or overlapping neural populations. Previous work has successfully exploited repetition effects to assess representational independence, and we adapted this approach to investigate visual regularity. Experiment 1 (N = 48) found that SPN amplitude increased when three reflectional symmetry patterns were presented sequentially. This SPN priming effect did not survive changes in retinal location (Experiment 2, N = 48) or non-orthogonal changes in axis orientation (Experiment 3, N= 48). However, SPN priming transferred between vertical and horizontal axis orientation (Experiment 4, N= 48) and between reflectional and rotational symmetry (Experiment 5, N= 48). We conclude that visual regularities at different retinal locations are coded independently. However, there is some overlap between different regularities presented at the same retinal location.


A wide range of products and services has been commoditized as a result of globalization of the economy, and companies have been increasingly seeking to derive their competitiveness from the knowledge creation of their staff. Social networking among employees is the basis of knowledge creation, and it has been pointed out that if management can support its social networks, it will be able to gain organizational strength. This paper uses the example of a company that has been evaluated highly for its utilization of ICT in business, we analyze the relationship between collaboration network and communication network. Based on the results, we propose how to manage the collaboration network by manipulating communication style.


Malpractice is a broad designation that generally encompasses any improper conduct in the performance of a professional's duty. Most often, it is considered synonymous with the term "negligence."


Data imbalance is a frequently occurring problem in classification tasks where the number of samples in one category exceeds the amount in others. Quite often, the minority class data is of great importance representing concepts of interest and is often challenging to obtain in real-life scenarios and applications. Imagine a customers' dataset for bank loans-majority of the instances belong to non-defaulter class, only a small number of customers would be labeled as defaulters, however, the performance accuracy is more important on defaulters labels than non-defaulter in such highly imbalance datasets. Lack of enough data samples across all the class labels results in data imbalance causing poor classification performance while training the model. Synthetic data generation and oversampling techniques such as SMOTE, AdaSyn can address this issue for statistical data, yet such methods suffer from overfitting and substantial noise. While such techniques have proved useful for synthetic numerical and image data generation using GANs, the effectiveness of approaches proposed for textual data, which can retain grammatical structure, context, and semantic information, has yet to be evaluated. In this paper, we address this issue by assessing text sequence generation algorithms coupled with grammatical validation on domain-specific highly imbalanced datasets for text classification. We exploit recently proposed GPT-2 and LSTM-based text generation models to introduce balance in highly imbalanced text datasets. The experiments presented in this paper on three highly imbalanced datasets from different domains show that the performance of same deep neural network models improve up to 17% when datasets are balanced using generated text.


BACKGROUND
Many suicide prevention strategies promote media guidelines on suicide reporting, given evidence that irresponsible reporting of suicide can influence imitative suicidal behavior. Due to limited resources, monitoring of guideline adherence has tended to focus on news outputs, with a risk of neglecting other journalistic content.

AIMS
To determine whether British newspapers' arts coverage adheres to media guidelines on suicide reporting.

METHOD
Purposive sampling was used to capture current national practice on suicide reporting within newspapers' arts coverage of exhibitions. Recent major UK exhibitions by artists who had died by suicide were identified: Kirchner, Rothko, Gorky, and Van Gogh. Content analysis of all UK national newspaper coverage of these exhibitions was performed to measure the articles' adherence to widely accepted media guidelines.

RESULTS
In all, 68 newspaper reviews satisfied inclusion criteria, with 100% failing to show full adherence to media guidelines: 21% used inappropriate language; 38% provided explicit descriptions of the suicide; 7% employed simplistic explanations for suicide triggers; 27% romanticized the suicide; and 100% omitted information on sources of support.

CONCLUSION
British newspapers' arts coverage of exhibitions deviates considerably from media guidelines on the reporting of suicide. The findings suggest scope to improve journalists' awareness of the importance of this component of suicide prevention strategies.


The United States and the other 153 members of the World Trade Organization (WTO) have been engaged in a set or "round" of negotiations called the Doha Development Agenda (DDA) since December 2001. The DDA's main objective is to refine and expand the rules by which WTO members conduct foreign trade with one another. This report is designed to assist the 112th Congress to understand and monitor progress of the negotiations and the major issues that the negotiators are addressing. The report provides a brief background section on the significance of services to the U.S. economy. It then explains briefly the General Agreement on Trade in Services (GATS) and the structure and agenda of the services negotiations in the DDA round, including U.S. objectives in the negotiations. The report concludes with a status report on the negotiations and an examination of potential results.


Equine bone blocks have osteogenic effects promoting bone regeneration with biocompatibility and osteoconductivity capacity. Human dental pulp stem cells (hDPSCs) can differentiate into osteoblasts enhancing biomineralization with such scaffolds. Melatonin is able to improve bone health and mediate bone formation. Collagenated equine bone blocks were coated with ammonia-functionalized graphene-oxide (G-N) at two different concentrations (2 μg/mL, G-N2; and 10 μg/mL, G-N10). The homogeneity of G-N coating was checked by Raman spectroscopy, whereas thermogravimetric analysis (TGA) allowed us to quantify the amount of G-N deposited on the blocks. The aim of this study was to investigate in vitro the effect of G-N-coated collagenated equine bone blocks on the proliferation and differentiation of hDPSCs with the addition of a melatonin. This evaluation was determined after 7, 14, and 21 days of culture by the expression of specific microRNAs, RUNX2 and SMAD5 gene expression, osteocalcin levels, and histological analysis. The results showed that equine blocks G-N2 and G-N10 and melatonin gave an optimal cell adhesion as shown by histological analysis, and an increase in the hDPSCs osteogenic potential as confirmed by microRNA and gene expression with an increase in osteocalcin levels. This study suggests that equine bone blocks coated with G-N2 and G-N10 and melatonin promote the osteogenic process.


Environmental sustainability is important to public health and of particular significance considering the rapidly growing ageing population. While advancement in chemical science has contributed to enhanced quality of life, increasing levels of chemical pollutions and the impact of chemicals on human health and the environment have led to serious concern. The deterioration of environmental quality has been largely due to chemical pollution and the elderly group are being more susceptible to the hazardous effects of industrial chemicals and airborne pollutants. It has also presented uphill challenges to the promotion of healthy ageing which requires a sustainable clean environment, contributed by the advancement of sustainable and green chemistry. However, innovations in green chemistry require a systems thinking mindset which is also important in realizing the impact of chemicals on human health and the environment. The adoption of the Sustainable Development Goals (SDGs) by the United Nations has called for immediate actions in adopting the SDGs as a central concern in the reform of different domains for the invention of a sustainable future. The practice of chemistry has various impacts on many interconnected systems, re-orientation of chemistry education has been proposed with the implementation of inter-disciplinary approaches as informed by systems thinking, with a growing number of reports suggesting its potentials and applications in chemical education. Despite the vast opinions suggesting the promising prospects of applying systems thinking in education, reports on the development of relevant tools and educational resources are only of a limited amount, with recent perspectives identifying the design of educational tools and resources as one of the priority areas. In this study, we report the collaborative work across the disciplines of health and chemical sciences in the pedagogic design of incorporating systems thinking in chemistry education adopting the theoretical framework. The design of a system-oriented concept map extension (SOCME) diagram is described, with reference to a case study of chemicals released from the degradation of plastics. The work presented illustrates the potential of systems thinking in sustainable education and adds to the collections of educational resources for incorporation of systems thinking in teaching and learning.


The study is based on the radiolarian assemblages of five radiolarite outcrops and two boreholes from the Darno and Szarvasko Complex, Hungary, and three radiolarite sections from the western Vardar Ophiolitic Unit in Serbia. These investigated sections belong to a Mesozoic volcano-sedimentary melange belt that can be followed from the Hellenides, through the Dinarides to the western Carpathians. Samples from radiolarite localities in the Darno and Szarvasko Complex contain a mixture of Middle Triassic (Illyrian to Longobardian) and Upper Triassic (Carnian) fairly poorly preserved radiolarian assemblages. Radiolarite samples from the western Vardar Ophiolitic Unit (Gostilje, Krs Gradac and Bukovi) yielded poorly preserved Upper Triassic (Carnian-?Norian) radiolarians. Co-occurrences of Middle and Upper Triassic radiolarian specimens in Darno and Szarvasko Complex suggest resedimentation during the Carnian or later. One new radiolarian species (Baumgartneria szarvaskoensis n. sp.) is described herein from the Darno and Szarvasko Complex.


In this research work a square corner cut rectangular wide band microstrip patch antenna is presented. A FR4 substrate is used to design a reference antenna of size 28 × 37 mm2 with partial ground structure feed using microstrip line and results are observed for impedance bandwidth, radiation patterns and antenna gain with the help of CADFEKO, proposed wide band antenna which is design on the FR4 substrate with Partial ground structure and square notch at the lower corners on radiating patch. Results are observed from simulated design and presented current distribution for the same. Simulated impedance band width is 4.21GHz (2.99GHz-7.2GHz). Gain is up to 2.049dBi. Improvement in design antenna is studied, comparison carried out between these designs. Proposed antenna VSWR bandwidth enhance from 31.8GHz to 4.21GHz.


BACKGROUND
Treatment of cancer cachexia partly involves the administration of adequate amounts of energy. The aim of this study was to assess the tolerance and efficacy of two equal volumes of tube feeding, one with a standard (1 kcal/mL) and one with a high energy density (1.5 kcal/mL), during the intensive phase of treatment.

METHODS
Nutritional status was assessed weekly, in 27 children with a solid tumor, by measuring weight, height, midupper arm circumference, biceps and triceps skinfold, and serum proteins. Tolerance was assessed by recording the occurrence of vomiting and by expressing the administered volume as a percentage of the required volume.

RESULTS
Both formulas were equally well tolerated, leading to a significantly higher energy intake in the energy-enriched formula group. In both formula groups, all anthropometric variables increased significantly (range of mean increase, 5.2% to 25.5%; p < .05) during the first 4 weeks of intervention. Between 4 and 10 weeks, variables continued to increase significantly in the energy-enriched group, resulting in adequate repletion, in contrast to the standard formula group. The concentration of serum proteins, low at initiation of tube feeding, returned to the normal range within 2 to 4 weeks with no significant differences between the two groups.

CONCLUSIONS
The energy-enriched formula was more effective in improving the nutritional status of children with cancer during the intensive phase of treatment than the standard formula. Intensive, protocolized administration of an energy-enriched formula should therefore be initiated as soon as one of the criteria for initiation of tube feeding is met.


An endo-xylanase was isolated from the culture of fungus Aspergillus oryzae variant D5. The purified enzyme had a molecular weight of 24,000 and the isoelectric point of 3.6. Xylanase crystals were obtained from a polyethylene glycol 6000 solution by the hanging-drop method. Seeding was used for the enlargement of the crystal size. Crystals belong to the monoclinic space group P2(1) with cell dimensions a = 54.9 A, b = 74.5 A, c = 50.8 A, and beta = 108.7 degrees. Crystals diffract beyond 2.5 A resolution.


PURPOSE
The purpose of this study was to determine if a week-long summer day camp for high school students to learn about various healthcare professions could influence the students' perceived self-efficacy and knowledge of healthcare careers related to sports medicine. Additionally, we investigated if there was a relationship between level of parent education and the participants' self-efficacy scores before and after camp.

SUBJECTS
We recruited 13 male and 13 female (n=26) students from five area high schools with an average age of 15.8 yrs (range, 15 to 17 yrs). Participants were predominantly of Hispanic origin.

METHODS
A pre- and post-intervention survey was used to collect participants' demographic data and to assess participants' perceived self-efficacy towards the healthcare field and their knowledge of different healthcare careers. A paired, two-tailed t-test was used to determine if perceived self-efficacy scores before and after the camp differed. A linear regression analysis was run to determine if parental education was a predictor for the difference in self-efficacy scores.

RESULTS
We found a statistically significant difference between perceived self-efficacy scores before and after the camp. Parental education was not found to be a significant predictor for the difference in participants' self-efficacy scores.

CONCLUSIONS
The evidence suggests that attendance at a summer program that allowed students to learn about and interact with various healthcare professionals significantly improves perceived self-efficacy towards pursuing a career in the healthcare field. Parental education may not be a predicting factor for the change in perceived self-efficacy after attendance at such educational camps.


PURPOSE
Interprofessional collaboration in health care is believed to enhance patient outcomes. However, where professions have overlapping scopes of practice (eg, chiropractors and physical therapists), "turf wars" can hinder effective collaboration. Deep-rooted beliefs, identified as implicit attitudes, provide a potential explanation. Even with positive explicit attitudes toward a social group, negative stereotypes may be influential. Previous studies on interprofessional attitudes have mostly used qualitative research methodologies. This study used quantitative methods to evaluate explicit and implicit attitudes of physical therapy students toward chiropractic.

METHODS
A paper-and-pencil instrument was developed and administered to 49 individuals (students and faculty) associated with a Canadian University master's entry-level physical therapy program after approval by the Research Ethics Board. The instrument evaluated explicit and implicit attitudes toward the chiropractic profession. Implicit attitudes were determined by comparing response times of chiropractic paired with positive versus negative descriptors.

RESULTS
Mean time to complete a word association task was significantly longer (t = 4.75, p =.00) when chiropractic was associated with positive rather than negative words. Explicit and implicit attitudes were not correlated (r = 0.13, p =.38).

CONCLUSIONS
While little explicit bias existed, individuals associated with a master's entry-level physical therapy program appeared to have a significant negative implicit bias toward chiropractic.


In economics, where the long resistance to reflecting on the effects of social interaction on economic behaviour is slowly waning, the concept of social capital may turn out to be a useful analytical tool. However, initial interest in social capital has produced a large variety of definitions, theoretical frameworks, empirical analyses, and even policy prescriptions. This paper provides a selective review and critique of some of the more recent literature on social capital. It then suggests that many of the problems in the existing literature can be addressed by lowering aspirations about what social capital is and reformulating it in terms of its impact on incentive problems in economic transactions in the presence of imperfect markets and costly or non-enforceable contracts. The paper finally advances a model of one of the ways that social capital resolves incentive compatibility problems, namely its role as a collateral asset.


The fixed–income portfolio strategy investigated here is designed to generate positive returns and be completely risk–based; it does not require any forecasts about future yield curve movements. The idea is to control the shortfall risk of a fixed–income portfolio dynamically, allowing portfolio managers to spend their available risk budgets flexibly (taking duration, yield curve, and credit positions). The total risk of the portfolio is adjusted on a daily basis to produce positive total returns (or a total return above a prespecified minimum–return threshold).


Waste to energy conversion is the current tend in disposing municipal solid waste. This solve dual problem, one Is the effective disposal of solid waste with safe norms of pollution control board and another one is to generate substantial amount of power either in the form of thermal or electrical. Total disposal of solid waste in the villupuram district amounts to 150 TPD. As per the pollution control board there are five category of waste such as Municipal solid waste, Bio medical waste,E-waste,Hazourdous waste and plastic waste. In villupuram district the current practice of handling the municipal waste is to collect, dump and compost the waste to form it as manure. This is the time consuming process which will delay in disposal and wastes that are accumulated over period of time. This issue is taken forward by this project to have a communal based incinerator using gasification which is appended by the RDF (Refused derived fuel) production and effective Tar management. In addition to it bio degradable waste can be converted into natural fertilizer with the aid of the residual heat emanated. As per the guidelines of NITI Ayog and National Green tribunal, This project combines both suggestions. One is to decentralizing waste management and having separate compartment for the composting of degradable waste.


Grid portals are emerging as convenient mechanisms for providing the scientific community with familiar and simplified interfaces to the Grid. Our experience in implementing Grid portals has led to the creation of GridPort: a unique, layered software system for building Grid portals. This system has several unique features: the software is portable and runs on most Web servers; written in Perl/CGI, it is easy to support and modify; it is flexible and adaptable; it supports single login between multiple portals; and portals built with it may run across multiple sites and organizations. The feasibility of this portal system has been successfully demonstrated with the implementation of several application portals. We describe our experiences in building this system, including philosophy and design choices. We explain the toolkits we are building, and we demonstrate the benefits of this system with examples of several production portals. Finally, we discuss our experiences with Grid web service architectures.


Nocturnal vision is a demanding task for insects with small eyes. As it gets dimmer the noise imposed by the stochastic nature of photon arrival makes vision unreliable. Despite this, there are quite a number of animal species that are active at night and apparently see well. In this thesis I show that the compound eyes of nocturnal insects are sufficiently flexible to adapt to the particular window of intensities in which the species is active. These ommatidial adaptations for vision in nocturnal insects are found in the optics and morphology of the eye (Chapters I - III) and in the physiology of the photoreceptors (Chapters IV & V). I have also discovered that the various visual adaptations that optimise sensitivity in a compound eye, and thus adapt the eye for a crepuscular or nocturnal lifestyle, do not contribute equally in different groups of insects. The crepuscular Caligo memnon has evolved large eyes with large facets but retained a reasonably high spatial and temporal resolution. In the nocturnal bee Megalopta genalis, the eyes and facets are enlarged, the rhabdoms are wide and the spatial and temporal acuity very poor compared to diurnal insects. In addition to this, M. genalis has a high gain of transduction present in its photoreceptors. The nocturnal dung beetle Onitis aygulus has refracting superposition eyes and increases optical sensitivity by possessing a wide superposition aperture. In addition, this beetle has slow photoreceptors with high gain. Thus, there are a variety of solutions to improve visual sensitivity and reliability in dim light. Exactly which solution evolved in which group most likely depends on constraints imposed by different phylogenetic histories, developmental constraints and different selection pressures due to different life styles. (Less)


INTRODUCTION
Outcome-based curriculum is adopted at the International Medical University (IMU), Malaysia, where specific learning objectives are laid out progressively under eight major outcomes. We present an outcome-guided, self-reported competency profile of our undergraduate students near the end of their training, focusing on elements that are considered most immediately relevant for their internship.

METHODS
Anonymous surveys were conducted on two cohorts of medical students in their final semester at IMU. The surveys covered a range of competencies, including practical skills, ward routines, generic attributes and evidence-based medicine, grouped under the exit outcomes as defined by the university.

RESULTS
A total of 92 students were assessed. In general, the students were confident of their ability on common practical skills and ward routines. They were comfortable with the level of professionalism and personal attributes required for internship, with the prospect of handling unexpected additional tasks and working away from home perceived as the main difficulties. Most students referred to at least three sources of clinical information to answer their clinical queries. However, they referred more to single journals than databases or collections. The majority could critically appraise journal articles to a variable extent, but nearly half took 30 minutes or longer to trace an abstract of interest.

CONCLUSION
This report demonstrates the strength of outcome-based curriculum in its ability to produce competent students that are well prepared for their internship. Assessing students using this educational approach provides a clear picture of their strengths and weaknesses, and identifies stages in their training where additional inputs are required.


BACKGROUND
The United States is in the midst of an unprecedented opioid crisis with increasing injection drug use (IDU)-related human immunodeficiency virus (HIV) outbreaks, particularly in rural areas. The Health Resources and Services Administration (HRSA)'s Ryan White HIV/AIDS Program (RWHAP) is well positioned to integrate treatment for IDU-associated HIV infections with treatment for drug use disorders. These activities will be crucial for the "Ending the HIV Epidemic: A Plan for America" (EHE) initiative, in which 7 southern states were identified with rural HIV epidemics.

METHODS
The RWHAP Services Report data were used to assess the IDU population and substance use services utilization among RWHAP clients in 2017, nationally and in the 7 EHE-identified states. THe HRSA held a 1-day Technical Expert Panel (TEP) to explore how RWHAP can best respond to the growing opioid crisis.

RESULTS
During the TEP, 8 key themes emerged and 11 best practices were identified to address opioid use disorder (OUD) among people with HIV. In 2017, among RWHAP clients with reported age and transmission category, 6.7% (31 683) had HIV attributed to IDU; among IDU clients, 6.3% (1988) accessed substance use services.

CONCLUSIONS
The TEP results and RWHAP data were used to develop implementation science projects that focus on addressing OUD and integrating behavioral health in primary care. These activities are critical to ending the HIV epidemic.


A theory of superefficiency and adaptation is developed under flexible performance measures which give a multiresolution view of risk and bridge the gap between pointwise and global estimation. This theory provides a useful benchmark for the evaluation of spatially adaptive estimators and shows that the possible degree of superefficiency for minimax rate optimal estimators critically depends on the size of the neighborhood over which the risk is measured. Wavelet procedures are given which adapt rate optimally for given shrinking neighborhoods including the extreme cases of mean squared error at a point and mean integrated squared error over the whole interval. These adaptive procedures are based on a new wavelet block thresholding scheme which combines both the commonly used horizontal blocking of wavelet coefficients (at the same resolution level) and vertical blocking of coefficients (across different resolution levels).


The static and dynamic characteristics calculating of the whole machine structure by finite element method lead to dense grid nodes, which is not conducive to rapid quantitative analysis. Therefore, a simplified model and the corresponding static and dynamic characteristics are needed. This paper presents a simplified model using key nodes kept principle and a corresponding software which reads data from resulting data file, extracts information such as coordinates, static and dynamic displacement of relevant nodes from reading data and draws simplified models of the whole machine structure and static and dynamic deformation of it. Take XK173 Vertical Milling Machine as the case research object, establish a complete machine model, analyze the static and dynamic characteristics and reproduce that using simplified model by software. The result shows that the Vertical Milling Machine nodes are reduced from the original 153 238 nodes to156 nodes. It well preserves machine structure and static and dynamic characteristics, and lays foundations for simplifying follow-up quantitative analysis.


In this paper, we study the dynamics of a vector-borne disease model with two transmission paths: direct transmission through contact and indirect transmission through vector. The direct transmission is considered to be a non-monotone incidence function to describe the psychological effect of some severe diseases among the population when the number of infected hosts is large and/or the disease possesses high case fatality rate. The system has a disease-free equilibrium which is locally asymptomatically stable when the basic reproduction number (R0) is less than unity and may have up to four endemic equilibria. Analytical expression representing the epidemic growth rate is obtained for the system. Sensitivity of the two transmission pathways were compared with respect to the epidemic growth rate. We numerically find that the direct transmission coefficient is more sensitive than the indirect transmission coefficient with respect to R0 and the epidemic growth rate. Local stability of endemic equilibria is studied. Further, the global asymptotic stability of the endemic equilibrium is proved using Li and Muldowney geometric approach. The explicit condition for which the system undergoes backward bifurcation is obtained. The basic model also exhibits the hysteresis phenomenon which implies diseases will persist even when R0 < 1 although the system undergoes a forward bifurcation and this phenomenon is rarely observed in disease models. Consequently, our analysis suggests that the diseases with multiple transmission routes exhibit bi-stable dynamics. However, efficient application of temporary control in bi-stable regions will curb the disease to lower endemicity. In addition, increase in transmission heterogeneity will increase the chance of disease eradication.


The driving range of an electric vehicle depends on the vehicle weight, road load conditions, battery capacity, and battery performance. The battery rated capacity and its characteristics could be heavily affected by the ambient temperature. This paper investigates the effects of ambient temperature on the electric vehicle driving range, equivalent fuel economy, and performance. A production-type battery electric vehicle is modeled and simulated in the AVL-Cruise platform using semi-empirical data. The modeled vehicle battery pack consists of 20Ah Lithium-Nickel-Manganese-Cobalt-Oxide (LiNiMnCoO2) cells. The battery cell characteristics are experimentally measured to build the battery pack model. The simulated driving range and equivalent fuel economy are correlated with the published information as vehicle model validation. Series of simulations on driving cycles (UDDS, HWFET, US06, and WLTP) with across a broad range of ambient temperatures are conducted to investigate the quantified effects of ambient temperature on driving range, equivalent fuel economy, and vehicle performance. Simulation results show that driving range and fuel economy are much reduced to 70% at low ambient temperature. Driving range and fuel economy are almost not affected by high ambient temperature, such as 50 C, since this model does not include accessory load of thermal management. The vehicle performance is almost not affected by the ambient temperature.


BACKGROUND
Usually quality of life self-reports are standard and consider that all the areas evaluated are equally important.

AIM
To explore the influence of specific domains on the overall quality of life self-assessment.

MATERIAL AND METHODS
The brief version of the quality of life questionnaire developed by the World Health Organization (WHOQoL bref) was applied to 1229 participants aged 19 to 60 years (53% women). The questionnaire explores four domains: physical and psychological health, social relationships and environment. At the end of each domain a new question asking the participant to assess the importance of the domain, using a scale of 1 (not important) to 5 (very important), was added. The analysis of data considered the assessment of the importance of each domain made by participants. The weight of each domain was analyzed using regression equations.

RESULTS
The physical health had the best evaluation followed by the social domain. The environmental domain received the lower evaluation. Among women, social domain was the best evaluated domain and among men, the physical health domain. According to participants, physical and psychological health had the higher weight. The environmental domain had the higher weight on the overall assessment of quality of life.

CONCLUSIONS
According to participants, physical and psychological health are the most important aspects that influence overall quality of life.


The major goal of dynamic load balancing is not primarily to equalize the load on the nodes of a parallel computing system, but to optimize the average response time of single requests or the throughput of all applications in the system. Therefore it is often necessary not only to keep all processors busy and all processor ready queue lengths within the same range, but to avoid delays and inefficient computations caused by foreseeable but ignored data flow and precedence constraints between related tasks. We present concepts for dynamic consideration of inter task dependencies within small groups of tasks and evaluate them observing real applications in a load balancing environment on a network of workstations. The concepts are developed from scheduling of single task graphs towards heterogeneous multi user operation scenarios.<<ETX>>


INTRODUCTION
Role of dentists in prevention and sustainable care of leprosy is known. Changing leprosy scenario has led to requirement of change in leprosy education. However, knowledge and attitude of dental students on leprosy remains unknown.

AIM
Hence a study was conducted to assess knowledge and attitude of dental students about Leprosy.

MATERIALS AND METHODS
A questionnaire based, cross-sectional survey was conducted among 350 undergraduate and the postgraduate dental students of two dental colleges in Faridabad, India. The score for knowledge ranged from 0 to 16 and scores for attitude ranged from 0 to 26. These scores were further coded as poor, fair and good.

RESULTS
Mean knowledge score for the sample was 7.64±3.23. A total of 32.29% participants were under poor knowledge category; 57.42% had fair knowledge about Leprosy while 10.29% had good knowledge. Mean attitude score was 15.5 ± 5.98. A total of 30.57% had poor attitude scores, 42.57% had fair scores while 26.86% had good attitude scores. Univariate analysis showed year of training to be a significant predictor for knowledge level (t=7.12; p<0.001).

CONCLUSION
The results indicate need for three important changes towards Leprosy in Dentistry. These changes are need for incorporation of leprosy education in Dentistry, need for incorporation of problem based as well as evidence based learning in Dentistry integrated with general health and need for reestablishing public health programs for Leprosy utilizing dental workforce.


We present critical assembly reaction rate data, and modeling of the same using the recently released ENDF/B-VII library. While some of the experimental measurements were performed as long as 50 years ago, the results have not been widely used/available outside of Los Alamos. Over the years, a variety of target foils were fabricated and placed in differing neutron spectrum/fluence environments within critical assemblies. Neutron-induced reactions such as (n,γ), (n,2n), and (n,f) on these targets were measured, typically referenced to 235 U(n,f) or 239 Pu(n,f). Because the cross section for the latter reactions are now well known, these experiments provide a rich data set for testing evaluated cross sections. Due to the large variety of critical assemblies that were historically available at Los Alamos, it was possible to make measurements in spectral environments ranging from hard (Pu Jezebel, center of Pu Flattop) through intermediate (Big Ten) to degraded (reflector region of Flattop). This broad range of configurations allows us to test both the cross section magnitudes and their energy dependencies. We will present data, along with reaction rate predictions using primarily MCNP5 in conjunction with ENDF/B-VII, for a number of target nuclei, including iridium, isotopes of uranium (e.g., 233, 235, 237, 238), neptunium (237), plutonium (239), and americium (241).


We investigate the problem of static and spherically symmetric solutions in the Starobinsky gravity model. By extending the Lichnerowicz and Israel theorems, William Nelson has demonstrated that the Schwarzschild solution is the unique static, spherically symmetric and asymptotically flat black hole solution in the Starobinsky model. However, Hong Lü et al. find that there are sign errors in the proof of Nelson. This raises the problem of whether Nelson's proof is correct or not. In order to answer this question, we explore the corresponding solutions by using the Taylor series expansion method. We find that Nelson's conclusion is indeed correct despite the flaw in the proof.


doi:10.1111/ene.13006 Background and purpose: Several studies have reported associations between brain iron deposits (IDs), white matter hyperintensities (WMHs) and cognitive ability in older individuals. Whether the association between brain IDs and cognitive abilities in older people is mediated by or independent of total brain tissue damage represented by WMHs visible on structural magnetic resonance imaging (MRI) was examined. Methods: Data from 676 community-dwelling individuals from the Lothian Birth Cohort 1936, with Mini-Mental State Examination scores >24, who underwent detailed cognitive testing and multimodal brain MRI at mean age 72.7 years were analysed. Brain IDs were assessed automatically following manual editing. WMHs were assessed semi-automatically. Brain microbleeds were visually counted. Structural equation modelling was used to test for mediation. Results: Overall, 72.8% of the sample had IDs with a median total volume of 0.040 ml (i.e. 0.004% of the total brain volume). The total volume of IDs, significantly and negatively associated with general cognitive function (standardized b = 0.17, P < 0.01), was significantly and positively associated with WMH volume (std b = 0.13, P = 0.03). WMH volume had a significant negative association with general cognitive function, independent of IDs (std b = 0.13, P < 0.01). The association between cognition and IDs in the brain stem (and minimally the total brain iron load) was partially and significantly mediated by WMH volume (P = 0.03). Conclusions: The negative association between brain IDs and cognitive ability in the elderly is partially mediated by WMHs, with this mediation mainly arising from the iron deposition load in the brain stem. IDs might be an indicator of small vessel disease that predisposes to white matter damage, affecting the neuronal networks underlying higher cognitive functioning.


Value at risk is perhaps the most common measure of a portfolio's exposure to loss. The simplest way to estimate value at risk is to calculate it directly from the portfolio's expected return and standard deviation under the assumption that the portfolio's returns are lognormally distributed. If the component returns of the portfolio are themselves lognormally distributed, however, it is incorrect to assume that the portfolio's returns are also lognormal. For portfolios that include only long positions, this technically false assumption is a reasonably good approximation of the portfolios' theoretical return distribution. For portfolios that include short positions, though, the authors explain why the assumption of lognormality for the total portfolio can be seriously misleading. In many typical cases, value at risk is substantially greater than indicated by a lognormal distribution.


The Schott term is the third order term in the electromagnetic self force of a charged point particle. The self force may be obtained by integrating the electromagnetic stress-energy-momentum tensor over the side of a narrow hypertube enclosing a section of worldline. This calculation has been repeated many times using two different hypertubes known as the Dirac Tube and the Bhabha Tube, however in previous calculations using a Bhabha Tube the Schott term does not arise as a result of this integration. In order to regain the Lorentz-Abraham-Dirac equation many authors have added an ad hoc compensatory term to the non-electromagnetic contribution to the total momentum. In this article the Schott term is obtained by direct integration of the electromagnetic stress-energy-momentum tensor.


OBJECTIVE
To explore the relationship betweensleep/psychological distress and temporomandibular disorders (TMD) and to discuss the possibility of disturbed sleep and psychological distress as risk indicators in relation to TMD in a Chinese population.

METHODS
The standardized and validated self-reported Chinese version questionnaires including Pittsburgh sleep quality index (PSQI) and depression, anxietyandstress scales-21 (DASS-21) were used to measure sleep quality and psychological distress. A total of 755 TMD patients (172 males and 583 females)with a mean age (29.99 ± 13.60) years were included in the study. The patients were divided into 7 diagnostic groups based on the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD), including Group I(exclusively myofascial pain), Group II(exclusively disc displacement), Group III (exclusively arthralgia or degenerative joint disease), Group IV (myofascial pain plus disc displacement), Group V (myofascial pain plus arthralgia or degenerative joint disease), Group VI (disc displacement plus arthralgia or degenerative joint disease) and Group VII (myofascial pain plus disc displacement plus arthralgia or degenerative joint disease). For statistical analysis, the patients were subsequently grouped into those with (181 patients) and without (574 patients) myofascial pain. Chi-square tests, independent-samples t test, partial correlation as well as stepwise Logistic regression analysis were used to analyze the data, using software SPSS 20.0 and P<0.05 was of significance.

RESULTS
The prevalence of moderate to (extremely) severe disturbed sleep and psychological distress was significantly higher in the myofascial pain group (27.1%, 28.7%, 60.8% and 32.0%) than in the non-myofascial pain group (disc displacement and arthralgia or degenerative joint disease, 11.1%, 10.1%, 27.4% and 11.0%, P<0.05).The comorbidity of self-reported disturbed sleep and psychological distress was significantly higher in the myofascial pain patients than those without myofascial pain (P<0.05). Stepwise logistic regression analysis demonstrated that disturbed sleep (OR=1.74), more specifically, subjective sleep quality (OR=1.69) and sleep disturbance (OR=1.63) respectively, anxiety (OR=3.14) and stress (OR=2.15) were possible risk indicators for myofascial pain, and the results were still significant even after controlling for age, sex, educational level, disease duration, sleep quality, depression, anxiety and stress respectively (P<0.05).

CONCLUSION
Disturbed sleep and psychological distress symptoms are common in TMD patients. Disturbed sleep, anxiety and stress are possible risk indicators for myofascial pain, compared with disc displacement and arthralgia or degenerative joint diseases.


Abstract We address the accurate single arm robotic garment folding. The folding capability is influenced mostly by the folding path which is performed by the robotic arm. This paper presents a new method for the folding path generation based on the static equilibrium of forces. The existing approach based on a similar principle confirmed to be accurate for one-dimensional strips only. We generalize the method to two-dimensional shapes by modeling the garment as an elastic shell. The path generated by our method prevents the garment from slipping while folding on a low friction surface. We demonstrate the accuracy of this approach by comparing our paths (a) with the existing method when one-dimensional strips of different materials were modeled, and (b) experimentally with real robotic folding. Graphical Abstract The paper proposes a robotic garment folding path generation procedure. It uses the garment model represented by a thin shell. The path computation seeks states satisfying a static equilibrium condition.


State construction is messy and complex, brimming with contradictions, fraught with conflict and unpredictability. This article identifies a few hurdles likely to be encountered in the simultaneous making and walking of this road. In order to do so, it examines the structure and behaviour of the state, the concept of political settlements, and the "good governance" agenda. The article outlines some implications for public policy that relate to issues of governance, and explores the possibility of working with clientelism and patronage as enablers and contributors to growth, rather than seeing them as pathologies that need to be "corrected" by administrative reforms. Successful delivery of socially inclusive and empowering developmental programmes and projects in the proposed framework hinges on the comprehension and negotiation of social change and transformation in novel and realistic ways.


An increasing number of universities offer user-centric innovation courses based on the principles of design thinking. Lecturers combine a plethora of design thinking elements in design thinking course syllabi and thereby adopt teaching
styles that range from autonomy-supportive to structured. Using a balance between these two teaching styles seems most suitable to optimally engage students and provide guidance through the innovation process. To develop a syllabus for innovation courses, we draw on best practices currently being undertaken in universities worldwide and examine 11 design thinking syllabi from different departments (Engineering, Design, Business, and Information Systems). We identify 17 common and 18 unique elements of design thinking courses and related course materials. Based on our results, we propose a design thinking syllabus that includes suggestions for course objectives, course setup, assignment
design, and team composition using a balance between autonomous-support and structural teaching styles.


There is increasing recognition in Europe that targeted services for the severely mentally ill, such as those developed in North America, may have a place within local sectorised services. Three high quality community support services were visited in Madison, Chicago and New Hampshire. All three services showed considerable similarity of organisation and work practices, with an emphasis upon continuity of care and an assertive style of case management. Substantial differences from U.K. practice and staffing patterns were evident. The clinical activities of Case Managers are described and the network of district services in which CSPs are embedded is outlined. Implications for integrating CSP-type programmes into British Mental Health Services are discussed.


ABSTRACT The Ebola virus VP35 protein was previously found to act as an interferon (IFN) antagonist which could complement growth of influenza delNS1 virus, a mutant influenza virus lacking the influenza virus IFN antagonist protein, NS1. The Ebola virus VP35 could also prevent the virus- or double-stranded RNA-mediated transcriptional activation of both the beta IFN (IFN-β) promoter and the IFN-stimulated ISG54 promoter (C. Basler et al., Proc. Natl. Acad. Sci. USA 97:12289-12294, 2000). We now show that VP35 inhibits virus infection-induced transcriptional activation of IFN regulatory factor 3 (IRF-3)-responsive mammalian promoters and that VP35 does not block signaling from the IFN-α/β receptor. The ability of VP35 to inhibit this virus-induced transcription correlates with its ability to block activation of IRF-3, a cellular transcription factor of central importance in initiating the host cell IFN response. We demonstrate that VP35 blocks the Sendai virus-induced activation of two promoters which can be directly activated by IRF-3, namely, the ISG54 promoter and the ISG56 promoter. Further, expression of VP35 prevents the IRF-3-dependent activation of the IFN-α4 promoter in response to viral infection. The inhibition of IRF-3 appears to occur through an inhibition of IRF-3 phosphorylation. VP35 blocks virus-induced IRF-3 phosphorylation and subsequent IRF-3 dimerization and nuclear translocation. Consistent with these observations, Ebola virus infection of Vero cells activated neither transcription from the ISG54 promoter nor nuclear accumulation of IRF-3. These data suggest that in Ebola virus-infected cells, VP35 inhibits the induction of antiviral genes, including the IFN-β gene, by blocking IRF-3 activation.


Theoretical ambiguities in curriculum studies result in conceptual mayhem. Accordingly, they hinder the development of the complicated conversation on curriculum as a verb. This article aims to contribute to reconceptualizing curriculum studies as a dynamic social practice that aspires to thinking and acting with intelligences and sensitivity so as to understand oneself and others. It also raises awareness that equating all forms of research on curriculum with curriculum studies dilutes the scope of the conversation. This exploration asks two key questions: What is the nature of doctoral theses in the field of education's theoretical contributions to nuances of curriculum (curriculum, curriculum development, and curriculum studies)? In what ways do these theses perpetuate or even add to current ambiguities in the discipline of curriculum studies? The exploration of these two questions draws on a critical meta-study of 511 theses completed in South African universities (2005–2012) conducted using a three level process. It appears that the main detractions of these theses are that some of them see curriculum studies as a dumping ground and others make no  theoretical contribution to the discipline. The article concludes by suggesting ways which would encourage the intellectual advancement of curriculum studies through rigorous disciplinarity. Keywords : curriculum; curriculum development; curriculum studies; doctoral theses; meta-analysis; meta-synthesis; meta-study


Control and flexibility may appear an unlikely pair. However, we propose that effective flexible software development processes must still provide clear control mechanisms to manage the progress and quality of the resulting software products. This paper presents our initial research to understand the types of control found in flexible software development processes. Control theory is used as a lens to study the control mechanisms found in plan-driven and flexible processes. We extend current thinking to include emergent outcome controls and clan controls for team coordination in our taxonomy of control mechanisms. Several popular flexible processes are analyzed for control mechanisms. We conclude with a brief discussion of our future research directions.


The principles of internal territorial and administrative division are a staple of Russia's statehood. The paper deals with the analysis of changes made to the territorial and administrative divisions of Northwest Russia over the Soviet period (1917-1991), mainly in upper-level units (gubernia, oblast, krai, and republic), and partly at the medium level, such as ouezd and okrug. The analysis presented here is heavily based on cartographic materials. The paper gives an overview of the large-scale administrative reforms of the Soviet period and determines the periods of stability and instability of administrative boundaries within the current territory of Northwest Russia. According to the analysis of the alterations in territorial and administrative divisions made during the Soviet period, within three decades after the 1927 enlargement reform the network of the upper-level units began to mirror those of pre-revolutionary time. Since 1957, the system of territorial and administrative divisions has been relatively balanced, with no significant changes made to it up to the present day. The results of this research will be used to construct the models of historical periodization and changes in the geography of Northwest Russia. Keywords: territorial and administrative units, Soviet period, Northwest Russia JEL Classifications: N9; P2; R00


The normal functions of genomes depend on the precise expression of messenger RNAs and noncoding RNAs (ncRNAs) such as transfer RNAs and microRNAs in eukaryotes. These ncRNAs and functional RNA structures (FRSs) act as regulators or response elements for cellular factors and participate in transcription, posttranscriptional processing, and translation. Knowledge discovery of these FRSs in huge DNA/RNA sequence databases is a very important step to reach our goal of going from genomic sequence data to biological knowledge for understanding RNA‐based regulation. Analyses of a large number of FRSs have indicated that the FRS can be well characterized by some quantitative measures such as significance and well‐ordered scores of the local segment. Various data mining tools have been developed and successfully applied to FRS discovery in genomic sequence databases. Here, we summarize our efforts in the computational discovery of structured features of ncRNAs and FRSs within complex genomes by EDscan and SigED. © 2011 John Wiley & Sons, Inc. WIREs Data Mining Knowl Discov 2011 1 88–95 DOI: 10.1002/widm.13


This paper proposes the application of unsymmetric multifrontal method to solve the differential algebraic equations (DAE) encountered in the power system dynamic simulation. The proposed method achieves great computational efficiency as compared to the conventional Gaussian elimination methods and other linear sparse solvers due to the inherent parallel hierarchy present in the multifrontal methods. Multifrontal methods transform or reorganize the task of factorizing a large sparse matrix into a sequence of partial factorization of smaller dense frontal matrices which utilize the efficient Basic linear algebra subprograms 3 (BLAS 3) for dense matrix kernels. The proposed method is compared with the full Gaussian elimination methods and other direct sparse solvers on test systems and the results are reported.


The production of clean water, the generation of nuclear power and the development of chemicals, petro-chemicals and pharmaceuticals all rely on liquid-based processes. They are fundamental to modern society, however the real-time monitoring of such processes is an inherently difficult challenge which has not yet been satisfactorily solved.Current methods of monitoring include on- and off-line spot checks and industrial process tomography. Neither of these methods provides the spatial or temporal resolution required to properly characterise the processes. This research project proposes a new monitoring method for processes which can tolerate foreign objects; a mobile underwater sensor network (MUSN).An MUSN has the potential to increase both the spatial and temporal resolution of measurements and could be used in real-time. The network would be formed by a number of mobile sensor platforms, in the form of micro-autonomous underwater vehicles (uAUVs) which would communicate using acoustics. The demonstrator for the technology is for use in the monitoring of nuclear storage ponds.Current AUV technology is not suitable for use in enclosed environments such as storage ponds due to the size and maneuverability. This thesis presents the research conducted in the development of a new vehicle uAUV. The work presented covers the mechatronic aspects of the vehicle; the design of the hull, propulsion systems, corresponding control circuitry and basic motion control systems. One of the main factors influencing the design of the vehicle has been cost. If a large number of vehicles are used to form a network, the cost of an individual uAUV should be kept as low as possible. This has raised a number of technical challenges as low-cost components are often of low-tolerance. Imbalanced time-varying thrust, low manufacturing tolerances and noisy indirect sensor measurements for the control systems have all been overcome in the design of the vehicle.The outcome of the research is a fully functional prototype uAUV. The vehicle is spherical in shape with a diameter of approximately 15cm, with six thruster units mounted around the equator (increasing the horizontal clearance to 20cm) to provide thrust in four degrees of freedom (surge, sway, heave and yaw). The vehicle has a sensor suite which includes a pressure sensor, digital compass and a gyroscope which provide inputs to the motion control systems. The controllers have been developed and implemented on the vehicle's custom built embedded system. Experiments have been conducted showing that the uAUV is able to move in 3D with closed-loop control in heave and yaw. Motion in surge and sway is open-loop, via a dead-reckoning system.


In this work, the effects of alumina additions on the properties of the ZrO2-Al2O3 ceramic composites were investigated. Samples of ZrO2 with Al2O3 additions varying between 0 and 30wt-% were prepared. The powder mixtures were milled, compacted by uniaxial cold pressing and sintered at 16000C, in air, for 2 hours. The sintered samples were characterized by their relative density, phase composition and microstructure. As mechanical properties at room temperature, their Vickers hardness and fracture toughness were determined: In all sintering conditions and Al2O3 amounts, the samples presented relative density higher that 99%. The Al2O3 addition produces a linear increase of the hardness, reaching values between 1350 and 1610 HV for the addition of 0 and 30% of alumina, respectively. The fracture toughness was near to 8 MPam1/2 in all conditions. The phase composition, microstructure and relative density were correlated in order to interpret the mechanical properties obtained.


Objective: To determine the prevalence of infantile hearing loss in a population of 0-5 years old treated in the Instituto Colombiano de Bienestar Familiar (Colombian Family Welfare Institute). Materials and Methods: Descriptive study, with correlational multivariate analysis in 300 children. A socio-demographic, environmental, home, and parental characterization was made as well as the one of the pre-natal and peri-natal child's background, and signals of factors related to audiological problems. The children were examined clinically and transient evoked otoacoustic emissions and brain-stem auditory evoked potentials were systematically performed. Children with abnormal tests were reevaluated by audiology and those with persistent abnormalities were evaluated by an otolaryngologist and a Clinical Neurophysiologist. Results: Prevalence of childhood hearing loss was 6.3% after the first evaluation, and 2.3% after the second: all of them with conductive hearing loss, in which two cases were mild, and five moderate hearing loss. The causes of hearing loss were: in four cases tonsillar hypertrophy and/or dysfunction of the Eustachian tube; otitis media and/or rhinoacute sinusitis with effusion were detected in two children; and adhesive otitis media with tympanic membrane perforation in one child. Conclusions: The most predictive factors for infant hearing loss in the studied population were environmental, including proximity to roads, exposure to industrial noise, landfills, and exposure to smoke. Logistic regression analysis yielded statistical significance only for factors in relation with audiological problems . Prevalence of childhood hearing loss is similar to the one described in developed countries in North America and Europe. All the identified disorders were the cause of conductive hearing loss.


Scour is the lowering of the sea or river-bed as a result of non-equilibrium sediment transport conditions and can be divided into several categories (Breusers and Raudkivi, 1991). Local scour, which may occur at the base of a structure because of the affected flow pattern, can severely endanger the stability of this structure. Many varieties of localscour systems downstream from hydraulic structures exist, each with its own particular geometry and hence local scour mechanism. Local scour is superimposed on general and constriction scour. The prediction of local-scour holes that develop downstream from hydraulic structures plays an important role in their design. Excessive local scour can progressively undermine the foundation of a structure. Because complete protection against scour is too expensive generally, the maximum scour depth and the upstream slope of the scour hole have to be predicted to minimize the risk of failure. In 1961 a systematical research with respect to scour holes started at Delft Hydraulics within the scope of the Dutch Delta works. After the catastrophic flood disaster in 1953 the Delta plan was made to protect the Rhine-Meuse-Scheldt delta for future disasters. Dams with large scale sluices were planned in some estuaries. The severe scour expected necessitated a better understanding of the scour process. To find detailed information about the physical processes playing a role in scour many experiments were carried out, in which various parameters of the f l ow and the scoured material were varied. From the results of experiments in flumes with all difficulties of scale effects and limitations in instrumentation some empirical relations were obtained, which describe the erosion process as function of time and place (Prins, 1963 and Breusers, 1966, 1967). In these empirical relations a not well defined turbulence coefficient was introduced. Up to now this coefficient was related to the geometry upstream of the scour hole, which relation was based on trial and error. Based on theoretical grounds an analytical relation for the depth-averaged turbulence intensity is derived. This relation, which implies a modification of the turbulence coefficient in the Breusers scour formula, is verified using approximately 300 experiments. The modified scour formula yields results that compare reasonably well to measured and computed developments of a scour hole in case of a uniform flow upstream of the scour hole corresponding with a large protected bed area. The computations were based on the two-dimensional Navier-Stokes and convection-diffusion equations (Hoffmans, 1992) . The present paper aims at extension of the domain of application of the scour formula to non-uniform flow conditions upstream.


Increased openness is seen by some as a panacea for development while for others it is a recipe for disaster for the poor. Using the example of Ethiopia, this paper discusses some of the key challenges faced by some of the poorest African countries in beneficially engaging in the world economy. Worldwide income growth has largely bypassed many African countries, and substantial parts of their populations risk increasing marginalization. This paper documents the challenges faced by one of these countries, Ethiopia, first by highlighting the impact of a first wave of liberalization in the early 1990s, using the evidence from a rural panel dataset. It was found that while liberalization had some positive effects in this particular period, the benefits were largely confined to households with good assets, not least in terms of geography and road infrastructure. Analysis of the subsequent years shows that access to infrastructure seems to have been causing even further growth and poverty divergence within rural Ethiopia. This evidence suggests that access to better infrastructure and communications is crucial to allow households to benefit from further liberalization and engagement with the world economy. Those without good local infrastructure are unlikely to benefit. Finally, some evidence is presented showing that liberalization has shifted the nature of risks faced by households towards a higher incidence of market related risks, such as sudden output price collapses or input price increases. While it is not possible to infer from this that vulnerability to poverty has necessarily increased, one would need to recognize that these shifts in risk require different responses from households themselves and from policymakers.


This paper aims to describe why we need to change the health care record paradigm that is currently accepted. The paper goes on to describe the new paradigm of a goal oriented health record (GOHR) and the relevance of computerization.


Abstract Several recent studies have suggested that antitaxial fibrous veins may form without fracturing, and not by the commonly invoked crack-seal mechanism. It has also been suggested that such veins would derive their nutrients locally by diffusional transport. This hypothesis was tested on carbonaceous shale-hosted antitaxial fibrous calcite veins from Oppaminda Creek in the northern Flinders Ranges, South Australia. Apart from their fibrous texture, these veins lack the classical features of crack-seal veins, such as wallrock-parallel inclusion bands. Diffusional transport of locally derived calcite cannot explain all major and trace element data of the veins and their adjacent wallrock and indicate that part of the calcite was transported over distances of at least >decimetres, probably ≫100m. Sr isotopic fingerprinting shows that an external fluid that carried radiogenic Sr must have percolated through the system. Fluid flow was pervasive as there is no evidence that this fluid preferentially percolated through the veins. Our data support the view that antitaxial fibrous veins of the type found at Oppaminda Creek grew in the absence of fractures, but show that such veins do not necessarily indicate local diffusional transport. Our data confirm a recently postulated basin-wide fluid flow event around 586 Ma that is probably related to copper mineralization in the area.


BACKGROUND: In recent years, there has been increasing contact between human beings that live in urban regions and the wild environment due to a series of activities. As a result, some poorly known dermatitis may present in private and dermatological clinics, especially early in the week and at the end of vacation periods. OBJECTIVES: To obtain and provide information for dermatologists on the problem. PATIENTS AND METHODS: The author observed adult and pediatric patients with acute dermatitis associated with plants or animals in Ubatuba, coastal city of Sao Paulo for 2 months (June / July 2006) and Medical School of Botucatu (June / July 2007). RESULTS: We observed 25 patients in the rural area and 43 in the coastal environment. In rural areas, the most common dermatitis were phytophotodermatitis and the stings of insects and in coastal areas, sea urchin injuries and phytophotodermatitis, but in both areas there were some other accidents that were difficult to identify by regular daily practice. CONCLUSION: We should be alert to the fact that patients seek a dermatologist after the acute phase of injuries. Information on the most common diseases and their characteristics can be very useful to practice in ermatologic clinics. The author suggests an algorithm to support diagnosis.


This paper investigates whether cannabis use leads to worse mental health. To do so, we account for common unobserved factors affecting mental health and cannabis consumption by modeling mental health jointly with the dynamics of cannabis use. Our main finding is that using cannabis increases the likelihood of mental health problems, with current use having a larger effect than past use. The estimates suggest a dose response relationship between the frequency of recent cannabis use and the probability of currently experiencing a mental health problem.


High speed milling cutter is a representative cutter for high efficiency cutting, there is the indeterminacy induced by small sample and lacking information in evaluating its performance. By the analysis of cutter characteristics, acquires the data of structure, material and cutting parameter affecting the performance of cutter, and constructs structural levels model of performance behavior in designing cutter. Using the theory of axiomatic design, investigates mapping approach among structural domain, material domain and functional domain, and propounds collaborative design method of multilevel high speed milling cutter. Results of performance analysis and high speed milling experiment show that the model indicates the interaction among structural levels of cutter, and the design method makes the performance of cutter satisfy the requirements of safety, stability and high efficiency cutting.


In this paper I discuss the potential role and utility of photographs in exploring the aesthetic dimension of processes of organizing. Beginning with a review of the growing significance within organization and management studies literature of the so-called 'non-rational' elements of human-being at work, I question why these issues appear to have become subjects worthy of specific scholarly attention at the turn of the century (Williams 2001). Within this discussion, I recognise the embodied nature of organization and make links between some of the characteristics of contemporary (Western) consumer culture, and aesthetics – with particular emphasis on the context of work and organizations. Following from this, I move to consider how it might be possible to gather data about these phenomena in an organizational setting. The limitations of language as a medium of articulating aesthetic experience due to the sensory nature of these phenomena are examined as a condition which undermines the efficacy of traditional text-based research methods and I argue that these issues necessitate the employment of a more 'sensually complete' methodology – introducing the idea of photography as one step towards this end. In order to discuss the epistemological and methodological implications of this approach, I reflect on my experiences during an ethnographic study of the web-site design department of a global IT firm to suggest that photographs taken by the respondents of their work environment helped them to express the largely ineffable aesthetic experiences that resulted from the relationships they had with their physical surroundings. The photographs were used by the respondents in this research as a means of communicating their aesthetic experience during semi-structured interviews where the images served both as an 'aesthetic lens' through which to explore my research questions and as foci for discussion and reflection about those questions. Some of these photographs are displayed in this paper, juxtaposed with my narrative accounts to create what Mitchell (1994) has called an image-text. This rests on the assumption that written texts and images have relative merits as modes of dissemination in their own right, with neither taking precedence over the other in terms of authority, or claim to 'truth'. As part of this discussion I problematize some assumptions about the capacity of images to serve as realist representations, arguing instead that photographic images are partial, selected and subjective interpretations of one reality wholly dependent on the photographers 'visual culture' (Pink 2001). In concluding, I briefly mention some of the practical and ethical issues surrounding the use of a camera and the taking of photographs in the research arena.


Efficacy of minipress in patients with hypertension stage II and its haemodynamic effects were studied after a single administration and during a course of treatment. It is shown that its main mechanism is in vasodilatation caused by relaxation of the muscular component of arterioles. The authors suggest that minipress can produce redistribution of the blood through peripheral venoconstriction. Decrease of the index of the external work of the heart points indirectly to decreased oxygen utilization by the myocardium which may reflect changes in haemodynamics under the influence of minipress or through direct action of the drug on the heart. Hypotensive effect of minipress is recorded already by the 5th day of its administration (p less than 0.001), however, its further effect is unstable. Increase of the circadian dose becomes necessary and also its combined use with thiazide diuretics. Positive chronotropic effect of Minipress has been recorded, with maximum towards the end of the 2nd week of treatment and seen as increased rate of cardiac contractions by 13.2% (p less than 0.01). To decrease this effect authors advise to use minipress in combination with beta-adrenoblockers.


This plant profile for Eriogonum fasciculatum provides information on species distribution; taxonomic relationships; ecological and evolutionary considerations for restoration; growth form and distinguishing traits; habitat characteristics; projected future suitable habitat; growth, reproduction and dispersal; biological interactions; ecological genetics; seed characteristics, germination requirements and processing; and plant uses including agriculture, restoration, and traditional products, plus an extensive bibliography. It is part of Riverside-Corona Resource Conservation District's resource materials collection on native plant recommendations for southern California ecoregions.


Deep learning systems have been successfully applied to Euclidean data such as images, video, and audio. In many applications, however, information and their relationships are better expressed with graphs. Graph Convolutional Networks (GCNs) appear to be a promising approach to efficiently learn from graph data structures, having shown advantages in many critical applications. As with other deep learning modalities, hardware acceleration is critical. The challenge is that real-world graphs are often extremely large and unbalanced; this poses significant performance demands and design challenges.In this paper, we propose Autotuning-Workload-Balancing GCN (AWB-GCN) to accelerate GCN inference. To address the issue of workload imbalance in processing real-world graphs, three hardware-based autotuning techniques are proposed: dynamic distribution smoothing, remote switching, and row remapping. In particular, AWB-GCN continuously monitors the sparse graph pattern, dynamically adjusts the workload distribution among a large number of processing elements (up to 4K PEs), and, after converging, reuses the ideal configuration. Evaluation is performed using an Intel D5005 FPGA with five commonly-used datasets. Results show that 4K-PE AWB-GCN can significantly elevate PE utilization by 7.7× on average and demonstrate considerable performance speedups over CPUs (3255×), GPUs (80.3×), and a prior GCN accelerator (5.1×).


The rise velocity of Taylor bubbles in small diameter bubble column was measured via cross-correlation between two planes of time-averaged void fraction data obtained from the electrical capacitance tomography (ECT). This was subsequently compared with the rise velocity obtained from the high-speed camera, manual time series analysis and likewise empirical models. The inertia, viscous and gravitational forces were identified as forces, which could influence the rise velocity. Fluid flow analysis was carried out using slug Reynolds number, Froude number and inverse dimensionless viscosity, which are important dimensionless parameters influencing the rise velocity of Taylor bubbles in different liquid viscosities, with the parameters being functions of the fluid properties and column diameter. It was found that the Froude number decreases with an increase in viscosity with a variation in flow as superficial gas velocity increases with reduction in rise velocity. A dominant effect of viscous and gravitational forces over inertia forces was obtained, which showed an agreement with Stokes law, where drag force is directly proportional to viscosity. Hence, the drag force increases as viscosity increases (5 < 100 < 1000 < 5000 mPa s), leading to a decrease in the rise velocity of Taylor bubbles. It was concluded that the rise velocity of Taylor bubbles decreases with an increase in liquid viscosity and, on the other hand, increases with an increase in superficial gas velocity.


Methodical approaches for studying the vertical vestibuloocular reflexes (VVOR) have been proposed. Eye movements were recorded by the electronystagmography: vertical movements of each ball of the eye was separately recorded and horizontal movements--in combination. Stimulation of the semicircular canals was performed by active movements of the head in the saggital plane with a frequency of 0.04 Hz (stimulus 1), 0.12 Hz (stimulus 2) and 0.24 Hz (stimulus 3). The VVORs have been recorded with the eyes closed (Program I) and with fixing the visual object on the eyes (Program II). Then, there has been recorded a vertical component of the horizontal vestibulovertical reflexes which evoked by active turn of the head around vertical axis of the body with the eyes closed (Program III) and fixation with the eyes of visual object (Program IV). The elaborated methods enable one to record steadily the VVOR in the all categories of test-subjects. As the VVOR indices there accepted the coefficient of reactivity, phase displacement; coefficients of asymmetry allowing one to compare the intensity of eye movements directed upwards and downwards; to reveal intraocular asymmetry.


The abundance of potential denitrifiers in full-scale wastewater treatment plants with biological nitrogen and phosphorus removal was investigated by FISH and various oligonucleotide probes. The potential denitrifiers were characterized as probe-defined populations that were able to consume radiolabelled substrate with oxygen, nitrate and nitrite as electron acceptor as determined by microautoradiography. The most abundant potential denitrifiers were related to the genera Aquaspirillum, Azoarcus, Thauera and Rhodocyclus, all within the Betaproteobacteria. They made up 20–49% of all bacteria in most of the 17 nitrogen removal plants investigated and were hardly present in four plants without denitrification. The ecophysiology of Aquaspirillum, Azoarcus and Thauera-related bacteria was consistent within each probe-defined group in the plants investigated. These three groups showed distinct physiological differences, with the Aquaspirillum-related bacteria appearing as the most specialized one, consuming only amino acids among the substrates tested, and Thauera as the most versatile consuming some volatile fatty acids, ethanol and amino acids. The coexistence of Aquaspirillum, Azoarcus and Thauera-related bacteria in a range of treatment plants with differences in wastewater, design and operation suggest that the populations ensure a functional stability of the plants by occupying different ecological niches related to the carbon transformation.


(NOTE: Most chapters conclude with a System Applications section.) 1. Semiconductor Basics. Atomic Structures. Semiconductors, Conductors, and Insulators. Covalent Bonds. Conduction in Semiconductors. N-Type and P-Type Semiconductors. The Diode. Biasing the Diode. Voltage-Current Characteristic of a Diode. Diode Models. Testing a Diode. 2. Diode Applications. Half-Wave Rectifiers. Full-Wave Rectifiers. Power Supply Filters and Regulators. Diode Limiting and Clamping Circuits. Voltage Multipliers. The Diode Data Sheet. Troubleshooting. 3. Special-Purpose Diodes. Zener Diodes. Zener Diode Applications. Varactor Diodes. Optical Diodes. Other Types of Diodes. Troubleshooting. 4. Bipolar Junction Transistors (BJTs). Transistor Structure. Basic Transistor Operation. Transistor Characteristics and Parameters. The Transistor as an Amplifier. The Transistor as a Switch. Transistor Packages and Terminal Identification. Troubleshooting. 5. Transistor Bias Circuits. The DC Operating Point. Transistor Packages and Terminal Identification. Troubleshooting. 6. BJT Amplifiers. Amplifier Operation. Transistor AC Equivalent Circuits. The Common-Emitter Amplifier. The Common-Collector Amplifier. The Common-Base Amplifiers. Multistage Amplifiers. The Differential Amplifier. Troubleshooting. 7. Field-Effect Transistors (FETs). The JFET. JFET Characteristics and Parameters. JFET Biasing. The MOSFET. MOSFET Characteristics and Parameters. MOSFET Biasing. Troubleshooting. 8. FET Amplifiers. FET Amplification. Common-Source Amplifiers. Common-Drain Amplifiers. Common-Gate Amplifiers. Troubleshooting. 9. Power Amplifiers. Class A Power Amplifiers. Class B and Class AB Push-Pull Amplifiers. Class C Amplifiers. Troubleshooting. 10. Amplifier Frequency Response. Basic Concepts. The Decibel. Low-Frequency Amplifier Response. High-Frequency Amplifier Response. Total Amplifier Frequency Response. Frequency Response of Multistage Amplifiers. Frequency Response Measurement. 11. Thyristors and Other Devices. The Basic 4-Layer Device. The Silicon-Controlled Rectifier (SCR). SCR Applications. The Diac and Triac. The Silicon-Controlled Switch (SCS). The Unijunction Transistor (UJT). The Programmable Unijunction Transistor (PUT). The IGBT. The Phototransistor. The Light-Activated SCR (LASCR). Optical Couplers. Fiber Optics. 12. The Operational Amplifier. Introduction to Operational Amplifiers. Op-Amp Input Modes and Parameters. Negative Feedback. Op-Amps with Negative Feedback. Effects of Negative Feedback on Op-Amp Impedances. Bias Current and Offset Voltage Compensation. Open-Loop Response. Closed-Loop Response. Troubleshooting. 13. Basic Op-Amp Circuits. Comparators. Summing Amplifiers. Integrators and Differentiators. Troubleshooting. 14. Special-Purpose Op-Amp Circuits. Instrumentation Amplifiers. Isolation Amplifiers. Operational Transconductance Amplifiers (OTAs). Log and Antilog Amplifiers. Converters and Other Op-Amp Circuits. 15. Active Filters. Basic Filter Reponses. Filter Response Characteristics. Active Low-Pass Filters. Active High-Pass Filters. Active Band-Pass Filters. Active Band-Stop Filters. Filter Response Measurements. 16. Oscillators. The Oscillator. Feedback Oscillator Principles. Oscillators with RC Feedback Circuits. Oscillators with LC Feedback Circuits. Relaxation Oscillators. The 555 Timer as an Oscillator. 17. Communications Circuits. Basic Receivers. The Linear Multiplier. Amplitude Modulation. The Mixer. AM Demodulation. IF and Audio Amplifiers. Frequency Modulation. The Phase-Locked Loop (PLL). 18. Voltage Regulators. Voltage Regulation. Basic Series Regulators. Basic Shunt Regulators. Basic Switching Regulators. Integrated Circuit Voltage Regulators. Applications of IC Voltage Regulators. 19. Programmable Analog Arrays. The Field-Programmable Analog Array (FPAA). Switched-Capacitor Circuits. A Specific FPAA. FPAA Programming. Appendix A: Table of Standard Resistor Values. Appendix B: Derivations of Selected Equations. Answers to Odd-Numbered Problems. Glossary. Index.


Abstract Background Ten percent of adult, outpatient visits result in an antibiotic prescription (Rx). At the start of our intervention, our VA healthcare system consisted of 13 community-based outpatient clinics (CBOCs), 9 of which did not have an onsite pharmacy but utilized automated dispensing cabinets (ADCs) for prepackaged outpatient Rxs. ADC antibiotic orders are generated from electronic medical record (EMR) order sets. The stewardship team shortened the durations of 5 antibiotics in the ADC order sets to make them consistent with current literature and guidelines. We assessed the impact of these changes on antibiotic prescribing habits. Methods We compared outpatient antibiotic Rx data between 10/1/2018-9/30/2019 (pre-intervention) and 10/1/19-9/30/20 (post-intervention) from 8 CBOCs with ADCs (1 closed during the pandemic). Amoxicillin-clavulanate 875/125mg (AMC), cephalexin 500mg (CPH), levofloxacin 500mg and 750mg (LEV 500 and LEV 750), and sulfamethoxazole-trimethoprim 800/160mg (SXT) prescription durations were all reduced by 3 days. Process metrics included days supplied/1000 prescriptions (DS/1000 Rx), median DS, and ADC utilization rates. We used Mann-Whitney U and correlation statistical analyses to assess differences and associations. Results The DS/1000 Rx of antibiotics with a default duration change decreased in the post-intervention phase for CBOCs with ADCs (AMC, -25.4%; CPH, -21.1%; LEV 500, -18.9%; LEV 750, -28.0%; SXT, -27.4%). The median DS for these antibiotics all reduced by 3 days in concordance with new ADC prescriptions defaults (AMC, 10 vs 7 days, P< 0.001; CPH, 10 vs 7 days, P< 0.001; LEV 500, 8 vs 5 days, P< 0.001; LEV 750, 8 vs 5 days, P< 0.001; SXT 10 vs 7 days, P< 0.001). Due to COVID-19, 7/8 ADC CBOCs closed for in-person visits from 3/20/20-5/4/20. ADC utilization was inversely proportional to DS/1000 Rx for most antibiotics (R: -0.51 to -0.77) except SXT. Conclusion EMR-driven reductions in ADC default Rx durations led to a corresponding decrease in overall outpatient antibiotic prescribing. Higher DS/1000 Rx were often associated with lower ADC utilization. Informatics-driven antibiotic interventions may be potential outpatient stewardship tools to increase guideline-concordant prescribing across multisite healthcare systems. Disclosures Sharanie Sims, PharmD, AbbVie (formerly Allergan) (Speaker's Bureau)


This study proposes a new method for estimating the parameters of a radar rain rate estimator, particularly of the dual-pol radar. The proposed method is similar to the probability matching method (PMM), except for being based on truncated data pairs. A truncation value is introduced to the log-transformed data in order to remove those in the low rain rate zone as well as to introduce Gaussian distribution. The parameters are then estimated by comparing the first- and second-order moments. The proposed method is applied to a total of six rainfall events observed by the Beaslesan Radar in Korea from 2014 to 2017. Summarizing the results, first, the truncation value should be applied to the horizontal reflectivity (dBZh) data. In this case only, the other two data, the rain rate (dBR) and the differential reflectivity (dBZdr), follow the Gaussian distribution well. It is also important to consider rather severe rainfall events for the parameter estimation. The parameters for only the severe rainfall events are all estimated rather reasonably. On the other hand, for the other moderate and light rainfall events, the parameters are estimated as being rather far from their normal ranges. This is mainly due to the relatively small variance of dBR compared to that of dBZh. That is, the variance of dBR is found to be greatly dependent on the peak rain rate, but the variance of dBZh remains almost unchanged, regardless of the peak rain rate. As a result, the peak rain rate plays a dominant role in the reasonable parameter estimation. These findings are also consistent with many previous studies.


Focusing on representation of quality characteristics variation in product process control, a measurement method based on medium logic was established. Representation model of quality detection index variation in process control was put forward, and fuzziness measurement of quality detection index was improved. Tack monitoring and maintenance of production line were researched by analyzing the variation of product quality index with disturbance. Furthermore, computer simulation was carried out by which influence of controllable variables on product quality with disturbance was analyzed and by which the efficiency of model built above was supported.


In the London circles of Dante Gabriel Rossetti and Frederic Leighton, the notion of "art for art's sake" became a shared concern: if art is not created for the sake of preaching a moral lesson, or supporting a political cause, or making a fortune, or any other objective, what might art be? Art historian Elizabeth Prettejohn traces the emergence of the debates over this issue in the 1860s and 1870s, focusing especially on the Rossetti, Whistler, Leighton, and other protagonists of the Aesthetic Movement and their paintings--some of the most haunting and memorable images in modern art. The English painters' search for the formula to best express the idea of "art for art's sake" was a unified and powerful artistic undertaking, Prettejohn demonstrates, and the Aesthetic Movement made important contributions to the history of modern art.


These Digests are issued in the interest of providing an early awareness of the research results emanating from projects in the NCHRP. By making these results known as they are developed and prior to publication of the project report in the regular NCHRP series, it is hoped that the potential users of the research findings will be encouraged toward their early implementation in operating practices. Per• sons wanting to pursue the project subject matter in greater depth may obtain, on a loan basis, an uncorrected draft copy of the agency's report by request to: NCHRP Program Director, Transportation Research Board, 2101 Constitution Ave., N.W., Washington, D.C. 20418


Significance Groundwater withdrawals are increasing across the United States, particularly in California, which faces a growing population and prolonged drought. Deep groundwater aquifers provide an alternative source of fresh and saline water that can be useable with desalination and/or treatment. In the Central Valley alone, fresh groundwater volumes can be increased almost threefold, and useable groundwater volumes can be increased fourfold if we extend depths to 3,000 m. However, some of these deep groundwater resources are vulnerable to contamination from oil/gas and other human activities. Our findings provide the first estimates, to our knowledge, of underground sources of drinking water depths and volumes in California and show the need to better characterize and protect deep groundwater aquifers. Deep groundwater aquifers are poorly characterized but could yield important sources of water in California and elsewhere. Deep aquifers have been developed for oil and gas extraction, and this activity has created both valuable data and risks to groundwater quality. Assessing groundwater quantity and quality requires baseline data and a monitoring framework for evaluating impacts. We analyze 938 chemical, geological, and depth data points from 360 oil/gas fields across eight counties in California and depth data from 34,392 oil and gas wells. By expanding previous groundwater volume estimates from depths of 305 m to 3,000 m in California's Central Valley, an important agricultural region with growing groundwater demands, fresh [<3,000 ppm total dissolved solids (TDS)] groundwater volume is almost tripled to 2,700 km3, most of it found shallower than 1,000 m. The 3,000-m depth zone also provides 3,900 km3 of fresh and saline water, not previously estimated, that can be categorized as underground sources of drinking water (USDWs; <10,000 ppm TDS). Up to 19% and 35% of oil/gas activities have occurred directly in freshwater zones and USDWs, respectively, in the eight counties. Deeper activities, such as wastewater injection, may also pose a potential threat to groundwater, especially USDWs. Our findings indicate that California's Central Valley alone has close to three times the volume of fresh groundwater and four times the volume of USDWs than previous estimates suggest. Therefore, efforts to monitor and protect deeper, saline groundwater resources are needed in California and beyond.


Targeted therapies like vemurafenib and dabrafenib that block oncogenic BRAF result in high response rates and improved overall survival in patients with melanoma. However, the response has limited durability and most tumors relapse. On the contrary, immunotherapy for melanoma results in low response rates that tend to be extremely durable. We hypothesized that combining immunotherapy with BRAF inhibitors and other targeted therapies being developed for melanoma may improve the anti-tumor effects by combining the benefits of both modes of therapy. To test this hypothesis, we developed a BRAFV600E-driven murine model of melanoma, SM1, that is syngeneic to immunocompetent mice. Combined treatment of vemurafenib plus adoptive cell transfer (ACT) immunotherapy demonstrated superior anti-tumor effect compared with single treatments alone in SM1. However, SM1 is an aggressive model in which the tumor bearing mice have to be sacrificed within two to three weeks, and this combination therapy did not lead to sustained tumor responses. We noticed that SM1 secreted colony stimulating factor-1 (CSF-1) that recruits immune suppressive tumor infiltrating myeloid cells (TIMs) including macrophages and myeloid derived suppressor cells (MDSC). We hypothesized that blocking CSF-1 receptor (CSF-1R) with a small molecule tyrosine kinase inhibitors such as PLX3397, as it would inhibit immune suppressive TIMs and synergize with immunotherapy. Combination of PLX3397 and ACT induced superior anti-tumor effect and PLX3397 increased number of tumor infiltrating lymphocytes (TILs) and IFN-gamma; production in T-cells by depleting TIMs. Based on the results of these two studies, we then combined PLX3397 and vemurafenib in the SM1 model and the combination mediated superior anti-tumor response. The macrophage inhibitory effects of PLX3397 treatment and paradoxical activation of immune cells with wild type BRAF mediated by vemurafenib resulted in more TILs with increased IFN-γ production. Taken together, we provide support for the testing of immunotherapy, BRAF, and CSF-1R inhibitors combinations in patients with BRAFV600 mutant metastatic melanoma.