OBJECTIVE
The purpose of the study was to replicate and extend previous findings regarding the hypnotizability of different clinical groups.

METHOD
The authors compared the differential hypnotizability of four psychiatric groups--patients with dissociative disorders (N = 17), schizophrenia (N = 13), mood disorders (N = 13), and anxiety disorders (N = 14)--and one normal group of college students (N = 63). Hypnotizability was assessed by four different measures: the eye roll sign and the induction score of the Hypnotic Induction Profile, the Stanford Hypnotic Susceptibility Scale, Form C, and two self-ratings of hypnotizability.

RESULTS
As predicted, dissociative disorder patients had significantly higher hypnotizability scores on all measures than all other groups. Schizophrenic patients, on the other hand, had significantly lower scores than normal subjects on the eye roll sign and induction score but not on the other measures of hypnotizability. Some other unpredicted between-group differences were also found. Nevertheless, despite the between-group differences, the intercorrelations between the various hypnotizability measures within the normal group were very similar to those observed in the combined patient groups.

CONCLUSIONS
The findings suggest that routine hypnotizability assessment may be useful in the differential diagnosis of patients with dissociative disorders.


Abstract. Purpose: To utilize a virtual clinical trial (VCT) construct to investigate the effects of beam collimation and pitch on image quality (IQ) in computed tomography (CT) under different respiratory and cardiac motion rates. Approach: A computational human model [extended cardiac-torso (XCAT) phantom] with added lung lesions was used to simulate seven different rates of cardiac and respiratory motions. A validated CT simulator (DukeSim) was used in this study. A supplemental validation was done to ensure the accuracy of DukeSim across different pitches and beam collimations. Each XCAT phantom was imaged using the CT simulator at multiple pitches (0.5 to 1.5) and beam collimations (19.2 to 57.6 mm) at a constant dose level. The images were compared against the ground truth using three task-generic IQ metrics in the lungs. Additionally, the bias and variability in radiomics (morphological) feature measurements were quantified for task-specific lung lesion quantification across the studied imaging conditions. Results: All task-generic metrics degraded by 1.6% to 13.3% with increasing pitch. When imaged with motion, increasing pitch reduced motion artifacts. The IQ slightly degraded (1.3%) with changes in the studied beam collimations. Patient motion exhibited negative effects (within 7%) on the IQ. Among all features across all imaging conditions studies, compactness2 and elongation showed the largest (−26.5  %  , 7.8%) and smallest (−0.8  %  , 2.7%) relative bias and variability. The radiomics results were robust across the motion profiles studied. Conclusions: While high pitch and large beam collimations can negatively affect the quality of CT images, they are desirable for fast imaging. Further, our results showed no major adverse effects in morphology quantification of lung lesions with the increase in pitch or beam collimation. VCTs, such as the one demonstrated in this study, represent a viable methodology for experiments in CT.


The tropical green algal genus Halimeda is one of the best studied examples of pseudo-cryptic diversity within the algae. Previous molecular and morphometric studies revealed that within Halimeda section Rhipsalis, Halimeda incrassata included three pseudo-cryptic entities and that the morphological boundaries between H. incrassata and Halimeda melanesica were ill-defined. In this paper, the taxonomy of H. incrassata is revised: two pseudo-cryptic entities are described as new species, Halimeda kanaloana and Halimed heteromorpha, while H. incrassata is redefined to encompass a single, monophyletic entity. Similarities and differences between the three species and H. melanesica are discussed. Monophyly of H. heteromorpha, which was questioned in a former study, is reinvestigated using sets of 32 ITS1–ITS2 and 21 plastid rps3 sequences and various alignment and inference methods. The phylogenetic relationships within Halimeda section Rhipsalis are inferred from nuclear 18S–ITS1–5.8S–ITS2 and concatenated plastid sequences (tufA & rpl5–rps8–infA) and interpreted in a biogeographic context.


Neurobiological studies have generated new ways of thinking about development of brain structure and function. Development involves more than just growth from simple to complex structures. The initial over‐abundance of neurons and synaptic connections is subsequently pruned of those that are non‐functional. In addition, as behavioural and cognitive functions emerge and become automatized, the underlying brain representations are reorganized. In this paper, I shall argue that these different modes of neurodevelopmental change provide a useful metaphor for examining language acquisition. It will be argued that language acquisition can involve learning to ignore and inhibit irrelevant information, as well as forming new ways of representing complex information economically. Modular organization is not present from the outset, but develops gradually. This analysis suggests a new way of assessing specific language impairment (SLI). There has been much debate as to whether children with SLI lack specific modular components of a language processing system. I propose instead that these children persist in using inefficient ways of representing language. Finally, I consider what we know about the neurobiological basis of such a deficit. There is mounting evidence that children with SLI have subtle structural anomalies affecting the language areas of the brain, which are largely genetically determined. We should not, however, conclude that the language difficulties are immutable.


This work presents the development of cooperative control technique applied to vessels equipped with dynamic positioning (DP) system. An illustrative case study is suggested: the launching of subsea equipment using two DP vessels. In this example, the cooperative system controls the relative distance between the DP vessels. One of the advantages of this method is the increase of operation's safety and operational window, since, among other factors, the tension in the launching cable is reduced by half. Initially, it was proposed the control of vessels relative positions, trying to keep the connection point movements in counter-phase. This avoids the slackening of the launching cable. For this, an algorithm based on phase estimator (Hilbert transform) associated with a PD control was implemented. The results showed that for regular waves this strategy was effective. A dynamic mapping was then obtained using simplified 2D simulator, previously validated by comparison with experimental tests. In these maps, two regions are defined occurrence or non-occurrence of cable slackening as a function of the distance of the vessels and the depth of the subsea equipment. This map defines the proper set-point for the DP systems for each depth of the subsea equipment. This map is used to define the best relative position for the vessels. In addition, the hoisting control receives the measurements of the vertical motion of the connection point, and compensates its motion, trying to maintain a constant lowering velocity. This control was implemented considering errors of 10% and delay of 0.5s in the measurements. The results confirmed that the control is able to eliminate the tension peaks and the occurrence of slackening in the launching cable. The conclusion is that the appropriate control strategy, considering regular waves, is to combine the control of both position of the vessels and hoisting of the cable. Therefore the position control, coupled with dynamic mapping, defines the "optimal path" to be followed during the line hoisting, trying to keep the vessels as close as possible to the "no slackening" region.


Rock is a type of natural material containing microcracks. The evolution of mining-induced fracture field is one of the main problems of gas comprehensive control and rock mass seepage. The distribution of fissures and porosity in overlying strata under the mining influence were studied in this paper. The stratum subsidence was represented quantitatively using elastic thin plate theory and key strata theory. Based on the stratum subsidence, a program calculating porosity in overlying strata was developed based on VB. The results demonstrate that the porosity increase with face advances. The porosity becomes small with the decrease of strata depth, and the bigger separation is located in the strata below the key strata. The amount of the fissures in the middle part of overlying strata is more than that in two ends, and the porosity curves present symmetric arch shape in the initial stage. With face advances, the curves of porosity in the strata located the upper position change symmetric arch shape into saddle shape.


The researchers of this study investigated the participants' (N = 177) use of a self-evaluation tool employed at the end of an online undergraduate music course that fulfilled the Texas general education requirement for the creative arts. Participants' use of the two aspects of the tool correlated at r = .5548 – interpreted as a high positive relationship. The Pearson coefficient for instructor final grade and the student desired grade was r = .4456 – a moderate positive correlation. A t-test of the instructor grade to the student desire grade was -2.814 with a p = .002. Free-response justifications for the desired grade generated a mean of 3.53 sentences each that were qualitatively coded into themes: Effort/Completed 22%, Generalized Statements 20%, and Positive Affirmations 11% as the larger categories. Participants consistently used the form to justify a desired grade, evaluate their work, and suggest a final grade. However, that grade was statistically significantly lower than the final grade issued by the professor.


Abstract Insights from the behavioural sciences are increasingly used by governments and other organizations worldwide to 'nudge' people to make better decisions. Furthermore, a large philosophical literature has emerged on the ethical considerations on nudging human behaviour that has presented key challenges for the area, but is regularly omitted from discussion of policy design and administration. We present and discuss FORGOOD, an ethics framework that synthesizes the debate on the ethics of nudging in a memorable mnemonic. It suggests that nudgers should consider seven core ethical dimensions: Fairness, Openness, Respect, Goals, Opinions, Options and Delegation. The framework is designed to capture the key considerations in the philosophical debate about nudging human behaviour, while also being accessible for use in a range of public policy settings, as well as training.


Background: At a macro level, Social Responsibility and Social Accountability are explicit priorities for medical schools in Canada and internationally, although the advancement of this vision is still developing. At a micro level, Health Advocacy is important for physicians-in-training as well as practicing physicians. The conceptual model being proposed is that Social Responsibility is connected to mastering Health Advocacy. The University of Toronto Faculty of Medicine has 16 years of experience through a mandatory 4th year clerkship course entitled the Ambulatory/Community Experience (ACE) which from inception emphasized Social Responsibility and Health Advocacy. The objective of this retrospective study was to provide a model to support the acquisition of Health Advocacy and the development of socially responsible medical students. Methods: A conceptual model with three distinct elements: 1) ambulatory/community placements, 2) individual pedagogical approaches and 3) narrative, reflective assignments was applied. Results: The three elements of the model, all based on the five ACE learning domains (objectives) and embedded in CanMEDS type competencies, are effective and appear to support  achievement of competency in Health Advocacy. Conclusion: A model which includes vetted ambulatory/community placements, individual pedagogical approaches, and narrative reflective assignments based on objectives with a Health Advocate perspective appears to encourage Social Responsibility in medical students.


Linezolid standard dosing is fixed at 600 mg every 12 h (q12h) for adults. Literature suggests critically ill, obese patients require higher doses. ABSTRACT Linezolid standard dosing is fixed at 600 mg every 12 h (q12h) for adults. Literature suggests critically ill, obese patients require higher doses. The study aim is 2-fold: (i) to describe linezolid pharmacokinetics (PK), and (ii) to evaluate if PK/pharmacodynamic (PD) target attainment is achieved with standard dosing in critically ill, obese patients with severe skin and soft tissue infections (SSTIs). Adult patients with a body mass index (BMI) of ≥30 kg/m2 and receiving intravenous (i.v.) linezolid from August 2018 to April 2019 were eligible for consent in this prospective study. Severe SSTIs were defined as necrotizing fasciitis, myonecrosis, or SSTI with sepsis syndrome. Four blood samples were collected at steady state at 1, 3, 5 h postinfusion and as a trough. Target attainment was defined as achieving area under the concentration-time curve from 0 to 24 h to MIC (AUC0–24h/MIC) of ≥100 h*mg/liter. Monte Carlo simulations were used to determine the probability of target attainment (PTA). Eleven patients were included in the study. The median BMI was 45.7 kg/m2, and median total body weight (TBW) was 136.0 kg. Seven patients received standard linezolid doses, and four received 600 mg q8h. A one-compartment model described linezolid PK. Based on AUC0–24h/MIC targets, for noncirrhotic patients at 140 kg, the PTA with standard linezolid doses was 100%, 98.8%, 34.1%, and 0% for MICs of 0.5, 1, 2, and 4 mg/liter, respectively. In conclusion, target attainment of ≥90% is not achieved with standard linezolid doses for noncirrhotic patients ≥140 kg with MICs of ≥2 mg/liter. This study adds to accumulating evidence that standard linezolid doses may not be adequate for all patients.


Long duration colonic inflammation increases the risk in developing intestinal dysplasia and further tumorigenesis, which is known as colitis-associated cancer (CAC). USP16, a deubiquitinase, is reported to regulate the T cell and macrophage function in acute colitis. But its function in CAC is never been studied.

 We analyzed USP16 expression in tumor tissues and para-tumor tissues from patients with CAC by immunofluorescent staining. Then we established a CAC model in USP16MKO (conditional knock out in macrophage cells) and wild type mice by azoxymethane (AOM) and dextran sodium sulfate (DSS). Associated inflammatory cytokines were examined in normal colon and CAC by real-time polymerase chain reaction. And the signaling pathways and molecular mechanisms were studied.

 Expression of USP16 was found to be increased in tumor tissues from CAC patients than that in para-tumor controls. USP16MKO mice had fewer and smaller colon tumors than their WT littermates. Various inflammatory cytokines, including Tnf, Il12a, IL12b, Il23a and Il1b, were decreased in the colon tissues of USP16MKO mice. USP16 deficiency leads to the decrease of p65 activation and nucleation in macrophage. Through co-IP and immunofluorescent staining, USP16 was found to have an interaction with p65. And p65 deubiquitination was decreased in USP16 deficient macrophages.

 USP16 is increased in colitis-associated cancer and regulates intestinal epithelial carcinogenesis by modulating pro-inflammatory responses in macrophages. USP16 serves as a deubiquitinase of P65 and thus promoting the activation and nucleation. Therefore, USP16 may serve as a novel therapeutic target to block inflammatory-cancer transformation


Mycobacterium ulcerans is an environmental bacterium which causes chronic skin ulcers. Despite significant epidemiological evidence to suggest that water is the source of infection, the organism has never been identified in the environment. Environmental water samples were collected from a small town in which an outbreak of 29 cases had occurred in a 3-year period. These were examined by mycobacterial culture and PCR amplification. Similar to previous studies, M. ulcerans was not cultured from the water samples. However, five samples were positive for M. ulcerans by PCR. These samples were collected from a swamp and a golf course irrigation system within the outbreak area. This is the first time that M. ulcerans has been demonstrated to be present in the environment and supports the postulated epidemiology of disease due to this organism.


Thenumber of hazardous waste disposals reported has increased in recentyearsdue to improper
management of chemical generated by chemical and petrochemical industries. Volatile organic
compounds are one of the major pollutants to the environment. Two of the volatile organics
compounds selected for this study are toluene and n-hexane are The adsorption measurement in
aqueous solutions has been carried out by using batch system at 35°C, 55°C and 65°C with the
range of initial concentration between 10 to 200ppm. There are three types of activated carbon
that have been used, which are Granular Activated Carbon (GAC) 2.5mm, Granular Activated
Carbon 0.25mm, and Powder Activated Carbon.
The objectives of this study are to determine the adsorption isotherms of toluene and n-hexane
on activated carbon through the adsorption process, to investigate the effect of temperature on
the adsorption capacity of toluene and n-hexane, and to model the experimental adsorption
isotherm databy using the established adsorption isotherm equations on activated carbon.
The equilibrium concentrations have been analyzed using UV-Vis Spectrophotometer and Gas
Chromatography with Purge and Trap after the solutions were adsorbed for 24 hours.
The toluene adsorption isotherm has the S-shaped form and of type V isotherm based on the
classification of Brunaeur, Deming, Deming and Teller (BDDT). Among the three temperature
conditions, it is found that the adsorption favors the lowest temperature (35°C). This indicates
that adsorption process is exothermic, lower the temperature will shift the adsorption
equilibrium to adsorption rather than desorption. GAC 2.5 mm is found to have the highest
adsorption capacityamongthe others. It is impossible to carry out the experimentwith n-hexane
due to its high volatility. The amount of n-hexane is considered negligible in aqueous solution
and adsorption process does not require.
Freundlich isotherm is the most popular model which is widely used in the correlation of liquid
adsorption. Sips isotherm which is the combination between Langmuirand Freundlichequation
is an alternative model. However, the techniques were not successful with toluene isotherm
measurement.


A study published this morning in Nature offers further insight into how dogs became domesticated. The comparative analysis of human, canine and wolf genomes suggests that humans and dogs have evolved in parallel as a response to the increasingly starchy diets on offer after the agricultural revolution. Such a wholesale change in diet has not necessarily been benign for either species.


This paper is devoted to the design of precoders maximizing the ergodic mutual information (EMI) of bi-correlated flat fading MIMO systems equipped with MMSE receivers. The channel state information and the second-order statistics of the channel are assumed available at the receiver side and at the transmitter side respectively. As the direct maximization of the EMI needs the use of nonattractive algorithms, it is proposed to optimize an approximation of the EMI, introduced recently, obtained when the number of transmit and receive antennas t and τ converge to ∞ at the same rate. It is established that the relative error between the actual EMI and its approximation is a O( [ 1/( t2)]) term. It is shown that the left singular eigenvectors of the optimum precoder coincide with the eigenvectors of the transmit covariance matrix, and its singular values are solution of a certain maximization problem. Numerical experiments show that the mutual information provided by this precoder is close from what is obtained by maximizing the true EMI, but that the algorithm maximizing the approximation is much less computationally intensive.


BACKGROUND
A fragility hip fracture is a serious injury in older adults. After experiencing a fracture, a large percentage of patients do not regain their pre-fracture level of mobility. There are several international guidelines recommending early mobility after surgery. We do not know the usage of these early mobility recommendations by health care providers within our institution. An evidence-to-practice gap occurs when there is a failure to implement best practices. Utilization of a systematic method allows for a strategic approach to assessment of an evidence-to-practice gap. There were two aims of this project: a) to describe early mobility activities undertaken on one post surgical unit and, b) to identify if there is an evidence-to-practice gap.

METHODS
At a large tertiary centre in Toronto, Ontario, medical records from one calendar year were abstracted for older adults (≥65 years of age) recovering from fragility hip fracture repair. Data were collected regarding demographics, co-morbidities, surgery type, post-operative mobility activities, and any post-operative complications. Primary outcomes were: evidence of early mobility activities and a comparison to Health Quality Ontario recommendations for fragility hip fracture care.

RESULTS
Between 11% and 50% of patients were not participating in early mobility activities. By postoperative day five only two patients had walked over 50 m. Those with low pre-fracture functional ability and a cognitive impairment consistently experienced lower rates of participation compared to patients with high pre-fracture functional ability and no cognitive impairment. Chi-square tests and regression analysis did not reveal any significant associations with variables.

CONCLUSIONS
There was very limited participation in early mobility activities after surgery. The study was unable to identify any significant relationships between several variables that may impact participation. This chart review identified the processes that have been sustained and highlights potential areas for future interventions.


BACKGROUND AND OBJECTIVES
High-powered magnets are among the most dangerous childhood foreign bodies. Consumer advocates and physicians have called for these products to be effectively banned, but manufacturers assert warning labels would sufficiently mitigate risk.

METHODS
Subjects from Injuries, Morbidity, and Parental Attitudes Concerning Tiny High-powered Magnets (IMPACT of Magnets), a retrospective, multicenter study of children with high-powered magnet exposures (ie, ingestion or bodily insertion), were contacted. Consenting participants responded to a standardized questionnaire regarding the presence and utility of warning labels, magnet product manufacturer, and attitudes around risk.

RESULTS
Of 596 patients in the IMPACT study, 173 parents and 1 adult patient were reached and consented to participate. The median age was 7.5 years. Subjects reported not knowing if a warning label was present in 60 (53.6%) cases, whereas 25 (22.3%) stated warnings were absent. Warnings were present in 28 (24.1%) cases but only 13 (46.4%) reported reading them. A manufacturer was identified by families in 28 (16.1%) exposures; 25 of these were domestic and 27 had warnings. Subjects reported knowing magnets were dangerous in 58% of the cases, although 44.3% believed they were children's toys and only 6.9% knew high-powered magnets were previously removed from the United States market.

CONCLUSIONS
Over 90% of subjects from the IMPACT study didn't know if warning labels were present or failed to read them if they were, whereas almost half believed high-powered magnets were children's toys. Warning labels on high-powered magnet products are, therefore, unlikely to prevent injuries in children.


The need for corrections officers is projected to increase by 16% by 2016 (Bureau of Labor Statistics). This is great news for students who want to work within a correctional facility as there will be ample employment opportunity. Drs. DeLisi and Conis provide their unparalleled research expertise/productivity and nearly 40 years of combined criminal justice practitioner experience to make American Corrections: Theory, Research, Policy, and Practice, Second Edition the ideal introductory text for the corrections course. They use a straightforward writing style that is scholarly, engaging, and fun. Updated throughout, it contains both classic and cutting-edge contemporary data on correctional topics drawing from the fields of criminology, criminal justice, sociology, psychology, government, and public policy. The text is broken down into four parts, starting with an overview of the correctional system, including the history and philosophy of corrections. It progresses to discuss the management of offender risk and covers the ways in which the correctional system classifies offenders according to the risks they exemplify. Part III delves into the prison system and includes discussions on the journey of prisoners, from prison, to parole, and reentry into society. This comprehensive introduction concludes with an examination of the special populations within the correctional system, including juveniles, women, and those sentenced to capital punishment and civil commitment. Key Features of the Revised Second Edition: -Now available in paperback! -Revised to be more sociologically-focused, this Second Edition includes boxes throughout highlighting the effects on community. -Provides an increased focus on gender, race, and immigration issues. -Contains more content discussing the philosophy of corrections, encouraging your students to see the big-picture and think critically of the subject. -Every new copy includes an access code to the accompanying student companion website featuring a variety of interactive study aids. Exciting new content added to the Second Edition: -New section on the correctional system and American society -New section on the fiscal costs of the correctional system and ways that correctional policies can save costs while reducing crime -New section on historical developments in corrections -New section on juveniles and the life imprisonment without parole sanction -Expanded correctional case law -New section on teen courts -New section on federal pretrial services -New section on crisis intervention teams -New section on cognitive behavioral therapy -New section on mental health probation -New section on effective correctional policies -New section on back-end sentencing and parole -New section on law enforcement reentry initiatives and reentry courts -New section on Graham v. Florida (2010) -New section on juvenile drug courts -Expanded discussion on women and reentry -New discussion on clemency and elected executions -Updated box features including 13 new box features -Thoroughly updated correctional data -Thoroughly updated literature with more than 300 new references Instructor Resources: Navigate Course Mgr., Instructor's Manual, PowerPoint Lecture Outlines, Test Bank


: Perinatal mortality in Cape Town has progressively decreased in all racial groups over the past 60 years. The perinatal mortality rate for Coloureds and Blacks, however, remains at 20 per 1 000 more than for Whites. While the stillbirth rate approximates the early neonatal death rate in Whites, the stillbirth rate for Coloureds and Blacks is double the rate for early neonatal deaths. Although there is a significantly higher early neonatal death rate for Coloureds and Blacks, the major component of perinatal loss is stillbirth and 80% of stillbirths occur before the onset of labour. Focus should be on the detection of the fetus at risk, with, perhaps, earlier intervention.


Concentric bracings (CB) are one of the most prevalent lateral load bearing systems in steel structures. These bracings have a remarkable lateral stiffness and strength, but their compressive buckling prevents them from being ductile and absorbing optimal energy. Consequently, in recent decades, researchers have conducted extensive studies to improve the concentric bracing behavior, which resulted in the development of different design and execution methods for concentric bracings. In this paper, by using numerical and experimental studies, a new method is proposed to improve the behavior of concentric bracings. In this method, a local fuse (LF) is used along the brace. This fuse is restrained by auxiliary elements (AE) to prevent its local buckling under compressive load. This makes the brace behaves in a similar manner in both tensile and compressive cyclic loads, resulting in ductile behavior and high-energy absorption. In this study, by using numerical results, an investigation is done for proper position of the fuse along the braces and its optimal shape and length. In addition, an analytical study has been performed comparing the structural behavior of concentric braces with LF-AE braces. The results have been demonstrated that LF-AE braces have better performance than concentric braces.


Ludics is a reconstruction of logic with interaction as a primitive notion, in the sense that the primary logical concepts are no more formulas and proofs but cut-elimination interpreted as an interaction between objects called designs. When the interaction between two designs goes well, such two designs are said to be orthogonal. A behaviour is a set of designs closed under bi-orthogonality. Logical formulas are then denoted by behaviours. Finally proofs are interpreted as designs satisfying particular properties. In that way, designs are more general than proofs and we may notice in particular that they are not typed objects. Incarnation is introduced by Girard in Ludics as a characterization of "useful" designs in a behaviour. The incarnation of a design is defined as its subdesign that is the smallest one in the behaviour ordered by inclusion. It is useful in particular because being "incarnated" is one of the conditions for a design to denote a proof of a formula. The computation of incarnation is important also as it gives a minimal denotation for a formula, and more generally for a behaviour. We give here a constructive way to capture the incarnation of the behaviour of a set of designs, without computing the behaviour itself. The method we follow uses an alternative definition of designs: rather than defining them as sets of chronicles, we consider them as sets of paths, a concept very close to that of play in game semantics that allows an easier handling of the interaction: the unfolding of interaction is a path common to two interacting designs.


Byzantine fault tolerance has been intensively studied over the past decade as a way to enhance the intrusion resilience of computer systems. However, state-machine-based Byzantine fault tolerance algorithms require deterministic application processing and sequential execution of totally ordered requests. One way of increasing the practicality of Byzantine fault tolerance is to exploit the application semantics, which we refer to as application-aware Byzantine fault tolerance. Application-aware Byzantine fault tolerance makes it possible to facilitate concurrent processing of requests, to minimize the use of Byzantine agreement, and to identify and control replica nondeterminism. In this paper, we provide an overview of recent works on application-aware Byzantine fault tolerance techniques. We elaborate the need for exploiting application semantics for Byzantine fault tolerance and the benefits of doing so, provide a classification of various approaches to application-aware Byzantine fault tolerance, and outline the mechanisms used in achieving application-aware Byzantine fault tolerance according to our classification.


OBJECTIVE: To review randomized trials involving the use of systemic hemostatic medications for reducing surgical blood loss. DATA SOURCES: Articles were obtained through searches of MEDLINE (1966–September 2000). The bibliographies of retrieved publications were reviewed for additional references. STUDY SELECTION: All randomized studies and pharmacoeconomic evaluations that involved medications used for systemic hemostasis in the perioperative period were included. DATA EXTRACTION: Randomized studies involving conjugated estrogens, aminocaproic acid, tranexamic acid, desmopressin, and aprotinin for systemic hemostasis were extracted. Studies of proton-pump inhibitors for upper gastrointestinal bleeding and octreotide for variceal bleeding were excluded, as were trials involving the use of any hemostatic agent for cardiovascular surgery. The primary outcome under review was a reduction in bleeding as defined by reduced transfusion requirements. DATA SYNTHESIS: There is limited efficacy and toxicity information concerning the use of conjugated estrogens for reducing surgery-related bleeding. Similarly, there are a limited number of randomized studies involving aminocaproic acid and tranexamic acid, and with the exception of tranexamic acid for reducing transfusion requirements with knee surgery, the study results are either conflicting or negative. For desmopressin, evidence from a substantial number of randomized trials documents its lack of efficacy. Aprotinin has reduced bleeding and transfusion requirements in a number of randomized studies involving patients undergoing orthopedic surgery, but cost-effectiveness studies are needed to better define its therapeutic role. Trials of aprotinin during hepatic surgery have yielded conflicting results. CONCLUSIONS: Most hemostatic medications used for reducing surgery-related bleeding have limited or contradictory evidence of efficacy.


: The combustion and exhaust emission characteristics in a spark ignition (SI) engine with various test fuels (bioethanol - gasoline blends) and air-fuel ratio were investigated in this research. To investigate the influence of the excess air ratio and ethanol blends on the combustion characteristics such as the cylinder pressure, rate of heat release (ROHR), and fuel consumption rate were analyzed. In addition, the reduction effects of exhaust emissions such as carbon monoxide (CO), unburned hydrocarbon (HC), and oxides of nitrogen (NOx) were compared with those of neat gasoline fuel under the various excess-air ratios. The results showed that the peak combustion pressures and the ROHR of bioethanol fuel cases were slightly higher than those of gasoline fuel at all test ranges and fuel ratio. As compared with gasoline fuel (G100) at each given excess air ratio, BSFC of bio-ethanol was increased. The CO, HC, NOx emissions of bio-ethanol blends were lower than those of gasoline fuel under overall experimental conditions.


This is a comprehensive guide to treating small pets such as dogs, cats, guinea pigs, rodents, reptiles and birds with homoeopathic remedies. It includes essential information on the principles and practice of homoeopathy, as well as practical guidance for owners, breeders and veterinary surgeons. There are sections on getting started with homoeopathic remedies, on homoeopathic first aid and on treating specific diseases. The advice is illustrated by selected case studies.


The interactions between a plasma and magnetic field are of great interest to the astrophysics and fusion power communities and may be modeled under a wide range of simplifying assumptions. Here, we investigate the fully electromagnetic ideal two- fluid plasma model and compare results with the ideal magnetohydrodynamic (MHD) model. In contrast to the MHD approach the two fluid-model simulates ions and electrons separately, allowing the assumptions of quasi-neutrality, small Larmor radius and small Debye length to be discarded. A two dimensional numerical method has been developed which draws on adaptive spatial resolution and locally implicit time stepping to allow for efficient simulation of the two-fluid plasma model. The KelvinHelmholtz instability, with background magnetic field, is simulated over a wide range of plasma regimes. Comparison with hydrodynamic and MHD solutions demonstrates the ability of the two fluid model to bridge the gap between these limiting solutions. The two fluid solutions also demonstrate various stages in the suppression of the Kelvin-Helmholtz instability due to the presence of a background magnetic field.


Imidazothiadiazole was discovered around the 1950s era, containing an imidazole ring fused to a thiadiazole ring. Imidazothiadiazole exhibit versatile pharmacological properties including anticonvulsant, cardiotonic, anti-inflammatory, diuretic, antifungal, antibacterial and anticancer. Despite of the being discovered in 1950s, the imidazothiadiazole derivatives are unable to being processed to clinical trials because of lack of bioavailability, efficacy and cytotoxicity. The recent patent literature focused on structural modification of imidazothiadiazole core to overcome these problems. This review limelight a disease-centric perspective on patented imidazothiadiazole from 2015-2023 and to understand their mechanism of action in related diseases. The relevant granted patent applications were located using patent databases, Google Patents, USPTO, EPO, WIPO, Espacenet and Lens.


The morphological status of affixes in Chinese has long been a matter of debate. How one might apply the conventional criteria of free/bound and content/function features to distinguish word-forming affixes from bound roots in Chinese is still far from clear. Issues involving polysemy and diachronic dynamics further blur the boundaries. In this paper, we propose three quantitative features in a computational model of affixoid behavior in Mandarin Chinese. The results show that, except for in a very few cases, there are no clear criteria that can be used to identify an affix's status in an isolating language like Chinese. A diachronic check using contextualized embeddings with the WordNet Sense Inventory also demonstrates the possible role of the polysemy of lexical roots across diachronic settings.


A random sample of 102 cases referred in 1983 by paramedicals to the Southern Highlands Provincial Hospital, Papua New Guinea, was analysed for agreement with the final hospital diagnosis and with standardized primary care therapies. Health centre diagnosis was judged accurate in 45% of cases; inaccuracies in a further 17% had no projected health consequences. However, resulting serious sequelae could be projected in half of the incorrect diagnoses. Diagnosis of surgical cases was more often accurate (P<0.05) than in medical cases. Treatment which was adequate or standard for the diagnosis made at the health centre had been given there in 80% of cases. However, there were serious diagnostic inaccuracies in 38% of all referral cases; this study suggests a need for problem-based paramedical education in diagnosis, especially in non-surgical problems. Visits by doctors to health centres could reinforce this diagnostic teaching and better evaluate paramedicals' clinical accuracy in the health centre.


We present the most relevant data of a series of 8 cases of PTA coming from our environment. We highlight the onset of PTA with low doses of amiodarone (equal or lower than 400 mg/day), the affectation of only aged patients (range 63-77 years) and always, except in one case, during the first five years of treatment with amiodarone. Dyspnea was the most frequent symptom. The definition of PTA is mainly clinical-radiological and it has no biochemical, radiological or functional unique characteristics, determining the need for a careful differential diagnosis. The prognosis was excellent when the administration of amiodarone was stopped and, in some cases, steroids were added.


The Industrial Predictive Analytics for Industry 4.0 is a system that predict and prevent machine failures and breakdown by analyzing time-series data (temperature, pressure, vibration etc.) received from sensors embedded in machines and equipment. The system can analyze machine parameters to identify patterns and predict breakdowns before they happen. The core of the proposed system is based on Artificial Neural Network approach (both Deep and Shallow Neural Networks). Artificial Intelligence and Artificial Neural Networks allow analyses the huge amounts of data collected from the manufacturing process and predict what will go wrong, and when. The proposed system works in the paradigm of Industry 4.0 and provides the abilities in the area of predictive maintenance. The Industrial Predictive Analytics for Industry 4.0 also contains a decision-making system and support system that significantly increases the level of maintenance.


Space is viewed by many as the next frontier and the next boundary to be crossed. This view, popularized in cinema and by science fiction writers, was recently reinforced by the successful suborbital flight of the privately owned SpaceShipOne. But is this view based on substance; will space become the new mass tourism experience of the 21st Century? In time this might be the case but as this paper argues the cost of travel is likely to be so high that non-physical travel based on cyber experiences is a strong possibility. This paper uses scenarios as a method to investigate the possibility of both physical and cyber-travel into space in the future.


We study tender offers for a firm which is owned by one large shareholder who holds less than half of the total shares, and many small shareholders who each hold a unit share. Each shareholder is privately informed, yet uncertain, about the raider's ability to improve the value of the firm, whereas the raider is unin- formed. In the benchmark model of complete information, the raider is unable to make a profit. As shown in Marquez and Y?lmaz (2008), the same obtains when the raider is facing only privately informed small shareholders. We show, however, that the combination of private information on the side of shareholders and the presence of a large shareholder can facilitate profitable takeovers. More precisely, for any given information structure, the raider can make a profit if the large shareholder holds a sufficiently large stake in the company. In the unique equilibrium outcome, neither the probability of a successful takeover nor the quilibrium price offer depends on the large shareholder's information. Therefore, the large shareholder's information is not reflected in the price. When the equilibrium price offer is positive, the large shareholder tenders all of his shares regardless of his information. Finally, we show that the same type of equilibria arise when there are several large shareholders, as long as their total stake in the company is smaller than one-half. Keywords: takeovers, tender offers, lemons problem, large shareholder. JEL Classification Numbers: D82, G34.


The bleaching of teeth has encountered some legislative problems over the past few years but it is now possible to use both vital and non-vital bleaching techniques in the UK. Hydrogen peroxide has a long history of use and would appear to be safe to use to change the appearance of discoloured teeth. It is conservative of tooth tissue and may delay the need for more invasive veneers and crowns. This article describes some of the methods of bleaching using hydrogen peroxide that are currently available.


This Newsletter, published by The Committee on Science and Technology in Developing Countries (COSTED), aims to disseminate information on science education, the impact of science and technology, and conferences and other communications ventures involving developing countries. The most recent issue (July 1977) contains articles on &dquo;Biological Control of Pests in Developing Countries&dquo;, &dquo;Scale and Appropriate Technology&dquo;, and many other informative reports, including one on the United Nations Conference on Science and Technology for Development.


Community forestry projects in Ethiopia have been implemented using the top–down approach, which may have contributed to the failure of most of these projects. The so-called community plantations practically belonged to the government and the labour contribution of the local communities in the establishment of the plantations was mainly in exchange for wages. In this paper, we use the contingent valuation method to examine the determinants of the value of community forestry in rural Ethiopia and its feasibility, when the plantations are established, managed, and used by the communities themselves. The value elicitation format used is discrete question with open-ended follow-up which is closer to the market scenario our respondents are familiar with compared, for example, with the single discrete choice format. Unlike most other studies, we use a tobit model with sample selection in the empirical analysis of the bid function to correct for the effect of excluding invalid responses (protest zeros, outliers and missing bids) from the analysis. The analysis of the bid function shows that household size, household income, distance of homestead to proposed place of plantation, number of trees owned and sex of household head are significant variables that explain willingness to pay. We also find that there are significant differences in willingness-to-pay across sites. It is hoped that this study contributes to the limited empirical literature on community forestry in developing countries by indicating some of the conditions under which community plantations will be acceptable and feasible.


BACKGROUND
The increasing shortage of financial resources requires optimal use of hospital care by patients. However, the studies carried out to date in France have been limited to patients who are hospitalized, and have not included those seen as out-patients.

POPULATION AND METHODS
All patients seen as out-patients in 10 hospitals in the Paris district (3 pediatric hospitals and 7 pediatric departments located in hospitals for adults and children), during the week of 19-26 April 1989, were given a questionnaire on the age, sex, nationality, socio-cultural and economic features of the family, history of earlier medical visits or admissions, the existence of pediatrician or practitioner, and the means and time taken to get to the hospital. Medical diagnosis was established for each patient following the WHO International Classification of Diseases (9th edition).

RESULTS
2,365 out of 2,675 questionnaires were usable. The main features were: 50% of patients were less than 3 years old, 55% were of French origin; 78% belonged to families with relatively low socio-economic status. Both parents had professional activities in 49% of families, 7% of mothers did not speak or write French. The ratio of patients aged less than 3 years admitted to the emergency ward was higher than the average. The most frequent diseases presented by these patients were respiratory (23%), infectious (14%), gastro-intestinal (10%) and neurological (7%); 14% of the patients were seen for symptoms that could not be assigned to a specific disease. 39% of patients were seen in out-patient clinics and 61% in emergency wards. 40% were sent by a health professional to out-patient clinics and only 25% to emergency wards.

CONCLUSIONS
Despite the fact that this study is subject to particular conditions, i.e., relative frequency of infectious diseases due to seasonal causes, it suggests that the hospital is becoming the primary source of health care with an increasing percentage of patients seen in "emergency", even though this emergency is often more apparent than real. Health care networks should be established.


In ad hoc networks, autonomous nodes collaborate to route information through the network. Commonly, nodes are end-systems and routers at the same time. In cases in which nodes have a notion of their geographic position, position-based routing protocols can be used; these protocols' properties of statelessness and fast adaptability to changes in the topology match very well with the characteristics of ad hoc networks.Position-based routing does not require the maintenance of routes; instead, forwarding decisions are made locally, based only on the node's own position, the positions of its neighbors, and the position of the destination. The routing algorithms are complemented by location services through which a node can obtain the position of a packet's destination.We will introduce the main components of position-based routing, discuss position-based routing algorithms as well as location services, and present an application scenario where position-based routing can be used for intervehicle communication.


In Frank Jackson's famous thought experiment, Mary is confined to a black-and-white room and educated through black-and-white books and lectures on a black-and-white television. In this way, she learns everything there is to know about the physical world. If physicalism -- the doctrine that everything is physical -- is true, then Mary seems to know all there is to know. What happens, then, when she emerges from her black-and-white room and sees the color red for the first time? Jackson's knowledge argument says that Mary comes to know a new fact about color, and that, therefore, physicalism is false. The knowledge argument remains one of the most controversial and important arguments in contemporary philosophy.There's Something About Mary -- the first book devoted solely to the argument -- collects the main essays in which Jackson presents (and later rejects) his argument along with key responses by other philosophers. These responses are organized around a series of questions: Does Mary learn anything new? Does she gain only know-how (the ability hypothesis), or merely get acquainted with something she knew previously (the acquaintance hypothesis)? Does she learn a genuinely new fact or an old fact in disguise? And finally, does she really know all the physical facts before her release, or is this a "misdescription"? The arguments presented in this comprehensive collection have important implications for the philosophy of mind and the study of consciousness.


This study aimed to show whether the ratio of CAMEL (Capital, Asset Quality, Management, Earnings and Liquidity) can be used as an indicator in predicting the health of banks in the future. This study was carried out on the banks listed on the Indonesia Stock Exchange in the period 2008-2012. Descriptive analysis and logistic regression analysis are used to analyze the data. Hypothesis testing is done with the normality test, Independent Sample T-Test and Mann Whitney test are used to determine if two sets of data are significantly different from each other. The result of this research showed that LDR and NIM variables of bank financial conditionhave no significant differents while CAR, ATTM, APB, NPL, P_PPAP, BOPO, ROA, and ROE have a significant differents. Hyphothesis testing result found that CAR, ATTM, APB, NPL, NIM, and LDR variables did not affected bank financial condition significantly while P_PPAP, ROA, ROE, and BOPO variables affected bank financial condition significantly.


1. Optic glands transplanted from one Octopus vulgaris into another cause enlargement of the gonads and ducts of the recipient. 2. Enlargement occurs whether or not the gland was secreting when implanted and regardless of the sex of the donor or recipient. 3. Glands derived from Eledone moschata or Octopus macropus implanted into O. vulgaris are as effective as glands derived from O. vulgaris. 4. Implants derived from Sepia officinalis or Loligo vulgaris appear to be ineffective.


The latent reservoir for human immunodeficiency virus type 1 (HIV-1) in CD4 + T cells is a major barrier to cure. HIV-1–infected persons who inject drugs (PWID) often struggle to maintain suppression of viremia and experience nonstructured treatment interruptions (NTIs). The effects of injecting drugs or NTIs on the reservoir are unclear. Using the intact proviral DNA assay, we found no apparent effect of heroin or cocaine use on reservoir size. However, we found significantly larger reservoirs in those with frequent NTIs or a shorter interval from last detectable HIV RNA measurement. These results have important implications for inclusion of PWID in HIV-1 cure studies.


The Cold War ran from roughly 1947 until the USSR collapse in 1991. Those years were marked by the arms race and the fear of a possible nuclear war between the USA and the Union of Soviet Socialist Republics (USSR). Sports were used as a vehicle for superiority of one political regime over the other. Champion athletes image and results were used as propaganda means because the international visibility, the public interest in major sports competitions and the national pride they aroused. U.S.A., after losing the top nation position in favor of Soviet Union in 1956 and 1960, considered winning in Olympic Games a matter of national prestige. The athlete for whom the flag is hoisted and the national anthem is sung, is the bearer of this prestige and his or her performance is inevitably associated with the country and system effectiveness. In the Olympics arena, the Cold War culminates in the boycott of the 1980 and 1984 Games. The main research question of this paper is if in present time we can address the sporting Cold War as an historic, past issue or a new stage of rivalry still persists influencing the Olympic movement? The changes that were made in the international political landscape since 1989 were reflected in the Olympic Games in Barcelona 1992 participation, when for the first time since 1972, no country boycotted the Olympic competition. Throughout the Cold War, U.S.A. and U.S.S.R. have used the Olympic Games and their athletes as opportunities for promoting their political agenda. The end of the Cold War could not prevent the politics to interfere in sport, especially in Olympic movement.


Proton exchange membrane (PEM) fuel cells have been progressively designed to become suitable for hightemperature operation to achieve further performance improvements. However, the current state-of-the-art fuel cell materials, such as long-side-chain (LSC) ionomers and membranes, are not suitable for high-temperature operation, requiring development and investigation of alternative materials. In this study, short-side-chain (SSC) membrane and ionomer are considered as potential materials, and performance of a membrane-electrode assembly (MEA) manufactured with the SSC ionomer and membrane is experimentally investigated in a scaled-up fuel cell (45 cm). Comparison is made with an MEA based on the LSC ionomer and membrane under identical preparation and testing conditions. The catalyst layers (CLs) made of either SSC or LSC ionomer are characterized through scanning electron microscopy (SEM) to understand their surface morphology and microstructure. Results show that the SSC ionomer embedded in the CL provides much more uniform surface morphology and well-proportioned microstructural characteristics than its LSC counterpart. Further, the MEA based on SSC ionomer and membrane demonstrates considerable performance superiorities under all the applied operating conditions. Furthermore, the performance of the MEA based on the SSC ionomer and membrane is found to be less sensitive to changes in operating conditions. KeywordsProton exchange membrane fuel cell; Short-sidechain ionomer; Short-side-chain membrane; High-temperature fuel


In many works dealing with national identity and national consciousness it
has become commonplace to restrict discussion of these to the post-medieval
period. Indeed, following Benedict Anderson's influential Imagined Communities,
the very possibility of the nation is often predicated on the decline of the
Middle Ages (Anderson, 1991). This approach has been challenged and criticised
by many medievalists, who note that it is testimony to wider perceptions
of the homogeneous otherness of the medieval past Johnson, 1995; Davis,
1998). To quote Carolyn Dinshaw: 'In some very influential theoretical and critical work developing out of postmodernism, the Middle Ages is still made
the dense, unvarying, and eminently obvious monolith against which modernity
and post modernity groovily emerge' (1999, p. 15)...


We propose that the behaviour of asymmetric binary fluid mixtures with a large class of attractive or repulsive interparticle interactions can be understood by mapping onto effective non-additive hard-sphere models. The latter are best analysed in terms of their underlying depletion potentials which can be exactly scaled onto known additive ones. By tuning the non-additivity, a wide variety of attractive or repulsive generalized depletion potential shapes and associated phase behaviour can be `engineered', leading, for example, to two ways to stabilize colloidal suspensions by adding smaller particles.


The effects of various deposition techniques on the photoluminescence spectra of the conjugated polymer poly[2-methoxy-5-(2′-ethylhexyloxy)-1,4-(1-cyanovinylene) phenylene] (MEH-CN-PPV) are investigated. Photoluminescence spectroscopy provides insight to the internal morphology of organic thin films through the identification of interchain or intrachain recombination peaks. Thin films were deposited on glass substrates by drop casting, spin casting, and resonant-infrared matrix-assisted pulsed laser evaporation (RIR-MAPLE) and were compared to the photoluminescence of the polymer in solution. The photoluminescence measurements reported in this article demonstrate that samples deposited by evaporative RIR-MAPLE have an internal morphology similar to that of MEH-CN-PPV in solution, leading to an enhancement of intrachain transitions in the conjugated polymer.


In the adhesive postinstalled method, headed anchor is anchored into concrete by means of a high strength epoxy resin adhesive. To measure the concrete compressive strength, the metal anchor is "pulled" from the concrete. There occur four types of failure when the metal anchor is pulled out. This paper introduces the rationale of the adhesive postinstalled method to estimate the in-place concrete strength. The embedment depth and the diameter of the reaction ring are specified by experimental phenomenon and theoretical analysis.


The inclusion of both micro and macro nutrients has been investigated in the field of animal production
and research, expressing promising effects. Perhaps incorporation of both dietary Selenium and
Protein at appropriate levels has presented a tremendous impact on productive and reproductive
performance of livestock, particularly in tropical environments. However the efficiency of growth and
normal physiological functions depends on composition and bioavailability of these nutrients in the
diets. These effects could be mediated via the hypothalamic- pituitary-axis in regulating thyroid and
growth hormones that have been shown to affect differentiation and proliferation of somatic and
gonadal cells. However, under high ambient temperature and humidity the efficiency of feed utilization
would be compromised and reproductive function deteriorates, as a consequence of impairment in
appetite and subsequent oxidative stress due to hyperthermia. In addition consequent effects of
thermal stress may also involved activation and or inhibition of the hypothalamus-pituitary liver axis.
Apparently rabbits require a high protein diet in order to compensate for low feed intake under hot
climatic conditions; and dietary selenium as a potent antioxidant. Therefore dietary protein and
selenium supplementation at appropriate level of inclusion apparently have the potential to improve
male rabbit general performance at reasonable cost.


Amplifying, Digitizing and compressing the signals from the sensors plays an important role in wireless data transmission. Nyquist sampling of bio– medical signals generates large amount of data from a single sensor which is to be stored and compressed by the processor. The proposed data acquisition platform provides amplification and digitisation at the source itself. Operational Trans conductance Amplifier and 1 bit sigma –delta ADC are designed and simulated using LT Spice.


Global 5-HT depletion improves serial spatial reversal learning in the ratLaura Nilsson SuonvieriSupervisor: Johan Alsio, Department of Psychology, University of CambridgeExaminer: Erika Roman, Department of Pharmaceutical Biosciences, Uppsala University BACKGROUND: Behavioural inflexibility, the inability to adapt to environmental changes, is a key deficit in many psychiatric disorders such as schizophrenia and obsessive-compulsive disorder (OCD). Unfortunately, no current drugs efficiently address this deficit. Behavioural flexibility is often assessed using reversal learning tasks. Previous research suggests that reversal learning is dependent on the orbitofrontal cortex (OFC) and may be modulated by serotonin (5-HT). AIM: This study aimed to further characterize the neural circuits underlying reversal learning by investigating the effects of global and selective OFC 5-HT depletion on rats' performance on a serial spatial reversal learning task. METHODS: Rats were initially trained to respond at only one of two lit nose-poke holes (e.g. left but not right). Prior to reversal, rats received either intracerebroventicular (global depletion/sham) or intra-OFC (OFC depletion/sham) infusions of either 5,7-DHT (a serotonergic neurotoxin causing a permanent depletion of 5-HT) or vehicle alone. This was followed by a series of reversals where the reward contingencies changed (e.g. right was correct instead of left). RESULTS: Global 5-HT depletion improved reversal learning by reducing the number of errors made. It also improved the retention of the reversals but did not affect the retention of preoperatively learned discrimination or the acquisition of a novel discrimination. OFC 5-HT depletion did not significantly affect any of the behavioural measures. CONCLUSION: In contrast to previous studies, our results show that global 5-HT depletion improves reversal learning whereas OFC depleted rats seem unaffected. Since no effect was seen of OFC 5-HT depletion, further studies are needed to investigate the possible brain region responsible for the facilitating effects of global 5-HT depletion on serial spatial reversal learning in rats.


The remarkable success of deep learning has prompted interest in its application to medical imaging diagnosis. Even though state-of-the-art deep learning models have achieved human-level accuracy on the classification of different types of medical data, these models are hardly adopted in clinical workflows, mainly due to their lack of interpretability. The black-box-ness of deep learning models has raised the need for devising strategies to explain the decision process of these models, leading to the creation of the topic of eXplainable Artificial Intelligence (XAI). In this context, we provide a thorough survey of XAI applied to medical imaging diagnosis, including visual, textual, example-based and concept-based explanation methods. Moreover, this work reviews the existing medical imaging datasets and the existing metrics for evaluating the quality of the explanations. In addition, we include a performance comparison among a set of report generation-based methods. Finally, the major challenges in applying XAI to medical imaging and the future research directions on the topic are also discussed.


People typically overestimate how much others are prepared to pay for consumer goods and services. We investigated the extent to which latent beliefs about others' affluence contribute to this overestimation. In Studies 1, 2a, and 2b we found that participants, on average, judge the other people taking part in the study to "have more money" and "have more disposable income" than themselves. The extent of these beliefs positively correlated with the overestimation of willingness to pay (WTP). Study 3 shows that the link between income-beliefs and WTP is causal, and Studies 4, 5a, and 5b show that it holds in a between-group design with a real financial transaction and is unaffected by accuracy incentives. Study 6 examines estimates of others' income in more detail and, in conjunction with the earlier studies, indicates that participants' reported beliefs about others' affluence depend upon the framing of the question. Together, the data indicate that individual differences in the overestimation effect are partly due to differing affluence-beliefs, and that an overall affluence-estimation bias may contribute to the net tendency to overestimate other people's willingness to pay.


In the last years software researchers have been looking for ways of assembling systems in a style of software construction similar to "LEGO blocks". Software components are reusable building blocks for constructing software systems. Component-based development may greatly increase the productivity of software engineers and improve the quality of software. There are many issues related with components that are of wide interest both to academics and people from industry. One of them is the retrieval of components that will be assembled into a new system. It is difficult to decide whether an implementation fits on a predefined design. In this work, we consider the problem of assessing that the implementation of a concrete component is consistent with the specification of the desired functionality. We assume that the component source code is not available and we have a formal specification of the system of interest. We propose to perform a dynamic assessment using tests derived from the specification (semantic criteria) but executed using the implementation of the candidate component.


Abstract This paper investigates the performance of conventional turning and ultrasonically assisted turning (UAT) processes with plane and textured cutting inserts. Simulations based on the finite-element method were carried out using a software package ABAQUS/Explicit (Dassault Systemes, France). The obtained results were validated experimentally by employing a specially developed UAT setup. The purpose of the paper is to analyze cutting-force variation by the use of textured cutting inserts. Optimized dimensions of the texture pattern were used to model textured cutting inserts. The cutting-force variation in UAT was assessed with finite-element method, confirming diminishing cutting forces at a tool–workpiece interface during a noncontact time. The use of the textured cutting inserts in the UAT process resulted in the lowest cutting forces when compared to a plane tool in UAT as well as both plane and textured tools in the conventional turning process.


Enhanced biological phosphorus removal (EBPR) has been used for decades to remove phosphorus from municipal wastewater because it allows facilities to meet water quality goals while minimizing chemical consumption and sludge production. However, there is still substantial variability in both the practices applied to achieve EBPR and the level of soluble phosphorus removal achieved.

The objective of this research project was to develop information that can be used to help municipal wastewater treatment plants more efficiently and cost effectively remove phosphorus through EBPR processes. This project included detailed analysis of routine water quality and operating data, field testing observations, and special studies conducted over the course of the project to evaluate the variability of EBPR, factors influencing EBPR performance, and the relationship between EBPR and the presence of glycogen accumulating organisms (GAOs).

This title belongs to WERF Research Report Series

ISBN: 9781843397403 (Print)

ISBN: 9781780404479 (eBook)


The need for better linkages between evidence and policymaking has been well established in the literature, with a heightened focus on the relationship between researchers, research utilisation and policy development. However, fostering such linkages using a policy network approach
 has seldom been discussed. This article revisits a key framework in the policy network literature: the policy community, to shed further light on such linkages. Using an empirical approach built on the experience of the Social Policy Research Centre, this article discusses the utility of a
 policy community network between academic researchers and policymakers. In doing so, the study makes clear that the establishment and strengthening of policy communities is time-bound. Furthermore, this paper argues the need to adhere to network conditions as interactions remain fluid and
 mature over time.


: Liver metastasis is a major cause of mortality in colorectal cancer (CRC). The current study was to investigate the ability of ulinastatin (UTI) and curcumin (CUR) to inhibit CRC liver metastases via modulating matrix metalloproteinase-9 (MMP-9) and E-cadherin expression. Human CRC HCT-116 cells were treated with compounds individually and in combination in order to understand the effect on cell migration and invasion. The HCT-116 cell line was established to stably express luciferase and green fluorescent protein (GFP) by lentiviral transduction (HCT-116-Luc-GFP). We identified an anti-metastasis effect of UTI and CUR on a CRC liver metastasis mouse model. Tumor development and therapeutic responses were dynamically tracked by bioluminescence imaging. Expression of MMP-9 and E-cadherin in metastatic tumors was detected by immunohistochemical assay. Results of wound healing and cell invasion assays suggest that treatment with UTI, CUR, and UTI plus CUR, respectively, significantly inhibit HCT-116 cell migration and invasion. Furthermore, results of CRC hepatic metastasis on a nude mouse model showed that treatment with UTI, CUR alone, and a combination notably inhibited hepatic metastases from CRC and prolonged survival of tumor-bearing mice, especially in the UTI plus CUR group. These results suggest that the combination of UTI and CUR together may offer greater inhibition against metastasis of CRC. CUR on CRCs to prevent metastases. Our findings revealed that compared with the untreated groups, those treated with UTI or CUR individu-Powered


Summary Complete or partial rupture of the cranial cruciate ligament (CCL) is a common injury of the canine stifle. Most practicing veterinarians would agree that optimal outcome is best achieved with surgical intervention. A popular method of stabilization is an extra-articular suture stabilization. The objective of this manuscript is to describe suture placement in a more isometric position as compared to traditional suture placement. A second objective is to introduce the veterinary surgeon to novel anchor products used for stabilization.


The paper is an attempt to summarize the available Lithuanian folk knowledge about the Moon. The ethnoastronomical materials that have been collected during expeditions since 1988 as well as ethnographic and folklore archive data in written sources are used in this work. Lithuanian ethnographical material gives far more information about the Moon (terms, narratives, folklore, ethnocosmography, popular meteorology, relics of lunar calendar, folk belief, etc.) than about other heavenly bodies.


With the development of fifth-generation (5G) communication networks, in order to meet the growing demand for high-speed and low-latency wireless communication services, channel capacity has become the main driving force for choosing millimeter wave (mm-wave) over over-crowded sub-6 GHz frequency bands. Recently, beamforming phased array attracts significant research efforts as it is a promising solution and unique in its ability to overcome the high path-loss at high frequency, provide fast beam steering and deliver better user-ends experience. However, to alleviate the issues that associated with beamforming phased array, such as imbalance between array elements and non-linearity caused by power-amplifiers (PAs) in beamforming channels, far-field (FF) based array calibration and digital pre-distortion (DPD) need to be performed, which is not practical in real world scenario. This thesis presents a low-cost 16-element dual-polarized mm-wave antenna-on-printed circuit board (PCB) transmitter RF beamforming array with embedded near-field probes (NFPs) at 37-40 GHz. The elements are orthogonal, proximity-coupled feed dual-polarized patch antenna with a spacing of 0.5λ within 2x2 subarray and 0.6λ between 2x2 subarray at 38.5 GHz, resulting in maximum 17.7 dB gain with a scan angle of +/-50◦, +/-20◦ in azimuth and +/-20◦, +/-50◦ in elevation for vertical polarization and horizontal polarization, respectively. Without affecting phased array performance, the NFPs achieve flat and comparable coupling magnitude and group delay to the closet RF chain for both polarizations, across operating frequency range. This ensures the quality of received output signal from phased array to implement array calibration and DPD. The configuration of embedded NFPs maintains the scalability of phased array and eliminate the needs of impractical FF reference probe for array calibration and DPD.


The purpose of the present study is to investigate systematically the mechanisms of alterations in the optical properties of whole blood immersed in the biocompatible agent dextran, and to define the optimal concentration of dextrans required for blood optical clearing in order to enhance the capability of light penetration depth for optical imaging applications. In the experiments, dextrans with different molecular weights and various concentrations were employed and investigated by the use of the optical coherence tomography technique. Changes in light attenuation, refractive index and aggregation properties of blood immersed in dextrans were studied. It was concluded from the results that the mechanisms for blood optical clearing are characteristic of the types of dextrans employed, their concentrations and the application stages. Among the substances applied, Dx500 at a concentration at 0.5 g dl−1 gives the best result in improving light penetration depth through the blood. The increase of light transmission at the beginning of the addition of dextrans is mainly attributed to refractive index matching between the scattering centres and the ground matter. Thereafter, the transmission change is probably due to a dextran-induced aggregation–disaggregation effect. Overall, light scattering in the blood could be effectively reduced by the application of dextrans. It represents a promising approach to increasing the imaging depth for in vivo optical imaging of biological tissue, for example optical coherence tomography.


In this study a novel method of science mapping is presented which combines bibliographic coupling, as a measure of document-document similarity, with an agglomerative hierarchical cluster method. The focus in this study is on the mapping of so called 'core documents', a concept presented first in 1995 by Glanzel and Czerwon. The term 'core document' denote documents that have a central position in the research front in terms of many and strong bibliographic coupling links. The identification and mapping of core documents usually requires a large multidisciplinary research setting and in this study the 2003 volume of the Science Citation Index was applied. From this database, a sub-set of core documents reporting on the outbreak of SARS in 2002 was chosen for the demonstration of the application of this mapping method. It was demonstrated that the method, in this case, successfully identified interpretable research themes and that iterative clustering on two subsequent levels of cluster agglomeration may provide with useful and current information.


On the basis of the data of metal ions influence it was established that Penicillium commune 266 alpha-L-rhamnosidases are dependent of metals. The cations of Cu2+, Mn2+, Ag+, Hg2+ essentially influenced the activity decreasing its up to 45-55%. Ba2+ and Mn2+ ions completely inhibited alpha-L-rhamnosidase 2 activity in concentration of 10(-3) M. The role of carboxylic group and histidine imidazole group in hydrolysis of rhamnoglycosides have been estimated by the Dixon, Lineweaver-Burke and photooxidation methods. It was also shown that sulfhydrilic groups which do not take part in catalysis, but are necessary for displaying the enzymatic activity are located at a certain distance from P. commune 266 alpha-L-rhamnosidase active centre.


Few people have changed the world like the Nobel Prize winners. Their breakthrough discoveries have revolutionised medicine, chemistry, physics and economics. Nobel Life consists of original interviews with twenty-four Nobel Prize winners. Each of them has a unique story to tell. They recall their eureka moments and the challenges they overcame along the way, give advice to inspire future generations and discuss what remains to be discovered. Engaging and thought-provoking, Nobel Life provides an insight into life behind the Nobel Prize winners. A call from Stockholm turned a group of twenty-four academics into Nobel Prize winners. This is their call to the next generations worldwide.


Vascular dementia (VaD) is a major contributor to the dementia syndrome and is described as having problems with reasoning, planning, judgment, and memory caused by impaired blood flow to the brain and damage to the blood vessels resulting from events such as stroke. There are a variety of etiologies that contribute to the development of vascular cognitive impairment and VaD, and these are often associated with other dementia-related pathologies such as Alzheimer disease. The diagnosis of VaD is difficult due to the number and types of lesions and their locations in the brain. Factors that increase the risk of vascular diseases such as stroke, high blood pressure, high cholesterol, and smoking also raise the risk of VaD. Therefore, controlling these risk factors can help lower the chances of developing VaD. This update describes the subtypes of VaD, with details of their complex presentation, associated pathological lesions, and issues with diagnosis, prevention, and treatment.


The medial olivocochlear complex (MOC) is an auditory nucleus that projects efferent nerve fibers to control the behaviors of both sides of the cochlea. Otoacoutsic emissions (OAEs) are by-products the activities of the outer hair cells (OHCs) in the cochlea and could be used as a noninvasive way to study the efferent control of the MOC. However, existing results regarding the efferent control are quite controversial and often restricted to a rather limited frequency range. In this study, a new method of measuring stimulus frequency otoacoustic emissions (SFOAEs) with the presence of a contralateral acoustic stimulation (CAS) was proposed to study the efferent control over the cochlea. SFOAEs were measured with swept tones with time varying frequencies so that SFOAE spectra with and without the presence of the CAS could be compared with high frequency-resolution. The results showed that there was consistent decrease in the amplitude of the swept-tone SFOAEs across a wide frequency range from 0.5 to 8 kHz when the CAS was presented, suggesting an outstanding attenuation of OHC activities by the efferent control from the MOC. The SFOAE decrease with the presence of the CAS might provide a new approach to measure the strength of the efferent control and to evaluate the functional status of the central auditory pathway.


This book analyzes in vivid detail the German debate about the importance and meaning of work as it changed under the impact of industrialization, with special emphasis on the period between the two world wars. A social history of ideas, it covers the writings of such thinkers as Hegel, Marx, and Weber, but also examines contributions made by industrial psychologists, engineers, educators, and others who actively promoted reforms designed to solve the problem of alienation whether by changing the nature of work or by altering worker attitudes. A final section deals with the National Socialists, who promised to reinvigorate the German work ethic, restore joy in work, and reintegrate the German worker into the Volk community. The author draws our attention particularly to the Third Reich's policies and institutions aimed at realizing these Nationalist Socialist objectives concerning the worker. In so doing, Joan Campbell shows how the history of the idea of work deepens our understanding of the origins, nature, and appeal of Nazism. In a broader context, she uses her sources to explore the relationship between social and intellectual change.Originally published in 1989.The Princeton Legacy Library uses the latest print-on-demand technology to again make available previously out-of-print books from the distinguished backlist of Princeton University Press. These paperback editions preserve the original texts of these important books while presenting them in durable paperback editions. The goal of the Princeton Legacy Library is to vastly increase access to the rich scholarly heritage found in the thousands of books published by Princeton University Press since its founding in 1905.


BACKGROUND
Randomized controlled surgical trials (RCST) are the optimal way to validate new surgical treatments, yet RCSTs comprise a very small fraction of published articles in the surgical literature. One of most frequent reasons for lack of success in RCSTs is the failure to recruit an adequate number of patients.

METHODS
We report the results of 14 months of recruitment for an RCST comparing two different surgical procedures for the treatment of painful hallux valgus. The study is an open-label non-inferiority parallel trial, with an accrual goal of 100 subjects in 24 months.

RESULTS
In the first 14 months of recruitment, 94 patients were assessed for eligibility, of which 54 were excluded and 40 were protocol-eligible. Of these 40 only 13 enrolled in the trial. Eleven patients were randomized and treated according to the protocol, the other two withdrew prior to randomization. Of the 27 eligible patients who did not enroll and the 2 eligible patients who withdrew prior to ramdomization, 22 declined to participate in the study and 7 elected to have surgical treatment but refused randomization.

CONCLUSIONS
The data show that investigators planning RCST's in surgery should be aware of the large amount of effort and significant financial resources needed to achieve patient recruitment goals.


Chronic actinic dermatitis (HAD) - immunologically mediated photodermatosis characterized by pruritic eczematous lesions on areas of skin exposed to sunlight. Examined 65 patients with the purpose of the study and analysis of clinical, allergological and photobiological characteristics of HAD, the manifestations of which occur during the spring-summer-autumn period, mimic allergic contact dermatitis, eczema, diffuse variant of atopic dermatitis. In accordance with the results of fototest all patients marked change of photosensitivity: both UVA and UVB – from 77.1 per cent, only to UVA - 10,7%, only to UVB is 9.2%. Almost all patients were marked sensitization to vegetable allergens.


OBJECTIVE
To investigate the neurodevelopmental outcome of childhood cancer survivors treated at the Eric Williams Medical Sciences Complex (EWMSC).

METHODS
Study participants were children treated at EWMSC from January 2003 to March 31, 2012 for various childhood cancers. All had completed treatment and were in remission. The McCarthy Scales of Children's Abilities (MSCA) was administered. The study was conducted from December 2011 to March 31, 2012.

RESULTS
Twenty-six children were evaluated, a response rate of 74%. There were 12 males and 14 females. Ages ranged from 3.25 to 9.00 years. Four (15.4%) children scored a general cognitive index (GCI) < 68. One child (3.8%) scored a GCI > 132. The children's mean estimated mental age was found to be significantly lower than their mean actual age (p = 0.0086). Children treated for solid tumours had the least difference between their actual ages and estimated mental ages (p = 0.0301). The mean GCI for the genders was 97.4 for females and 81.0 for males; this difference was statistically significant (p = 0.0302). Age at diagnosis, type and length of treatment were not found to significantly affect development.

CONCLUSION
The paediatric cancer survivors in this survey were found to have delays in their development. This group of children should have their development closely monitored. This would ensure that any delays in development can be discovered early and appropriate interventions instituted, so that childhood cancer survivors are adequately prepared for adult life beyond cancer.


At present, there is a general lack of information regarding the spatial genetic architecture and genetic diversity of estuarine and coastal freshwater fish in Australia or about the interacting intrinsic, extrinsic and historical influences responsible for sculpting these patterns. This thesis represented the first investigation of the phylogeographic structure and recent evolutionary histories of teleost fishes from the coastal and estuarine environments of south-western Australia, using the resolution afforded by mtDNA sequence data. Available evidence indicated that, to different degrees, these species have limited potential for dispersal amongst local assemblages from different water bodies. As this theoretically reduces the confounding effects of recent gene flow on extant genetic structure, these fishes were well suited to studying the influences of historical factors. Historical influences were expected to be particularly profound, given that these coastal environments underwent massive modifications during Late Quaternary eustatic fluctuations.

The thesis consists of four major components, which explored different aspects of interspecific and intraspecific phylogeny and p hylogeograp hy of three teleost species, based on mtDNA control region and cytochrome b fragments. First, the relationship between the endemic, 'strictly estuarine' Leptatherina wallacei (Atherinidae) and the more widespread, 'estuarine and marine' 6. presbyteroides was examined, with a view to establishing whether 6. wallacei represents a monophyletic or polyphyletic lineage and whether this species was derived recently (i.e. in Holocene estuaries). Second, the phylogeographic structure and genetic diversity of L. wallacei were investigated and compared with data from L. presbyteroides, with a view to using this information to interpret the recent evolutionary histories of each congener. Third, the divergence between assemblages of L. wallacei inhabiting two isolated coastal lakes was used to estimate a maximal substitution rate for the control region, which was then used to infer general time frames for the divergence between the two Leptatherina species and between the major phylogeographic partitions within each species. Fourth, investigations were initiated into phylogeographic patterns and levels of genetic diversity within and among assemblages of Pseudogobius olorum (Gobiidae) from several coastal lakes and an estuary.

Phylogenetic analyses indicated that the two Leptatherina species were characterised by exclusive and reciprocally-monophyletic lineages of aplotypes from both mtDNA regions, supporting the monophyletic origins of L. wallacei. Both 6. wallacei and 6. presbyteroides exhibited high levels of genetic diversity and extensive overall subdivision (e.g. Qsr = 0.691 and 0.644 respectively for control region data). There was a profound phylogeographic break in both species between all conspecific assemblages from the lower west coast (LWC phylogroup) and all those from the south coast (SC phylogroup), which suggested the influences of shared extrinsic and/or historical factors. There was limited genetic structuring within the two major phylogroups of either Leptatherina species, apparently reflecting recent connectivity amongst local assemblages, with subsequent fragmentation and insufficient time for lineage sorting. However, two major phylogeographic breaks distinguished monophyletic control region phylogroups of L. wallacei from the isolated coastal Lake Clifton and Lake Walyungup, consistent with their independent evolution following lacustrine entrapment during the Holocene.

The divergence between these two isolated lacustrine assemblages of Leptatherina wallaceiformed the basis for an estimate of the maximal substitution rate of the control region. While these data were unable to provide a precise estimate of the actual rate of molecular evolution, all the evidence suggested that it was proceeding very rapidly. The maximal rate estimate of 172.3% lineage-' MY-' was among the fastest ever reported. Based on this rate, the two Leptatherina species diverged at least 1 SKya, thus rejecting a Holocene origin for L. wallacei. The divergence between the LWC and SC phylogroups of L. wallacei has been ongoing for at least GKya, while the equivalent divergence in L. presbyteroides has been ongoing for at least 11 Kya. As the time frames of these divergences were consistent with periods of massive environmental modifications associated with the end-Pleistocene fall in sea level and the HMT, it was likely that these factors have played important roles in sculpting the species' divergence and intra-specific genetic structure. Although useful in temporally scaling genetic divergences within and between the two Leptatherina species, wider application of this rate estimate to questions regarding other taxa was limited. For example, evident rate heterogeneity between the genera precluded its use with even the relatively closely-related atherinid Atherinosoma elongafa.

Phylogeographic analyses identified high levels of genetic diversity and extensive genetic subdivision (e.g. st = 0.652 for control region) amongst an estuarine and several lacustrine assemblages of Pseudogobius olorum, although phylogeographic structure was shallower than in either Leptatherina species. There was increased divergence between three assemblages from the lower west coast and two from the south coast, consistent with the profound break evident in the Leptatherina. One lacustrine assemblage appeared to represent a distinct lineage and a preliminary maximal rate estimate (~61.4% lineage-1 MY-1) was calculated based on the minimum divergence of this assemblage from its nearest conspecifics. Although slower than the rate calculated for L. wallacei, this was still high for teleost fishes.

Overall, this study indicated that historical environmental factors, especially those related to Quaternary eustatic changes, have played important roles in sculpting the phylogeography and evolution of three teleost species from south-western Australia. Moreover, as these species have differential dependencies on estuarine environments (is. 'strictly estuarine' vs 'estuarine and marine') and represented two different taxonomic groups (i.e. Atherinoidei and Gobioidei), historical environmental factors may have exerted similar influences on other coastal species in the region.


The lactococcal phage bIL41 belongs to the small isometric-headed phages of the 936 quasi-species and is resistant to the abortive infection determined by abiB. A 10.2-kb segment from this phage, in which late transcription is initiated, has been sequenced. Thirteen open reading frames (ORFs) organized in one transcriptional unit have been identified. The location of two of them and the structural features of the proteins they code for are evocative of terminase subunits. Five other ORFs specify proteins which are highly homologous to structural proteins from the closely related phage F4-1. By comparing the phage bIL41 sequence with partial sequences available for four related phages, we were able to deduce a chimerical phage map covering the middle- and a large part of the late-expressed regions. Phages from this quasi-species differ by the insertion or deletion of either 1 to about 400 bp in noncoding regions or an entire ORF. Transcription was initiated 9 min after infection at a promoter with a -10 but no -35 consensus sequence. Synthesis of a phage activator protein was needed for initiation of transcription. A large 16-kb transcript covering all of the late-expressed region of the genome was synthesized. This transcript gave rise to smaller units. One of these units most probably resulted from a RNase E processing.


ABSTRACT This article introduces a symposium of three ethnographic papers on the relational work of policy implementation in the context of international development. Relational work is usually unrecognized in the policy process, creating misunderstandings and barriers as well as promoting improvisation and innovation. Implementers in the cases presented – democracy promotion in Angola, rural livelihoods in India, and birth registration in Tanzania – use interpretive labor and sometimes deceit in order to carry out the creative and interpersonal work of development. Implementers often further local development goals, but ignore and subvert the disciplinary aims of development governance that seek to remake their economic, political, and social habits. These articles identify that it is the social work of forging and managing interpersonal relationships that allows development workers and intended beneficiaries to make policy.


Purpose Blinatumomab is a bispecific T-cell engager antibody construct targeting CD19 on B-cell lymphoblasts. We evaluated the safety, pharmacokinetics, recommended dosage, and potential for efficacy of blinatumomab in children with relapsed/refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Methods This open-label study enrolled children < 18 years old with relapsed/refractory BCP-ALL in a phase I dosage-escalation part and a phase II part, using 6-week treatment cycles. Primary end points were maximum-tolerated dosage (phase I) and complete remission rate within the first two cycles (phase II). Results We treated 49 patients in phase I and 44 patients in phase II. Four patients had dose-limiting toxicities in cycle 1 (phase I). Three experienced grade 4 cytokine-release syndrome (one attributed to grade 5 cardiac failure); one had fatal respiratory failure. The maximum-tolerated dosage was 15 µg/m2/d. Blinatumomab pharmacokinetics was linear across dosage levels and consistent among age groups. On the basis of the phase I data, the recommended blinatumomab dosage for children with relapsed/refractory ALL was 5 µg/m2/d for the first 7 days, followed by 15 µg/m2/d thereafter. Among the 70 patients who received the recommended dosage, 27 (39%; 95% CI, 27% to 51%) achieved complete remission within the first two cycles, 14 (52%) of whom achieved complete minimal residual disease response. The most frequent grade ≥ 3 adverse events were anemia (36%), thrombocytopenia (21%), and hypokalemia (17%). Three patients (4%) and one patient (1%) had cytokine-release syndrome of grade 3 and 4, respectively. Two patients (3%) interrupted treatment after grade 2 seizures. Conclusion This trial, which to the best of our knowledge was the first such trial in pediatrics, demonstrated antileukemic activity of single-agent blinatumomab with complete minimal residual disease response in children with relapsed/refractory BCP-ALL. Blinatumomab may represent an important new treatment option in this setting, requiring further investigation in curative indications.


An unbiased place preference conditioning procedure was used to determine whether the repeated administration of cocaine results in sensitization to its conditioned rewarding effects. Rats received noncontingent injections of saline or cocaine (10 mg/kg i.p.) for 5 days. Place preference conditioning commenced 72 hr later. A minimum of three drug conditioning sessions was necessary for the establishment of cocaine-induced conditioned place preferences (CPP) in saline-pretreated rats. The minimum dose producing this effect was 10.0 mg/kg. In contrast, pre-exposure to cocaine resulted in significant place preferences occurring after only two drug conditioning sessions. Furthermore, CPP was observed in response to doses as low as 5.0 mg/kg. This shift in the cocaine dose-response curve was apparent when conditioning commenced either 3 or 7, but not 14, days after the cessation of cocaine pretreatment. An increased sensitivity to cocaine was also observed in rats which received only two cocaine (25.0 mg/kg) injections before conditioning and in those which had received either d-amphetamine (0.5 mg/kg) or morphine (5.0 mg/kg) for 5 days. Repeated administration of the D1 dopamine (DA) receptor antagonist, SCH-23390 (0.01-0.05 mg/kg), or the D2 antagonist, raclopride (0.1-1.0 mg/kg), for 5 days did not modify cocaine-induced place conditioning. Administration of SCH-23390 (0.05 mg/kg) in combination with cocaine, however, prevented the sensitized response to cocaine. In contrast, raclopride did not influence the sensitized response to cocaine. These data demonstrate that sensitization occurs to the conditioned rewarding effects of cocaine and suggest an involvement of D1 DA receptors in the development of this phenomenon.