Abstract Purpose: Acknowledging the key role of knowledge transfer as the primarily mechanism, through which firms replicate organizational routines, this paper addresses the role of reverse knowledge flows in routine replication programs and attempts identifying a set of mechanisms that could facilitate these knowledge flows. Furthermore, the article aims to provide a proposal for a structured approach to reverse knowledge flow management that would combine in the same framework (1) the deployment of routines in new contexts and (2) the collection, transformation, and redeployment of local knowledge. Methodology: The applied methodology follows the interpretative research approach. It draws from a longitudinal study of a seven-year-long replication program, during which an ERP template has been deployed in twenty-five manufacturing sites and five regional offices of a leading multinational FMCG company. The main research method was participant observation complemented with interviews, project documentation, and e-mail communication analysis. Findings: The paper shows that, in the course of multiple replications, the replicated template becomes subject to several adjustments in order to fit new requirements, eliminate observed shortcomings, and adopt learnings from previous deployment sites. The article further demonstrates that keeping such template enhancement process effective requires deliberate management of reverse knowledge flows, which maturity should grow in parallel to the scope of the program and number of replications. This means that reverse knowledge flows must increasingly base on well-established processes with assigned resources, clear responsibilities, and socio-material mechanisms. This is a prerequisite for the subsequent deployments and retrofits of an enriched template to become the key vehicle for the diffusion of local learnings on a company-wide scale. Originality: This paper contributes to the literature on organizational routines by addressing the role of reverse knowledge flows in routine replication processes, proposing a structured approach to reverse knowledge flow management in routine replication programs, and presenting a maturity model for a reverse knowledge flow management system.


The equilibrium depth of scour is an important parameter for estimation of the foundation depth. The equilibrium depth of scour development under steady flow is depending on time and can be reached in equilibrium time. The aim of the study is to find the equilibrium time near elliptical guide banks at clear water and uniform river bed, which allows to predict the equilibrium depth of scour near structures in flow. The literature analysis shows that there are no methods or formulas to calculate equilibrium time of scour near elliptical guide banks. In formulas for equilibrium time calculation at piers or abutments the different parameters are not taken into consideration: contraction rate of the flow, Froude number, bed layering, sediment movement parameters, local flow modification, relative local and critical velocities ratio and relative depth. The differential equation of the bed sediment movement in clear water was used and method for computing equilibrium time of scour near elliptical guide banks was elaborated. New hydraulic threshold criterion is proposed for calculation of equilibrium time of scour. Computer modeling results were compared with equilibrium time of scour calculated by the presented method and they were in good agreement.


To assess the effects of an oil price bust on individual labor market outcomes, we leverage the 2015 exogenous decline in international oil prices with geographical variation in oil-dependency in Ecuador. To account for propagation mechanisms, we also test the causal effect of the oil price bust on public transfers to local autonomous governments. Reduced form results suggest a moderate oil price pass-through channel on wages and nonlabor earnings but not on labor supply and participation. Public transfers play an amplification role, as a one percentage point decrease in these funds implies workers in oil-dependent areas to experience a wage reduction of 1.5%. Spillover effects to nonextractive industries, with reduced economic activity at the firm level, seem to be the transmission channels explaining the drop in individual earnings during the oil price bust.


In this work, the diffusion coefficient of sucrose was determined in four experiments by varying the initial concentrations at different time rates. The amount of sucrose that diffused into the solvent column was determined via a coulometric assay developed by Dubois et al. In 200secs and at initial concentration of 0.5gmL-1, the rate of diffusion was 99.43% while at the initial concentration of 3.0gmL-1 and in 800 secs the rate of diffusion was 99.88%. From the concentrations obtained after diffusion was allowed at the different time ranges, the average diffusion coefficient of 4.64 x 10-8cm2s-1 was obtained. This value is in agreement with that obtained from literature (4.586 x 10-8cm2S-1). The hydrodynamic radius of the sucrose was consequently evaluated to be 51.34pm


Abstract In this report analysis of foreign exchange rates time series are performed. First, triangular arbitrage is detected and eliminated from data series using linear algebra tools. Then Vector Autoregressive processes are calibrated and used to replicate dynamics of exchange rates as well as to forecast time series. Finally, optimal portfolio of currencies with minimal Expected Shortfall is formed using one time period ahead forecasts


Renal artery stenosis (RAS) is one of the main correctable causes of secondary systemic arterial hypertension. Color Doppler ultrasound (DUS), a non-invasive imaging modality, has been used to diagnose RAS in hypertensive patients. This study was conducted in the period between June 2008 and March 2010 to compare the sensitivity, specificity, accuracy and predictive values of DUS using contrast-enhanced magnetic resonance angiography (CEMRA) as the gold standard for the diagnosis of RAS. Fifty-seven consecutive patients with clinical findings suggestive of RAS (32 males and 25 females) with a mean age of 56 years (±7.92 years) were referred to the University Kebangsaan Medical Center to be screened for RAS using DUS and CEMRA. RAS was considered significant if the reduction in diameter was >60%. A total of 114 arteries were assessed, 65 in males (57%) and 49 in females (43%). On DUS, the parameters measured were the peak systolic velocity at the proximal main renal artery (PSV-P), distal main renal artery (PSV-D) and the suprarenal aorta (PSV-A) at the level of the renal hila and the acceleration time (AT) at the main renal artery. The renal-renal ratio (RRR), which is the value of PSV-P/PSV-D, and the renal-aortic ratio (RAR), which is the value of PSV-P/PSV-A, were then calculated. The accuracy, sensitivity, specificity and positive and negative predictive values of DUS in the detection of significant RAS were determined. All measured DUS parameters were positive for the detection of RAS, with an accuracy of 98.3%. On retrospective review, all the arteries that showed significant stenosis on CEMRA demonstrated an irregular outline on DUS. We conclude that DUS is accurate in the diagnosis of significant RAS but is not very sensitive as a screening tool.


The effective surf ace area of a parenteral drug in suspension, that which is exposed to body fluids a~ the injection site, is a major determinant of its in vivo absorption rate. Precise methods o f determining the effective surface area without disturbing the in vivo system have not been developed . A method to estimate the effective surf ace area of a subcutane ously injected suspension based on the urinary excretion of drug from solid disk implants of known surface area is presented. Standard curves for the mean surf ace area of from two to four subcutaneously implanted cylindrical disks of pure sulfadiazine versus cumulat ive urinary sulf adiazine excretion to 48 hours were developed for three test animals . By applying the urinary excretion data obtained following the subcutaneous injection of an aqueous suspension of sulfadiazine to the appropriate standard curve for area, a preliminary estimate of the apparent or effective in vivo surface area for the suspension formu lation was obtained. Improvements i n the experimental methodology which would control certain biopharmaceutical factors related to parenteral drug ab sorption from subcutaneous sites, and increase the statistical significance of the surf ace area estimate are suggested.


This essay examines possible routes to achieving significant health improvements in the underserved populations of developing countries. It argues that unconventional strategies, largely outside the health sector as conventionally defined, have the greatest potential to scale sustainably. The essay describes two such strategies—nutrition and safe drinking water. In particular, the essay argues that impact investors focused on social enterprises can best maximize their health impact by looking closely at the strategies described herein.


Using the image feedback system is an effective way to the realize sticking protective film automatically for the screen of mobile phone. System using CCD industrial camera as the testing core, get the image of the film and the screen continuously, and real-time detect the center location of the film and the screen. To accelerate the speed and accuracy of the detection, this design use Sobel's edge detection algorithm for determining the position of the edge points.


We propose in this paper the use of artificial intelligence, especially deep learning algorithms, for the isotopic ratio determination for hydrogen–deuterium mixtures. Our approach is based on the Balmer-α line emitted by hydrogen and deuterium, but unlike the standard method, it does not consist of fitting the Hα/Dα line spectra. Instead, only some basic spectroscopic features such as the line peak-to-dip wavelength separation, peak-to-peak and dip-to-peak intensity ratios of the Zeeman–Doppler-broadened Hα/Dα line spectra are used by the regression algorithm for training. We demonstrate the proof-of-principle of our approach by applying deep learning from the open-access machine-learning platform TensorFlow to Hα/Dα line profiles, which we have synthetized with pre-determined parameters such as neutral temperatures, the magnetic field strength and the H/(H+D) isotopic ratio. The used regression algorithm allowed us to retrieve with a good accuracy the isotopic ratios used for the synthetized line profiles.


We have developed our next generation Nb integrated circuit process which offers higher performance, particularly for SFQ-type logic, and increased density compared to our present 2000 A/cm/sup 2/ foundry process. The new process is based on our existing Nb foundry process, but has been optimized to utilize more of the sub-micron alignment and exposure capabilities of our optical lithography tools. Minimum linepitch and junction size have been reduced to 2.5 /spl mu/m (from 4 /spl mu/m) and 1.75 /spl mu/m (from 2.5 /spl mu/m), respectively, and J/sub c/ has been increased to 4000 A/cm/sup 2/. These goals have been achieved by an overall reduction in layer thicknesses, implementation of SF/sub 6/ dry etch for metal line definition, and optimization of the photolithography process. The new process offers lower inductance wiring and substantially lower parasitic circuit inductances compared with the existing Nb foundry process. In this paper, we discuss these improvements and report parametric test data for devices fabricated in this process.


The incidence of abnormal displacement continues to show a gradual increase. The need for preventive measures has therefore become a pressing matter. Successful prevention of abomasal displacement is based on adequate knowledge of the aetiology and pathogenesis. The present state of affairs is reviewed on the basis of the literature, personal experience and studies. Obviously, a large number of factors may play a role in the pathogenesis of abomassal displacement. Although the knowledge of the aetiology of abomasal displacement is anything but complete, a number of (probably useful) preventive measures are suggested.


We consider signal and receiver design for space-time Viterbi equalization for wireless transmission. We propose a search method to find good training sequences, termed min-norm training sequences, for least-square channel estimation. Compared to either a maximum-length sequence or a randomly generated training sequence, the training sequence obtained can drastically reduce the channel estimation error. We also derive a simple lower bound on the achievable channel estimation error of any training sequence. Knowledge of this lower bound helps the search for min-norm training sequences in that it facilitates a measure of the goodness of the best sequence examined so far. For operation under the situation with unknown channel response lengths, we propose a simple method to select the memory length (tap number) in the Viterbi equalizer based on the SNR of the received signal. The resulting equalization performance is found to be comparable with the case where a preset, fixed memory length is used. However, the proposed method often results in use of a smaller tap number, which translates into a reduction in the computational complexity. Simulation results show that at symbol error rate below 10 (SNR > 5 dB) the amount of complexity reduction is of the order of 5% to 25% on the average, for typical wireless channels.


From the 1910s through the 1930s, Midwestern writers were conspicuously prominent in American literary life. A generation of writers from the Midwest had come of age and had shared an important and motivating cultural experience: the encompassing transformation of rural and urban Midwestern life from traditional craftsmanship, manual labor, and local community to a fragmented, machine-driven, and intensely capitalistic mode of existence. A profound sense of lost possibilities pervaded the literary mood of these authors. An organic Midwestern village culture that had only just begun to take definite shape was swept away, and a fruitful and promising region was sacrificed to crass commercialism. In Sacred Land, author Mark Buechsel shows that Sherwood Anderson, Willa Cather, and F. Scott Fitzgerald, among others, turned to two potential sources for grounding their region's and nation's life authentically: nature itself-particularly the super-abundant nature to be found in Midwestern states and the model provided by the traditional sacramental culture of medieval Europe. The result was a new sacramental vision of how life in the Midwest-and, by extension, life in modern America-might be lived differently. Buechsel demonstrates that each author painted his or her spiritual and cultural vision with different shades and nuances and looked to America's future with varying degrees of optimism. Of crucial importance in each author's work are the characters' encounters with the Midwestern land, a recalcitrant objective reality that refuses to yield to the wrong kinds of dreams. Characters who are genuinely open to what their engagement with the land has to teach them generally find some personal blessing and learn how to claim a fully human place in the order of things. Characters who fail to learn the lessons nature offers become distorted and grotesque, in a way that expresses the modern condition emblematically. Sacred Land shows that in the process of critiquing American culture, Midwestern writers redefined the American pastoral myth so central to the national psyche.


The cookie consumption and purchase characteristics of households were investigated in six cities in Uganda using household survey data. Cookies can be fortified with vitamins to improve child nutrition. The application of a Logit model permitted the identification of factors significantly affecting household decision to eat cookies. They are household food buyer/preparer's age, employment status, education level, household monthly income, household location, number of children from 4 to 18 years-old and its squared value. The purchase decision was modeled as a two-stage or double-hurdle process. The household purchase decision is shaped by its main food buyer/preparer's employment status and education level, household location, household monthly income, and the number of children age 4 to 18 years old as well as its squared value. Higher values of these variables, but the squared number of children encourage the purchase decision. However, the decision of purchase counts of cookie boxes is shaped by another set of variables, including the frequency of eating cookies, household location, household monthly income, the number of children age 4 to 18, the type of cookie box purchased (cookie purchase is made as per piece purchase and per packet purchase ), and its price. The findings provide important insights for the local cookie producers and marketers, as the identified characteristics and the directional effects are of direct use in the formulation of the marketing and merchandising decisions. The findings are also valuable for policymakers, who concerned about improving nutrition for school children.


: A rapid and high performance gas chromatographic method for the determination of 20 organchlorinated pesticides in oils, fruits and vegetables has been developed. The samples of fruits and vegetables were extracted with petroleum ether-acetone, while those of oils were extracted with acetonitrile-hexane. The extract was purified by Florisil column with ethyl ether-hexane(15:85, V/V) or ethyl ether-petroleum ether(15:85, V/V) as eluent. Chromatographic analysis was performed on wide-bore capillary column with ECD detector. Satisfactory separation and detection of these organchlorinated pesticides are presented with the proposed method. The detection limits of this method were 1.0 ng/g-20.0 ng/g(S/N = 5), the recoveries 83.2%-106.8% and the relative standard deviations 2.0%-9.5%.


Purpose
Identifying ideas for frugal innovations could substantially support engineers and managers in their work. Patents may be a promising source of ideas for frugal innovations. The purpose of this paper is to show how patents of this kind can be identified.

Design/methodology/approach
Prior work has developed a generic process model to identify frugal patent candidates. They use semantic analysis and a frugal thesaurus for searching and characterizing frugal patent candidates. The question is, whether and how this process model can be applied to a different industry successfully? The field of small household appliances is selected as a testbed because it is known for including frugal innovations while having a different business model than the industrial field in which the thesaurus was developed.

Findings
Applying the process model leads to a number of 22 strongly frugal patent candidates, which are manually evaluated based on three frugal characteristics. Due to this analysis, a high fraction of the candidates could be identified as frugal patents, which validates the process model. In addition, this paper outlines several options for enhancing the process model, e.g. by separating between a frugal search and a frugal evaluation thesaurus.

Originality/value
The process model to identify frugal patent candidates can be used by engineers and technology managers to find ideas for frugal innovations. This paper not only shows its applicability in the industry of small household appliances but gives the basis for its successful transfer to other industries.


By means of computer simulation technique, this paper builds an artificial sto ck market model consisting of decision making agents. Through the fundamental and technical analysis in the aspects of investors, trading cost, transaction volume, risk-free interest, tick size and price-limit system, the model is used to indicate the volatility and liquid ity. The results show that the stock index time series has obtained the characteristics of steep-peak and heavy-tail, wh ich is in accordance with that of real stock market. It is also found that an appropriate increase of tick size or relax of price limit would help imp rove the market liquidity, but to some extent, increase the market volatility. The irrational behavior of institutional investors and lar ge volume of transaction are also easy to result in stock market fluctuation.


Improvement of ALMA observatory requires increase of bandwidth, sensitivity and number of antennas. All these improvements will meet a bottleneck if ALMA digital system is not addressed. Currently a 2 bit digitizer supporting <8 GHz bandwidth per polarization is employed limiting correlation efficiency at 88%. Implementation of ALMA downconverter substantially limits line searches compared to sensitivity limit and it's bandwidth is not extendable. We have initiated study on possible implementation of ALMA digital front-end system which includes modular digitizer, digital processing at antenna and TCP/IP optical fiber data transfer. We report on requirements, trade-offs and possible implementation of modular digital front-end and analyze its impact on sensitivity of current ALMA system as well as future one. We review technology and performance available in near future. Significant performance improvement can be realized at moderate cost.


"Fish Conservation" offers, for the first time in a single volume, a readable reference with a global approach to marine and freshwater fish diversity and fishery resource issues. Gene Helfman brings together available knowledge on the decline and restoration of freshwater and marine fishes, providing ecologically sound answers to biodiversity declines as well as to fishery management problems at the subsistence, recreational, and commercial levels. Written in an engaging and accessible style, the book: considers the value of preserving aquatic biodiversity; offers an overview of imperiled fishes on a taxonomic and geographic basis; presents a synthesis of common characteristics of imperiled fishes and their habitats; details anthropogenic causes of decline; examines human exploitation issues; and, addresses ethical questions surrounding exploitation of fishes.The final chapter integrates topics and evaluates prospects for arresting declines, emphasizing the application of evolutionary and ecological principles in light of projected trends. Throughout, Helfman provides examples, explores case studies, and synthesizes available information from a broad taxonomic, habitat, and geographic range."Fish Conservation" summarizes the current state of knowledge about the degradation and restoration of diversity among fishes and the productivity of fishery resources, pointing out areas where progress has been made and where more needs to be done. Solutions focus on the application of ecological knowledge to solving practical problems, recognizing that effective biodiversity conservation depends on meeting human needs through management that focuses on long-term sustainability and an ecosystem perspective.


Deaf asylum seekers are a marginalized group of people in refugee and forced migration studies. The aim of this paper is to explore and highlight the experiences of deaf asylum seekers in the asylum procedure in Finland. The data come from linguistic ethnographic methods, interviews, and ethnographic observation with 10 deaf asylum seekers. While living in the reception centers, the study participants have faced a range of linguistic and social challenges. The findings show that language barriers appeared from day one after the participants' arrival in Finland. The investment and initiatives of deaf volunteers played a crucial role for deaf asylum seekers in their access to and participation in Finnish society. In addition, receiving formal Finnish sign language instruction had a positive effect on their well-being. Drawing on content analysis of deaf asylum seekers' experiences, I argue that greater awareness, recognition, and support of deaf asylum seekers are needed in the Finnish asylum system. I conclude this paper with a discussion of and suggestions for a better asylum system for deaf individuals.


Background: In the unprecedented times of the COVID-19 pandemic, majority of the outpatient departments have been closed including psychiatry community outreach clinics (COCs). The only way to reach out to these patients has been the newly evolved telemedicine services. Aim and Objectives: The aim of the study is to study the need and accessibility of telemedicine services among patients of COCs. Methodology: The case record files of patients who got them registered in the COCs during January to March 2020 were taken out and sociodemographic, clinical, and contact details were retrieved. A 12-item questionnaire was prepared to know the current status of these patients and information about need and accessibility of telemedicine service for mental health over phone. Results: A total of 78 patients were interviewed. Mean age of the respondents was 43.90 years. The most common clinical diagnoses were neurotic, stress-related, and somatoform disorders followed by substance use disorders, mood disorders, and schizophrenia, including other psychotic disorders. About two-third of the respondents reported that their condition worsened over a period of 4 months after closure of COCs, while one-fourth patients could not purchase medicines due to nonrenewal of prescription. Only 2.4% of the respondents were aware about the existing telemedicine services in the hospital and 100% of the respondents agreed to consult telemedicine services after imparting the information and scope of telemedicine services. Conclusion: Sudden closure of COCs led to worsening of mental health status of already registered patients in the clinics. There were poor knowledge and accessibility of telemedicine service by the respondents. Information, education, and communication about telemedicine services increase the feasibility, acceptability, and accessibility of services.


Background: Childhood fitness is an emerging area of concern as prevalence of childhood obesity is rising. Indian studies, have identified decreased fitness levels and increased obesity in urban children. However, studies incorporating a comprehensive fitness evaluation are unavailable. In order to establish appropriate school fitness programs, baseline fitness levels in the target children is essential. Aims: The aim of this study is to evaluate health and performance related fitness levels of school going children between the ages of 8 and 14 years old. Settings and Design: Schools from Udupi Taluk, observational design. Materials and Methods: Fitness testing battery adapted from Presidential fitness challenge. Statistical Analysis Used: Descriptive statistics, parametric tests of comparison, and correlation were carried out using Pearson's correlation coefficient. Results: Children were divided into age groups consisting of 1 year age intervals. Reference values are guidelines given by President's challenge. Children who scored 25-32 points were considered as very fit; 17-24 as being adequately fit and 8-16 as unfit. Children from vernacular schools were more fit than those from English medium schools, with boys doing better (P = 0.01). Conclusions: From the results of this study, we can conclude that basic levels of health-related fitness are low among school children of Udupi Taluk, Karnataka.


Magnesium alloys have been known as the best lightweight metallic materials for various applications of electronic equipments and automobile parts due to high specific strength and stiffness. The needs for wrought magnesium alloys have been increased for the application to structural parts in the form of sheets and bars. However, magnesium has a hexagonal closed-packed (HCP) crystal structure with a limited number of operative slip systems at room temperature, and its formability is restricted to mild deformation. The improvement of the formability of magnesium sheets for real applications is important. In order to increase formability of magnesium sheets at elevated temperature, one promising way is a grain refinement.


Preoperative localization of an insulinoma was possible using a technique of transhepatic pancreatic venography, with measurement of insulin levels in six pancreatic veins. Surgical exploration confirmed the presence of an insulinoma at the site predicted by venography. Peripheral plasma insulin levels were only minimally elevated at the time of hypoglycemia. However, complete suppression of ketogenesis during a 74-hour fast was observed, and felt to be a biological marker for hyperinsulinism. These observations suggest that transhepatic pancreatic venography and the measurement of plasma ketones in addition to glucose and insulin during fasting, may be useful supplementary studies in the evaluation of patients with fasting hypoglycemia.


Simple approximations for the reflection coefficients and differential scattering cross sections per unit area of a random distribution of arbitrary protuberances on a ground plane are given in terms of the scattering amplitude of an isolated protuberance, their average number in unit area, and the given incident wave. These functions take into account multiple coherent scattering, and are mutually consistent in fulfilling the energy principle. It is shown, in general, that if the horizon angle approaches zero, then the reflection coefficients approach unity linearly, and the horizontal/vertical back scattering vanishes like the fourth/second power of the angle. General results are then specialized to arbitrary hemispheres and circular semicylinders, and applied to limiting cases of perfect conductors with radii very small or very large compared to wavelength.


Due to the nonlinear of the Black-Scholes option pricing model, r and σ were not easy to be solved by analytic method. Quantum-behaved Particle Swarm Optimization (QPSO) algorithm was proposed to estimate the parameters because of its global search ability and robustness. In the process of optimization, Black-Scholes option pricing formula was used as the research object to establish the algorithm model of parameter estimation and weighted sum of squared errors between experimental values and predicted values was used as the objective optimization function. Experimental results show that QPSO algorithm is more effectively than Particle Swarm Optimization (PSO) algorithm and Deferential Evolution (DE) algorithm.


Despite the increasing relevance, ranging from academic research to industrial applications, only a limited number of nonconventional, oleaginous Yarrowia lipolytica strains are characterized in detail. Therefore, we analyzed three strains in regard to their metabolic and physiological properties and in respect to important characteristics of a production strains. A flow cytometry method was set up to evaluate their fitness in a rapid manner. By investigating different cultivation conditions and media compositions, similarities and differences between the distinct strain backgrounds could be derived. Especially sugar alcohol production, as well as a agglomeration of cells were found to be connected with growth at high temperatures. In addition, sugar alcohol production was independent of high substrate concentrations under these conditions. To investigate particular traits, including growth characteristics and metabolite concentrations, genomic analysis were performed. We found sequence variations for one third of the annotated proteins but no obvious link to all phenotypic features.


Fitness responses to environment can shape species distributions, though
opposing eco-evolutionary processes can obscure environmental effects.
For example, host specificity influences parasite dynamics, but is
unclear how adaptation of parasites to local host communities may scale
up to continental distributions. Here, we develop a macroecological
framework to determine how host community structure affects the
distribution of specialist and generalist populations of Striga
hermonthica, an African parasitic plant of cereal crops. Combining data
from global crop production and parasite experimental trials, we find
that parasites perform best on the host species that is most common in
their location of origin. Moreover, niche model contrasts predict
parasite specialization on two hosts that evolved
alongside Striga during domestication (pearl millet and
sorghum), indicating that specialist parasites may be most likely
to occur where host niches differ most in multivariate environmental
space.  Our study demonstrates that patterns of parasite local
adaptation to host communities can emerge at continental scales and that
differential environmental tolerances of hosts indirectly shape the
distribution of specialist and generalist parasites.  By predicting
spatial dynamics of parasite specialization versus generalization
directly from environmental data, our approach may help inform current
and future management of pests and disease.


Importance: In the open-label phase III POSEIDON randomized clinical trial (RCT), a limited course of tremelimumab plus durvalumab and chemotherapy (T + D + CT) indicated in the first-line treatment of metastatic non-small cell lung cancer (mNSCLC), progression-free survival, and overall survival (OS) were substantially improved without significant additional tolerance burden compared to chemotherapy (CT). However, given the high cost of T + D + CT, its value needs to be evaluated in terms of both potency and cost. Objective: To evaluate the cost-effectiveness of T + D + CT versus CT in individuals with previously untreated mNSCLC from a U.S. payer perspective. Design, setting, and participants: A three-state Markov model was adopted to weigh the lifetime costs and effectiveness of T + D + CT versus CT for the treatment of first-line mNSCLC, according to the results of the POSEIDON phase III RCT involving 675 individuals with mNSCLC. Individuals were simulated to undergo either T + D + CT for up to four 21-day cycles, followed by durvalumab once every 4 weeks until disease progression or unacceptable toxic effects and one additional tremelimumab dose, or CT for up to six 21-day cycles (with or without pemetrexed maintenance; all groups) in the analysis. Main outcomes and measures: Lifetime costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER) were evaluated with a willingness-to-pay (WTP) threshold of $ 100,000 to $ 150,000 per QALY. The uncertainty of the model was investigated using univariate and probabilistic sensitivity analysis. Results: T + D + CT produced additional 0.36 QALYs with additional costs of $ 217,694, compared to CT, giving rise to ICERs of $ 608,667.86/QALY. The univariate sensitivity analysis demonstrated that the outcomes were most sensitive to the cost of durvalumab. Other variables with a large or moderate influence were the utility of progression-free survival state, utility of progressive disease state, and cost of tremelimumab. Probability sensitivity analysis revealed that T + D + CT had a 0% probability of cost-effectiveness in individuals with mNSCLC at a willingness-to-pay threshold of $ 100,000 to $ 150,000 per QALY. Conclusion and relevance: In this model, T + D + CT was estimated to be less cost-effective than CT for patients with mNSCLC at a WTP threshold of $ 100,000 to $ 150,000 per QALY in the United States. When new combination therapies with remarkable effect become pivotal in the first-line treatment, the price reduction of durvalumab and tremelimumab may be necessary to achieve cost-effectiveness in future possible context.


Traumatic brain injury (TBI) leads to mossy fiber reorganization, which is considered to be a causative factor in the development of temporal lobe epilepsy. However, the underlying mechanism is not fully understood. Emerging evidence suggests that TrkB–ERK1/2–CREB/Elk-1 pathways are highly related to synaptic plasticity. This study used the rat fluid-percussion injury model to investigate activation of TrkB–ERK1/2–CREB/Elk-1 signaling pathways after TBI. Rats were subjected to 2.0-atm parasagittal TBI followed by 30 minutes, 4 hours, 24 hours, and 72 hours of recovery. After TBI, striking activation of TrkB–ERK1/2–CREB/Elk-1 signaling pathways in mossy fiber organization were observed with confocal microscopy and Western blot analysis. ERK1/2 was highly phosphorylated predominantly in hippocampal mossy fibers, whereas TrkB was phosphorylated both in the mossy fibers and the dentate gyrus region at 30 minutes and 4 hours of recovery after TBI. CREB was also activated at 30 minutes, peaked at 24 hours of recovery, and returned to the control level at 72 hours of recovery in dentate gyrus granule cells. Elk-1 phosphorylation was seen in CA3 neurons at 4 hours after TBI. The results suggest that the signaling pathways of TrkB–ERK1/2–CREB/Elk-1 are highly activated in mossy fiber organization, which may contribute to mossy fiber reorganization seen after TBI.


&NA; Infantile myofibromatosis is one of the most prevalent soft tissue tumors of infancy and childhood. Multifocal nodules with visceral lesions are associated with a poor prognosis. A few familial cases have been linked to mutations in various genes including PDGFRB. In this study, we sequenced PDGFRB, which encodes a receptor tyrosine kinase, in 16 cases of myofibromatosis or solitary myofibroma. Mutations in the coding sequence of PDGFRB were identified in 6 out of 8 patients with the sporadic multicentric form of the disease and in 1 out of 8 patients with isolated myofibroma. Two patients had the same mutation in multiple separated lesions. By contrast, a third patient had three different PDGFRB mutations in the three nodules analyzed. Mutations were located in the transmembrane, juxtamembrane and kinase domains of the receptor. We showed that these mutations activated receptor signaling in the absence of ligand and transformed fibroblasts. In one case, a weakly‐activating germline variant was associated with a stronger somatic mutation, suggesting a two‐hit model for familial myofibromatosis. Furthermore, the mutant receptors were sensitive to the tyrosine kinase inhibitor imatinib, except D850V, which was inhibited by dasatinib and ponatinib, suggesting a targeted therapy for severe myofibromatosis. In conclusion, we identified gain‐of‐function PDGFRB mutations in the majority of multifocal infantile myofibromatosis cases, shedding light on the mechanism of disease development, which is reminiscent of multifocal venous malformations induced by TIE2 mutations. Our results provide a genetic test to facilitate diagnosis, and preclinical data for development of molecular therapies.


I have documented the recanalization of a venous graft placed in the peripheral venous system to replace a severely disrupted peripheral vein. This case demonstrates the feasibility of such a maneuver, where indicated, to preclude large vein ligation or permanent venous obstruction resulting from inappropriate venography.


The increased growth of the body as a whole at the time of sexual maturation early suggested a causal interrelationship of these two phenomena. This was further emphasized by the development of precocious puberty in association with gonadal tumors. In this situation a rapid increase in body weight and height, maturation of the musculature and skeleton, deepening of the voice, and growth of sexual hair may be observed together with precocious development of the genitalia. When the gonadal steroids became available for study in man, Kenyon and his co-workers1demonstrated that testosterone propionate exerts anabolic effects on tissues other than those of the genital system. Thus a person eating a constant diet may gain as much as 9 kg. in body weight during testosterone administration, which is more than can be accounted for by growth of the genitals. Metabolic balance studies have shown that under the influence of androgenic


Lee Friedlander (b. 1934) has been tackling the challenge of self-portraiture throughout his prolific career. What began as an unorthodox investigation of the genre has become a masterful engagement spanning five decades. In this extraordinary compilation, which includes hundreds of previously unpublished pictures, we follow the famous photographer through the years as his personal and creative lives unfold and intertwine. Produced to the highest production standards and featuring over 400 duotone images-from his first self-portraits, taken with cable release in hand, to recent images of the photographer with his family and extended network of friends-In the Picture explores Friedlander's various guises throughout a rich and colorful life.


OBJECTIVE
Epithelial ovarian cancer is associated with high mortality, mostly because of delayed diagnosis, necessitating the search for novel diagnostic and prognostic markers. Here we evaluated the association between expression levels of phosphatase and tensin homolog (PTEN), hypoxia-inducible factor (HIF)-1α, and vascular endothelial growth factor (VEGF), and ovarian cancer.

PATIENTS AND METHODS
Expressions of these proteins were assessed by immunohistochemistry in 21 specimens of normal ovary tissues and 76 specimens of ovarian cancer tissues. Associations with pathological characteristics and prognosis were determined using chi-square test, Kaplan-Meier method, log-rank test, and Cox regression model.

RESULTS
Expression of PTEN in ovarian cancer tissue was negatively associated with clinical stage and differentiation degree. A reverse trend was observed in association between expression of HIF-1α and VEGF, and the clinical stage of the disease. PTEN expression negatively correlated with HIF-1α and VEGF expression levels, whereas both latter positively correlated with each other. The overall survival of patients with positive PTEN expression was significantly longer than that of those with negative expression; the opposite trend was observed with HIF-1α and VEGF. The differentiation degree and expressions of HIF-1α and PTEN were dependent predictors, whereas VEGF expression, clinical stage and lymph node metastasization were independent prognostic factors in these patients.

CONCLUSIONS
PTEN, HIF-lα, and VEGF were found to be prognostic markers in ovarian cancer, with VEGF also being as an independent prognostic factor. Combined detection of their expression levels may be useful for determination of the degree of malignancy, metastasis, and prognosis of ovarian cancer.


Introduction EUS FNA is accepted as the primary modality for tissue diagnosis of solid pancreatic lesions. The presence of on-site cytopathology for immediate evaluation during endoscopic ultrasound-guided fine needle aspiration (EUS FNA) has previously been shown to improve performance characteristics. Due to service pressures EUS FNA is also undertaken in the absence of in-room cytopathology assistance. This is a review of current practice. Method We retrospectively assessed 700 consecutive EUS-FNA procedures from January 2011 to January 2016. 459 (65.5%) solid pancreatic lesions were included in the final analysis after excluding 230 for biliary strictures, hepatic lesions, lymph nodes, gastric, oesophageal lesions, pancreatic cysts and 11 for insufficient information. Results In 399 (86.9%) cases on-site cytopathology support was available, while the remaining was unsupported. There were 228 males (57.1%) in the supported and 29 (48.3%) in the unsupported group. Mean age was 64.6(SD: 11.4) and 67.4(SD: 11.9) respectively. The mean number of passes in the two groups were 2.8 (SD: 1.12) and 1.9 (SD: 1.0) (p<0.0001). A conclusive diagnosis (malignant, benign, NET, GIST) was made in 84% (67%, 12%, 5%, 0%) of the supported group and in 38% (23%, 10%, 3%, 2%) of the unsupported (p<0.0001). The mean follow up for the entire cohort was 14.2 months (SD:14.1) and mean survival of in patients diagnosed with malignancy was 10.9 months (SD: 8.7). Overall performance characteristics of EUS FNA were Sensitivity: 90.8% Specificity: 86.9% PPV: 91.8% NPV: 85.4% Conclusion This review confirms high performance characteristics of EUS FNA. The presence of on-site cytopathologist significantly increases the diagnostic yield. Disclosure of Interest None Declared


Technology in education can be used in a variety of different ways. The most obvious is its direct application to help facilitate learning. However, technology can also be used in more subtle ways to benefit student learning and to ease the burden on academics and staff so that they in turn are able to spend more time interacting with students. The Engineering Schools at Loughborough University approached the Centre For Engineering and Design Education (CEDE), looking to the Centre, with its blend of pedagogy and technology skills to unpick and resolve the issues that the Schools were facing with regard to assessing students. With myriad modules on multiple programmes, live oversight of the assessment demands on students was difficult to achieve with the Schools' existing practices; the potential for over burdening students due to assessment bunching was a real issue. There were also practical issues of managing coursework hand in and return for large numbers of students. Working in close collaboration with the Engineering Schools CEDE has developed, piloted and rolled out CASPA, a Coursework and Assessment Scheduler for Programme Administration. This paper describes CASPA and shares the key findings of a study, undertaken by CEDE into CASPA' s reception and impact on students and administrators and how they would like to see CASPA enhanced. Research was undertaken with administrative staff in the form of focused discussions and an online questionnaire survey. Student views have been provided using a paper based questionnaire survey of 88 students. The key findings of the research are presented in this paper, including the findings that students value the reassurance that CASPA gives by keeping a record of assessment submissions and work returned whilst providing a centralised place for their assessment deadlines to help them keep track of their schedules and organise their work. The introduction of CASPA has had a huge impact on the demands of administrators time, greatly reducing the time needed to receive and return coursework. With this freed up time it has been possible for Schools to make greater use of their administrators for the benefit of the students. One school in particular has introduced feedback quality monitoring into the coursework return process. Having trained the administrators in the level and quality of feedback to students, administrators are now able to monitor and flag any issues in feedback quality.


Several α,β,α- or α,γ,α-tripeptides, consisting of a central cyclobutane β- or γ-amino acid being flanked by two d- or l-proline residues, have been synthesized and tested as organocatalysts in asymmetric aldol additions. High yields and enantioselectivities have been achieved with α,γ,α-tripeptides, being superior to peptides containing a cyclobutane β-amino acid residue. This is probably due to their high rigidity, which hinders some of the peptide catalysts to adopt the proper active conformation. This reasoning correlates with the major conformation of the peptides in the ground state, as suggested by 1H NMR and computational calculations. The configuration of the aldol products is controlled by the proline chirality, and consequently, the R/S configuration of aldol products can be tuned by the use of either commercially available d- or l-proline. The enantioselectivity in the aldol reactions is reversed if the reactions are carried out in the presence of water or other protic solvents such as methanol. Spectroscopic and theoretical investigations revealed that this effect is not the consequence of conformational changes in the catalyst but rather caused by the participation of a water molecule in the rate determining transition state, in such a way that the preferential nucleophilic attack is oriented to the opposite enantiotopic aldehyde face.


Many Hox proteins are thought to require Pbx and Meis co-factors to specify cell identity during embryogenesis. Here we demonstrate that Meis3 synergizes with Pbx4 and Hoxb1b in promoting hindbrain fates in the zebrafish. We find that Hoxb1b and Pbx4 act together to induce ectopic hoxb1a expression in rhombomere 2 of the hindbrain. In contrast, Hoxb1b and Pbx4 acting together with Meis3 induce hoxb1a, hoxb2, krox20 and valentino expression rostrally and cause extensive transformation of forebrain and midbrain fates to hindbrain fates, including differentiation of excess rhombomere 4-specific Mauthner neurons. This synergistic effect requires that Hoxb1b and Meis3 have intact Pbx-interaction domains, suggesting that their in vivo activity is dependent on binding to Pbx4. In the case of Meis3, binding to Pbx4 is also required for nuclear access. Our results are consistent with Hoxb1b and Meis3 interacting with Pbx4 to form complexes that regulate hindbrain development during zebrafish embryogenesis.


BACKGROUND
Aminolevulinic acid photodynamic therapy (ALA-PDT) is an effective treatment for multiple actinic keratosis (AK). However, PDT-induced pain often discontinues the therapy to reduce its efficacy, limiting its application. If modified painless PDT schedule with shorter photosensitizer dressing and higher dose illumination could achieve good efficacy in AK, it is still unknown.

OBJECTIVES
To explore the efficacy and pain tolerance of the modified painless PDT (M-PDT) in facial multiple AK.

METHODS
A split-face controlled clinical study including 14 patients with facial multiple AK was conducted. The patients received conventional PDT (C-PDT) on the left and M-PDT in the contralateral area. The left area (C-PDT) was illuminated by a red light-emitting diode light (144 J/cm2 ) after applying the 10% ALA cream for 3 h; the other had illumination for a total light dose of 288 J/cm2 after applying the 10% ALA cream for 0.5 h. The primary endpoint was the lesion clearance rate at 1-month postthree sessions of PDT. Secondary endpoints included pain scores, the incidence of adverse events during treatment, and cosmetic outcomes.

RESULTS
At 1 month following three treatments, the total lesion clearance rate was comparable between M-PDT and C-PDT (91.6% vs. 89.0%). While the lesion clearance rate of M-PDT was higher than that of C-PDT in the Grade III lesions (86.5% vs. 72.0%, respectively) (p < 0.05). M-PDT achieved a 100% lesion clearance rate for Grade I lesions earlier than C-PDT, with M-PDT treated twice and C-PDT treated thrice. Moreover, the pain score during illumination was significantly lower for M-PDT than for C-PDT (p < 0.01). Regarding photoaging, the Global Subjective Skin Aging Assessment score showed that the total and atrophy scores of C-PDT and M-PDT were significantly improved, and M-PDT also reduced discoloration. There was no significant difference in adverse reactions between C-PDT and M-PDT.

CONCLUSIONS
M-PDT is comparable to C-PDT's efficacy for treating facial multiple AK, resulting in much lower pain scores.


Some ultra-compact dwarf galaxies (UCDs) have elevated observed dynamical V-band massto-light (M/LV) ratios with respect to what is expected from their stellar populations assuming a canonical initial mass function (IMF). Observations have also revealed the presence of a compact dark object in the centers of several UCDs, having a mass of a few to 15% of the present-day stellar mass of the UCD. This central mass concentration has typically been interpreted as a super-massive black hole, but can in principle also be a sub-cluster of stellar remnants. We explore the following two formation scenarios of UCDs, i) monolithic collapse and ii) mergers of star clusters in cluster complexes as are observed in massively star-bursting regions. We explore the physical properties of the UCDs at different evolutionary stages assuming different initial stellar masses of the UCDs and the IMF being either universal or changing systematically with metallicity and density according to the Integrated Galactic IMF (IGIMF) theory. While the observed elevated M/LV ratios of the UCDs cannot be reproduced if the IMF is invariant and universal, the empirically derived IMF which varies systematically with density and metallicity shows agreement with the observations. Incorporating the UCDmass-dependent retention fraction of dark remnants improves this agreement. In addition we apply the results of N-body simulations to young UCDs and show that the same initial conditions describing the observed M/LV ratios reproduce the observed relation between the half-mass radii and the present-day masses of the UCDs. The findings thus suggest that the majority of UCDs that have elevated M/LV ratios could have formed monolithically with significant remnant-mass components that are centrally concentrated, while those with small M/LV values may be merged star-cluster complexes.


BACKGROUND Murine intraepithelial lymphocytes kill Giardia lambia; responses of human intestinal lymphocytes to this parasite are unknown. AIMS To examine giardia induced proliferation, interferon γ production, migration, and cytotoxicity by lymphocytes from the human intestine and peripheral blood. METHODS Giardia were added to intraepithelial lymphocytes, lamina propria lymphocytes, and peripheral blood lymphocytes, obtained from jejunal mucosa and blood of otherwise healthy patients undergoing gastric bypass surgery for morbid obesity. Proliferation was measured by 3H-thymidine incorporation; frequency of proliferation precursors, by limiting dilution analysis; interferon γ production, by ELISA; cytotoxicity, by 51Cr release of radiolabelled giardia and by release of serine esterases by effector lymphocytes that mediate cytotoxicity. RESULTS The CD4+ T lymphocytes from intestine and blood proliferated in response to giardia. The stimulus by the parasite was mitogenic rather than antigenic due to the fact that the peak response was on day 3 rather than day 6, and the large number of precursors was in the range of that for mitogens. CD4+ T lymphocytes from both sites produced interferon γ in response to giardia. Lymphocytes did not migrate towards or kill the parasite. CONCLUSIONS Giardia induced the same degree of proliferation and interferon γ production by CD4+ T lymphocytes in intestine and blood, but did not trigger cytotoxicity or migration.


ABSTRACT In principle, the generation, transmission, and dissipation of supercoiling forces are determined by the arrangement of the physical barriers defining topological boundaries and the disposition of enzymes creating (polymerases and helicases, etc.) or releasing (topoisomerases) torsional strain in DNA. These features are likely to be characteristic for individual genes. By using topoisomerase inhibitors to alter the balance between supercoiling forces in vivo, we monitored changes in the basal transcriptional activity and DNA conformation for several genes. Every gene examined displayed an individualized profile in response to inhibition of topoisomerase I or II. The expression changes elicited by camptothecin (topoisomerase I inhibitor) or adriamycin (topoisomerase II inhibitor) were not equivalent. Camptothecin generally caused transcription complexes to stall in the midst of transcription units, while provoking little response at promoters. Adriamycin, in contrast, caused dramatic changes at or near promoters and prevented transcription. The response to topoisomerase inhibition was also context dependent, differing between chromosomal or episomal c-myc promoters. In addition to being well-characterized DNA-damaging agents, topoisomerase inhibitors may evoke a biological response determined in part from transcriptional effects. The results have ramifications for the use of these drugs as antineoplastic agents.


With one stroke of a pen and a simple rule-change, landless agricultural workers on military-operated farms in Pakistan have found themselves facing eviction from lands their families have worked for generations. While exploring the dynamics of this legal change of status from share-croppers to cash renters I explore whether a rule of classical Islamic Hanafi land law that gave tillers responsibility for paying a tax to the state for lands they worked, creating a common interest between lessors and tillers, can be a legal mechanism for vesting land ownership. In the process I examine the broader dynamics of the pressures for norm change as well as evaluate the roles and capacities of classical jurists and judges in the modern era. The historical protections in the pre-classical and classical periods of Hanafi law flowed from a complex set of interconnected assumptions about the needs of different social classes and the particular need to integrate the least powerful into society by giving them a stake in its functioning and future outcomes. At a time of increasing social pressures and rising resource inequality the process is proof of the great power of the law to shape the legal, social and economic conceptualization of particular groups and to be able to change the way that particular groups are viewed in society.


The effect of oral supplementation of �-lipoic (LA) on growth of Ehrlich ascites carcinoma cells (EACs) and hepatic antioxidant state in mice was investigated. The results revealed that �-lipoic (LA) acid at 50 �mg/kg body wt reduced the viability and volume of EAC cells and increased the survival of the treated animals. In addition, LA normalized oxidative stress in liver of mice-bearing EAC cells evidenced by increasing the levels of total thiols, glutathione, glutathione-S-transferase, superoxide dismutase, and catalyse. On the other hand, significant decreases in the levels of malondialdehyde and protein carbonyl were demonstrated in liver indicating controlled oxidative stress in these animals. As a consequence, LA regulated liver enzymes, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyl transferase. The data also indicated the efficiency of LA as cancer inhibitor and therapeutic influence. In conclusion, the present data suggest LA as a potential therapeutic complement in the treatment or prevention of different pathologies that may be related to an imbalance of the cellular oxidoreductive status associated with malignancy.


Adiponectin has many beneficial effects on cardiovascular and obesity-related disorders. It is part of a class of proteins that contains short collagenous domains, along with surfactant proteins A and D, and complement protein C1q. This class of biomacromolecules requires post-translational modifications to form biologically active assemblies. By introducing a set of post-translational modifying enzymes into Escherichia coli , we have created a prokaryotic expression system that functionally assembles adiponectin, as assessed by the ability of produced adiponectin multimers to suppress human endothelial cell apoptosis. This study represents the first example of the assembly of functional high order multimers of any member of this class of proteins outside of eukaryotic cells. Furthermore, the results give fundamental insight into the process of assembly such as the necessity and sufficiency of various post-translational steps for functional assembly. We expect that fine-tuning of the expression system will allow for efficient production and functional assembly of biomolecules that assemble via short collagenous domains.


Dioxin stimulates transcription from the cytochrome P-450IA1 promoter by interaction with the intracellular dioxin receptor. Upon binding of ligand, the receptor is converted to a form which specifically interacts in vitro with two dioxin-responsive positive control elements located in close proximity to each other about 1 kb upstream of the rat cytochrome P-450IA1 gene transcription start point. In rat liver, the cytochrome P-450IA1 gene is marked at the chromatin level by two DNase I-hypersensitive sites that map to the location of the response elements and exist prior to induction of transcription by the dioxin receptor ligand beta-naphthoflavone. In addition, a DNase I-hypersensitive site is detected near the transcription initiation site and is altered in nuclease sensitivity by induction. The presence of the constitutive DNase I-hypersensitive sites at the dioxin response elements correlates with the presence of a constitutive, labile factor which specifically recognizes these elements in vitro. This factor appears to be distinct from the dioxin receptor, which is observed only in nuclear extract from treated cells. In conclusion, these data suggest that a certain protein-DNA architecture may be maintained at the response elements at different stages of gene expression.


Beginning with the philosophical underpinnings of politics and aesthetics, I proceed to centrally locate dramaturgy as a political practice/process that unites artistic production and consumption. By discussing some of the major tenets of narrative-based, or poetic dramaturgy, through this lens, I attempt to unearth its more fundamental constitutive relationships and redirect current discourse and pedagogy. Distinct from its particular expressions within specific regimes of the arts, it can be inclusively defined as the act of uniting contradictory elements in the processes of creation and spectatorship: unconscious/conscious, and active/passive. I then address alternative dramaturgical presences of composition in Martha Clarke's Threepenny Opera at the Atlantic Theater Company, and her dance theater piece Chéri at the Signature Theater, allowing for a more complete read of the pieces. Ultimately, I hope to begin a discussion of Aesthetic and Critical Dramaturgy that does not reject Poetic Dramaturgy, but expands upon it, inviting new forms of exchange and collaboration among artists.


Hard ceramic materials like tungsten carbide (WC) are extensively used in high value manufacturing, and micromachining of these materials with sufficient quality is essential to exploit its full potential. A new micro-machining technique called droplet assisted laser micromachining (DALM) was proposed and demonstrated as an alternative to the existing nanosecond (ns) dry pulse laser ablation (PLA). DALM involves injecting liquid micro-droplets at specific frequency during the nanosecond laser micromachining to create impulse shock pressure inside the laser irradiation zone. The impulse shock pressure is generated due to the explosive vaporisation of the droplet, during its interaction with high temperature laser irradiation zone. In this paper, the DALM uses a nanosecond pulsed Nd:YAG laser to machine tungsten carbide substrate. The results suggest that the impulse shock pressure generated during the DALM process can transform the melt ejection mechanism of the ns laser micromachining process. The change in ejection mechanism results in a 75% increase in material removal rate and 71% reduction in the spatter redeposited compared to conventional dry ns laser micromachining. © 2016 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).


In the present work, warm tension tests for DP steel LTWB (B340/590DP) with 1.0mm/1.0mm thickness are performed on the CMT5205 universal tester, and its microstructure in the region adjacent to weld line is observed by the JSM-7001F scanning electron microscopy. Moreover, Imagetool software is applied to deal with the SEM photographs in order to study the influence of forming temperature on the martensite volume fraction, average length and thickness. By building the relationship of martensite structure volume fraction, feature size, configuration with macro-mechanical properties including stress peak, yield strength, elongation at failure and temperature, the mechanism of improving the formability of DP steel LTWB at the elevated temperature level is revealed, which is vital for optimizing the warm forming process parameters of DP steel LTWB and setting up the precise material constitutive model to enhance the FEM simulation accuracy.


At the ISAC 2000 Congress, the Clinical Cytometry Society organized a meeting of international experts to reach consensus on the minimum number of antibodies required for a full evaluation of hematologic and lymphoid neoplasias. A questionnaire was distributed prior to the meeting to numerous experts from US and European institutions and 13 responses were received. At the meeting, 25 individuals, including most of those who returned responses, participated in the discussions and voted on the issues presented. In chronic lymphoproliferative disorders (CLD), 9 antibodies (anti-CD5, CD19, kappa, lambda, CD3, CD20, CD23, CD10, and CD45) were deemed essential for initial evaluation by 75% of the participants. There was near unanimity that additional markers (selected from CD22, FMC7, CD11c, CD103, CD38, CD25, CD79b and heavy chains for B-cell disorders, and CD4, CD7, CD8, CD2, CD56, CD16, TCRa/b, and TCRg/d for T-cell disorders) would be needed to fully characterize CLD, although not every marker would be useful in all cases. Tissue lymphomas were believed to be similar to CLD, needing a minimum of 12--16 markers. However, for some cases, CD30, bcl-2, TdT, CD71, CD1a, and CD34 were cited as useful by the participants. Markers mentioned for plasma cell disorders included kappa, lambda, CD38, CD45, CD56, CD19, CD20, CD138, and heavy chains. Of 17 voting participants, 16 agreed that between 5 to 8 markers would be essential reagents for plasma cell disorders. For acute leukemia (AL), 10 markers (CD10, CD19, CD13, CD33, CD34, CD45, CD7, CD14, CD3, and HLADR) were considered essential by 75% of participants for initial characterization of the leukemia lineage. Most (>75%) agreed that at least one more B (CD20, CD22, CD79a, IgM), T (CD1a, CD2, CD4, CD5, CD8), myeloid (CD11b, CD15, CD64, CD117, myeloperoxidase), erythroid (CD36, CD71, glycophorin A), and megakaryocytic (CD41, CD61) reagents should be included in the essential panel. However, there was no agreement as to which was optimal. Thus, approximately 13--15 of those reagents would be considered essential in all cases of AL, whereas others (CD16, CD56, CDw65, TdT, and cytoplasmic CD3) were mentioned as useful in some cases. Almost all voting participants believed that the appropriate number of markers for complete characterization of AL would average 20--24. The majority of the responders (11 of 13) indicated that fewer reagents could be used in monitoring or staging patients with previously characterized disease, but not all ventured a specific number of reagents. From the above results, we conclude that the phenotypic analysis of hematologic and lymphoid neoplasia requires a rather extensive panel of reagents. Supplementary reagents might even be necessary if they prove to become relevant for diagnostic purposes. Reducing the number of antibodies could significantly compromise the diagnostic accuracy, appropriate monitoring, or therapy of these disorders.


This study determined the exposures and risks associated with the ingestion of lead in the diets of three age groups: 5-19; 20-39 and ≥ 40 living in Kumasi. Frequently consumed foods were sampled from the study area and their lead concentration quantified using the graphite furnace AAS method. The @Risk software was used to fit distributions for all elements of exposure. Subsequently, the chronic daily intake (CDI) was determined, and then used to estimate the risks in terms of the margin of exposure (MoE) and incremental lifetime cancer risk (ILTCR). Across the three age groups, the modal CDI ranged between 0.007 and 0.06 μg/kg bw-day. Significantly low modal MoEs (0.009-0.05) were recorded for developmental neurotoxicity, nephrotoxicity and cardiovascular toxicity. De minimis (<10-6) modal lifetime cancer risks were recorded, however, the 95th percentile risks show that some consumers are still at risk (>10-6). These findings suggest serious public health concerns.


Federal agencies are deeply involved in legislative drafting — both in the forefront by drafting the substantive legislation the Administration desires to submit to Congress and in the shadows by providing confidential "technical drafting assistance" on legislation that originates from congressional staffers. This technical drafting assistance helps Congress avoid considering legislation that would unnecessarily disrupt the current statutory scheme by leveraging agency expertise on the subject matter. But it also allows the agency to play an active yet opaque role in drafting legislation from the very early stages. In fact, the empirical findings presented in this Article, based on extensive interviews and surveys at some twenty federal agencies, suggest that agencies provide technical drafting assistance on the vast majority of proposed legislation that directly affects them and on nearly all such legislation that gets enacted. The under explored yet widespread practice of legislating in the shadows has important implications for administrative law theory and doctrine and the conventional principal–agency bureaucratic model. On the one hand, this phenomenon perhaps supports the growing scholarly call that agencies should be allowed to engage in more purposivist interpretation (than their judicial counterparts) because of their expertise in legislative history and purpose and their role in statutory drafting. On the other, the phenomenon may cast some doubt on the foundations for judicial deference to agency statutory interpretations, in that agencies are intimately involved in drafting the legislation that ultimately delegates to the agencies the authority to interpret that legislation. In other words, many of the agency self-delegation criticisms raised against Auer deference could apply with some force to agency statutory interpretation and Chevron deference as well. Or we should at least be considering more closely the administrative state's role in drafting legislation — especially drafting legislation in the shadows — when considering to what degree courts should defer to agency statutory interpretations. Such reconsideration is particularly warranted in light of the transparency concerns implicated by agency legislating in the shadows.


Xanthine oxidase is a molybdenum-containing hydroxylase that catalyzes the hydroxylation of sp(2)-hybridized carbon centers in a variety of aromatic heterocycles as well as aldehydes. Crystal structures of the oxidase form of the bovine enzyme in complex with a poor substrate indole-3-acetaldehyde and the nonsubstrate guanine have been determined, both at a resolution of 1.6 Å. In each structure, a specific and unambiguous orientation of the substrate in the active site is observed in which the hydroxylatable site is oriented away from the active site molybdenum center. The orientation seen with indole-3-acetaldehyde has the substrate positioned with the indole ring rather than the exocyclic aldehyde nearest the molybdenum center, indicating that the substrate must rotate some 30° in the enzyme active site to permit hydroxylation of the aldehyde group (as observed experimentally), accounting for the reduced reactivity of the enzyme toward this substrate. The principal product of hydroxylation of indole-3-acetaldehyde by the bovine enzyme is confirmed to be indole-3-carboxylic acid based on its characteristic UV-vis spectrum, and the kinetics of enzyme reduction are reported. With guanine, the dominant orientation seen crystallographically has the C-8 position that might be hydroxylated pointed away from the active site molybdenum center, in a configuration resembling that seen previously with hypoxanthine (a substrate that is effectively hydroxylated at position 2). The ∼180° reorientation required to permit reaction is sterically prohibited, indicating that substrate (mis)orientation in the active site is a major factor precluding formation of the highly mutagenic 8-hydroxyguanine.


The foreland fold and thrust belt of the Carpathians extends from Austria through the Carpathians to the south Carpathian bend in Romania where most structural units plunge beneath younger Pliocene-Pleistocene cover. Folds continue westward until all surface expression disappears before reaching Danube River. The belt is flanked by elements of the European, Russian, and Moesian cratonal areas which are overlain by foredeep deposits that are themselves involved within the external fold and thrust belt and overridden by it. Within the fold and thrust belt are older parts of the Carpathian orogene formed on continental crust with evolutionary differences between the western and eastern Carpathians. The foreland fold and thrust belt consists of an inner flysch and an outer molasse cut into thrust sheets verging cratonward. Oldest flysch units are Middle Jurassic in the U.S.S.R., Upper Jurassic in Romania, and Upper Cretaceous in C.S.S.R. Oceanic crust may have underlain the flysch, and continental crust the molasse. Timing of thrusting is constrained locally, but suggests deformation in the western Carpathians developed during Oligocene to Miocene time progressively outward. Deformation in the eastern Carpathians began in the Albian or early Cenomanian internally and proceeded to late Miocene deformation externally. The convex east loop of the Carpathian foreland fold and thrust belt resulted from subduction beneath inner Carpathian continental elements fragmented during collision within the European alpine system and driven or pulled eastward, molding the rocks of the fold and thrust belt against a recess in the craton. A Miocene volcanic arc lies internal to the fold and thrust belt, suggesting subduction of a few hundred kilometers of lithosphere. Basins developed contemporaneous with thrusting within the Carpathian loop. Two types of basins occur: (1) peripheral (Vienna, Transcarpathian, and Transylvanian), showing fast initial subsidence followed by slower linear subsidence, and (2) central intra-Carpathian (Pannonian), showing only fast linear subsidence. Structural and thermal models indicate the peripheral basins formed by twofold stretching and some dike intrusion, End_Page 683------------------------------ whereas the Pannonian basin formed by either twofold stretching accompanied by subcrustal attenuation or by attenuation and erosion of the subcrustal lithosphere. End_of_Article - Last_Page 684------------


In studying molecular mechanisms of specialised transduction, the lacI (E. coli)-Ea47 (lambda) DNA junction in transducing bacteriophage lambda plac 5 has been structurally elucidated, thus yielding the complete sequence of lambda plac 5 DNA including the lac5 substitution, a well-known segment of lambdoid vectors. The lambda plac5 DNA is shown to consist of 19368 bp (lambda left arm) + 3924 bp (lac5 substitution) + 25353 bp (lambda right arm), totally amounting to 48645 bp. The presence of the phage rho bL promoter near to the right end of the lac5 insert is shown. The lacI gene distal end in lambda plac5 proved to be much longer than it was postulated earlier, coding for 224 C-terminal amino acid residues of lac repressor. Both the recombination studied in this paper and the earlier studied abnormal prophage excision (2, 3) occur near to Chi-like structures (chi*lacI and chi*lom, respectively). On the basis of the data obtained, a key role of the E. coli RecBCD system and Chi-like sequences in the formation of deletions in bacterial cells is suggested.


Earth's life support systems are breaking down, including the stratospheric ozone layer, which protects all higher life on the planet from deadly ultraviolet radiation. This breakdown is a direct result of human activities including the large-scale manipulation of processes that affect Earth's climate, otherwise known as geoengineering. We present further evidence that coal fly ash, utilized in tropospheric aerosol geoengineering, is the primary cause of stratospheric ozone depletion, not chlorofluorocarbons, as "decreed" by the Montreal Protocol. The misdiagnosis was a potentially fatal mistake by mankind. Coal fly ash particles, uplifted to the stratosphere, are collected and trapped by polar stratospheric clouds. In springtime, as these clouds begin to melt/evaporate, multiple coal fly ash compounds and elements are released to react with and consume stratospheric ozone. Contrary to the prevailing narrative, the stratospheric ozone layer has already been badly damaged and now increasingly deadly ultraviolet radiation, UV-B and UV-C, penetrates to Earth's surface. Our time is short to permanently end all geoengineering activities, and to reduce and/or eliminate all sources of aerosolized coal fly ash, including first and foremost the jet-sprayed emplacements into the troposphere that are systematically breaking down Earth's support systems and poisoning life on this planet.


This article considers tropes of fragmentation and immersion in photographs made by Frederick Sommer (1905–1999) in the 1940s. It problematizes Kant-derived conceptions of the sublime, arguing that the radical nature of Sommer's work of this period challenges dyadic relationships of the figure/ground that are associated with depictions of the Kantian sublime. Reviewing some of the writing on Sommer's work to date, the article draws upon a close reading of his photographic prints and technique in the context of his wider practice, and alongside work done over the past four decades in Literature Studies, Feminist Studies, Lesbian and Gay Studies, and Classical Studies, to propose that a model of the Sapphic sublime is appropriate to Sommer's work of this period.


Abstract. In France, nuclear facilities were designed around very low probabilities of failure. Nevertheless, some extreme climatic events have given rise to exceptional observed surges (outliers) much larger than other observations, and have clearly illustrated the potential to underestimate the extreme water levels calculated with the current statistical methods. The objective of the present work is to conduct a comparative study of three approaches to extreme value analysis, including the annual maxima (AM), the peaks-over-threshold (POT) and the r -largest order statistics ( r -LOS). These methods are illustrated in a real analysis case study. All data sets were screened for outliers. Non-parametric tests for randomness, homogeneity and stationarity of time series were used. The shape and scale parameter stability plots, the mean excess residual life plot and the stability of the standard errors of return levels were used to select optimal thresholds and r values for the POT and r -LOS method, respectively. The comparison of methods was based on (i) the uncertainty degrees, (ii) the adequacy criteria and tests, and (iii) the visual inspection. It was found that the r -LOS and POT methods have reduced the uncertainty on the distribution parameters and return level estimates and have systematically shown values of the 100 and 500-year return levels smaller than those estimated with the AM method. Results have also shown that none of the compared methods has allowed a good fit at the right tail of the distribution in the presence of outliers. As a perspective, the use of historical information was proposed in order to increase the representativeness of outliers in data sets. Findings are of practical relevance, not only to nuclear energy operators in France, for applications in storm surge hazard analysis and flood management, but also for the optimal planning and design of facilities to withstand extreme environmental conditions, with an appropriate level of risk.


The steel slags produced and the available stocks are considerable. Managing these co-products requires finding a solution for their future that is
satisfactory from both an environmental and economic point of view. The research aims to propose an integrated, sustainable and economically rational solution to this problem. It includes the development of physical and hydrometallurgical processes for the basic recovery of metals and metal oxides and the evaluation of phytostabilisation methodologies, already tested on steel slags, for secondary residues resulting from these treatments. The integrated solution concept will also be based on the control of environmental impacts and/or the study of sustainable eco-compatibility.
In addition, HYPASS plans to list and map former slag heaps, carry out "Life-Cycle Analyses" (LCA) for the various recovery methods and build a "Decision-Support Tool" (DST) to facilitate the identification of the best treatment methods, both from an economic and environmental point of view.


This work examines dairy and sheep farmer attitudes toward antimicrobial use (AMU) in New Zealand. There is increasing public demand on livestock producers to reduce AMU in livestock. The demand stems from concerns about potential antimicrobial resistance (AMR) that could originate from food animals. There is limited practical data on farmer knowledge of AMU. An electronic survey was sent to dairy (n= 378) and sheep farmers (n= 551). Seventy-six dairy farmers (20%, n=76/378) returned the survey. Dairy farmers (69%) showed low levels of concern about antimicrobial resistance and awareness of the need to reduce AMU. Additionally, 76% of dairy farmers didn't think it was possible to reduce AMU. Thirty-nine sheep farmers (7%, 39/551) returned the survey. 76% of sheep farmers were supportive of restricted use of AMU. The dairy and sheep farmers sourced most of the advice from veterinarians (>90%), the livestock industry (>80%) and their colleagues (>70%). This study shows that farmers showed varied concerns about AMR and AMU. Moreover, sheep farmers were more amenable to increased restriction on AMU than dairy farmers. This study suggests that knowledge gaps in farmers may best be filled by veteri-


PCR-based screening of microdeletions in the azoospermic factor (AZF) on the Yq chromosome is an accepted means of identifying a common genetic cause of male infertility, responsible for 5-15% of cases associated with a low sperm count (</=5 x 10(6) sptz/ml). Based on an extensive analysis of the literature, we have established a cost-effective preliminary PCR-based diagnostic screening test, with a set of six pairs of primers ("set-of-6") that have the capability of detecting up to 95% of the Y microdeletion cases already published. These primers are: sY84 in AZFa, sY114, sY129, sY143 in AZFb, and sY149, sY254 in AZFc. Initially, the set-of-6 was tested with 13 other pairs of primers covering the three AZF subregions. A sample of 114 infertile men was tested and 10 (8.8%) microdeletions were found, 3 of which were among the 26 (11.5%) idiopathic azoospermic men. These results showed that all detected microdeletions would be identified using the set-of-6 only. Another sample of 34 patients was subsequently tested using the set-of-6 and 3 (8.8%) microdeletions were found in this group. A comparison of our results with those reported in the literature showed similar microdeletion detection frequencies, demonstrating that the set-of-6 primers provides a reliable, simple and cost-effective way of detecting AZF deletions.


This article describes the experiences of Danisco (a global food ingredients company) as it followed a growth-by-acquisition business strategy, focusing on how a new CIO built the IT resources to ensure the IT organization was "ready to acquire." We illustrate how these IT capabilities expedited the IT integration following two acquisitions, one of which involved Danisco expanding the scale of its business and the other extending the scope. Based on insights gained from Danisco, we provide lessons for CIOs to realize business benefits when managing post-acquisition IT integration.


I n dental school, we were taught the scientific principle ''inflammation is necessary for healing''. This principle needs to be updated due to the further characterization of the role inflammation plays in the healing process. Early bone healing occurs via specific cellular signaling events: (i) proinflammatory, (ii) antiinflammatory, (iii) proangiogenic, and (iv) osteogenic. Research has increased our understanding of the connection between the immune system and bone healing. The significance of controlling the immediate inflammatory response for successful bone formation has been confirmed. When an osteotomy is performed, multiple proinflammatory cytokines (1st signaling event) are stimulated, such as interleukin (IL)-1a, IL-1b, IL-6, and tumor necrosis factor alpha (TNF-a). Einhorn et al. identified this early inflammatory cytokine expression profile in 2002 and 2003; however, the down-regulation or modulation of cytokine expression was not considered until more recently. Controlling cytokine expression (inflammation) can help create the ideal environment for healing and bone formation. If the cytokine expression is not in a proper balance, compromised bone healing is observed.; for example, excessive concentrations and time-exposure of TNF-a can lead to delayed bone formation. Franchimont et al. controlled the level of TNF-a by increasing the release of the anti-inflammatory cytokine IL-10 (2nd signaling event), thus creating a positive environmental impact at the surgical site. IL-6 has been shown to have a bi-phasic proor anti-inflammatory concentration-dependent effect on bone healing. Other events necessary for healing include the migration to, and accumulation of, stem and osteoprogenitor cells at the surgical site. The accumulation and activation of these osteogenic cells (4th signaling event) are dependent upon angiogenesis (3rd signaling event). Proinflammatory cytokines in the surgical site can inhibit stem cell differentiation and therefore bone formation. Controlling inflammation is thought to have a positive effect on all signaling events. Modulating the immune response during early bone formation may provide a favorable environment for improved predictability of bone grafting procedures. Schmidt-Bleek et al. concluded: ''The modulation of the immune response is a promising approach to improve bone regeneration.'' This greater understanding of the interconnection between the immune system and bone healing may well play a significant role in the future of implant dentistry. As clinicians, our responsibility is to provide efficient and predictable treatments with minimal discomfort; modulating the inflammatory response may be instrumental in meeting these treatment goals. Strategies to control the immune response will undoubtedly be forthcoming and play an important role in our clinical practices.


Abstract There is an acknowledged need for improved conservation of plastic and rubber objects within collections, including improved methods of condition assessment, material identification, and better understanding of material degradation. This reflects the inherent instability and wide-ranging formulations of many such objects and also the relative lack of knowledge in this field. Analysis of volatile organic compounds (VOCs) is a useful method for understanding the chemical processes involved in polymer degradation and for the identification of materials. Conservators and curators have used odor analysis to identify historical plastics for many years, and techniques ranging from acid detection strips to laboratory-based techniques such as solid-phase microextraction-gas chromatography-mass spectrometry have been used to characterize plastic and rubber materials and to understand their degradation. VOC analysis also has potential as a technique for bulk material identification, as a complementary tool to spectroscopic analysis of the surface. A significant advantage of VOC analysis is its potential to be non-invasive, avoiding destructive sampling or even contact with an object. However, there is a greater potential for VOC analysis to be of benefit within conservation than is currently being exploited and significant scope for future research. In fields such as construction or waste management, there is also significant research into analysis of VOC emissions from plastic and rubber materials. The goal of this paper is to systematically review research from a range of fields including conservation, polymer degradation, and plastics recycling and it includes the use of VOC analysis to understand the causes of damage to plastic and rubber objects, to provide evidence of degradation and to monitor degradation progress, and to identify materials and distinguish between different formulations. Summaries of relevant studies are given, and volatile markers of object damage and polymer degradation and key volatile identifiers of a particular material are highlighted.


Abstract: A test system was evaluated for assessing chronic toxicity of waterborne chemicals with early life stage mussels. To determine if the test system could result in ≥80% survival in a control (unexposed) group, fat mucket mussels (Lampsilis siliquoidea Barnes, 1823) and plain pocketbook mussels (L. cardium Rafinesque, 1820) 1 day post transformation were stocked into test chambers (250 mL beakers, water volume, 200 mL, 21 °C, 40 mussels of 1 species per chamber) within a test system constructed for conducting chronic, continuous exposure, flow-through toxicity tests. The test system contained 60 chambers containing silica sand, 30 chambers with L. siliquoidea, and 30 with L. cardium. Each chamber in the continuous feeding system received 1 of 6 food types prepared with concentrated algal products. After 28 days, mussels were harvested from chambers to assess survival and growth. For L. siliquoidea, mean survival ranged from 34 to 80% and mean shell length ranged from 464 to 643 µm. For L. cardium, mean survival ranged from 12 to 66% and mean shell length ranged from 437 to 612 µm. The maximum mean growth rate for L. siliquoidea was 12.7 µm/d and for L. cardium was 11.8 µm/d. When offered a continuous diet of Nannochloropsis, Tetraselmis, and Chlorella for 28 days in the test system, the survival of 1 day post transformation L. siliquoidea was 80%. The test system can be easily enhanced with a pumping system continuously delivering test chemical to the test system's flow stream allowing for chronic toxicity tests with 1 day post transformation mussels.


The honey bee Apis mellifera is experiencing colony losses across the world, this is not the first time in history colony losses have been reported. New molecular detection methods such as real-time PCR allow the detection and analysis of pathogens present in colonies, quickly and reliably.  Of the pathogens that the honey bee is host to, trypanosomes are one of the least understood and trypanosome interactions within the honey bee host remain largely unknown. Using the bumble bee as a model for this host-parasite relationship. The trypanosome C. bombi is known to cause a reduced ability to gain nutrients from food and an overall decrease in efficiency of queens in founding colonies in spring. These negative correlations are significant enough in the bumble bee to warrant investigation into trypanosomes in the honey bee.  The trypanosome C. mellificae was first described in the honey bee in 1967. A screening study in 2009 included a test for and detected the trypanosome in modern honey bee samples. In 2013 C. mellificae was identified as a contributory factor to overwintering colony losses when co-infected with N. ceranae. Following studies detected trypanosomes and led to the characterisation of a new species, L. passim in 2013. Lotmaria passim was first detected in New Zealand in 2014 however no subsequent studies had been undertaken to identify the distribution and dynamics of trypanosomes in New Zealand honey bee colonies.  My goal in this study was to identify the presence of trypanosomes in New Zealand. In an overview study of 47 honey bee colonies from across New Zealand, 46 were positive for the L. passim species. Identified by sequencing of the GAPDH gene. A yearlong study of 15 colonies revealed that the infection rate of L. passim was consistent throughout the year and very low genetic variation was detected. Lotmaria passim was detected in all parts of New Zealand sampled in this study and often in high levels. A positive correlation was detected when L. passim was present in addition to N. apis. There was no detection of C. mellificae in my study. The lack of detection of C. mellificae may suggest that the species is not present, or that it is in such low levels it cannot yet be detected.  In parallel to this trypanosome study two Nosema spp. and DWV were also examined. Nosema apis was found to be more prevalent than N. ceranae, which was not present in any South Island samples. A strong positive correlation was detected between the two Nosema spp. DWV showed a high level of variation likely a reflection of differing Varroa management practices in apiaries in this study.  This study of trypanosomes is the first of its kind in New Zealand identifying the presence and population dynamics of L. passim. This in conjunction with data on Nosema spp. and DWV will be of value to the New Zealand apiculture industry and contribute to global honey bee health studies.


The impact of mega events such as the Olympic Games on the host cities is a matter of continuing debate and controversy. The expectations for increasing the profile of the city as well as the opportunities to improve infrastructure and transport operations are widely recognized. Their effects on the city transport patterns particularly towards sustainable urban transport have proved to be significant. By reviewing the challenges and impacts of previous Olympic Games to the transport system of host cities, it is found that understanding the travel behaviour changes along with mega events can improve future transportation planning, including for the increasing number of special events. In addition, the potential of 'legacy planning' is identified. This can help to optimize the background transport system and contribute to the development of transport facilities with far-reaching significance and value on the urban transportation development towards sustainability. In the absence of the continuing records and sufficient knowledge of travellers' responses towards the changes of transport facilities and policies, many host cities had to repeatedly face similar challenges in forecasting, planning and running the mega events. This lack of knowledge in the travel behaviour changes associated with the Olympic Games and potential concerns have been the main motivation for this research. On the basis of understanding what the short-term and long-term impacts on transportation have been in previous Olympic Games, this thesis investigates the travel behaviour changes under the circumstance of the Beijing Olympics 2008 by examining the information from a series of continuous Beijing residents household travel surveys and supplementary surveys. The comparison found that the local residents' daily travel pattern was interrupted by the Travel Demand Management (TDM) measures and significantly changed during the Olympic Games. Though some impacts seemed to continue after the Games, most changes the residents made during the Games didn't appear to have a lasting effect on local travel patterns. Using Weighted-Euclidean distance Probability Mass function (PMF) tests and cluster analysis, the individual behaviour changes were examined in terms of trip rates, primary travel modes and commuting trips. This showed that travellers with different demographic characteristics might have significantly different behaviour changes and responses to the Games-related Travel Demand Management (TDM) measures. Particularly, the car users and the public transport passengers reacted differently to the changes brought by the Olympics, in both the short-term and the long-term. The data analysis also indicated the travellers' actual behaviours were significantly different from what they planned before the Games, especially on walking and subway. Understanding the difference between groups of travellers is essential for future planning and strategic decisions.


The application of a pulsed laser ablation technique for the generation of cerium-doped garnet nanoparticles in liquids is investigated. The morphological and optical properties of the obtained nanoparticles are demonstrated. Features introduced by the single crystals of Gd3Al2.4Ga2.6O12:Ce3+, Lu3Al5O12:Ce3+, and Y3Al1.25Ga3.75O12:Ce3+ from which the nanoparticles are generated, as well as the parameters of a liquid media on the garnet nanoparticle generation are experimentally studied using TEM and UV-Vis spectroscopy methods. It is shown how the size, shape, and internal structure of the nanoparticles are related to the external laser ablation conditions, as well as to the laser melting processes of NPs in the colloidal solutions. This work provides important information about the generated nanoparticles, which can be used as building blocks for specially designed structures with predetermined optical properties.


Background: The use of post-exposure prophylaxis (PEP) is effective in reducing HIV risk, but it is underused by men who have sex with men (MSM) due to certain psychological and sociostructural factors. This article assessed the awareness and use of PEP among MSM in an effort to increase the visibility and uptake of PEP among at-risk populations. Methods: We conducted a systematic literature search of the PubMed, Web of Science, PsycINFO, and Google Scholar electronic databases. Studies were screened for inclusion, and relevant data were abstracted, assessed for bias, and synthesized. Pooled effect estimates were calculated using random effects meta-analysis, meta-regression and subgroup analysis, and a qualitative review and risk of bias assessment were performed (PROSPERO, CRD42019123815). Results: Twenty eligible studies involving 12,579 MSM were included in the meta-analysis. The pooled estimate of the proportions of MSM who were aware of PEP was modest at 59.9% (95% CI: 50.5~68.7) and that of MSM who previously used PEP was very low at 4.9% (95% CI: 2.4~9.8). PEP awareness showed no clear change over time, while PEP use significantly changed over time. Multiple factors affected awareness, including educational attainment, race/ethnicity, levels of HIV stigma, access to condoms, and so on. Many factors could potentially impede or facilitate the use of PEP, such as income, lack of PEP information, and partnership. Conclusion: We observed that PEP is an underused HIV prevention strategy among MSM and that once MSM become aware of PEP, the majority are willing to use it if they are supported appropriately in terms of a range of individual, social, and structural barriers. Systematic Review Registration: http://www.cdr.york.ac.uk/prospero, PROSPERO [CRD42019123815].