Previous studies have revealed a somewhat paradoxical strong positive correlation between per capita GDP and the intensity of anti-government demonstrations observed for the vast majority of countries (indeed, it turns out that the better people live, the more likely they are to join anti-government protests). The goal of this article is to identify possible causes of this unusual correlation. Our tests show that the processes of democratization and urbanization, as well as the expansion of formal education, are likely to be the main factors determining the positive relationship between per capita GDP and the intensity of antigovernment demonstrations, as urbanization, democratization, and expansion of education lead to an increase in the intensity of protests. Moreover, when controlling for these factors, the relationship between per capita GDP and anti-government protests becomes negative. Thus, high per capita GDP turns out to be a direct (proximate) significant negative factor affecting the intensity of anti-government demonstrations, but at thesame time it is an ultimate, even more significant positive factor in the intensity of protests. The growth of per capita GDP is quite naturally accompanied by an increase in the level of urbanization, democratization and education, which more than compensates for the direct inhibiting effect on the protests on the part of the growing per capita GDP (at least for low- and middle-income countries). In addition, the negative binomial regression model that we propose can explain not only the strong positive correlation between per capita GDP and the intensity of protests, which can be traced for a range of GDP per capita values of less than $20,000, but also the weaker negative correlation recorded for the range exceeding $20,000. The fact is that in rich countries urbanization, democratization and education indicators reach saturation levels and the vast majority of high-income countries have more or less similar levels for all three indicators. As a result, for a zone of per capita GDP values of more than $20,000, we are essentially dealing with automatic control of the correlation between GDP per capita and the intensity of protests for factors of democratization, education and urbanization, and, as our model predicts, the final effect of GDP per capita on the intensity of protests for high-income countries becomes negative, not positive.


My work in the field of the European Convention on Human Rights (ECHR) and domestic family law grew out of concern as to whether the so-called 'paramountcy principle' contained in the Children Act 1989 (CA 1989) was compatible with the ECHR as incorporated by the Human Rights Act 1998 (HRA). My first examination of its compatibility took place within the context of the extension of the paramountcy principle from private law children proceedings to public law adoption proceedings by the Adoption and Children Act 2002. This evolved into a larger and more detailed analysis with Professor Helen Fenwick, an expert in the field of human rights, of the compatibility of the principle in both private and public law proceedings under the CA 1989 within the broader context of the merits of adopting a rights-based approach to applications by parents under the act. This also examined in detail what I considered to be a great deal of sceptism about the adoption of a rights based approach and the possible reasons for it within the domestic family law field. After this, I was able to provide a detailed analysis of the merits of adopting a rights based approach to the issue of domestic violence with Professor Jonathan Herring in two further publications. All of these publications therefore form part of the body of work on which the PhD is based.


In well-control optimization problems, the goal is to determine the time-varying well settings that maximize an objective function, which is often the net present value (NPV). Various proxy models have been developed to predict NPV for a set of inputs such as time-varying well bottomhole pressures (BHPs). However, when nonlinear output constraints (e.g., maximum well/field water production rate or minimum well/field oil rate) are specified, the problem is more challenging because well rates as a function of time are required. In this work, we develop a recurrent neural network (RNN)–based proxy model to treat constrained production optimization problems. The network developed here accepts sequences of BHPs as inputs and predicts sequences of oil and water rates for each well. A long-short-term memory (LSTM) cell, which is capable of learning long-term dependencies, is used. The RNN is trained using well-rate results from 256 full-order simulation runs that involve different injection and production-well BHP schedules. After detailed validation against full-order simulation results, the RNN-based proxy is used for 2D and 3D production optimization problems. Optimizations are performed using a particle swarm optimization (PSO) algorithm with a filter-based nonlinear-constraint treatment. The trained proxy is extremely fast, although optimizations that apply the RNN-based proxy at all iterations are found to be suboptimal relative to full simulation-based (standard) optimization. Through use of a few additional simulation-based PSO iterations after proxy-based optimization, we achieve NPVs comparable with those from simulation-based optimization but with speedups of 10 or more (relative to performing five simulation-based optimization runs). It is important to note that because the RNN-based proxy provides full well-rate time sequences, optimization constraint types or limits, as well as economic parameters, can be varied without retraining.
 NOTE: This paper is published as part of the 2021 Reservoir Simulation Conference Special Issue.


BACKGROUND
Flavonoid class phytochemicals are natural compounds found to be present in different medicinal plants, vegetables and fruits. Ginkgo biloba contain significant amounts of bioflavonoid 'bilobetin'. Bilobetin is an active phytochemical used for treatment of human health complications due to its medicinal properties and therapeutic benefit. The purpose of this work is to collect and reviewed scientific data of bilobetin from different literature sources; highlight their biological properties, pharmacological activities and analytical aspects.

METHODS
Health beneficial aspects of bilobetin have been investigated in the present work through scientific data analysis. PubMed, Google Scholar, Google, Scopus etc. has been searched in the present work in order to collect scientific information of bilobetin in the present work. Medicinal importance and therapeutic benefit of bilobetin has been searched in the present work through these databases in the present work. Detailed pharmacological activities of bilobetin have reviewed in the present work through literature data analysis of various scientific research works. However, analytical data were also collected and reviewed in the present work.

RESULTS
Literature data analysis of bilobetin in the present work revealed the medicinal properties and therapeutic potential of bilobetin mainly due to its anti-fungal, anti-inflammatory, anti-oxidant, anti-hyperlipidemic, and anti-proliferative activities. Literature data analysis revealed the effectiveness of bilobetin on osteoporosis, glucose metabolism, adipocytes, SARS CoV-2, Influenza A virus and human thrombin. Scientific data also revealed the importance of different analytical techniques for the isolation, separation, identification, and quantification of bilobetin.

CONCLUSION
Scientific data analysis revealed biological importance and pharmacological activities of bilobetin in the health sectors.


A flexible method is presented for calculating the conductance coefficients of small multiprobe devices in terms of real-space Green functions in a discretized space. Within the independent-particle approximation systems with arbitrary magnetic field and local potential can be dealt with. The method is based on a transparent analytical formula for the differential current flowing across an interface dividing the phase-coherent conductor: the Green function is required only on sites at this interface and for energies at the Fermi surface as T to 0. The derivation of this formula is relatively simple and based on physical arguments. This formula is proved to be equivalent to rigorous linear-response expressions for conductance coefficients. Its lower information requirements are particularly important for the efficiency when calculating the conductance by finite-different approaches.


This study investigates age-specific prostate-specific antigen (PSA) distributions in Taiwanese men and recommends reference ranges for this population after comparison with other studies. From January 1999 to December 2016, a total of 213,986 Taiwanese men aged above 19 years old without history of prostate cancer, urinary tract infection, or prostate infection were recruited from the Taiwan MJ cohort, an ongoing prospective cohort of health examinations conducted by the MJ Health Screening Center in Taiwan. Participants were divided into seven age groups. Simple descriptive statistical analyses were carried out and quartiles and 95th percentiles were calculated for each group as reference ranges for serum PSA in screening for prostate cancer in Taiwanese men. Serum PSA concentration correlated with age (r = 0.274, p<0.001). The median serum PSA concentration (5th to 95th percentile) ranged from 0.7 ng/ml (0.3 to 1.8) for men 20–29 years old (n = 6,382) to 1.6 ng/ml (0.4 to 8.4) for men over 79 years old (n = 504). The age-specific PSA reference ranges are as follows: 20–29 years, 1.80 ng/ml; 30–39 years, 1.80 ng/ml; 40–49 years, 2.0 ng/ml; 50–59 years, 3.20 ng/ml; 60–69 years, 5.60 ng/ml; 70–79 years, 7.40 ng/ml; over 80 years, 8.40 ng/ml. Almost no change occurred in the median serum PSA value in men 50 years old or younger, while a gradual increase was observed in men over 50. Taiwanese men aged 60 years above showed higher 95th percentile serum PSA values compared to Caucasian men and men in other Asian countries but were closer to those of Asian American and African American men. Results indicate significantly different PSA levels correlating to different ethnicities, suggesting that Oesterling's age-specific PSA reference ranges might not be appropriate for Taiwanese men. Our results should be further studied to validate the age-specific PSA reference ranges for Taiwanese men presented in this study.


STUDY OBJECTIVE
To determine longitudinal effects of experiences related to the Fukushima nuclear disaster on March 11, 2011, on insomnia risk among workers of nuclear power plants on identified disaster-related potential risk factors for the subtypes of insomnia.

METHODS
We included a total of 1403 workers who responded to a questionnaire on insomnia-related symptoms measured by the Athens Insomnia Scale from 2011 to 2014 and on disaster-related experiences in 2011. We examined the longitudinal relationships between disaster-related experiences and insomnia using mixed-effect logistic regression models. We also used path analysis to examine the potential effects of disaster-related experiences on the subtypes of insomnia (i.e. initial, sleep maintenance, and early morning awakening).

RESULTS
All disaster-related experiences were significantly associated with insomnia, except death of a family member or colleague. We found that most of these types of traumatic exposure were associated with the risk of insomnia in a time-independent way. However, the effect of experiencing life-threatening danger decreased with time. Based on the results of the path analysis, we found that life-threatening experiences, such as experiences of life-threatening danger or witnessing the explosion, may conjure up disturbing scenes that hamper sleep initiation. On the other hand, early morning awakening may be related to life uncertainty. We found that social discrimination/slurs was associated with all three types of insomnia and was also influenced by other experiences, such as life-threatening danger, property loss, and colleague death.

CONCLUSION
Our findings emphasize the importance of comprehensive psychosocial support for workers with disaster-related experiences.


In grid connected multiple inverter systems, it is normal to synchronize the output current of each inverter to the common network voltage. Any current controller deficiencies, which result in low order harmonics, are also synchronized to the common network voltage. As a result the harmonics produced by individual converters show a high degree of correlation and tend to be additive. Each controller can be tuned to achieve a different harmonic profile so that harmonic cancellation can take place in the overall system, thus reducing the net current total harmonic distortion level. However, inter-inverter communication is required. This paper presents experimental results demonstrating an alternative approach, which is to arrange for the tuning within each inverter to be adjusted automatically with a random component. This results in a harmonic output spectrum that varies with time, but is uncorrelated with the harmonic spectrum of any other inverter in the system. The net harmonics from all the inverters undergo a degree of cancellation and the overall system yields a net improvement in power quality.


Predictably augmenting alveolar bone is a significant challenge in implant site development. A restorative-driven approach to implant placement aids in achieving esthetic harmony in the final restoration. This case report demonstrates techniques for treating patients with significant bony defects using a titanium mesh scaffold along with prosthetic steps in molding and conditioning soft tissues with the provisional restoration and the fabrication of a custom impression coping. This case is part of a larger consecutive case series of 77 titanium mesh units in 62 patients treated in a private periodontal practice setting and restored in private restorative practices, which will be published subsequently. In this titanium mesh case series, 14 other cases (a total of 15) were treated in a similar fashion as described in this case report in the category of "single implant placement in the maxillary anterior region." This case illustrates the primary advantages of the use of titanium mesh in such clinical situations.


combinFormation is a tool that enables browsing and collecting information elements in a generative space. By generative, we mean that the tool is an agent that automatically retrieves information elements and visually composes them. A combinFormation session presents a dynamic, evolving recombination of information elements from different sources. The elements are manipulable in the information space. Recombination is the process of taking previously unconnected elements, and combining them to create new configurations.One purpose of this space is to support the formation of ideas, through more and less focused processes of foraging. While ideas are forming, the criteria that underlie information foraging activities may not be well defined. Collecting the specific subset of related information elements is challenging. Cognitive scientists have established that combinations of images and textual elements are examples of preinventive structures that can lead to the emergence of new ideas. These preinventive structures often combine existing representations.Our program generates recombinant visualizations that develop interrelationships between the information elements. The generative visualization is based on a procedural model of the information, and the user's interests. The user model reflects interactions in which s/he explicitly expresses interest. The agent retrieves information based on the evolving model. The visual composition is also developed to emphasize the user's evolving sense of what is important. This involves solving problems in the dynamic visualization of dynamic, heterogeneous collections. In our novel interaction model, the human being shares control of the evolving information space with the agent. The user can express interest in information elements as they stream in, and design the visual space, using interactive tools. Expressions feed back through the model to drive the program's retrieval and visual composition decisions.


The authors present the analysis of the asymptotic stability of multiple slope-restricted nonlinear (Lur'e) systems. By providing a Lyapunov function, they obtain a matrix-language criterion in terms of algebraic Riccati equations and linear matrix inequalities, which are discussed at the point of computational issues. Additionally, they consider the frequency-domain interpretation of the result.


These data are being released in BETA version to facilitate early access to the study for research purposes. This collection has not been fully processed by NACDA or ICPSR at this time; the original materials provided by the principal investigator were minimally processed and converted to other file types for ease of use. As the study is further processed and given enhanced features by ICPSR, users will be able to access the updated versions of the study. Please report any data errors or problems to user support and we will work with you to resolve any data related issues.The Biomarker study is Project 4 of the MIDUS longitudinal study, a national survey of more than 7,000 Americans (aged 25 to 74) begun in 1994. The purpose of the larger study was to investigate the role of behavioral, psychological, and social factors in understanding age-related differences in physical and mental health. With support from the National Institute on Aging, a longitudinal follow-up of the original MIDUS samples [core sample (N = 3,487), metropolitan over-samples (N = 757), twins (N = 957 pairs), and siblings (N = 950)] was conducted in 2004-2006. Guiding hypotheses, at the most general level, were that behavioral and psychosocial factors are consequential for health (physical and mental). A description of the study and findings from it are available on the MIDUS Web site. The Biomarker Project (Project 4) of MIDUS II contains data from 1,255 respondents. These respondents include two distinct subsamples, all of whom completed the Project 1 Survey: (1) longitudinal survey sample (n = 1,054) and (2) Milwaukee sample (n = 201). The Milwaukee group contained individuals who participated in the baseline MIDUS Milwaukee study, initiated in 2005. The purpose of the Biomarker Project (Project 4) was to add comprehensive biological assessments on a subsample of MIDUS respondents, thus facilitating analyses that integrate behavioral and psychosocial factors with biology. The broad aim is to identify biopsychosocial pathways that contribute to diverse health outcomes. A further theme is to investigate protective roles that behavioral and psychosocial factors have in delaying morbidity and mortality, or in fostering resilience and recovery from health challenges once they occur. The research was not disease-specific, given that psychosocial factors have relevance across multiple health endpoints. Biomarker data collection was carried out at three General Clinical Research Centers (at UCLA, University of Wisconsin, and Georgetown University). The biomarkers reflect functioning of the hypothalamic-pituitary-adrenal axis, the autonomic nervous system, the immune system, cardiovascular system, musculoskeletal system, antioxidants, and metabolic processes. Our specimens (fasting blood draw, 12-hour urine, saliva) allow for assessment of multiple indicators within these major systems. The protocol also included assessments by clinicians or trained staff, including vital signs, morphology, functional capacities, bone densitometry, medication usage, and a physical exam. Project staff obtained indicators of heart-rate variability, beat to beat blood pressure, respiration, and salivary cortisol assessments during an experimental protocol that included both a cognitive and orthostatic challenge. Finally, to augment the self-reported data collected in Project 1, participants completed a medical history, self-administered questionnaire, and self-reported sleep assessments. For respondents at one site (UW-Madison), objective sleep assessments were also obtained with an Actiwatch(R) activity monitor. The MIDUS and MIDJA Biomarker Clinic Visits include collection of comprehensive information about medications of all types, as well as basic information about allergic reactions to any type of medication. Respondents were instructed to bring all their medications, or information about their medications, to the clinic visit to ensure the information about those medications was recorded accurately. Information regarding Prescription Medications (FDA approved medications prescribed by someone authorized/licensed under the Western medical tradition, or medications prescribed by individuals authorized under Japanese law to prescribe Western and/or Eastern/Chinese traditional medicine), Quasi Medications (including Over the Counter Medications i.e. vitamins, minerals, non-prescription pain relief, antacids, etc. that can be purchased without a prescription) and Alternative Medications (i.e. herbs, herbal blends (excluding herbal teas), homeopathic remedies, and other alternative remedies that may be purchased over the counter or "prescribed" by a health care practitioner trained in a non-western tradition)was collected at this time.The following information was collected for each medication type Medication name, dosage, and route of administration; How often the medication is taken(frequency); How long the participant has been taking a given medication; Why they think they are taking the medication; After basic cleaning protocols were completed, standardized protocols were applied to both MIDUS and MIDJA medication data to link medications first to Generic Names and associated DrugIDs and then to therapeutic and pharmacologic class information from the Lexicomp Lexi-Data database, and also to code text data describing why participants think they are taking a given medication. The scope of this collected medication data lends itself to within person analysis of medication use, thus the medication data are also released in a standalone stacked format. The stacked file only contains data about medications used where each case represents an individual medication, thus it does not include any data about medication allergies.


Human resource management scholars and practitioners have recognized the importance of understanding the complexities of staffing personnel. This study focused on the perceived importance of attributes for entry-level applicants to collegiate athletic departments. A total of 315 NCAA athletic administrators who were randomly selected responded to a web-based survey. Respondents were asked to rate the importance of 10 easily observable attributes during the screening process, and 10 non-readily observable skills during the hiring process. Results indicated that career-related work experience was considered to be most important during the screening, followed by the applicant's recommendation, and leadership experience. While in the hiring stage, work ethic, communications skills and motivation were considered the most important attributes. This study adds to the literature in human resource management and athletic administration and has practical implications for prospective employees, athletic administrators and sport management faculty members.


This paper is based on an Internet-based questionnaire survey with both qualitative and quantitative questions was selected as the research method in order to collect data about the designer's experience of their used design methods and tools. The result is that the general formal follow-up and reflection on used design methods and tools is experienced as low and this implies a risk that inefficient design methods and tools are used. Even though design method and tool utilization represents more than half of the total working time, the number of different types of utilized design methods and tools are low. Despite the low degree of formal follow up, designers experience that most utilized design methods and tools to a high degree fulfills their experienced needs and contributes in making the final product better. Finally, the reasons why designers use design methods and tools can be concluded in three interlinked major overall reasons for designers to use design methods and tools. The design method or tool must help to fulfill specified requirements of the prospective product, reduce the risk that important moments in the product development process are forgotten, reduce the total calendar time (from start to end) to solve the design task.


Background: An estimated 155,000 people are living with metastatic breast cancer (MBC) in the US. With new developments in treatment, people are living longer with MBC. Advances in treatment are handicapped by patients' limited (3-5%) participation in cancer clinical trials (CCTs). While much effort has been placed on better training physicians and health care providers in talking to their patients about the appropriateness of such participation, barriers remain. Methods: Since March 2013, the Cancer Support Community has registered 909 people living with MBC to the Cancer Experience Registry, an online initiative designed to learn and raise awareness about the psychosocial impact of cancer. 557 registrants responded to questions about their beliefs, attitudes and experience with CCTs. This sample was 99% female, 91% Caucasian, and 69% with a college degree and median age 56. Median time since MBC diagnosis was 3 years. Results: Only half of registrants reported that a member of their health care team spoke to them about participating in CCTs. Nearly one-quarter (23%) report that they took part in a CCT. 48% considered a CCT as a treatment option for their MBC and 34% did not know if a CCT was available to them. 67% are uncomfortable with being randomly assigned to a treatment. 18% do not trust the medical establishment and fear they will be used as a "guinea pig" for research. 63% fear receiving a placebo in a CCT; however, only 6% report that they don't understand what clinical trials are. The table below shows differences in beliefs between those who report participating in a CCT and those who have not participated in one.MCTConclusion: This population of MBC patients reports a range of experiences and often conflicting beliefs about CCTs. While this survey is limited to self-report data, there is persistent suspicion among these women about participating in CCTs. Although these women report that they understand what a CCT is, they fear receiving a placebo and being randomized to different treatment arms without at least the standard of care. These misconceptions persist even among people who have participated in a CCT. These findings highlight the need for treatment decision counseling that educates patients about all their treatment options including CCTs and for training of health care providers to better inform patients about CCTs. Citation Format: Anne Morris, Melissa Miller, Allison Harvey, Mitch Golant, Joanne Buzaglo. Perceptions about cancer clinical trials among metastatic breast cancer patients: Findings from a patient powered registry [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-12-02.


Friction represents a major energy dissipation mode, yet the atomistic mechanism of how friction converts mechanical motion into heat remains elusive. It has been suggested that excess phonons are mainly excited at the washboard frequency, the fundamental frequency at which relative motion excites the interface atoms, and the subsequent thermalization of these nonequilibrium phonons completes the energy dissipation process. Through combined atomic force microscopy measurements and atomistic modeling, here we show that the nonlinear interactions between a sliding tip and the substrate can generate excess phonons at not only the washboard frequency but also its harmonics. These nonequilibrium phonons can induce resonant vibration of the tip and lead to multiple peaks in the friction force as the tip sliding velocity ramps up. These observations disclose previously unrecognized energy dissipation channels associated with tip vibration and provide insights into engineering friction force through adjusting the resonant frequency of the tip-substrate system.


Dipstick analysis is a screening test for urinary tract infection (UTI) in office practice. Standard urine microscopy is available offsite. We evaluated the usefulness of these tests on consecutive urine samples obtained by bladder catheterization in young children with a possible UTI. Thirty of 230 children had positive cultures. Dipstick analysis was specific (98%) but not sensitive (70%). Standard microscopy was not specific. Dipstick analysis and urine culture are useful tests for the diagnosis of UTI.


Aims In this pilot mixed-methods study, we examined the participants experiences of engaging in virtual drawing tasks and the impact of an olfactory stimulus (calming fragrance blend) on outcomes of affect, stress, self-efficacy, anxiety, creative agency, and well-being (satisfaction with life). Methods This study used a parallel mixed-methods, simple block randomization design. The study participants included 24 healthy adults aged 18 to 54 years, including 18 women and six men. The participants completed two 1-h immersive virtual art making sessions and were randomly assigned to receive either a fragrance or a non-fragrance condition for the first session. Quantitative (standardized self-report measures) and qualitative (open-ended survey responses and virtual artwork) datasets were collected concurrently and integrated during data analysis. Results The quantitative results indicated that the fragrance condition demonstrated a significant reduction in negative affect (e.g., feeling hostile, jittery, upset, distressed, etc.), namely, reduced feelings of negativity when compared to the non-fragrance condition. A trend toward improvement in self-efficacy was also seen in the fragrance condition. No significant changes were found for fragrance or non-fragrance conditions for positive affect, anxiety, and creative agency. The qualitative findings included five themes related to art making experiences in virtual reality in both conditions: fun and joy; novelty of virtual media, experimentation, and play; relaxation and calm; learning curve; and physical discomfort and disorientation. Four themes were identified for virtual art content and visual qualities: nature imagery, references to memories and personal symbols, fantasy and play within imagery, and depiction of everyday objects. Conclusions Overall, the participants reported positive responses to the novel virtual art making experiences which were further heightened by the inclusion of the fragrance stimulus for negative affect. These preliminary findings need to be replicated with larger sample sizes to confirm the outcomes and the trends that were seen in this pilot study. Further research is recommended to examine the differences between experiences of virtual and traditional art media and to examine different olfactory stimuli promoting focus and concentration.


Taiping is a heritage town in Perak and one of the attractions in Taiping is Maxwell Hill, the oldest hill resort as well as one of the popular highland destinations in Malaysia. Visitors' nature-based recreation experience and perception are known as integral elements of visitor satisfaction study. Therefore, this study focuses on visitors' naturebased recreation experience and perception towards Taiping Maxwell Hill. Meanwhile, researcher aims to identify the activities and facilities available in Maxwell Hill.
However, study on nature and leisure experience in depth is still lacking as well as understanding the expectation of visitors is a challenging task for researcher.
Researcher used the method of quantitative and qualitative to collect the data and information for this study. There are total of 188 out of 200 random respondents are achieved in the questionnaires of this study. In addition, a set of open-ended questions
were prepared to Raja Nur Syamimi, the assistant manager in management office of Taiping Maxwell Hill in order to obtain additional information about Maxwell Hill.
Studying visitors' experience in terms of their perceptions is essential as the experience of visitors is the main key for management improvement in order to provide a better service for visitors.


PURPOSE: The prognostic value of circulating tumor cells (CTCs) number in patients with head and neck carcinoma (HNSCC) has been reported to be positive. The hypothesis of the additional markers on CTCs might predict clinical outcomes have been proposed. This study aimed to elucidate the prognostic/predictive value of CD133-expressing CTCs in HNSCC patients. PATIENTS AND METHODS: In a prospective single-center study, CTCs were enumerated in the peripheral blood of 24 subjects, including 14 patients with HNSCC and 10 healthy donors, at baseline and 2 weeks after starting first dose of chemotherapy. CTCs were measured using an immunomagnetic separation technique by combined negative and positive selection strategies. Immunofluorescence staining methods were applied for surface marker identification. Tumor response at 12 weeks after chemotherapy of the whole cohort was performed by computed tomograpgy or magnetic resonance imaging scans following RECIST criteria 1.1. RESULTS: In the first step of efficacy evaluation phase, an average recovery rate of 85.5% and a R2 value of 0.9932 were found when compared between spiked and recovered blood samples. A CTCs detection rate of 100.0% (14/14) was found by this protocol and the number could successfully differ HNSCC patients from healthy donors (P = 0.001). The mean and median (range) of baseline CTC number were 105.0 and 87.2 (34.5-358.1) cells/mL of blood. The higher baseline CTCs number was associated with higher tumor stage (AJCC 7th edition, P = 0.003). The higher absolute number (>5cells/mL of blood) of baseline CD133-expressing CTCs could predict poor survivals (Kaplan-Meier survival curves, P = 0.013). In all assessable patients, a high correlation rate of 92.9% was found between changes of CTCs (decline or elevation) and CT responses (progressive disease [PD] and partial response [PR]/Stable disease [SD]) with a P value of 0.005 (Fisher exact test). CONCLUSION: The number of CD133-expressing CTCs might be a useful prognostic for survivals and predictors for imaging response evaluation at 12 weeks in patients with HNSCC. Further investigation in large-scale prospective trials is warranted on the basis of the findings in this study. Citation Format: Jason Chia-Hsun Hsieh, Harber Hung-Bo Shiao, Bill Yuan-Jhih Chao, Ming-Jung Lin, John Wen-Cheng Chang, Hung-Ming Wang, Tyler Min-Hsien Wu. CD133-expressing circulating tumor cells might predict poor prognosis in patients with head and neck cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1590. doi:10.1158/1538-7445.AM2015-1590


Functional dyspepsia (FD) is defined by the presence of chronic gastroduodenal symptoms in the absence of organic or systemic disease that explains them, and a negative upper endoscopy. According to the Rome III consensus, FD can be subdivided into PDS (postprandial distress syndrome) and EPS (epigastric pain syndrome). In patients with mild symptoms, reassurance and lifestyle adjustments are often sufficient. Pharmacotherapy, for those with more severe or persisting symptoms, includes the use of proton pump inhibitors (PPIs), prokinetics and psychotropic agents. In those diagnosed with Helicobacter pylori infection, eradication is recommended, although the symptom impact is often limited. PPIs are the initial therapy of choice for EPS, while prokinetics can be used in PDS. Tricyclic antidepressants can be used for refractory symptoms, especially in EPS. Emerging therapies include the novel gastroprokinetic agent acotiamide for PDS, fundus-relaxing 5-HT1A agonists in patients with PDS/early satiation and mirtazapine for FD with weight loss.


Chinese Fusion Engineering Test Reactor (CFETR) is a new superconducting tokamak device being designed in China, which aims at bridging the gap between ITER and DEMO, where DEMO is a tokamak demonstration fusion reactor. Two diagnostic cases, ITER-like case and towards DEMO case, have been considered for CFETR early and later operating phases, respectively. In this paper, some preliminary consideration of ITER-like case will be presented. Based on ITER diagnostic system, three versions of increased complexity and coverage of the ITER-like case diagnostic system have been developed with different goals and functions. Version A aims only machine protection and basic control. Both of version B and version C are mainly for machine protection, basic and advanced control, but version C has an increased level of redundancy necessary for improved measurements capability. The performance of these versions and needed R&D work are outlined.


Fattening pigs are commonly kept in intensive housing systems with slatted floor which represent a very barren environment, causing poor animal welfare. To improve such conditions a small amount of straw or hay (100 g per animal per day laid daily in a rack) was used in our study as an environmental enrichment (EE). Two replications, each including 96 fattening pigs of both sexes (3 pens of 16 females and 3 pens of 16 male castrates) from 60 kg to slaughter at average 96 kg live weight, were used to test the effect of EE and sex on behaviour, growth rate, and carcass composition. EE significantly increased the proportion of total activity during the illumination period (between 6 a. m. and 2 p. m.) on account of increased occupation with substrate (P<0.01). EE also significantly reduced time spent biting pen bars and frequency of aggressive encounters (P<0.01). The EE increased total activity in female animals during the observation period, but not in male castrates. None of the EE significantly influenced pigs' growth rate and lean meat percentage; however females in enriched environment grew slower and had greater lean meat percentage than the castrated males. Provision of a small amount of straw or hay to pigs in intensive housing systems can enrich barren environment in inexpensive and efficient way. Therefore such enrichment can be widely used also in large commercial pig production systems.


In some Calderon's autos sacramentales the character of the Devil draws the plot and establishes the dramatic action as a demiurge. He elaborates plans and strategies to confuse the Man, but he always fails. This function approaches the autos to the metatheater. Finally certain parallels with Shakespeare are suggested.


Channel-aware assignment of subchannels to users in the downlink of an OFDMA system requires extensive feedback of channel state information (CSI) to the base station. Since bandwidth is scarce, schemes that limit feedback are necessary. We develop a novel, low feedback, distributed splitting-based algorithm called SplitSelect to opportunistically assign each subchannel to its most suitable user. SplitSelect explicitly handles multiple access control aspects associated with CSI feedback, and scales well with the number of users. In it, according to a scheduling criterion, each user locally maintains a scheduling metric for each subchannel. The goal is to select, for each subchannel, the user with the highest scheduling metric. At any time, each user contends for the subchannel for which it has the largest scheduling metric among the unallocated subchannels. A tractable asymptotic analysis of a system with many users is central to SplitSelect's simple design. Extensive simulation results demonstrate the speed with which subchannels and users are paired. The net data throughput, when the time overhead of selection is accounted for, is shown to be substantially better than several schemes proposed in the literature. We also show how fairness and user prioritization can be ensured by suitably defining the scheduling metric.


The mechanisms underlying the immunometabolic disturbances during skeletal muscle atrophy caused by a plethora of circumstances ranging from hospitalization to spaceflight missions remain unknown. Here, we outline the possible pathways that might be dysregulated in such conditions and assess the potential of physical exercise to mitigate and promote the recovery of muscle morphology, metabolism and function after intervals of disuse. Studies applying exercise to attenuate disuse‐induced muscle atrophy have shown a pivotal role of circulating myokines in the activation of anabolic signalling pathways. These muscle‐derived factors induce accretion of contractile proteins in the myofibers, and at the same time decrease protein breakdown and loss. Regular exercise plays a crucial role in re‐establishing adequate immunometabolism and increasing the migration and presence in the muscle of macrophages with an anti‐inflammatory phenotype (M2) and T regulatory cells (Tregs) after disease‐induced muscle loss. Additionally, the switch in metabolic pathways (glycolysis to oxidative phosphorylation [OXPHOS]) is important for achieving rapid metabolic homeostasis during muscle regeneration. In this review, we discuss the molecular aspects of the immunometabolic response elicited by exercise during skeletal muscle regeneration. There is not, nevertheless, consensus on a single optimal intensity of exercise required to improve muscle strength, mass and functional capacity owing to the wide range of exercise protocols studied so far. Despite the absence of agreement on the specific strategy, physical exercise appears as a powerful complementary strategy to attenuate the harmful effects of muscle disuse in different scenarios.


Experimental renal tubulointerstitial disease is induced in guinea-pigs by anti-tubular basement membrane autoantibodies. The complete mechanism of mononuclear cell accumulation in the target organ is not known; however, in addition to antibody, complement and radiosensitive leucocytes are important. In the present experiments we explored the influence of adjuvant in the accumulation of mononuclear cells in kidneys of actively or passively immunized guinea-pigs. We found that renal disease could be induced without adjuvant, by multiple injections of rabbit tubular basement membrane. Lesions were comparable to those groups which received a single dose of antigen in Freund's complete or pertussis vaccine adjuvant. Passive transfer of nephritis confirmed that adjuvant is not necessary for either the accumulation of mononuclear cells or the formation of antibodies with particularly potent pathogenicity.


Considering the most suitable relationship between ventilation and media in this study, two mixtures of perlite and coir (3:1, light and 1:3, heavy v/v) were applied to determine the growth characteristics var. Sante of potato plantlets. As potato has high potential in minituber production, different levels of supplemental aeration (0, 12.5, 25 and 75%, v/v/min) were compared for providing root oxygen demand and increasing potato minituber yield. Applying sufficient aeration led to significant increase in dry matter, number, size, quality of minituber and most of the growth parameters such as leaf area index (LAI), leaf area index duration (LAID), harvest index (HI) and root : shoot ratio. The results showed that by applying aeration at 25% (v/v/min), tuber yield was increased significantly up to 162% and increase in tuber number was predominant at the rate of 3678 tuber/m2. Desirable performance of aerated plant can be resulted from root oxygen demand of potato which is higher than normal ventilation in media. Heavy media was more responsive to aeration than light one. Thus, aeration at 25 and 12.5% (v/v/min) in heavy and light media respectively was considered as favorable level in rizo-sphere and had positive effect on tuberization.


Gamification has been described as the employment of game thinking and game mechanics to support long-term user engagement, behaviour change and problem solving. It has driven novel approaches in diverse industries ranging from education, healthcare, sales, or travel, opening up disruptive channels of interaction and enriched means to foster motivation. In the business world, gamification can be put into action in a wide variety of areas within an enterprise, such as recruitment, training, project management, performance management, employee collaboration, team-building, etc. The role of gamification is to enable goals to be reshaped in order to make them more appealing and achievable for end-users (learners, employees, or customers). The golden rule behind gamification is to motivate users with a challenging blend of contests, quests, and good performance incentives. Even if the concept of gamification is widely popular, it remains a very specific challenge to engage individuals in a smart way and be innovative in the process. To better comprehend how gamification can revolutionize daily activities (training/learning, hiring, team-building, performance management, staff evaluation), this paper explores the perception of gamification and opportunities for its exploitation in work environments. Based on the case study carried out, the authors present examples of gamification systems that can be applied in training and work environments.


Student inability to explain concepts learnt in lessons using their own words academically and intellectually and their lack of interest in learning the subject are a cause of their incompetence in the development of their personality. This presents a challenge to lecturers that they should not rely entirely on conventional lectures and tutorials. Instead, there is a need to employ a variety of teaching methods to stimulate student minds and encourage them to pursue knowledge. As an effort to diversify learning and teaching methods, a study was conducted to improve weaknesses of teaching and learning methods by organizing to motivate students. This was done to help students realize that concepts learnt in the course are relevant to their daily life and to encourage them to seek knowledge of self development which can be applied outside the class. The fora were followed with an action research. This action research was aimed at analyzing the effectiveness of the forum as an alternative method of teaching and learning of the Self Development Course. A sample of 73 students of various academic faculties 2012/2013 were involved in the forum competition. The sample was divided into two groups: panelists group and audience group. Panelists wrote two reports on their experience from the beginning stage of preparing forum materials until the final stage of conducting the forum itself. Listeners 89 groups were assessed as to their interest and observation to the forum content and its discussion while it was being conducted. The effectiveness of this strategy is based on analysis of student reports on the conducted forum and debates in it. Results show that forum received a positive response among the students. The forum approach increased student skills to relate to current issues in explaining facts they have learnt, encouraged cooperation among them to solve problems and increased interaction skill as well as built self-confidence. Therefore they could sharpen their soft skills and were able to solve problems and human-related issues.


The authors analyzed the constituents of effuse transcutaneous fluid, labeled suction effusion fluid (SEF), and monitored its glucose concentration during glucose loading in rabbits (Japan White, female) under pentobarbital anesthesia. The SEF was sampled by suctioning corneal layer-stripped skin at 400 mmHg absolute pressure. The SEF proved to have nearly the same concentrations as serum for lower-molecular-weight substances such as glucose, creatinine, and urea nitrogens, but not for higher-molecular-weight substances such as serum proteins. The SEF protein concentration was one-fourth that of serum protein. Proteins > 100 kDa molecular mass were barely detectable in the SEF. Monitoring of SEF glucose change every 10 min during intravenous glucose loading was successfully accomplished, and SEF glucose concentration followed blood glucose concentration with a 10-min delay. The SEF was thought to consist of interstitial fluid and/or effuse fluid from small vessels in subcutaneous tissue.


Artificial intelligence (AI) is a group of techniques that have quite a potential to be applied to pavement engineering and management. In this study, we developed a practical, flexible and out of the box approach to apply genetic algorithms to optimizing the budget allocation and the road maintenance strategy selection for a road network. The aim is to provide an alternative to existing software and better fit the requirements of an important number of pavement managers. To meet the objectives, a new indicator, named Road Global Value Index (RGVI), was created to contemplate the pavement condition, the traffic and the economic and political importance for each and every road section. This paper describes the approach and its components by an example confirming that genetic algorithms are very effective for the intended purpose.


Consider a continuous flow of automorphisms of a G-principal bundle which is chain transitive on its compact Hausdorff base. Here G is a connected noncompact semi-simple Lie group with finite center. The finest Morse decomposition of the induced flows on the associated flag bundles were obtained in previous articles. Here we describe the stable sets of these Morse components and, under an additional assumption, their Conley indices. AMS 2000 subject classification: Primary: 37B30 37B35, Secondary: 22E46.


Aluminum coatings were deposited onto Al7075 T651 structural alloy using both cold spraying and arc spraying. Arc spray coatings were produced using optimized parameters for two atomizing gases, namely air and nitrogen. Cold spray coatings were produced using a low pressure system with air and nitrogen as propelling gases. Six surface preparation procedures prior to deposition were evaluated. Interface quality of as-deposited coatings was investigated by means of fluorescent dye interface penetration technique, bond strength testing and backscattered electron microscopy. Environmentally assisted cracking tests were performed to study the corrosion protection capability of the resulting coatings for structural applications. Micrographs of samples taken before and after cyclic load testing in salt water immersion were compared. The results demonstrated that the Al coatings produced by both arc spray and cold spray provide to Al7075 alloy a cathodic protection against cracking and localized corrosion. However, to obtain such coating properties arc spray technique required advanced surface preparation prior to deposition. For cold spray, the surface preparation has minimal influence on the coating properties thus making this process more advantageous than arc spraying for this application.


Not all students are well motivated in the classroom activities. Some students often show disruptive behaviors that influence the teacher in conducting learning process. In particular case, there is special issue regarding behavioral problems in elementary school such as talking without permission and disturbing other friends while studying in class. Accordingly, this study aims at discerning behavior interruptions found in English teaching class. Moreover, it also describes the classification of students" disruptive behaviors and explores teachers" actions in order to overcome those behaviors. In this research, depth-interview with the English teacher, classroom observation and documentation were used to collect the data for two perceived classes and interactive model was used to analyze the data. Each class has been chosen based on specific characteristics for being observed. Though the study reported that there were several disruptive behaviors exhibited by primary school students, it could be classified as non-violence behavior since no one was injured by physical force. It seems possibly categorized as normal behavior by considering the students" age and level in school. In the EFL context, students will be more focus and motivated if they are studying in comfortable class because students are required to master several skills of English. Comfortable class will lead them to comfortable learning. Henceforth, it was suggested that teacher should have adequate knowledge of the students" psychology based on their age in order to give the proper strategies to control disruptive behaviors in the classroom.


The aim of this study is to reveal the effects of the written and combined warning statements which are obligatorily covered on cigarette packs on students. The participants of the study were fourteen volunteer undergraduate students. The data of the study were collected through semistructured interview forms. During the interviews the participants were shown cigarette packs with written and combined warning statements. Then they were asked to answer the interview items. The items were developed based on the review of the related literature. Lastly, these items were reviewed by the field experts. These were used in a pilot study on three students. The data gathered were analysed through content analysis.It was found that for participants the effects of the written warning statements were less than those of combined warning statements. However, they also reported that all warning statements were not so influential in quitting smoking. More research is needed on this topic.


The problem of unemployment in Nigeria, especially among the youths has been variously expressed to be alarming if not endemic. As a result of this, various recommendations had been proffered toward ameliorating the menace unfortunately to no avail. Hence, the essence of this research work is to examine the repositioning of Technical and Vocational Education (TVE) as a panacea to unemployment in Nigeria. Data were sourced through primary and secondary means - use of structured questionnaire, review of necessary literature, direct interview with Stakeholders in Technical and Vocational Education. Purposive sampling method was adopted in which those that matter in TVE in Federal Polytechnic, Ado-Ekiti were interviewed. 100 sets of questionnaire were administered. Five (5) each were administered in each academic office within the campus. Result of findings showed that the original intention of Vocational and Technical Education had been distorted, hence the need for a sincere repositioning in the area of adequate funding, infrastructural development, human capital development, educational policy restructuring toward skill acquisition, research development, and the need to reposition the regulatory body (NBTE) among others.

 Key words: Education, eradication, Nigeria, repositioning, technical, unemployment, vocational.


We evaluated the role of several proteins that are likely to be involved in alzheimers disease (AD) and type 2 diabetes mellitus (T2DM). By employing multiple sequence alignment using Clustalw tool, we have constructed a phylogenetic tree based on the functional protein sequences extracted form NCBI. The phylogram was constructed using neighbor joining algorithm. Our bioinformatic analysis reported that the two proteins such as AChE and BChE are playing major role in both the diseases out of ten common proteins between these two diseases. Our in silico study may pave way for new therapeutic interventions/biomarker identification in alzimers disease associated diabetes mellitus.


Abstract:Recent international development efforts in Africa have promoted education as the key to helping children overcome poverty, improve their lives and change their communities. Mobilizing local governments to build safe, healthy, and environmentally sound educational institutions for African children, however, has proven difficult at best. This paper discusses problems involved in improving the conditions for education in Nairobi, Kenya, and describes the process undertaken by children in one inner-city slum to envision a safe, healthy school made of quality, inexpensive local materials and designed for the community's unique environmental and social conditions. The purpose of the paper is to propose progressive, participatory ways to design, develop and deliver educational facilities in adverse environments, considering that the priorities of children, parents, local authorities, development agencies, and other groups often conflict.


Fibre modification might be a way to improve the performance of paper, to increase its cost competiveness and enable new paper-based products to be developed. Therefore, the influence of fibre modification (with polyelectrolytes or by fibre cross-linking) on the mechanical properties of special importance for packaging paper grades was studied. Creep deformation under varying humidity conditions (i.e. mechano-sorptive creep) is of outmost importance for the stacking life of paper-based boxes. The influence on creep behaviour of adsorbing polyallylamine (a cationic polyelectrolyte) to fibre surfaces or throughout the fibre walls was studied. Adsorption to fibre surfaces reduced the creep at constant humidity. The mechano-sorptive creep was not however influenced. The use of polyelectrolytes did not thus appear to be a feasible strategy for reducing mechano-sorptive creep. Polyelectrolytes can however be efficient in improving other mechanical properties. The use of multilayers consisting of polyallylamine (PAH) and polyacrylic acid (PAA) was for example shown to significantly increase the strength of paper with much less densification and build-up of residual stress than is obtained by beating. Cross-linking by oxidation with periodate radically decreased the mechano-sorptive creep of sheets made from the oxidised fibres. The basic mechanism behind the reduction in mechano-sorptive with cross-linking was found to be that the cross-linking slowed down the moisture sorption kinetics. A lower sorption rate led to smaller moisture content variations during the mechano-sorptive creep testing, and thus less sorption-induced swelling and stress concentrations at fibre/fibre joints. However, for cross-linking to be a practical way to reduce creep, the large problem of embrittlement must be solved. The shear strength of couched sheets was measured to study the interaction between the sheets at different solids content. The shear strength was low until a solids content of approximately 60−70% was reached, which suggests that interactions important for the strength at complete dryness start to develop at this solids content. The effect of different fibre modifications and additives on how the fibres interact during the consolidation process is not always well understood. The method of shear strength determination could in the future be applied to modified fibres to hopefully increase the understanding of how different modifications influence the fibre/fibre interactions. A deeper understanding might reduce the time for the development of new and improved fibre modifications.


We discuss the application of an analytic approach called the analytic perturbation theory (APT) to the QCD analysis of DIS data. In particular, the results of th e QCD analysis of a set of 'fake' data on the polarized nonsinglet Δq3 and the nonsinglet fragmentation function D π + uv by using the Q 2 - evolution within the APT are considered. The 'fake' data are constructed based on parametriza- tion of the polarized PDF and nonsinglet combination of the pion fragmentation functions. We confirm that APT can be successfully applied to QCD analysis o f Δq3(x, Q 2 ) and D π + uv (z, Q 2 ) and that the inequality ΛAPT > ΛPT obtained previously for the xF3(x) structure function takes place.


In a recent paper, Ward, Wynn-Williams, and Cave have described a method of counting accurately the number of α-particles emitted per second from a radiactive source. This method,-the practicability of which was first shown by Greinacher,-involves the amplification by means of thermionic valves of the small ionisation current caused by an α-particle in a few millimetres of its path in air. The amplification can be made linear, so that the final current which actuates the recording instrument is proportional to the ionisation produced by the particle in the ionisation chamber. Compared with that produced by an α-particle, the ionisation produced by an β -particle is too small to be recorded under working conditions. In their work on the determination of the number of α-particles emitted per second from a gram of radium, the magnified current was passed through an Einthoven galvanometer, and clear photographic records were obtained when the α-particles were entering the chamber at a rate of several hundred a minute. Under the conditions of the experiment, the β and γ-radiations were too weak to cause any disturbance, thus enabling the determination to be carried out with accuracy. For many purposes, however, it is seecential to count particles in the presence of strong γ-radiation, and to achieve this end special attention had to be paid to the amplifying and recording system. An account will be given in a later paper by Wynn-Williams and Ward, of the arrangements employed for this purpose, but it suffices to say here that the ions produced by a particle in the detecting vessel should be driven on to the collecting electrode in a time of the order of 10-3 sec, and that the process of amplifying and recording should be sufficiently rapid to give a trace in an interval of less than 10-3 seconds. For this purpose, a special oscillograph was constructed which has been found to be very effective. With these modifications it has been found possible to count α-particles at the rate of several hundred per minute even in the presence of strong γ-radiation.


This paper investigated the effect of productive failure (PF) as an instructional strategy in computer-supported collaborative learning (CSCL) groups using Facebook and a discussion forum. PF is an instructional mode design that advocates the delaying of support for the learners during learning — the more they struggle, and even fail, while trying to master new information, the better they are likely to recall and apply that information later. PF has been used successfully in the classroom. However, it is not known whether the use of a PF instructional modewith adult learners in CSCL groups such as Facebook and discussion forums will produce such a positive effect. A discussion forum is an important platform used to deliver teaching and learning via the Web, while the use of social media, especially Facebook, for teaching and learning has gained prominence lately. This paper reports an initial study that compares a 'productive failure' instructional design in CSCL groups through Facebook and a discussion forum. Five Facebook and five discussion forum groups participated in the study. Both groups solved ill-structured complex problems in small groups without the provision of any support or scaffolding from their instructors. The findings suggest that the Facebook groups produced a variety of scope for discussion and deliberation for solving the problems and were more successful in sustaining the discussion compared to the discussion forum groups. Facebook groups also had a higher critical thinking ratio than the discussion forum groups. Based on these findings,the implications of a PF instructional design for adult learners are presented.


In recent years, due to the increasing rate of elderly people in Japan, the needs to detect adults' diseases at the early stage becomes a high priority. In particular, an increased interest in detecting heart and cerebrovascular diseases at an early stage may allow clinicians to begin treatment sooner, when interventions are generally more effective and less expensive. Recently, the Wave Intensity (WI) has been proposed as a new hemodynamic index that provides information about the dynamic behavior of the heart and the vascular system and their interaction. However; the repetitiveness and accuracy of the WI measurement depend on the precision of the positioning of the ultrasound probe. Therefore a positioning device for ultrasound probe is required. Such a device should not only be used to keep the position but also for the fine positioning of the probe. For this purpose, at Waseda University, we have proposed the development of a robot system to assist a carotid blood flow measurement using ultrasound diagnostic equipments. In this paper, the development of Waseda-Tokyo Women's Medical-Aloka Blood Flow Measurement System No. 1 Refined II (WTA-1RII) is detailed. The system consists of an ultrasound diagnostic device, a 6-DOFs parallel link manipulator, a serial link passive arm, ball joint, and a joystick type controller. The WTA-1RII has improved the design of the gravity compensation mechanism. In addition, a genetic algorithm has by implemented to determine the optimal link's position of the 6-DOFs parallel manipulator to increase the workspace. Finally, a set of experiments were carried out to determine the usability of the proposed system.


Transition-edge sensors (TES) are detectors able to count single photons from x-ray to infrared, generating pulses with amplitudes proportional to the absorbed photon energy. The TES performance depends on the sensor parameters and also on the noise level. The evaluation of the energy resolution is thus dependent on the type of signal analysis applied.


Hybrid Liposomes (HL) composed of 90 mol% L-α-dimyristoylphosphatidylcholine (DMPC) and 10 mol% polyoxyethylene (25) dodecyl ether (C12(EO)25) was examined to study the stimulation of apoptosis and antiinvasive actions against in vitro cultured human breast cancer (MCF-7) cells. The results obtained from the study reveals that HL suppressed the growth of MCF-7 cells without any drugs. Apoptosis for MCF-7 cells after subjecting them to HL treatment was noticed. To study the non-invasive actions of HL on the drifting of MCF-7 cells, we exercised Wound scratch assay. Non-invasive effects of HL on the migration of MCF-7 cells were obtained on the basis of wound scratch assay. HL suppressed the pseudopodium formation of MCF-7 cells. The study to determine the non-invasive effects of HL against MCF-7 cells were done by matrigel invasion assay which gave positive results due to inhibition of MT1MMP/MMP14 by HL.


Generative networks are known to be difficult to assess. Recent works on generative models, especially on generative adversarial networks, produce nice samples of varied categories of images. But the validation of their quality is highly dependent on the method used. A good generator should generate data which contain meaningful and varied information and that fit the distribution of a dataset. This paper presents a new method to assess a generator. Our approach is based on training a classifier with a mixture of real and generated samples. We train a generative model over a labeled training set, then we use this generative model to sample new data points that we mix with the original training data. This mixture of real and generated data is thus used to train a classifier which is afterwards tested on a given labeled test dataset. We compare this result with the score of the same classifier trained on the real training data mixed with noise. By computing the classifier's accuracy with different ratios of samples from both distributions (real and generated) we are able to estimate if the generator successfully fits and is able to generalize the distribution of the dataset. Our experiments compare the result of different generators from the VAE and GAN framework on MNIST and fashion MNIST dataset.


BACKGROUND
Little is known about subclinical atherosclerosis on coronary computed tomographic angiography (CCTA) in asymptomatic individuals with metabolic syndrome (MetS).

METHODS AND RESULTS
We analyzed 5,213 asymptomatic individuals who underwent CCTA. A cardiac event was defined as a composite of all-cause death, myocardial infarction, unstable angina, or coronary revascularization. Of the study participants, 2,042 (39.2%) had MetS. MetS was an independent predictor of significant coronary artery disease (CAD) in at least 1 coronary artery (odds ratio [OR]=1.992, 95% confidence interval [CI]=1.623-2.445, P<0.001) and significant CAD in the left main (LM) or proximal left anterior descending (LAD) artery (OR=2.151, 95% CI=1.523-3.037, P<0.001). During the follow-up period (median 28.1 [interquartile range, 19.2-36.5] months), 111 individuals had 114 cardiac events. Individuals with MetS were significantly associated with more cardiac events than those without (RR [rate ratio]=1.67, 95% CI=1.15-2.43, P=0.007). In the MetS group, individuals with significant CAD had the majority of cardiac events (RR=64.33, 95% CI=29.17-141.88, P<0.001). Furthermore, in the MetS with significant CAD group, those with significant CAD in the LM or proximal LAD had more cardiac events (RR=2.63, 95% CI=1.51-4.59, P=0.001).

CONCLUSIONS
MetS was associated with subclinical atherosclerosis on CCTA with subsequent high risk for cardiac events. These findings suggest the importance of reducing unfavorable metabolic conditions in asymptomatic individuals.


The great efforts of many researchers have brought down some of the barriers that exist to turn a good in vitro compound into a potential in vivo drug. The advent of pharmaceutical nanotechnology has allowed an arsenal of drugs with poor stability, low solubility, high off-target toxicity and other disadvantageous features, to be accessible as pharmaceutical products that could be administered to a patient. Nanotechnology was introduced in drug delivery very long ago, but has flourished with unprecedented intensity during the last twenty years and now a diversity of nano-based preparations are at clinical stage of development or already available in the market. Undoubtedly, nanotechnology plays a key role in future pharmaceutical development and pharmacotherapy. In the first part of this review, we have already discussed recent (2008-2012) patents on linear polymer-based nanosystems (nanogels, nanospheres and nanocapsules) applications to cancer therapy. Here, we have expanded such analysis to branched polymers (dendrimers), self-assembling nanomicelles and lipid-based nanocarriers.


An 83-year-old patient developed erosions and a blister of the gingival mucous membrane, 6 months after discontinuation of the anti-programmed death-1 (anti PD-1) pembrolizumab therapy administered for 10 months for a metastatic melanoma. A diagnosis of mild mucous membrane pemphigoid (MMP) was made. Complete remission of MMP was rapidly obtained with minimal therapy (doxycycline). MMP remained in complete remission after a 3-month follow-up since discontinuation of the doxycycline therapy and no evidence of relapse of the melanoma was observed after a 14-month follow-up since discontinuation of the pembrolizumab therapy. The widespread use of anti PD-1 and anti-programmed death-ligand-1 (PD-L1) in several malignancies reveals new adverse events. MMP describes a group of chronic, inflammatory, mucous membrane-predominant, subepithelial auto-immune blistering diseases. It is clinically distinct from bullous pemphigoid another autoimmune blistering disease but shares some immunological similarities with it. Twenty-nine cases of bullous pemphigoid associated with anti PD-1/PD-L1 have been reported in the literature and one of MMP. Here, we described the case of a MMP developed after pembrolizumab and discussed the accountability of anti PD-1/PD-L1 in our case and the previous reported bullous pemphigoid and MMP cases using the Begaud system scoring.


Purpose: To evaluate the efficacy of automated lamellar therapeutic keratoplasty (ALTK) for the management of anterior corneal stromal scarring caused by trachoma. Methods: Seventeen cases of trachomatous keratopathy that were treated by ALTK were retrospectively evaluated. The main outcome measures were uncorrected visual acuity, best-corrected visual acuity (BCVA), keratometry, pachymetry, time to epithelialization, graft clarity, and complications, if any. Results: The mean age of the patients was 50.3 ± 14.1 years. Five of the 17 cases had Salzmann nodular degeneration. The mean decimal BCVA was 0.06 ± 0.05 preoperatively, which improved to 0.41 ± 0.16 at 12 months, and 12 eyes (70.6%) had a postoperative BCVA of 6/18 or better. The median epithelialization time was 6 days (range, 1–38 days). Persistent epithelial defect developed in 6 eyes, and 1 eye developed graft infection. Conclusions: Anterior stromal corneal scarring caused by trachoma can be effectively treated with ALTK. However, occurrence of persistent epithelial defects may complicate the success of this surgery.


Inter- and intramolecular hydrogen bonding and their temperature-dependent changes in a poly(4-vinylphenol)/poly(methyl methacrylate)(PVPh 30%/PMMA 70%) blend were investigated using near-infrared (NIR) and infrared (IR) spectroscopy. Band assignments of the fundamentals and first overtones of the OH stretching mode of a free OH group and OH groups in C=O···HO and OH···OH (dimer, trimer, and oligomer) hydrogen bonding of PVPh 30%/PMMA 70% were carried out by comparison between its NIR and IR spectra and comparison with NIR and IR spectra of phenol. The comparison of the NIR spectra of the PVPh 30%/PMMA 70% blend (hereafter, we denote it as PVPh30%) with the corresponding IR spectra reveals that to observe bands arising from the free OH and OH···OH dimer, which is a weaker hydrogen bonding, NIR is better while to investigate bands originating from OH groups in the OH···O=C and OH···OH (oligomer) hydrogen bonds, which are stronger hydrogen bonding, IR is better. Thus, a combination of IR and NIR spectroscopy has provided convincing results for the hydrogen bonding of PVPh30%. The relative intensity of the two bands at 7058 and 6921 cm–1 (I7058/I6921) due to the first overtones of the OH stretching modes of the free OH group and the OH group in the dimer, respectively, increases significantly above 90 °C, which is close to Tg of PVPh. In concomitance with the intensity increase in the relative intensity of the free OH band, the intensity of a band at 1706 cm–1 due to the C=O stretching mode of the C=O···HO hydrogen bond of PVPh30% decreases above 90°C. These results suggest that above the Tg of PVPh the C=O···HO hydrogen bond is broken gradually and that the free OH increases. Of note is that below Tg the intensities of NIR bands due to the OH first overtones of free OH group and OH groups in the OH···OH dimer gain intensity in parallel with temperature increase, and above Tg the intensity of the band derived from the OH···OH group increases linearly much slower than that of the band due to the free OH. Moreover, a band due to an OH···OH oligomer decreases linearly. Hence, it is very likely that the OH···OH oligomers dissociate into free OH groups. Anharmonicity of O–H bonds, which is sensitive to a hydrogen bond, was estimated for the free OH and OH bonds in the C=O···HO and OH···OH (dimer, trimer, and oligomer) hydrogen bonding by comparison between the NIR and IR spectra in the OH stretching band regions. Graphical Abstract


A mathematical model for dilution crystallization of spectinomycin dihydrochloride pentahydrate was established on the basis of the population and mass balance. Three operating modes, i.e., constant mass rate addition of diluent, constant mass fraction of diluent and constant size-independent growth rate, were investigated over a wide range of controlled parameters. The intrinsic characteristics of the crystallization process and the influence of operation parameters were analyzed in detail. Suitable strategy for better performance was suggested.


With the departure of Bob White as Administrator of the National Oceanic and Atmospheric Administration (NOAA), both the government and the scientific community have lost a capable leader. He has performed outstandingly with NOAA and its predecessor agencies under five different U.S. Presidents. White's administrative competence combined with his scientific ability has enabled him to lead NOAA through its formative stages, which have involved increasingly complex problems with oceans and atmosphere. His dedication has been unquestioned. If there has been any tinge of lasting criticism of White's tenure, it might be said that to a certain extent he favored atmospheric over oceanic affairs. This would be natural and understandable considering his meteorological background.


The collection is usually adopted in the international trade.But it is a kind of international settlement which is on the base of commercial credit and contains bigger risk for the exporters.This paper mainly analyzes the risk being existed in the collection business and puts forward to some measure against the risk.


Numerical modeling of the neutron imaging system for the National Ignition Facility (NIF), forward from calculated target neutron emission to a camera image, will guide both the reduction of data and the future development of the system. Located 28 m from target chamber center, the system can produce two images at different neutron energies by gating on neutron arrival time. The brighter image, using neutrons near 14 MeV, reflects the size and symmetry of the implosion "hot spot." A second image in scattered neutrons, 10-12 MeV, reflects the size and symmetry of colder, denser fuel, but with only ∼1%-7% of the neutrons. A misalignment of the pinhole assembly up to ±175 μm is covered by a set of 37 subapertures with different pointings. The model includes the variability of the pinhole point spread function across the field of view. Omega experiments provided absolute calibration, scintillator spatial broadening, and the level of residual light in the down-scattered image from the primary neutrons. Application of the model to light decay measurements of EJ399, BC422, BCF99-55, Xylene, DPAC-30, and Liquid A suggests that DPAC-30 and Liquid A would be preferred over the BCF99-55 scintillator chosen for the first NIF system, if they could be fabricated into detectors with sufficient resolution.


Paraphrasing is a useful natural language processing task that can contribute to more diverse generated or translated texts. Natural language inference (NLI) and paraphrasing share some similarities and can benefit from a joint approach. We propose a novel methodology for the extraction of paraphrasing datasets from NLI datasets and cleaning existing paraphrasing datasets. Our approach is based on bidirectional entailment; namely, if two sentences can be mutually entailed, they are paraphrases. We evaluate our approach using several large pretrained transformer language models in the monolingual and cross-lingual setting. The results show high quality of extracted paraphrasing datasets and surprisingly high noise levels in two existing paraphrasing datasets.


A study conducted to assess the effectiveness of cold application on Pain and Anxiety during Chest Tube Removal (CTR) among post operative cardiac surgery adult patients. Pre-test post-test control group experimental design was used. Post operative cardiac surgery adult patient of the selected hospital of Delhi were selected. The study sample was purposive sampling technique with random assignment of subjects into two groups: experimental group and control group. The sample size was 60 i.e. 30 in experimental group and 30 in control group. The control group received usual standard care during chest tube removal whereas experimental group received cold application with gel pack (Temp: 0–20C) after wrapping it with sterile gauze, around chest tube (5cms) for a period of 15 minutes before CTR. The tools used for the study were structured questionnaire to obtain demographic data, standardized Numerical Pain Intensity Scale (NPIS) scale to assess pain, C.D. Speilberger's State Trait Anxiety inventory (STAI) scale to assess anxiety. The obtained data was analysed and interpreted in terms of the objectives of the study using descriptive and inferential statistics. The mean post test pain scores with cold application (1.13 ± 1.31; 0.27 ± 0.44; 0.27 ± 0.44) at zero minute, 15 minute and 30 minute respectively were significantly (< 0.05) lower than the mean pre-test score of 6.10 ± 1.27 in the experimental group without cold application. In control group, pre test mean pain score was 6.57 ± 1.12 as compared to mean post test pain score of 8.57 ± 0.49; 8.73 ± 0.57; 8.63 ± 0.48 at zero minute, 15 minute and 30 minute respectively. It indicates that cold application was effective to reduce pain among post operative cardiac surgery patients while removing chest tube. To evaluate the effectiveness of cold application on anxiety related to chest tube removal, in experimental group the mean post cold application anxiety scores 41.93 ± 2.21 were significantly lower (< 0.05) than the mean anxiety score of 53.47 ± 1.84 before cold application. In addition, the mean anxiety score were 53.31 ± 1.81 before CRT and 57.87 ± 3.21 after CRT among post operative cardiac surgery patient in control group. It indicates that the cold application on chest tube removal was effective in reducing anxiety among post operative cardiac surgery patient. Cold application is simple, cheap, non pharmacological anxiety and pain management strategy ensuring good results.


The radiation patterns of cylindrical dielectric resonator antennas excited with a TM11 mode is computed numerically. The numerical data obtained is found in good agreement with available experimental results. The symmetry of the radiation patterns is improved by reducing the ground plane dimensions, while the backlobe level is reduced by placing the antenna in a topless cylindrical cavity.


This paper examines the construction of the public/private divide under the Indian Constitution, within the broader debate on the nature, scope, and contours of the right to privacy. It takes as its basis a little-known, now forgotten judgment of the Andhra Pradesh High Court (T. Sareetha vs Venkatasubbaiah), which struck down Section 9 of the Hindu Marriage Act ("Restitution of conjugal rights") as unconstitutional, on the ground that it violated women's right to privacy (in terms of their decisional autonomy) within marriage, as well as having a disparate and unequal impact upon the lives of wives and husbands. Although T. Sareetha was swiftly overruled by the Supreme Court, this paper attempts to rehabilitate it as a crucial part of the Indian Constitutional canon, arguing that it advanced a transformative vision of the Constitution, one that defined privacy not in terms of spaces, or institutions, but in terms of a right to decisional autonomy within spaces and institutions (the "private sphere") that is commonly believed to be off-limits to State and constitutional intervention. In other words, the judgment in T. Sareetha was an attempt to democratise relationships within the private sphere, and this attempt - I shall argue - conformed both with judicial precedent, as well as with the Constitution's text, structure, and overarching vision of social transformation.


Through observation and modeling, a great deal has been learned about the viscosity structure of the Earth and its influence on such processes as plate tectonics, mantle convection, postglacial rebound, and continental uplift. In particular, it has been shown that where the crust is unusually thick and/or warm, the lower crust is able to flow to relax stresses produced by crustal thickness variations and crustal extension or shortening [e.g., McKenzie et al., 2000]. Viscous relaxation models have been applied to other planets since the 1960s, and the results show that some large impact basins may have formed in the presence of a warm, ductile lower crust [e.g., Solomon et al., 1982].


ABSTRACT The xanthan-degrading bacterium Paenibacillus alginolyticus XL-1, isolated from soil, degrades approximately 28% of the xanthan molecule and appears to leave the backbone intact. Several xanthan-degrading enzymes were excreted during growth on xanthan, including xanthan lyase. Xanthan lyase production was induced by xanthan and inhibited by glucose and low-molecular-weight enzymatic degradation products from xanthan. A xanthan lyase with a molecular mass of 85 kDa and a pI of 7.9 was purified and characterized. The enzyme is specific for pyruvated mannosyl side chain residues and optimally active at pH 6.0 and 55°C.


ABSTRACT Objective To verify the association between nutritional status and traditional and non-traditional cardiovascular risk factors in haemodialysis patients. Methods A cross-sectional study with 132 patients over 18 years of age on haemodialysis to evaluate nutritional status through Subjective Global Assessment. Information on traditional and non-traditional cardiovascular disease risk factors were obtained using a structured questionnaire; the Framingham score was also used to assess cardiovascular risk. Data analysis was performed using the Chi-square Test or Fischer Exact Test and a Log-binomial Regression Model. Results Malnutrition affected 31.1% of patients. Among them, a higher percentage of smokers (p=0.016), former smokers (p=0.034) and diabetes Mellitus patients (p=0.001) were detected. Malnutrition was found to be 4.53 times more prevalent in diabetic individuals (95%CI: 1.99-10.27) and 2.26 times more prevalent among former smokers (95%CI: 1.04-4.95). Malnourished individuals exhibited a 4.03 times prevalence of moderate to severe cardiovascular risk. Conclusion A high prevalence of malnutrition and of other risk factors for cardiovascular disease were observed. Such factors included diabetes Mellitus, smoking and former smoker conditions and were associated with malnutrition. Inaddition, it was found that malnourished individuals were more likely to develop cardiovascular disease within 10 years.


Globally, a green hydrogen economy rush is underway, and many companies, investors, governments, and environmentalists consider it as an energy source that could foster the global energy transition. The enormous potential for hydrogen production, for domestic use and export, places Africa in the spotlight in the green hydrogen economy discourse. This discourse remains unsettled regarding how natural resources, such as land and water, can be sustainably utilized for such a resource-intensive project, and what implications this would have. This review argues that green hydrogen production (GHP) in Africa has consequences where land resources (and their associated natural resources) are concerned. It discusses the current trends in GHP in Africa, and the possibilities for reducing any potential pressures it may put on land and other resource use on the continent. The approach of the review is interpretive, and hinges on answering three questions, concerning the what, why, and how of GHP and its land consequences in Africa. The review is based on 41 studies identified from Google Scholar, and sources identified via snowballed recommendations from experts. The GHP implications identified relate to land and water use, mining-related land stress, and environmental, ecological, and land-related socioeconomic consequences. The paper concludes that GHP may not foster the global energy transition, as is being opined by many renewable energy enthusiasts but, rather, could help foster this transition as part of a greener energy mix. It notes that African countries that have the potential for GHP require the institutionalization of, or a change in, their existing approaches to land-related energy governance systems, in order to achieve success.


This article presents a theoretical analysis of the educational policies for ethnic minorities, using the example of Russia. To this end, the Russian educational minority policies are analyzed from the perspective of a theory of cultural transmission in minorities recently proposed by the author. It is argued that the theory is able to explain important aspects of the educational policies of a majority for indigenous minorities that are not easily accounted for by existing theoretical approaches, and can therefore contribute to a better understanding of the Russian educational policy for minorities during history and more generally, the educational policies of nation states for ethnic minorities. Keywords: Russia; minorities; minority politics; educational policies; nationalities policy; cultural transmission in minorities


Today we know the pathobiochemical mechanism of gallstone formation. Cholecystectomy is the therapy of choice with a mortality-rate 0,5% in uncomplicated cases. The mortality-rate increases in patients with recurrent stones in the biliary tract system after cholecystectomy. In addition the liver produces a lithogenic bile. We propose the prophylactic use of chenodesocycholic acid in patients after choledochal revision, if the bile duct system is altered in such a way that cholesterol crystals can aggregate and grow to stones. A low dose of cheno acid is sufficient. Moreover a fibre rich diet increases the chenodesoxycholic acid synthesis in the liver.


A human steroid hormone, ouabain, has been shown to play a role in several types of cancer cell behavior; however, its effects on cancer metastasis are largely unknown. Herein, we demonstrate that sub-toxic concentrations of ouabain facilitate cancer cell detachment from the extracellular matrix in human lung cancer cells. Ouabain at concentrations of 0-10 pM significantly enhanced cell detachment in dose- and time- dependent manners, while having minimal effect on cell viability. The detachment-inducing effect of ouabain was found to be mediated through focal-adhesion kinase and ATP-dependent tyrosine kinase pathways. Alpha-5 and beta-1 integrins were found to be down-regulated in response to ouabain treatment. Since detachment of cancer cells is a prerequisite process for metastasis to begin, these insights benefit our understanding over the molecular basis of cancer biology.


Foreclosure is a prominent concept in the antitrust laws and across economics. In the world of exclusionary conduct—foreclosure is the concept. But, despite its prominence in antitrust law and economics—including taking center stage in the Department of Justice's complaint against Google—it is still a relatively unsettled area of the law. Foreclosure does not enjoy a commonly understood definition. There is no agreed upon method for measuring it. And there is no well-settled threshold at which antitrust concerns are triggered. In short, foreclosure analysis is a mess. As the last major law-defining case on exclusive dealing, Tampa Electric, nears its sixtieth birthday, the black letter law of naive foreclosure has an increasingly unbearable disconnect with modern economic antitrust methods. Courts are left with relatively little guidance as to how to understand the competitive effects of a world with and without the contracts being challenged—and the naïve approach is precisely of zero help on that question. Courts have adapted on their own to bridge the gap between the foreclosure analysis in the early cases—built from discredited foreclosure theory—and modern economics by adopting process-based foreclosure inquiries. This is the future of foreclosure, and the sooner we get there, the better.


BACKGROUND
The National Center for Health Statistics reported that obesity is at epidemic levels in the United States, with an estimated 70.7% of adults affected by overweight and obesity. The disease state of obesity affects all generations and is pervasive among all socioeconomic groups.

PURPOSE
This study was designed to examine the impact of implementing educational modules to determine if the intervention improved knowledge and comfort levels for Nurse Practitioner students when managing patients with obesity.

METHODS
Nurse Practitioner students completed a survey regarding knowledge and comfort level in managing patients with obesity. Students then completed modules designed to train health care providers on the management of obesity. A postmodule assessment was administered to determine if the obesity management modules improved competency and perceived skills when treating patients with overweight and obesity.

RESULTS
Participants' mean score on the knowledge test represented a significant improvement following training. Their comfort level in managing patients with obesity increased.

IMPLICATIONS FOR PRACTICE
Implementing these modules in graduate education may be a helpful avenue to improve competency in obesity management. Acknowledging that obesity is a disease and requires a multifaceted approach when helping patients improve their health. This change in perception may lead to better goal-setting with the patient, empathetic understanding, and broader patient involvement in the treatment.


270, 5.8%), and entrapment of device (n 5 104, 2.2%). The most reported patient complications were airway obstruction (n 5 156, 20.6%), foreign body retention (n 5 107, 14.1%), unintended radiation exposure (n 5 69, 9.1%), aspiration/inhalation (n 5 59, 7.8%), and pain (n 5 53, 7.0%). A number of cases reported unspeci fi ed complications with insu ffi cient information (n 5 50, 6.6%). Conclusion: The Bravo pH capsule is routinely utilized by Gastroenterologists for ambulatory pH monitoring. Our analysis of the FDA MAUDE database revealed a predominance of reported device complications related to capsule adherence and placement di ffi culties. In our study, airway obstruction represented the most commonly reported patient adverse event. This database has notable limitations, including limited information on patient comorbidities, detailed endoscopy reports, and an absence of a total volume of procedures performed in the United States. Furthermore, reporting can be inconsistent and underreported.Thisstudy provides insight into themost commonlyreported complicationsof theBravo pH capsule thatwill help inform therisk/bene fi t conversationwith patients and maylead to a more detailed approach on how to mitigate and manage complications.


A large spectrum of technologies are collectively dubbed as physical layer security (PLS), ranging from wiretap coding, secret key generation (SKG), authentication using physical unclonable functions (PUFs), localization / RF fingerprinting, anomaly detection monitoring the physical layer (PHY) and hardware. Despite the fact that the fundamental limits of PLS have long been characterized, incorporating PLS in future wireless security standards requires further steps in terms of channel engineering and pre-processing. Reflecting upon the growing discussion in our community, in this critical review paper, we ask some important questions with respect to the key hurdles in the practical deployment of PLS in 6G, but also present some research directions and possible solutions, in particular our vision for context-aware 6G security that incorporates PLS.


Impulse control disorders (ICDs), a wide spectrum of maladaptive behaviors which includes pathological gambling, hypersexuality and compulsive buying, have been recently suggested to be triggered or aggravated by treatments with dopamine D2/3 receptor agonists, such as pramipexole (PPX). Despite evidence showing that impulsivity is associated with functional alterations in corticostriatal networks, the neural basis of the exacerbation of impulsivity by PPX has not been elucidated. Here we used a hotspot analysis to assess the functional recruitment of several corticostriatal structures by PPX in male rats identified as highly (HI), moderately impulsive (MI) or with low levels of impulsivity (LI) in the 5-choice serial reaction time task (5-CSRTT). PPX dramatically reduced impulsivity in HI rats. Assessment of the expression pattern of the two immediate early genes C-fos and Zif268 by in situ hybridization subsequently revealed that PPX resulted in a decrease in Zif268 mRNA levels in different striatal regions of both LI and HI rats accompanied by a high impulsivity specific reduction of Zif268 mRNA levels in prelimbic and cingulate cortices. PPX also decreased C-fos mRNA levels in all striatal regions of LI rats, but only in the dorsolateral striatum and nucleus accumbens core (NAc Core) of HI rats. Structural equation modelling further suggested that the anti-impulsive effect of PPX was mainly attributable to the specific downregulation of Zif268 mRNA in the NAc Core. Altogether, our results show that PPX restores impulse control in highly impulsive rats by modulation of limbic frontostriatal circuits.


Observational studies suggest that cardiovascular disease (CVD) increases the risk of developing Alzheimer's disease (AD). However, the causal relationship between the two is not clear. This study applied a two-sample bidirectional Mendelian randomization method to explore the causal relationship between CVD and AD. Genome-wide association study (GWAS) data from 46 datasets of European populations (21,982 cases of AD and 41,944 controls) were utilized to obtain genetic instrumental variables for AD. In addition, genetic instrumental variables for atrial fibrillation (AF), heart failure (HF), myocardial infarction (MI), coronary heart disease (CHD), angina pectoris (AP), and ischemic stroke (IS) (including large-artery atherosclerotic stroke [LAS] and cardioembolic stroke [CES]) were selected from GWAS data of European populations (P < 5E-8). The inverse variance weighting method was employed as the major Mendelian randomization analysis method. Genetically predicted AD odds ratios (OR) (1.06) (95% CI: 1.02–1.10, P = 0.003) were linked to higher AP analysis. A higher genetically predicted OR for CES (0.9) (95% CI 0.82–0.99, P = 0.02) was linked to a decreased AD risk. This Mendelian randomized study identified AD as a risk factor for AP. In addition, CES was related to a reduced incidence of AD. Therefore, these modifiable risk factors are crucial targets for preventing and treating AD.