The efficacy of LY146032 was compared with that of vancomycin in experimental pneumonia due to methicillin-resistant Staphylococcus aureus (MRSA). Emphysematous hamsters were challenged intratracheally with MRSA and given LY146032 (20 mg/kg 24h), vancomycin (40 mg/kg/24h) or normal saline by subcutaneous injection. Following infection with 2 X 10(9) cfu, survival among antibiotic-treated animals was significantly greater than that of the control group (P less than 0.01 at 96 h); however, no significant difference in survival between the hamsters given LY146032 and vancomycin was seen. To evaluate the influence of the antibiotics on the rate of bacterial killing within the lungs (pulmonary clearance), animals were challenged with a high inoculum (1 X 10(9) cfu) or low inoculum (1 X 10(6) cfu). Animals treated with LY146032 demonstrated a significant advantage in pulmonary clearance versus controls at both inocula; however, animals treated with vancomycin showed a statistically significant increase in pulmonary clearance versus controls only at the lower inoculum. We conclude that in this experimental model, LY146032 was as effective as vancomycin in treating infection with MRSA.


By analyzing mathematical models, it is shown that combining channel borrowing with a coordinated sectoring or overlying scheme provides effective ways to handle hot-spots in the system. Blocking probabilities with these arrangements are derived, and the dynamic sharing with bias (DSB) rule is suggested for increasing the trunking efficiency. A simple handoff model is formulated and analyzed for comparing the probabilities of additional handoffs due to sectoring and overlaying of cells. With the nominal allocation of 60 channels per cell and a donor cell having a load of 30 Erlangs, numerical results show that at a blocking requirement of 1%, the traffic load in the hot-spot cell can be increased from 47 to 63 Erlangs with the use of the channel borrowing with the cell sectoring scheme: while with the use of the DSB rule, the load can be increased further to 71 Erlangs. A slightly higher load can be carried in the hot-spot cell with the use of cell overlaying arrangement. >


The purpose of this study was to determine the effects of red dragon fruit (Hylocereus polyrhizus) powder and swimming exercise on fat distribution in the liver organ of white male rats model with obesity. The design of this study was experimental study with randomly factorial design. There were 24 rats divided into two groups, 20 rats were induced to be obese by giving high fat diet, and 4 rats were given standard diet. For intervention period (4 weeks) 20 obese rats were divided into 5 groups namely (1) standard diet (SD), (2) high fat diet (HFD), (3) high fat diet plus swimming exercise (HFD+SE), (4) high fat diet plus red dragon fruit powder (HFD+RDFP), and (5) high fat diet plus red dragon fruit powder plus swimming exercise (HFD+RDFP+SE). Research results showed that fat distribution and visceral fat weight were different significantly among intervention groups (p<0.05). The lowest percentage of fat distribution was occured in RDFP+HFD+SE group (21.44%) and the lightest weight of central fat was also occurred in the same group (7.73 g). This study showed that in four weeks intervention, red dragon fruit powder and swimming exercise had a relatively similar clinical effects on reducing percentage of fat in the liver and visceral fat weight.


The authors have revealed a positive and statistically significant correlation between the sum of T-"pure" and T-rich pyrimidine DNA clusters and radiosensitivity of animals of different species. It was demonstrated that the share of a DNA fraction rich in AT-pairs and denaturing within the temperature range from 55 to 75 degrees increases with increasing specific radiosensitivity of animals.


Abstract Prosthesis-based techniques are the predominant form of breast reconstruction worldwide, with two-stage tissue expander procedures being the most popular. In the past decade, there has been increasing interest in performing single-stage implant reconstruction immediately following mastectomy as an attempt to simplify the reconstructive course and improve psychosocial morbidity. However, there is a paucity of large-scale, multi-institutional data comparing the outcomes of these two reconstructive strategies. Patients who underwent immediate tissue expander or implant reconstruction following mastectomy from 2006–2010 were identified using standardised operation codes. Demographic information for patients, 30-day outcomes, and adverse events for each type of reconstruction were analysed and compared between groups. A total of 10,561 patients underwent immediate breast reconstruction. There were 9033 patients who underwent tissue expander placement (2752 bilateral), and 1528 patients who underwent immediate implant placement (485 bilateral). Patients who had implant placement demonstrated increased rates of overall complications (6.8% compared with 5.4%, p = 0.02) and prosthesis failure (1.4% compared with 0.8%, p = 0.04). There was no difference in the rate of any surgical site infections (3.9% compared with 3.4%, p = 0.39), reoperation (7.5% compared with 6.9%, p = 0.40), or major medical complications (1.8% compared with 1.6%, p = 0.57). Both immediate one-stage, direct-to-implant, and two-stage tissue expander reconstructions result in low rates of morbidity. One-stage reconstruction suggests a slightly higher complication rate related to prosthesis failure.


Background Venous leg ulcers (VLUs) are the most prevalent type of lower extremity ulcers and can be difficult to manage. Clinicians are challenged to provide care and recommendations that promote timely healing, minimize the risk of recurrence, and are cost-effective. Compression therapy is generally considered the primary intervention for both ulcer management and prevention of recurrence. However, recent studies suggest that surgical correction of venous insufficiency may enhance healing of venous ulcers or help prevent recurrence. Purpose The objective of this systematic review was to compare wound healing and recurrence rates in patients managed with compression therapy alone versus compression therapy plus surgery. Search strategy The author conducted a literature review selecting primary studies published between 2002 and 2012, using the electronic databases MEDLINE/PubMed and CINAHL/EBSCOhost. The following key words were applied: leg ulcer; varicose ulcer; bandage; "stockings, compression," venous ulceration; venous ulcer; compressive therapy; compression therapy; stocking; venous surgery. Inclusion criteria included randomized controlled trials that compared VLU healing rates and recurrence rates among patients receiving compression therapy alone, and patients receiving both compression therapy and surgical intervention to correct venous incompetence. Studies published in English, Spanish, or Portuguese were included. Results Sixty-seven studies were retrieved and 4 were identified that met inclusion criteria. In 3 of the studies, researchers reported no differences in healing rates for patients managed with compression plus surgery when compared to patients managed with compression alone. One study reported higher healing rates in the surgical group. Most studies revealed lower recurrence rates in patients who were managed with surgery plus compression, but these differences were not statistically significant. Conclusions Existing evidence supports compression therapy as the most critical element in the management of venous leg ulcers. However, evidence also suggests that surgical obliteration of incompetent perforator veins may promote longer ulcerfree periods and lower rates of recurrence.


Land use and land cover change as a result of human-induced transitions is a major environmental challenge in Lake Victoria Basin. The study adopted a mixed-method consisting of remote sensing and GIS-based analysis, key informant interviews, and household survey consisting of 384 households to asses Land Use and Land Cover Dynamics and associated human-induced transformations in Ombeyi wetland. The study aimed at generating a characterized area estimate of Ombeyi wetlands land use and land cover change schema for the study period (1990-2017), and examining the spatial and temporal characteristics of anthropogenic impacts and their relationship with land use and land cover change in Ombeyi wetland. The gis-based analysis revealed that built-up area/settlements and agricultural lands extensively increased in area at the expense of wetland vegetation. Key informants attributed the changes to population increase (29.2%) and an associated demand for land and natural resources as the major driving forces for the changes. Analysis of household-survey results validated the observed patterns during the remotely sensed data analysis phase of the research, as 90.1% (n=384) of the respondents reported to own land within the wetland through inheritance. 92.2% of the respondents are farmers practicing farming in the wetland with 72.4% of the same respondents attaining primary level education and below. Poverty and education levels were significant factors in influencing unsustainable land use and land cover changes observed in this study. The present state of land cover and its dynamics have had negative impacts on the riparian rural livelihoods and natural resource management.


This research examines religious beliefs as a new antecedent to brand love, and proposes a new construct, that of Islamic brand love. Brand love as a construct has been linked with different constructs such as brand loyalty, brand trust, brand likeability, brand commitment and word-of-mouth (Albert and Merunka, 2013; Batra et al., 2012; Cengiz and Yayla, 2007; Nguyen et al., 2013). In addition, brand love can be influenced by other psychological factors such as cultural identity, religiosity or strongly held values (Batra et al., 2012). Therefore, it is suggested that religious beliefs as a cultural component can be one of the antecedents of brand love. To address the research objectives, a conceptual model was developed with 19 hypotheses to assess Islamic brand love as a focal construct, considering its antecedents (religious beliefs, subjective norms and perceived behavioural control) and consequences (word-of-mouth, brand loyalty and purchase intention).
This study employed mixed-method research following a positivist research philosophy (Malhotra and Birks, 2003). From the positivist perspective, qualitative methods can be applied in the initial stages of research in order to gain a deeper understanding of the nature of the research problem and also to improve the primary research model and hypotheses (Malhotra and Birks, 2003). Since this study proposes a new construct, Churchill's (1979) paradigm is adopted to develop a new scale that measures Islamic brand love and its related constructs.
The data collection process was conducted in two stages. The first stage included an assessment of the conceptual model on the basis of the qualitative study (semi-structured interviews and focus groups), while the second stage included a quantitative assessment of the model. The quantitative assessment included 539 self-administered questionnaires, which were collected to examine Muslim consumers' perceptions of Islamic brand love in Saudi Arabia. In order to make sure that the data collected was valid and reliable, exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were employed. All the research hypotheses were tested using structural equation modelling (SEM). The model indicated an acceptable fit with the data and a good level of validity (discriminant, nomological and convergent).
The outcomes of the empirical tests indicated that religious beliefs are a key factor of the Islamic brand love construct, as the proposed correlation between the two constructs was confirmed by both the qualitative findings and the empirical results. Additionally, the results of the hypothesis testing revealed that religious beliefs have a direct effect on brand loyalty and purchase intention. However, the findings showed unexpected results regarding the proposed correlation between religious beliefs and word-of-mouth, as this was not significant. The empirical results indicate that the subjective norms construct is a key determinant of Islamic brand love, word-of-mouth, brand loyalty and purchase intention, and all the proposed correlations were significant. Perceived behavioural control had a positive effect on Islamic brand love. However, the outcomes included some surprising results, as perceived behavioural control showed no relationship to three constructs (word-of-mouth, brand loyalty and purchase intention). The empirical results indicated that subjective norms were a key determinant of Islamic brand love, word-of-mouth, brand loyalty and purchase intention, and all the proposed correlations were significant. Similarly, Islamic brand love as a focal construct was considered as a key factor of its consequences (word-of-mouth, brand loyalty and purchase intention). Finally, the proposed correlation between word-of-mouth and brand loyalty, and between brand loyalty and purchase intention, were not significant.
This study contributes to the existing literature by offering a new construct, Islamic brand love. This construct was developed by investigating the correlation between religious beliefs and brand love within the Islamic context. The outcomes show that Islamic brand love includes three factors: religious beliefs, subjective norms and perceived behavioural control. The findings demonstrate that Islamic brand love is an important concept for managers who want to have their brands loved by Muslim consumers. Finally, this study recommends that future research should validate the scales used, and examine the proposed correlations in different contexts.


An inconsistent knowledge base can be abstracted as a set of arguments
and a defeat relation among them. There can be more than one consistent way to
evaluate such an argumentation graph. Collective argument evaluation is the prob-
lem of aggregating the opinions of multiple agents on how a given set of arguments
should be evaluated. It is crucial not only to ensure that the outcome is logically
consistent, but also satisfies measures of social optimality and immunity to strategic
manipulation. This is because agents have their individual preferences about what
the outcome ought to be. In the current paper, we analyze three previously introduced
argument-based aggregation operators with respect to Pareto optimality and strategy
proofness under different general classes of agent preferences. We highlight funda-
mental trade-offs between strategic manipulability and social optimality on one hand,
and classical logical criteria on the other. Our results motivate further investigation
into the relationship between social choice and argumentation theory. The results are
also relevant for choosing an appropriate aggregation operator given the criteria that
are considered more important, as well as the nature of agents' preferences.


Abstract. We present measurements utilizing the Filter Inlet for Gases and Aerosols (FIGAERO) applied to chamber measurements of isoprene-derived epoxydiol (IEPOX) reactive uptake to aqueous acidic particles and associated SOA formation. Similar to recent field observations with the same instrument, we detect two molecular components desorbing from the IEPOX SOA in high abundance: C5H12O4 and C5H10O3. The thermal desorption signal of the former, presumably 2-methyltetrols, exhibits two distinct maxima, suggesting it arises from at least two different SOA components with significantly different effective volatilities. Isothermal evaporation experiments illustrate that the most abundant component giving rise to C5H12O4 is semi-volatile, undergoing nearly complete evaporation within 1 hour, while the second, less volatile, component remains unperturbed and even increases in abundance. We thus confirm, using controlled laboratory studies, recent analyses of ambient SOA measurements showing that IEPOX SOA is of very low volatility and commonly measured IEPOX SOA tracers, such as 2-methyltetrols and C5-alkene triols, result predominantly from artifacts of measurement techniques associated with thermal decomposition and/or hydrolysis. We further show that IEPOX SOA volatility continues to evolve via acidity enhanced accretion chemistry on the timescale of hours, potentially involving both 2-methyltetrols and organosulfates.


Harmonious and stable labour-management relations are sine qua non to the development process in Nigeria. For economic and social stability, Nigeria needs to sustain the existing democracy, encourage social dialogue with a view to coping with conflictual issues nationwide. It is against this backdrop that this paper seeks to examine social dialogue as a set of roles for trade unions, and the degree to which this function is enabled or constrained by the dynamics of the political environment in Nigeria. To achieve this objective the authors adopted the qualitative research method. Secondary data such as collective agreements, newspapers reports and official state records were used and supplemented with in-depth interviews with key union representatives and employers' organizations.  The authors outline essential elements for social dialogue and how it can contribute to healthy labour-management relations. The authors addressed the positive contributions that social dialogue can make towards minimising open expression of conflicts with the negative consequences on the tripartite social partners, as well as the impacts of political milieu on the effectiveness of trade unions and by extension social dialogue in Nigeria.


There are several approaches to analyse the worst-case response times of sporadic packets transmitted over priority-preemptive wormhole networks. In this paper, we provide an overview of the different approaches, discuss their strengths and weaknesses, and propose an approach that captures all effects considered by previous approaches while providing tight yet safe upper bounds for packet response times. We specifically address the problems created by buffering and backpressure in wormhole networks, which amplifies the problem of indirect interference in a way that has not been considered by the early analysis approaches. Didactic examples and large-scale experiments with synthetically generated packet flow sets provide evidence of the strength of the proposed approach.


Migraine belongs to the group of primary headaches, in whose pathogenesis, despite the involvement of neurovascular, significant part, has the genetic factors, as well. The prevalence of migraine with aura in patients with atrial septal defect ranges from 11-22%.We present a case of a patient at the age of 28, with persistent headaches,18 months backwards. Headaches were usually preceded by phosphenescence, blurred vision, buzzing in both ears, nausea, feeling of tingling of the right hemicranium. An incomplete hour later severe headaches appeared, followed by tingling and a feeling of weakness on the left arm and lower extremities. Neurological examination was with left sided  paresthesias and hemiparesis. Routine biochemical examinations, hormone status, magnetic nuclear resonance of the brain and magnetic resonance angiography of intracranial vessels, cerebrospinal fluid analysis, and neurophysiological examinations was normal. At the transthoracic, and then transoesophageal echocardiography, was proved the presence of Atrial septal defect (ASD) in the central part of the interatrial septum. In the patient, an occlusion of ASD with ASD occluder was made, there was a reduction in the frequency of occurrence of migraine headaches. Controlled echocardiography was performed where the absence of the pre-established ASD occluder was observed in the aortic arch, where the removal of the dive (occlusion) was done and the closing of the ASD with a direct suture. A pathogenetic mechanism that explains the association of ASD / PFO with migraine is interatrial communication, which may result in the occurrence of paradoxical embolism and humoral factors of the pulmonary circulation.


During the last centuries historic observations revealed the magnetic activity of the sun. The large-scaled poloidal magnetic field reverses during a cycle of about 11 years. Especially during the maximum of particular cycles, dark sunspots can occur on the solar surface, which can store a huge amount of magnetic energy. If magnetic reconnection happens in the solar atmosphere, strong explosions and eruptions of material can be generated, which are called Flares. It is of special interest to study numerous stars with properties similar to the sun to draw meaningful statistics on flares in high energy ranges. In previous studies the first 120 d and 500 d of Kepler-data have been investigated (Maehara u. a., 2012; Shibayama u. a., 2013). It could be shown, that sun-like stars are able to create flares which are one to six orders of magnitude larger than the strongest events on the sun (called superflares). These results provide a challenge for theorists working on hydrodynamical dynamo-models of partly convective stars with spectral type similar to the sun. This thesis presents a data analysis for the full data-set of Kepler-observations (observation time span 3,4 yr). A special aim of this work is to estimate an absolute and relative superflare frequency for sun-like Kepler-stars and to compare these results with the sun. Results of a rough reinvestigation of several so far known sun-like superflare stars are presented which turn out the necessity for a more detailed analysis strategy. A key aspect of the improved data analysis is to minimize the false alarm probability. Using the sample of sun-like stars within the Kepler field of view, a relative superflare frequency of one event per 100 yr for superflares with energies up to 1034 erg was estimated which is more than one order of magnitude larger than in previous studies.


This paper presents a designed and produced electroacoustic system assisting the tour of an exhibition intended for a great number of visitors. The microprocessor operated electroacoustic system fulfills two functions: transfers the commentary to the exhibition andcontrols the visitor's traffic. A sound amplification system" which makes it possible to relay at the same time six language versions of the explanatory commentary to different groups of listeners through loudspeakers and earphones" is presented. Such a system enables simultaneous transmission of two different commentaries to two groups in the same interior. Fundamental elements of technological designs applied in the electroacoustic system are also discussed here.


Over the past three decades, two movements became apparent in the field of psychotherapy: (1) a movement towards therapies targeting processes of mindfulness, acceptance and compassion, and (2) a movement towards therapies wherein well-being is an important outcome. The overarching aim of this thesis was to add to the scientific evidence base underlying a rapidly emerging psychotherapeutic intervention that suits both developments: Compassion Focused Therapy (CFT). CFT aims to build a compassionate mind which encompasses the capacity to notice, tolerate and empathize with suffering of self and others as well as the commitment to tackle or mitigate (the impact of) suffering through directing one's attention towards resources for care, generating soothing thoughts and feelings, and performing caring behaviours. At the heart of this thesis, lies a large-scale waitlisted randomised controlled trial (RCT) conducted so as to test whether CFT offered as guided self-help is effective in improving mental health in adults with low to moderate levels of well-being. Findings from the RCT indicate that CFT is a feasible, acceptable and effective form of intervention, not only for relieving psychological distress but also for improving well-being. Based on the outcomes of closely related interventions, utilising online delivery formats is deemed a promising strategy for reaching the full potential of CFT as a scalable public mental health strategy. CFT was found to impact mental health through multiple pathways, namely through cultivating self-reassurance, reducing self-criticism and regulating positive and negative affect. For enhancing well-being, cultivating self-reassurance seems to be the central mechanism of change, and more specifically the ability to experience compassionate feelings and/or sensations. The Forms of Self-Criticising/Attacking and Self-Reassuring Scale (FSCRS) offers a valid and reliable instrument for measuring two major processes of change in CFT, namely building self-reassurance and reducing self-criticism. To advance research on change processes in CFT, a short form of the FSCRS was created suited to large-scale trials with multiple assessment times. Taken altogether, despite that CFT is still a fairly young area of research, this thesis provides promising evidence for the effectiveness of CFT and preliminary evidence for multiple theory-driven processes of change.


The purpose of this study was to compare eye hand coordination between Basketball and Volleyball players. In this study thirty (30) male players were selected. The subjects selected for this study were randomly selected from Basketball and Volleyball group from S.R.T.M. University, Nanded, Maharashtra, India. Total thirty (30) players, fifteen (15) Basketball and fifteen (15) Handball players were selected. The age of the subject ranged from 18 to 25 years. Eye-Hand coordination variable was selected for this study. Eye-Hand coordination variable was measured by Eye-Hand coordination test. Descriptive statistics and independent "t" test was used for this study. Significant difference is found in respect of Neuroticism and Extraversion between track & field and handball players.


The road safety benefits of intelligent speed assist (ISA) have been demonstrated in a number of projects worldwide. These benefits, however, are yet to be replicated in the heavy vehicle industry. With freight travel by road predicted to double by 2020, fuel costs predicted to rise and environmental issues looming large, the role of speed management in helping companies to reduce crashes, contain costs and remain competitive is likely to play an increasingly important role in the operational plans of many transport operators. In this regard, ISA may have an important role to play. A small-scale trial conducted by the Transport Accident Commission (TAC) in collaboration with the Victorian Transport Association (VTA) and with the cooperation of several heavy vehicle companies sought to assess the relative merits of ISA in terms of speed choice, fuel consumption, and driver acceptability. This paper discusses some preliminary results from phase one of the data analysis.


AP-913 (Equipment Reliability Process Description) describes an equipment reliability process offered to assist member utilities to maintain high levels of safe and reliable plant operation in an efficient manner. This document based on AP-913 process document, this paper generally describes its determination by logic and analysis method. Combining with the types of failure and consequences in the actual problems, it created a more simplified maintenance strategy optimization mind maps (including the system stability, the design necessity, the economic efficiency, the equipment reliability four factors, refining the equipment and benefit related factors, its relationship and influence between the four are clarified), that can raise efficiency of maintenance and enhance the stability of the system. Through its application in the maintenance cases, it takes some cases for example: Increase the PM project of replacing the power board card of the transformer group, shorten the PM project cycle of the transformer group power transmitter, and change the control operation mode of the main transformer cooler;cancel the design of outdated manual working frequency excitation equipment and its PM items, cancellation of electric disk cabinet timer, etc. It is proved that the reliability of the equipment is improved after the implement of the maintenance strategy optimization. Time costs and labor costs are saved, and the cost of equipment procurement is decreased too. Responding to control the company's cost positively, some ideas at the same time also can provide reference for other similar plant maintenance work.


Background/Aims
This study analyzed the diagnostic accuracy of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) for pancreatic solid masses in patients with or without chronic pancreatitis as well as the clinical parameters relevant to a malignancy when EUS-FNA was negative or inconclusive.

Methods
A total of 97 patients, who underwent EUS-FNA for solid pancreatic masses over 2 years at a single institution, were evaluated. All patients underwent EUS-FNA for 3-5 passes with 22 or 25 G needles without an on-site cytopathologist. The final diagnosis was obtained by surgery or compatible clinical outcomes for a more than 12 month follow-up. The diagnostic yields in the patients with or without chronic pancreatitis were compared and the histories and laboratory data relevant to pancreatic ductal adenocarcinoma (PDAC) or pseudo-tumor were analyzed.

Results
The final diagnoses were adenocarcinoma in 88 patients (90.7%) and inflammatory pseudo-tumor in 9 (9.3%). The results of EUS-FNA were adenocarcinoma (74), suspicious (7), atypical (5), negative (10), and inadequate specimen (1). The diagnostic accuracies were 76.9% and 91.6% in patients with or without chronic pancreatitis, respectively. Among the 23 cases with non-diagnostic results of EUS-FNA, PDAC was finally diagnosed in 5 out of 7 suspicious, 3 out of 5 atypical, and 5 out of 10 negative cytology cases. The clinical parameters related to a pseudo-tumor were a history of alcohol consumption and pancreatitis, and normal alkaline phosphatase levels.

Conclusions
The diagnostic accuracy of pancreatic masses in the background of chronic pancreatitis was low. When EUS-FNA produced inconclusive results, the histories of alcohol consumption, pancreatitis, and serum levels of alkaline phosphatase are useful for making a final diagnosis.


Allocating of people in multiple projects is an important issue considering the efficiency of groups from the point of view of social interaction. In this paper, based on previous works, the Multiple Team Formation Problem (MTFP) based on sociometric techniques is formulated as an optimization problem taking into account the social interaction among team members. To solve the resulting optimization problem we propose a Genetic Algorithm due to the NP-hard nature of the problem. The social cohesion is an important issue that directly impacts the productivity of the work environment. So, maintaining an appropriate level of cohesion keeps a group together, which will bring positive impacts on the results of a project. The aim of the proposal is to ensure the best possible effectiveness from the point of view of social interaction. In this way, the presented algorithm serves as a decision-making tool for managers to build teams of people in multiple projects. In order to analyze the performance of the proposed method, computational experiments with benchmarks were performed and compared with the exhaustive method. The results are promising and show that the algorithm generally obtains near-optimal results within a short computational time.


We present the Extreme-Horizon (EH) cosmological simulation, which models galaxy formation with stellar and active galactic nuclei (AGN) feedback and uses a very high resolution in the intergalactic and circumgalactic medium. Its high resolution in low-density regions results in smaller-size massive galaxies at a redshift of z = 2, which is in better agreement with observations compared to other simulations. We achieve this result thanks to the improved modeling of cold gas flows accreting onto galaxies. In addition, the EH simulation forms a population of particularly compact galaxies with stellar masses of 1010−11 M⊙ that are reminiscent of observed ultracompact galaxies at z ≃ 2. These objects form primarily through repeated major mergers of low-mass progenitors and independently of baryonic feedback mechanisms. This formation process can be missed in simulations with insufficient resolution in low-density intergalactic regions.


The aim of the conference hosted by IFA Wales/Cymru Group was to stimulate debate on a national research strategy for Welsh archaeology. The result was two intensive days of discussion by archaeologists representing all aspects of Welsh archaeology on themes ranging from the need for research frameworks and the organization of Welsh archaeology to initial thoughts regarding what the priorities might be. The 26 papers published here from the conference cover all topical buzzwords in research agenda development - 'sustainability', 'social inclusion', 'joined up thinking', and 'sense of place'. As a result, the volume informs and stimulates constructive debates at all levels - from grass-roots to national.


OBJECTIVES
There is evidence that yoga practice is associated with decreased stress, worry, and depression, and with improved mindfulness-based skills. These findings had not been previously replicated for a sample of college students. This study evaluated whether iRest yoga-nidra practice was associated with reduced perceived stress, worry, and depression, and increased mindfulness in a sample of college student s.

METHODS
Sixty-six students age 18-56 completed an 8-week iRest yoga-nidra intervention that was offered for 8 semesters. Assessment occurred 1 week prior to intervention onset and during the class period following the intervention. Qualitative data were collected at Weeks 4 and 8.

RESULTS
Statistically significant pre- to posttest improvements in perceived stress, worry, and depression were found. Pre-existing depression accounted for most of the change in worry and perceived stress scores. Pre- to post test improvements in mindfulness-based skills were also detected.

CONCLUSIONS
iRest yoga-nidra practice may reduce symptoms of perceived stress, worry, and depression and increase mindfulness-based skills.


Addicts are people who have learned how to give themselves a quick chemical fix or achieve an emotional high when they either want to or have to change how they feel, and when they want to ignore real-life problems. Most people do that, but the next morning, they feel sick or foolish. They don't do it again because it didn't work for them. What makes addicts different is that they are willing-or feel compelled-to do it again and again even though they "know" that doing so will get them into trouble.


It is important to differentiate normal aging from a disease process in the elderly. Normal aging must not be equated with "no treatment required." Conversely, all disease processes in the elderly must not mean "treatment required." The decision to treat elderly patients should be made on an individual basis and must be considered in relation to age, quality of life, benefit-risk ratio, presence or absence of symptoms, and the multiplicity of diseases in each patient.


We study the problem of identifying correlations in multivariate data, under information constraints: Either on the amount of memory that can be used by the algorithm, or the amount of communication when the data is distributed across several machines. We prove a tight trade-off between the memory/communication complexity and the sample complexity, implying (for example) that to detect pairwise correlations with optimal sample complexity, the number of required memory/communication bits is at least quadratic in the dimension. Our results substantially improve those of Shamir [2014], which studied a similar question in a much more restricted setting. To the best of our knowledge, these are the first provable sample/memory/communication trade-offs for a practical estimation problem, using standard distributions, and in the natural regime where the memory/communication budget is larger than the size of a single data point. To derive our theorems, we prove a new information-theoretic result, which may be relevant for studying other information-constrained learning problems.


BACKGROUND
Most Americans die in the acute care hospital, where aggressive, life-prolonging interventions are readily performed. Although patients with incurable illness might prefer palliative care, perceived differences in prognosis by physicians may influence the type of care provided. Patients with advanced cancer and advanced dementia represent 2 extremes in the use of hospice services and may also be treated differently in the acute care hospital. We tested this hypothesis and quantitated the use of nonpalliative interventions in hospitalized, incurably ill patients.

METHODS
Charts of elderly patients with advanced dementia or metastatic solid tumor malignancy who died during a 13-month period in a tertiary care acute teaching hospital were reviewed. Main outcome measures included the number of patients receiving invasive of noninvasive (but complex) diagnostic tests, invasive nonpalliative treatments, cardiopulmonary resuscitation, systemic antibiotics, and do-not-resuscitate orders.

RESULTS
Charts of 164 patients (80 with dementia and 84 with cancer) were reviewed. Overall, 47% received invasive nonpalliative treatments. Controlling for age, sex, length of stay, and insurance status, the groups were equally likely to receive nonpalliative treatments (P = .75), but patients with dementia were more likely to receive new feeding tubes (P = .02). Cardiopulmonary resuscitation was attempted for 24% of each group. Patients with cancer more often received invasive (41% vs 13%; P = .002) and complex noninvasive diagnostic tests (49% vs 23%; P = .02). Overall, 88% received antibiotics, often empirically, but, controlling for neutropenia and invasive tests and treatments, patients with dementia were significantly more likely to receive antibiotics for an identifiable infection (P = .004).

CONCLUSIONS
Incurably ill patients often receive nonpalliative interventions at the end of life. Patients with cancer receive more diagnostic tests, but patients with dementia receive more enteral tube feeding. Patients commonly receive systemic antibiotics, often empirically. Cardiopulmonary resuscitation is equally applied, but is out of proportion to expected survival.


Candida parapsilosis is yeast capable of forming biofilms on medical devices. Novel approaches for the prevention and eradication of the biofilms are desired. This study investigated the anticandidal activity of sixteen essential oils on planktonic and biofilm cultures of C. parapsilosis complex. We used molecular tools, enumeration of colony-forming units, the colourimetric MTT assay, scanning electron microscopy (SEM) and a chequer- board assay coupled with software analyses to evaluate the growth kinetics, architecture, inhibition and reduction in biofilms formed from environmental isolates of the Candida parapsilosis complex; further, we also evaluated whether essential oils would interact synergistically with amphotericin B to increase their anticandidal activities. Of the environ- mental C. parapsilosis isolates examined, C. par- apsilosis and C. orthopsilosis were identified. Biofilm growth on polystyrene substrates peaked within 48 h, after which growth remained relatively stable up to 72 h, when it began to decline. Details of the architectural analysis assessed by SEM showed that C. parapsilosis complex formed less complex bio- films compared with C. albicans biofilms. The most active essential oil was cinnamon oil (CO), which showed anticandidal activity against C. orthopsilosis and C. parapsilosis in both suspension (minimum inhibitory concentration—MIC—250 and 500 lg/ml) and biofilm (minimum biofilm reduction concentra- tion—MBRC—1,000 and 2,000 lg/ml) cultures. CO also inhibited biofilm formation (MBIC) at concen- trations above 250 lg/ml for both species tested. However, synergism with amphotericin B was not observed. Thus, CO is a natural anticandidal agent that can be effectively utilised for the control of the yeasts tested.


Swedish teacher education has undergone several reforms in recent decades aimed at incorporating teacher education into the university setting and strengthening the teaching profession. In view of earlier research that has shown how arts education in schools is ruled by dominant knowledge ideologies, the purpose of the project is to critically scrutinize current discourses related to arts learning and arts education in teacher education. The study is based on social constructionist theory and data were collected by various means, including 19 focus group interviews with teachers and students at 10 Swedish teacher education institutes. Our analysis shows that an academic discourse focusing on theory, reflection and textual production has pushed aside skills-based practice. A second discourse, characterized by subjectivity and relativism vis-a-vis the concept of quality, is also found in the material. Finally, a therapeutic discourse is articulated and legitimized based on an idea that student teachers should be emotionally balanced.


The film "We will meet in the blind spot" takes its point of departure from the architecture in and around the Esposizione Universale di Roma (EUR) area in Rome. The EUR was built during the fascist rule and was meant to be the site of the World Exposition in 1942, in addition to being a celebration of the 20-year jubilee for fascism in Italy. The World Exposition in 1942 never took place due to WWII, and the area intended as Mussolini's "Third Rome" wasn't completed until the 1960's – though not in the shape the utopian project was given from the onset. Since then Italian filmmakers have made extensive use of EUR as an exterior location. We will meet in the blind spot is intended as a document of stories and voices that are often lacking in the discussion on migration, both in an Italian context as well as within a broader European perspective. Through encounters with a local Filipino community that is centred around a church in EUR, stories and voices were revealed and the film departs from their personal accounts. In the film, which is situated between documentary and fiction, the focus is on leisure time, interests described by individuals in the group and referencing scenes from Italian film of the 60's. HD film, 38 min in Italian - with English subtitles (Less)


Sesame ( Sesamum indicum L) is one of the oldest cultivated plants. Its seed contains about 42-54 % quality oil, 22-25 % protein, 20-25 % carbohydrates and 4-6% ash. This composition varies with genetic and environmental factors. Conditioning of oil seeds which include roasting, flaking, size reduction, cooking, pre-pressing and drying, is an important operation in the production line of sesame oil. This work investigated effects of initial moisture content, roasting duration and temperature on initial Peroxide Value (PV) and Oxidative Stability (OS) of un-refined sesame oil using response surface methodology. Goza-25, a variety of sesame seed that is commercially cultivated in Nigeria was used for the study. Initial moisture content levels were 4, 7, 10, 13 and 16 % wet basis (wb). Roasting duration and temperature levels were 5, 10, 15, 20 and 25 minutes, and 50, 70, 90, 110 and 130 oC respectively. The recorded minimum and maximum PV were 3.9 and 15.4 meq/kg respectively. Mean value was 9.85 ± 3.9 meq/kg. Peroxide value increased with increasing moisture content and reduced with increasing roasting duration. Analysis of variance and regression analysis of obtained data showed that application of quadratic model to predict effect of initial moisture content, roasting duration and temperature on peroxide value is significant at p ≤ 0.05. Within the studied range, 13 h was the minimum OS recorded while maximum were 63.3 h. Mean of the data was 38.37 ± 16.02. Using the conversion factor of one hour of an active oxygen hour as being equivalent to 15 days; the expressed sesame oil in its present form will retain its quality for a maximum period of 949 days. Rise in roasting temperature and duration increased the oxidative stability, a reverse was observed with initial moisture content. High moisture content reduced the quality and storage life while heat treatment increased both the initial quality and storage life of the mechanically expressed oil. Peroxide value and oxidative stability of crude sesame oil significantly (p ≤ 0.05) depend on moisture content of the seed, roasting duration and temperature. Key words: Sesame, Oil, Crude, Oxidation, Storage


Three new sea cucumbers collected in the intertidal and subtidal zone of southern Japan, Taeniogyrus mijim sp. nov., Rowedota chippiru sp. nov., and R. motoshimaensis sp. nov., are described. All three species display a small body size (approximately 10–20 mm), light body colour (primarily a transparent solid colour), and a small number of digits in their tentacles (one pair or two). They are easily distinguished from each other and from other congeners by the number of digits and by ossicle size and shape. Among these species, the state of the tooth series on the inner margin of the wheel ossicles is an important defining feature, i.e., a continuous row in Taeniogyrus but interrupted by concavities in Rowedota. Also, each tooth is sharp in T. mijim, trapezoidal in R. chippiru, and semicircular in R. motoshimaensis. The number of teeth per radiant is 7–16 (means of 10–13 in different specimens) in T. mijim, 7–15 (means 9–12) in R. chippiru, and 8–21 (means 11–19) in R. motoshimaensis. Among these three new species, only R. chippiru has thick rod ossicles in the body wall.


PURPOSE OF REVIEW
Community-acquired pneumonia (CAP) is associated with significant morbidity and mortality and is the most common cause of death from infectious diseases. CAP patients requiring intensive care unit (ICU) admission carry the highest mortality rates. This paper aims to review the current literature regarding epidemiology, risk factors, severity criteria and reasons for admitting the hospitalized patient to the ICU, and the empiric and specific antibiotic therapeutic regimens employed.

RECENT FINDINGS
Multiple sets of clinical practice guidelines have been published in the past few years addressing the treatment of CAP. The guidelines all agree that CAP patients admitted to the hospital represent a major concern, and appropriate empiric therapy should be instituted to improve clinical outcomes.

SUMMARY
The cost, morbidity and mortality of CAP patients requiring ICU admission remain unacceptably high. These are heterogeneous groups of patients, so it is important to use risk-stratification based on clinical parameters and prediction tools. Appropriate antibiotic therapy is an important component in the management of both groups of patients. In particular, it is essential to administer an appropriate antimicrobial agent from the initiation of therapy, so that the risks of treatment failure and the morbidity of CAP may be minimized.


Many National Forest Inventory (NFI) stakeholders would benefit from accurate estimates at finer geographic scales than most currently implemented in operational estimates using NFI sample data. In the past decade small area estimation techniques have been shown to increase precision in forest inventory estimates by combining field observations and remote-sensing. We sought to demonstrate the potential for improving the precision of forest inventory growing stock volume estimates for counties in United States of North Carolina, Tennessee, and Virginia, by pairing canopy height models from digital aerial photogrammetry (DAP) and field plot data from the United States NFI. Area-level Fay-Herriot estimators were used to avoid the need for precise (GPS) coordinates of field plots. Reductions in standard errors averaging 30% for North Carolina county estimates were observed, with 19% average reductions in standard errors in both Tennessee and Virginia. Accounting for spatial autocorrelation among adjacent counties provided further gains in precision when the three states were treated as a single forest land population; however, analyses conducted one state at a time showed that good results could be achieved without accounting for spatial autocorrelation. Apparent gains in sample sizes ranged from about 65% in Virginia to 128% in North Carolina, compared to the current number of inventory plots. Results should allow for determining whether acquisition of statewide DAP would be cost-effective as a means for increasing the accuracy of county-level forest volume estimates in the United States NFI.


Abnormal expression of CXC motif chemokine ligand 16 (CXCL16) has been demonstrated to be associated with tumor progression and metastasis, served as a prognostic factor in many cancers, with higher relative expression behaving as a marker of tumor progression. However, its role and mechanisms underlying progression and metastasis of gastric cancer (GC) are yet to be elucidated. In our investigation, public datasets and human GC tissue samples were used to determine the CXCL16 expression levels. Our results revealed that CXCL16 was upregulated in GC. The high expression CXCL16 in GC was significantly associated with histologic poor differentiation and pTNM staging. And high CXCL16 was positively correlated with the poor survival of GC patients. Gain-and loss-of-function experiments were employed to investigate the biological role of CXCL16 in proliferation and migration both in vitro and in vivo. Mechanically, Gene set enrichment analysis (GSEA) revealed that the epithelial-mesenchymal transition (EMT), Akt and MAPK signal pathway related genes were significantly enriched in the high CXCL16 group, which was confirmed by western blot. Moreover, overexpression CXCL16 promoted the disintegrin and metalloproteases (ADAM10) and the CXC motif chemokine receptor 6 (CXCR6) expression, which mediated the CXCL16/CXCR6 positive feedback loop in GC, with activating Akt and MAPK signaling pathways. Knocking down ADAM10 would interrupted the CXCL16/CXCR6 axis in the carcinogenesis and progression of GC. In conclusion, our findings offered insights into that CXCL16 promoted GC tumorigenesis by enhancing ADAM10dependent CXCL16/CXCR6 axis activation.


This bibliography on agriculture in Cuba covers the period from 1959 through the present. It is based upon a careful search of a large number of reference sources including: AGRICOLA library reference database, ECONOLIT, the Latin American Library Collection at the University of Florida, the University of Florida general library holdings and selected bibliographic listings. While a great deal of time has been spent compiling this bibliography, the authors recognize that it is not an exhaustive listing. Nonetheless, it is hoped that this publication serves as a useful reference for individuals performing research on Cuban agriculture. The authors welcome suggestions for additional references to be included in updates of this bibliography. Please refer all correspondence to: William A. Messina, Jr. International Agricultural Trade and Development Center IF AS Department of Food and Resource Economics P. 0. Box 110240. University of Florida Gainesville, FL 32611-0240 U.S.A.


Flagrant and widespread racism that characterized the criminal justice system during the early part of the twentieth century has largely been eliminated, but racial disparities persist. Whether because of overt racism, implicit bias, or laws and practices that have racially disparate effects, black (and Hispanic) men and women make up a disproportionate number of people in American prisons and on death row. Researchers have conducted dozens of studies designed to untangle the complex relationships between race and punishment to determine the causes of racial disparities. Findings vary somewhat, but most conclude that the share of racial disproportionality in imprisonment that can be explained by differential involvement in crime has declined over time; attribute the continuing—possibly worsening—disparity to policies pursued during the war on drugs and officials' race-linked stereotypes of culpability, dangerousness, and likelihood of reoffending; and contend that race affects the capital sentencing process. Remedying this will require reducing the size of the prison population, reforming the sentencing process so that many more offenders convicted of nonserious crimes receive alternatives to incarceration, and abolishing or severely restricting use of the death penalty.


Supplemental digital content is available in the text. BACKGROUND Psychological distress is common following a traumatic injury event. The Injured Trauma Survivor Screen (ITSS) was developed at a level 1 trauma center to assess for posttraumatic stress disorder (PTSD) and major depressive episode (MDE) following admission for a traumatic injury. The ITSS sensitivity and specificity were analyzed 1 to 3 and 6 to 9 months postinjury to test the validity across trauma centers. METHOD Four level 1 trauma centers from the East, Midwest, South, and West in the United States recruited 375 eligible adult inpatients (excluded participants included those with moderate or severe traumatic brain injury, whose injury was self-inflicted, were noncommunicative, or were non-English speaking). Baseline sample (White/Caucasian, 63.2%; male, 62.4%; mean (SD) age, 45 (17.11) years; injured by motor vehicle collision, 42.4%) measurements were conducted during index hospitalization. At first follow-up, 69.6% (n = 261) were retained; at second follow-up, 61.3% (n = 230) were retained. Measurements included the ITSS, PTSD Checklist for DSM-5, Center for Epidemiologic Studies Depression Scale—Revised, and Clinician-Administered PTSD Scaled for DSM 5. RESULTS At follow-up 1, the ITSS PTSD subscale had a sensitivity of 75% and specificity of 78.8%, and the MDE subscale had a sensitivity of 80.4% and specificity of 65.6%. At follow-up 2, the PTSD subscale had a sensitivity of 72.7% and specificity of 83.1%, and the MDE subscale had a sensitivity of 76.1% and specificity of 68.3%. A combined risk group using two symptom based measures administered at baseline produced increased specificity. CONCLUSION The nine-item ITSS continues to be an efficient and effective risk screen for PTSD and MDE following traumatic injury requiring hospitalization. This multi-institutional validation study creates a solid foundation for further exploration of the generalizability of this screen's psychometric properties in distinct populations. LEVEL OF EVIDENCE Prognostic study, level III


Stroke is a dramatic complication of sickle cell disease (SCD) and is associated with aneurysms, moya moya, intravascular thrombi, cerebral hyperemia and increased vessel tortuosity. We show that aged SCD mice spontaneously develop the characteristics features of cerebral vasculopathy seen in human SCD. Thirteen month old Townes SCD mice and age-matched controls had a cranial windows implanted over the somatosensory cortex. Cortical capillaries were imaged using in vivo two-photon microscopy after the blood plasma was labeled with a fluorescent dye. Results showed that SCD mice compared to controls, had significantly higher red blood cell (RBC) velocity and capillary vessel diameter. SCD mice also had a significantly higher number of occlusive events in the capillary bed, resulting in more stalling of RBC flow. Microvascular topology was also altered, as SCD mice had significantly higher vessel tortuosity and shorter capillary branch lengths. Finally, post-mortem analyses revealed a greater number of cortical microinfarcts, likely caused by vascular occlusion since local tissue hypoxia and blood-brain barrier leakage was prominent. We concluded that aged Townes sickle cell mice spontaneously develop SCD-associated cerebral vasculopathy, and that in vivo two-photon imaging is a powerful approach to investigate the mechanisms of vascular complications in SCD.


Rubidium-strontium and potassium-argon dating of whole rocks and separated biotites from charnockites and granites of the Eastern Ghats delineate two episodes after the culmination of the Eastern Ghats orogeny 1600 m.y. ago: (1) emplacement of charnockites and granites 1300 to 1520 m.y. ago and (2) their subsequent metamorphism and uplift 500 m.y. ago (postdating the deposition of the Cuddapahs). The 500-m.y. cycle is represented in the southwest coast of India (Travancore) and Ceylon, and the age data are consistent with structural and other geological evidence. Whole-rock K-Ar ages of five dolerites emplaced in the Lower Cuddapahs in the western part of the Cuddapah Basin, and of two slates of the Cumbum stage of the Nallamalai series, permit the dating of the following events in the history of the Cuddapah Basin: (1) the initiation of the Cuddapah sedimentation sometime after the completion of the Eastern Ghats orogeny (1600 m.y. ago), but before 1160 m.y. ago (minimum age limit for dolerites), and (2) metamorphism of the Cuddapahs about 500 m.y. ago (as indicated by the slate ages).


Background: Dominant-activating mutations in the RET protooncogene, a receptor tyrosine kinase, have been identified as a cause of medullary thyroid carcinoma. Such oncogenic RET mutations induce its ligand-independent constitutive trans-autophosphorylation. We investigated the role of endogenous oncogenic RET autophosphorylation in maintaining the neoplastic phenotype in medullary thyroid carcinoma cells and orthotopic medullary thyroid carcinomas in RET transgenic mice. Methods: We constructed adenoviral vectors expressing a dominant-negative truncated form of RET, termed RET , and analyzed its effect on cell viability, apoptosis, and proliferation of TT medullary thyroid carcinoma cells. We investigated the effect of RET TK on downsteam signaling by assessing alterations in phosphorylation or in gene expression. The effect of RET TK in primary medullary thyroid carcinomas in transgenic mice was assessed by monitoring tumor growth. All statistical tests were two-sided. Results: Cell viability was reduced. Phosphorylation of Akt and extracellular signal-regulated kinase (ERK), components of downstream signal transduction pathways, was abolished, and cell cycle progression was reduced. Expression of cell cycle regulator cyclin D1 was decreased, and expression of cell cyle regulators p21 and p27 was increased. Apoptosis was stimulated and concurrently the expression of BCL-2 was decreased. All in vitro experiments compared TT cells expressing RET TK with untreated control cells or control vector-treated cells. Furthermore, 2 weeks after injecting adenovirus-carrying RET TK into thyroid glands of transgenic mice with orthotopic medullary thyroid carcinoma, tumors were statistically significantly smaller than their initial size in mice treated with RET TK (43.6%, 95% confidence interval [CI] 30.7% to 56.5% ; P .010; two-sided unpaired Student's t test), whereas tumors in mice treated with a control vector were larger than their initial size (139.8%, 95% CI 120.3% to 159.3%; P<.001). Conclusion: Selective disruption of oncogenic RET signaling in medullary thyroid carcinoma in vitro and in vivo is associated with loss of the neoplastic phenotype of medullary thyroid carcinoma and should be investigated further as the basis for new therapeutic approaches for this disease. [J Natl Cancer Inst 2004;96: 1231–9]


When specimens are tested in compression the lateral expansion is usually confined by friction between the loading platens and the specimen. For design purposes, a value for the compressive strength of a material, without these confining effects is desired. The amount of confinement depends on the friction properties of the surfaces of the specimen and the steel loading platens and on the mechanical properties of the specimen. Consequently, different conversion factors for size and dimensions, so called shape factors, for different materials are required to obtain a design value for strength. Compression tests on specimens of various sizes made of calcium silicate and aircrete were performed. Various dimensions of the loaded areas in combination with various height over thickness ratios were used. Slender specimens showed vertical splitting cracks, squat specimens showed the well known hour glass fracture model, indicating the different effects of confinement by the loading platens and the effects of the material structure. Multiple regression analysis with linear models, in which thickness, length, slenderness and moisture content were the main parameters, gave more insight in their effects on compressive strength. The research shows that shape factors must depend on the material used. For calcium silicate shape factors were found that are smaller than those given in EN 772-1. For AAC it is reasonable to use a shape factor equal to one as described in the Dutch code NEN 6790:2005.


Voice acting is common in computer games in many genres. The recording and processing of voice acting is a time-consuming process that involves, for instance, voice actors, directors, audio engineers, and game writers. Changes to the script of a game after the voice acting has been recorded are expensive. At the same time, playtests of games without voice acting may give different results than testing where it is present. This creates a situation where improvements identified from play testing are either ignored or leads to extensive re-recording of voice acting. This article presents a design science research project where text-to-speech (TTS) synthesis is used as a substitute for recorded voice acting in the early stages of game production. We propose a set of design principles that have been evaluated in a sharp game production. Our results indicate several benefits of using TTS as a prototyping tool: It can be a source of inspiration for game writers, it gives good estimations on timing and pacing of the game, and it allows for early tests of how the dialog will be perceived by players. The quality and characteristics of the voices provided by the TTS system play an important role in this process. The rapid development in the speech technology field opens many future possibilities.


The goal of the new Danish Road Safety Action Plan is to reduce the number of traffic accident fatalities and serious casualties by 40% from 1998 to the year 2012. This plan is ambitiously titled "Each Accident is One Too Many". The four main areas of the accident plan are accidents caused by speeding, accidents caused by intoxicated drivers, accidents with bicyclists, and accidents at intersections. This paper deals with the first type of accident in the plan - accidents caused by speeding. Specifically, the paper describes the automatic speed control pilot project in Denmark.


Genetic marker tests were performed on 997 strains of poliovirus isolated from patients with neurological disease and from healthy people in England and Wales. Before the introduction of live attenuated vaccine most strains could multiply at raised temperatures. Now, however, many strains isolated from cases of poliomyelitis or from healthy persons with no known contact with vaccine cannot grow above 37 degrees C, and in this respect resemble the vaccine strains. The three serotypes are also much more evenly represented. Hence probably to a limited extent the vaccine-like strains have established themselves in the community.


The geographical data, both raster (satellite images, aerial photographs, scanned maps, ...) and vector (DCW, IGN products like BDTopo and BDCarto, ...) are growing up exponentially in amount, complexity and variety. Need of geographical data are growing in the same way among governmental and local autorithies and commercial and industrial operators for various applications like urban planning, environment monitoring, civil engineering project impact studies and communication networks design . Therefore, potential users have a ever increasing need of services provided by responsive organisations (data distributors) using efficient tools for acquiring geographical data, i.e. identifying, locating, selecting, purchasing and retrieving it. The ESPRIT III project n°8017 GEographical Object Oriented heterogeneous Data Information Server (GEO2DIS) was born out of this need for efficient tools for geographical data acquisition. It was entrusted to a Consortium whose partners are MATRA SYSTEMES & INFORMATION from France. DORNIER from Germany and INTECS from Italy, with associated partners : IGN, O2 Technology, CNUCE-CNR, Region Toscana and the municipality of Pisa. Project goals were the definition of consolidated user requirements at the European level, the definition of a common architecture of the geographical data server and the validation of the concept and of the architecture through three applications. The project has designed, implemented and validated a system based on two types of stations the data distributor station and the data user station, connected through LAN or WAN. The data user station allows users to submit queries to the catalogue and to define and issue a request for data and to receive them using powerful MMI, where the footprint of the data are located on a Reference Background. This MMI is customisable to the user''s needs. The data distributor station answers to the requests of the data user station and offers the services of managing the catalogue and the data. managing the For the description of the heterogeneous geographical data sets a common data model has been defined as an object class. For GDS (and GDS descriptions) request, the Geographical Object Query Language (GeOQL, extension of the OQL (Object Query Language), which is part of the standard ODMG 93. This architecture allows to build the system on various GIS or DBMS, according to the operational requirements of the data distributor. It was actually implemented on the GIS Arc-Info and the OODBMS O2 which has been fitted with a spatial indexing module giving responses times divided by ten compared with previous tools. The system has been validated by three users using it for acquiring data for three very different applications : Assessment of the Visual Impact of a sport and leisure centre in Deulemont (France), monitoring of the land use, suitability analysis for an waste disposal site near Pisa. The innovation and benefits of the system are that, even now, no other


Sumoylation is a post-translational modification in which SUMO (small ubiquitin-related modifier) proteins are covalently attached to their substrates. In vertebrates, developmental roles for sumoylation have been studied, but the function of sumoylation during mammalian oocyte growth and maturation is not known. As a prelude to conducting studies on the role of sumoylation during oocyte development, we analyzed the temporal and spatial pattern of expression of UBE2I, a SUMO-conjugating E2 enzyme. Immunocytochemical analysis of UBE2I revealed a punctate nuclear staining pattern, with transcriptionally quiescent, fully-grown GV-intact oocytes having larger UBE2I-containing bodies than transcriptionally active, meiotically incompetent growing oocytes. Inhibiting transcription in incompetent oocytes resulted in an increase in the size of the UBE2I-containing bodies. Over-expression of either wild type UBE2I or catalytically inactive UBE2I resulted in an increase in size of the UBE2Icontaining bodies but also an increase in BrUTP incorporation, suggesting that transcriptional activation by UBE2I is independent of its catalytic activity. Although UBE2I-containing bodies did not completely co-localize with SUMO1 or SUMO2 and SUMO3, which mainly were localized on the nuclear membrane and in the nucleoplasm, UBE2I strikingly co-localized with SFRS2, which is a component of nuclear speckles and critical for mRNA processing. These results suggest a novel function for UBE2I and therefore sumoylation in gene expression.


European hazelnut (Corylus avellana L.) is a tree crop of economic importance worldwide, but especially to northern Turkey, where the majority of production takes place. Hazelnut production is currently challenged by environmental stresses such as a recent outbreak of severe powdery mildew disease; furthermore, allergy to hazelnuts is an increasing health concern in some regions. In order to provide a foundation for utilizing the available hazelnut genetic resources for crop improvement, we produced the first fully assembled genome sequence and annotation for a hazelnut species, from Corylus avellana cv. 'Tombul', one of the most important Turkish varieties. A hybrid sequencing strategy combining short reads, long reads and proximity ligation methods enabled us to resolve heterozygous regions and produce a high-quality 370 Mb assembly that agrees closely with cytogenetic studies and genetic maps of the 11 C. avellana chromosomes, and covers 97.8% of the estimated genome size. The genome includes 28,409 high-confidence protein-coding genes, over 20,000 of which were functionally annotated based on homology to known plant proteins. We focused particularly on gene families encoding hazelnut allergens, and the MLO proteins that are an important susceptibility factor for powdery mildew. The complete assembly enabled us to differentiate between members of these families and identify novel homologs that may be important in mildew disease and hazelnut allergy. These findings provide examples of how the genome can be used to guide research and develop effective strategies for crop improvement in C. avellana.


Abstract. Evaluating socio-economic losses due to natural disasters is a challenging task because of the combined complexity of the social and ecological systems affected. However, also under pressure from the expected effects of climate change, evaluating the socio-economic costs of natural catastrophes has become a vital need for policy makers, urban planners, and private agents (such as insurance companies and banks). This paper suggests a general framework encompassing all the important concepts which should be taken into account by the above agents in the assessment of natural disasters. In particular, we propose a simple and consistent set of relationships among vulnerability, resilience, hazard, risk, damage, and loss which can guide socio-economic assessment.


1. The effects of noradrenaline (0.025 micrograms kg-1 min-1) and atrial natriuretic factor (0.04 micrograms kg-1 min-1) alone, and in combination, were studied in eight healthy salt replete men. 2. Atrial natriuretic factor increased urinary sodium excretion and flow rate without changing glomerular filtration rate or systemic haemodynamics. 3. Noradrenaline decreased urinary sodium excretion without changing glomerular filtration rate, urinary flow rate or systemic haemodynamics. 4. When atrial natriuretic factor was administered against a background infusion of noradrenaline the natriuretic response to the peptide was significantly attenuated. 5. Further analysis showed that this attenuation was due to the additive antinatriuretic effect of noradrenaline rather than to a specific interaction between atrial natriuretic factor and noradrenaline. 6. The possible significance of this interplay between noradrenaline and atrial natriuretic factor is discussed in the context of experimental evidence for an important role of the sympathetic nervous system in modulating the renal effects of atrial natriuretic factor in animals.


1. Various improvements in the diver-balance technique are described, which are based partly on an improved knowledge of diver-balance theory and partly on practical experience. 2. Certain theoretical aspects concerning the strength of the magnetic field and the force prevailing between this and the diver magnet are outlined. 3. Devices for improving the temperature constancy in the flotation vessel are described. 4. A new electronic design of the amplifier has been devised, which makes it possible to adjust the gain without changing the flotation level, and which efficiently suppresses diver oscillations. With this equipment it is possible to work with high amplifier gain, which implies that the displacement due to loading is so slight that the calibration curve approaches linearity. 5. To prevent rotation two magnets are introduced into the diver, and the tip of the core is made wedge-shaped. The latter is made of remanence-free material. The magnets in the diver are made of material with low coercive force, and they are shaped so as to minimize the demagnetization.


A literature search on furazolidone in pigs was made in order to be able to answer a number of questions raised by a court regarding possible furazolidone intoxication. The following review of the literature is the result of this study. Attention is also paid to the residual toxicology of this drug. As one of the court's questions concerned carbadox alone and combined with furazolidone, a brief review of the pharmacology of this drug is included.


Small-scale electrical power generation (<100 kW) from biogas plants to provide off-grid electricity is of growing interest. Currently, gas engines are used to meet this demand. Alternatively, more efficient small-scale solid oxide fuel cells (SOFCs) can be used to enhance electricity generation from small-scale biogas plants. Most electricity generators require a constant gas supply and high gas quality in terms of absence of impurities like H2S. Therefore, to efficiently use the biogas from existing decentralized anaerobic digesters for electricity production, higher quality and stable biogas flow must be guaranteed. The installation of a biogas upgrading and buffer system could be considered; however, the cost implication could be high at a small scale as compared to locally available alternatives such as co-digestion and improved digester operation. Therefore, this study initially describes relevant literature related to feedstock pre-treatment, co-digestion and user operational practices of small-scale digesters, which theoretically could lead to major improvements of anaerobic digestion process efficiency. The theoretical preamble is then coupled to the results of a field study, which demonstrated that many locally available resources and user practices constitute frugal innovations with potential to improve biogas quality and digester performance in off-grid settings.


The genus Vanilla comprises around 110 species distributed throughout Earth's tropical regions, with the largest number of reported species growing in the American continent. Vanilla farming is associated with many Mexican cultures such as the Totonac, Mayan, Chinantec, and Mazatec, among others. Currently, this crop is threatened by technical, social, ecological, and climatic conditioning factors, limiting its production and the preservation of wild and cultivated species. It is therefore necessary to ascertain the current diversity status of each of these species, as well as some of their main bioclimatic profile indicators, in order to help decision-making, aimed at preserving and genetically improve these species. During 2008, we gathered data from IPN, MEXU, and XAL herbaria, as well as from CONABIO's World Information Network on Biodiversity (REMIB), the Global Biodiversity and Information Facility (GBIF), and we also used data from live access to BUAP's vanilla germplasm bank, obtained between 2008 and 2014. Distribution maps were generated using a geographical information system. Bioclimatic profiles for each species were obtained considering 19 WorldClim variables and altitude at a spatial resolution of approximately 1 Km 2 . Variance, Mean, and standard deviation for each of the 19 variables were calculated at each of the registered points. Extreme environmental condition intervals (minimum, average, and maximum) were also obtained. In order to determine the most important distribution variables of the species, we performed a principal component analysis and carried out Kruskal-Wallis and Dunn's tests on the variables identified as significant. Results indicated records for V. planifolia, V. pompona, V. insignis, V. inodora V. odorata, V. cribbiana, and V. sprucei in Mexico, distributed throughout nine states in the country. V. planifolia presented wide intervals of temperature and rain precipitation, while V. pompona , V. odorata , V. insignis and V. inodora presented intermediate intervals. The amplitudes of extreme data for each species can be considered in locating areas where ex situ regional preservation strategies could be put in place, as well as in establishing areas for cultivation. The bioclimatic profile we found, allows for an indirect inference of each species' genetic condition, which could be used in genetic improvement programs; for instance, V. odorata grows at high altitudes and tolerates low temperatures, while V. inodora tolerates high temperatures, and V. odorata, V. pompona and V. planifolia tolerate low rain precipitation.


This paper explores factors such as socio-demographics, income and wealth and e-skills that may influence the adoption of the ICTs at the individual level. We examine to what extent these factors contribute to the digital divide between different social groups in Serbia. We use the panel data from the survey "ICT usage in Republic of Serbia" in 2006 and 2007, covering over 3000 individuals/households, to perform a quantitative analysis of the digital divide and ICT adoption. Based on a classification tree and a logistic regression model, a profile of the typical ICT adopter and non-adopter is identified. The empirical results show the following: (i) the digital divide between age group 55-74 and those younger that 55 slightly increased in 2007 in case of regular Internet use; (ii) at the individual level the ICT adoption (use of PC, Internet and mobile phones) in Serbia is mainly influenced by the income and wealth of an individual, its computer and Internet skills and age; (iii) this result is quite robust across the methodological approaches used; and (iv) the classification tree approach is preferable since it gives the same predictive accuracy as the logistic regression with a more parsimonious model. The policy implications of these results are discussed.


ABSTRACT Analyses of sediment from four bays on the north Texas coast reveal that sand distributions in microtidal bays and lagoons can be related to wind regimes and bay geometries (i.e., fetch and water depth). In order to examine this relationship, bottom profiles were constructed and sediment samples were collected along the profiles in Christmas, West, Trinity, and Galveston Bays. Grain-size analyses of these samples showed a point of marked change in the sand:mud ratio along each profile. This marked change from muddy bay center sediment to sandy bay margin sediment occurs at increasingly greater depths in the larger, deeper bays, and at greater depths along the southeast side of the bays than along the northwest side. The difference in the depth of the sand:mud "break point" between the northwest (76 cm) and southeast (92 cm) sides of Christmas Bay, the northwest (132 cm) and southeast (147 cm) sides of West Bay, the northwest (160 cm) and southeast (174 cm) sides of Trinity Bay, and the south side of Galveston Bay (220 cm) can be related foremost to the wind regime of the Texas coast. During nine to ten months of the year, moderate southeasterly winds dominate, creating waves that mainly affect the northwest side of the bays. During the winter months, however, strong northerly winds create larger waves, effectively winnowing sediments to a greater depth along the southeast side of the bays. In addition to the difference between break point depths on the northwest and southeast bay sides, minor differences in break point depths occur along the same side within a bay; such differences are related to variations in bottom geometry. On the basis of these preliminary analyses, it appears that sand distributions in analogous bays can be predicted using wind, fetch, and water depth data.


BACKGROUND:
 During a Primary Stroke Center recertification survey by The Joint Commission at this 504 bed community hospital a knowledge gap was discovered in applying the National Institutes of Health Stroke Scale (NIHSS) at the bedside and correlating it with clinical findings. Since 2009, this stroke program has required nurses caring for acute stroke patients to complete NIHSS certification annually. The purpose of this simulated educational competency program was to verify performance of the NIHSS and provide education correlating symptoms with brain physiology.

 METHODS:
 Nurses caring for acute stroke patients attended this mandatory educational program which included a review of anatomy, NIHSS application and scoring on a simulated patient, and a debriefing discussion. The simulated patients were assigned specific deficits to portray. Immediate feedback was provided to participants upon completion. Symptoms of each patient were correlated with the affected brain physiology during a group debriefing discussion. Participants evaluated their perceived competency performing the NIHSS and associating brain physiology before and after the session using a four point Likert-type scale with 1 being strongly disagree and 4 being strongly agree.

 RESULTS:
 Competency was demonstrated by 196 nurses with 174 completing evaluations expressing high satisfaction with the material and mode of learning. Evaluation data was analyzed using descriptive statistics and a paired
 t
 test showing improvements in self perceived NIHSS competency and ability to correlate the affected brain physiology. The mean self perceived NIHSS competency prior to the session was 3.28 compared to 3.90 post session (
 t
 (172) = 13.99,
 p
 < 0.01). The mean self perceived ability to correlate the affected brain physiology prior to the session was 2.61 compared to 3.57 post session (
 t
 (173) = 18.09,
 p
 < 0.01).

 CONCLUSION:
 The current NIHSS certification examination has known limitations. Integrating simulated learning experiences together with NIHSS certification resulted in perceived improvement in understanding and competency. Follow up is necessary to determine if this translates into improved bedside clinical practice.


Abstract Background CART-19 therapy is an immunotherapy treatment based in extracorporeal and synthetic modification of T-lymphocytes from the patient that goes through the therapy. This therapy is used in treatment of haematological cancers like chronic lymphocytic leukaemia (CLL) and acute lymphoblastic leukaemia (ALL) and it can be administered through one aliquot or three aliquots. It is a new therapy recently introduced in cancer treatment which introduces multiple challenges like side effects management. Its main side effect is cytokine release syndrome (CRS). The aim of this study is to compare the side effects observed in patients treated with CART-19 therapy versus side effects described in the literature. Methods This is an observational, transversal and retrospective study based in medical records review. The patients included in this study are adults treated with CART-19 therapy in Hospital Clinic Barcelona between January 2017 and April 2019. Data analysis has been done through Excel programme and taking into account clinical variables like: age, diagnosis, arterial pressure, heart rate, number of aliquots and Intensive Care Unit (UCI) requirement. Results A total of 27 CART-19 therapies have been administered. 70,4% from infusions have been done in patients with a diagnosis from ALL. The main side effects that have been observed are hypotension in a 29,6%, tachycardia in 22,2% and headache in 11,1%. Fever has been observed in a 85,2% of the infusions and it has appeared in the first 24 hours post-infusion in a 63% of the cases. A high percentage of the infusions have been administered in one aliquot (70,4%). Only in an 29,8% of the cases the patient needed a transfer to an UCI and a 22,2% needed Tocilizumab administration for CRS decrease. Conclusions The main conclusion obtained is that observed side effects in patients that have received CART-19 therapy coincide with the ones described in literature, without any new appearance. It is important to emphasise that fever has appeared in patients independent of the number of aliquots received and clinical variables affected. On the other hand, low incidence of neurological and gastrointestinal affections has been observed. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.


Taking up where "Invitation to the Waltz "left off, "The Weather in the Streets" shows us Olivia Curtis ten years older, a failed marriage behind her, thinner, sadder, and apprently not much wiser. A chance encounter on a train with a man who enchanted her as a teenager leads to a forbidden love affair and a new world of secret meetings, brief phone calls, and snatched liaisons in anonymous hotel rooms. Years ahead of its time when first published, this subtle and powerful novel shocked even the most stalwart Lehmann fans with its searing honesty and passionate portrayal of clandestine love."


People of the modern world consume more than they ever used to do. Because of the close correlation between consumption and the amount of waste, the waste volume is also expected to increase. The purpose of this study is to examine if some measures in the recycling process from Sweden could be implemented in Indonesia. In fact, Indonesia is one of the countries in which the waste management system is struggling. Tetra Pak, one of the world leading producer of food packaging, is studied in this report. Tetra Paks recycling rate of their beverage cartons is relatively low, 8.42 %, in Indonesia compared with their recycling rate in other countries. To answer the purpose, information was collected from scientific reports, by interviews carried out in both Sweden and Indonesia and by study visits in Indonesia. The results of the study shows that there are measures which could be made in the recycling process to increase the recycling rate in Indonesia. School projects and deposit systems could increase the collection rate and a drumscreen and a buffertank could make the recycling process more profitable for the papermills. There is also some alternative end products which could make the whole recycling process more public visible. One of the conclusions of this study is that the paper mills should adjust their drumscreens, this to increase the fibre yield which is crucial for the recycling value. Another conclusions is that Tetra Pak should consider to initiate a recycling business by their own, in order to reduce the burden on the environment.


(a) You are an affected source subject to this subpart if you meet all of the criteria listed in paragraphs (a)(1) and (2) of this section: (1) You own or operate a vegetable oil production process that is a major source of HAP emissions or is collocated within a plant site with other sources that are individually or collectively a major source of HAP emissions. (i) A vegetable oil production process is defined in § 63.2872. In general, it is the collection of continuous process equipment and activities that produce crude vegetable oil and meal products by removing oil from oilseeds listed in Table 1 to § 63.2840 through direct contact with an organic solvent, such as a hexane isomer blend. (ii) A major source of HAP emissions is a plant site that emits or has the potential to emit any single HAP at a rate of 10 tons (9.07 megagrams) or more per year or any combination of HAP at a rate of 25 tons (22.68 megagrams) or more per year. (2) Your vegetable oil production process processes any combination of eight types of oilseeds listed in paragraphs (a)(2)(i) through (viii) of this section: (i) Corn germ; (ii) Cottonseed; (iii) Flax; (iv) Peanut; (v) Rapeseed (for example, canola); (vi) Safflower; (vii) Soybean; and (viii) Sunflower. (b) You are not subject to this subpart if your vegetable oil production process meets any of the criteria listed in paragraphs (b)(1) through (4) of this section: (1) It uses only mechanical extraction techniques that use no organic solvent to remove oil from a listed oilseed. (2) It uses only batch solvent extraction and batch desolventizing equipment. (3) It processes only agricultural products that are not listed oilseeds as defined in § 63.2872. (4) It functions only as a research and development facility and is not a major source. (c) As listed in § 63.1(c)(5) of the General Provisions, if your HAP emissions increase such that you become a major source, then you are subject to all of the requirements of this subpart.


A fixed exchange rate regime eliminates one degree of freedom in absorbing macroeconomic shocks. Therefore, there is a call for higher labor market flexibility in countries which are members of the monetary union or those which intend to join the monetary union. Focusing on the cross-country analysis of labor markets in the enlarged European Union, this paper aims to assess empirically the role of aggregate wages as a correction mechanism for dealing with economic disturbances. We apply classical time series/panel, state-space and cointegration techniques to determine the extent to which aggregate wages can accommodate shocks in the economy.


Neurodegenerative diseases such as Alzheimer's and Parkinson's are associated with protein misfolding and aggregation. Recent studies suggest that the small, rare and heterogeneous oligomeric species, formed early on in the aggregation process, may be a source of cytotoxicity. Thioflavin T (ThT) is currently the gold-standard fluorescent probe for the study of amyloid proteins and aggregation processes. However, the poor photophysical and binding properties of ThT impairs the study of oligomers. To overcome this challenge, we have designed Thioflavin X, (ThX), a next-generation fluorescent probe which displays superior properties; including a 5-fold increase in brightness and 7-fold increase in binding affinity to amyloidogenic proteins. As an extrinsic dye, this can be used to study unique structural amyloid features both in bulk and on a single-aggregate level. Furthermore, ThX can be used as a super-resolution imaging probe in single-molecule localisation microscopy. Finally, the improved optical properties (extinction coefficient, quantum yield and brightness) of ThX can be used to monitor structural differences in oligomeric species, not observed via traditional ThT imaging.


Background: The Arm function in Multiple Sclerosis Questionnaire (AMSQ) has been developed as a self-reported measure of arm and hand functioning for patients with multiple sclerosis (MS). The AMSQ was originally developed in Dutch and to date translated into five languages (i.e. English, German, Spanish, French, and Italian). Objective: The aim of this study was to evaluate differential item functioning (DIF) of the AMSQ in these languages. Methods: We performed DIF analyses, using "language" as the polytomous group variable. To detect DIF, logistic regression and item response theory principles were applied. Multiple logistic regression models were evaluated. We used a pseudo R2 value of 0.02 or more as the DIF threshold. Results: A total of 1733 male and female patients with all subtypes of MS were included. The DIF analysis for the whole dataset showed no uniform or non-uniform DIF on any of the 31 items. All R2 values were below 0.02. Conclusion: The AMSQ is validated in six languages. All items have the same meaning to MS patients in Dutch, English, German, Spanish, French, and Italian. This validation study enables use of the AMSQ in international studies, for monitoring treatment response and disease progression.


The rapid development of technology and science has made vegetable oil not only as a consumption material, but also into something more useful, namely alternative renewable fuel oil, one of which is biodiesel which is an alternative fuel to replace diesel. The purpose of this study was to examine the effect of temperature and time of the transesterification reaction on the characteristics of the biodiesel produced. The expected results are results that are in accordance with the characteristics of biodiesel with SNI parameters. This research was conducted by mixing sunflower seed oil with methanol as a solvent with a NaOH catalyst with a mole ratio of reactants 1:6. Then the variation of reaction time was determined, namely 70 minutes, 80 minutes and 90 minutes, and the reaction temperature was 50°C, 55°C, 60°C and 65°C, respectively. After biodiesel is obtained, characteristic testing is carried out. The results showed that the best biodiesel quality was obtained at a temperature of 60°C with a reaction time of 90 minutes with the following characteristics: Yield = 80.76%; density = 0.85 gr/ml; viscosity = 2.38 cSt; water content = 0.03 %vol and acid number = 0.5 mg-KOH/g. Thus, it can be concluded that the biodiesel produced is in accordance with the characteristics of the standardization parameters of SNI-7182-2019 regarding biodiesel.


We examine whether and how democratic procedures can achieve socially desirable public good provision in the presence of deep uncertainty about the benefits of the public good, i.e., when citizens are able to identify the distribution of benefits only if they aggregate their private information. Some members of the society, however, are harmed by socially desirable policies and try to manipulate information aggregation by misrepresenting their private information. We show that information can be aggregated and the socially desirable policy implemented under a new class of democratic mechanisms involving an experimentation group. Those mechanisms reflect the principles of liberal democracy, are prior{free, and involve a differential tax treatment of experimentation group members which motivates them to reveal their private information truthfully. Conversely, we show that standard democratic mechanisms with an arbitrary number of voting rounds but no experimentation do not generally lead to the socially desirable policy. Finally, we demonstrate how experimentation can be designed in such a way that differential tax treatments occur only off the equilibrium path.


Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC

The scale-up of synthetic methods for producing small molecule therapeutics can often prove to be problematic and expensive. Synthetic mechanisms can be inefficient and purification methods used to select specific isomers or remove reactants or other contaminants can often be difficult to scale. The modular approach we developed for creating small molecule targeting agents called SHALs (Selective High Affinity Ligands) as therapeutics and diagnostics for B-cell lymphoma circumvents many of these problems by using off the shelf components as "recognition elements" that collectively contribute to the molecules high affinity and selectivity and miniPEG and common amino acids to build up the scaffold using solid phase chemistry. Here we present the results of our efforts to scale up the synthesis of the first of these promising new drug candidates, SH7139, to provide the compounds needed for pre-IND animal testing and a pet dog lymphoma clinical trial. Working with AmbioPharm Inc,, a CRO with extensive expertise in the GMP synthesis of peptide pharmaceuticals, we recently completed small pilot production scale syntheses of SH7139 and several closely related analogs. The simple solid phase peptide-based chemistry used to synthesize the compounds coupled with preparative HPLC adapted well to scale-up and resulted in the production of highly purified compounds identical in structure (as determined by mass spectrometry and nuclear magnetic resonance spectroscopy) to the bench scale syntheses we performed in house. However, one unexpected and notable difference between the scaled-up synthetic products and their bench-scale synthesis counterparts was their solubility. SH7139 and two of its analogs, which are essentially insoluble in water and PBS when synthesized in house, were observed to be highly soluble (>100mg/ml) when synthesized using the scale-up protocol. While the reason for this is still under investigation, microscopic analyses of the dried product suggest the solubility difference may relate to the lyophilization step used to produce the dried product. The majority of the insoluble SH7139 we produce in bench-scale syntheses is amorphous in form, while the soluble SH7139 produced by AmbioPharm appears to be in a semi-crystalline or glass-like state. This research was supported, in part, by NIH/NCI SBIR grant 1R43CA159843-01 to Rod Balhorn.

Citation Format: Monique Balhorn, Saphon Hok, Rod Balhorn. Optimizing a modular synthetic approach for producing SH7139, a new drug candidate for treating B-cell lymphomas. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2453. doi:10.1158/1538-7445.AM2013-2453


Visual extension has been an essential issue because the visual information accounts for a large part of sensory information which human processes. There are some instruments which are used to watch distant, objects or people, such as a monocle, a binocular, and a telescope. When we use these instruments, we firstly take a general view without them and adjust magnification and focus of them. These operations are complicated and occupy the user's hands. Therefore, a visual extension device that is capable of being used easily without hands is extremely useful. A system developed in the previous work recognizes the movement of the user's eyelid and operating devices by using it [Hideaki et al. 2013]. However, a camera is placed in front of the eye, and that obstructs the field of view. In addition, image recognition needs much calculation cost and it is difficult to be processed in a small computer. When human intends to move his/her muscles, bioelectrical signal (BES) leaks out on the surface of skin. The BES can be measured by small and thin electrodes attached to the surface of the skin. By using the BES, user's operational intentions can be detected promptly without obstructing the user's field of view. Moreover, using BES sensors can reduce electrical power, and contribute to downsizing systems.