Background. The increasing awareness of cost issues in health care has led to the increasing use of policy-driven substitution of branded for generic medications, particularly relative to statin treatment for cardiovascular diseases. While there are potential short-term health care savings, the consequences for primary care are under-researched. Our objective was to review data on intensive statin therapy and generic substitution in patients at high cardiovascular risk. Results. Current treatment guidelines for the prevention of cardiovascular disease are consistent in their recommendations regarding statin therapy and treatment targets. Clinical trials demonstrate that to reduce cardiovascular events, a statin is more effective than placebo, intensive statin therapy is more effective than moderate statin therapy in patients with established coronary disease, and in patients receiving intensive statin therapy the lowest risk is associated with the lowest low-density lipoprotein levels. However, in clinical practice, patients at high cardiovascular risk are prone to be undertreated. Observational studies suggest that mandatory statin substitution may increase the gap between achieved and recommended therapeutic targets. Conclusions. Substitution of generic statins may be cost-saving, particularly at the primary prevention level. However, statin substitution policies have not been adequately studied on a population level. Data raise concern that mandated statin substitution may lead to unfavourable treatment choices at the level of the individual high-risk patient.


Detailed hydrothermal surveys over ridges with spreading rates of 50–150 mm/yr have found a linear relation between spreading rate and the spatial frequency of hydrothermal venting, but the validity of this relation at slow and ultraslow ridges is unproved. Here we compare hydrothermal plume surveys along three sections of the Gakkel Ridge (Arctic Ocean) and the Southwest Indian Ridge (SWIR) to determine if hydrothermal activity is similarly distributed among these ultraslow ridge sections and if these distributions follow the hypothesized linear trend derived from surveys along fast ridges. Along the Gakkel Ridge, most apparent vent sites occur on volcanic highs, and the extraordinarily weak vertical density gradient of the deep Arctic permits plumes to rise above the axial bathymetry. Individual plumes can thus be extensively dispersed along axis, to distances >200 km, and ∼75% of the total axial length surveyed is overlain by plumes. Detailed mapping of these plumes points to only 9–10 active sites in 850 km, however, yielding a site frequency Fs, sites/100 km of ridge length, of 1.1–1.2. Plumes detected along the SWIR are considerably less extensive for two reasons: an apparent paucity of active vent fields on volcanic highs and a normal deep‐ocean density gradient that prevents extended plume rise. Along a western SWIR section (10°–23°E) we identify 3–8 sites, so Fs = 0.3–0.8; along a previously surveyed 440 km section of the eastern SWIR (58°–66°E), 6 sites yield Fs = 1.3. Plotting spreading rate (us) versus Fs, the ultraslow ridges and eight other ridge sections, spanning the global range of spreading rate, establish a robust linear trend (Fs = 0.98 + 0.015us), implying that the long‐term heat supply is the first‐order control on the global distribution of hydrothermal activity. Normalizing Fs to the delivery rate of basaltic magma suggests that ultraslow ridges are several times more efficient than faster‐spreading ridges in supporting active vent fields. This increased efficiency could derive from some combination of three‐dimensional magma focusing at volcanic centers, deep mining of heat from gabbroic intrusions and direct cooling of the upper mantle, and nonmagmatic heat supplied by exothermic serpentinization.


Objective. Intracortical brain–machine interfaces (BMIs) have predominantly utilized spike activity as the control signal. However, an increasing number of studies have shown the utility of local field potentials (LFPs) for decoding motor related signals. Currently, it is unclear how well different LFP frequencies can serve as features for continuous, closed-loop BMI control. Approach. We demonstrate 2D continuous LFP-based BMI control using closed-loop decoder adaptation, which adapts decoder parameters to subject-specific LFP feature modulations during BMI control. We trained two macaque monkeys to control a 2D cursor in a center-out task by modulating LFP power in the 0–150 Hz range. Main results. While both monkeys attained control, they used different strategies involving different frequency bands. One monkey primarily utilized the low-frequency spectrum (0–80 Hz), which was highly correlated between channels, and obtained proficient performance even with a single channel. In contrast, the other monkey relied more on higher frequencies (80–150 Hz), which were less correlated between channels, and had greater difficulty with control as the number of channels decreased. We then restricted the monkeys to use only various sub-ranges (0–40, 40–80, and 80–150 Hz) of the 0–150 Hz band. Interestingly, although both monkeys performed better with some sub-ranges than others, they were able to achieve BMI control with all sub-ranges after decoder adaptation, demonstrating broad flexibility in the frequencies that could potentially be used for LFP-based BMI control. Significance. Overall, our results demonstrate proficient, continuous BMI control using LFPs and provide insight into the subject-specific spectral patterns of LFP activity modulated during control.


The communication between the grid control center (GCC) to aggregator and aggregator to Electrical Vehicles (EV) is very important in order to support the grid requirements and meet the load demand in a short duration of time. The aggregator sends the power requirement information to EVs and EVs have to receive this information irrespective of either being parked or moving. The EVs which have received this information can communicate the same to other EVs which have not received it. The Long Term Evolution (LTE) protocol is proposed for EV to EV communication in V2G to facilitate the participation of EVs in power transaction. The downlink physical layer of LTE protocol is modeled using MATLAB/SIMULINK and its performance is investigated.


Hyperledger Fabric is a flexible operating system for permissioned blockchains designed for business applications beyond the basic digital coin addressed by Bitcoin and other existing networks. A key property of this system is its extensibility, and in particular the support for multiple ordering services for building the blockchain. However, version 1 was launched in 2017 without an implementation of a Byzantine fault-tolerant (BFT) ordering service. To overcome this limitation, we designed, implemented, and evaluated a BFT ordering service for this system on top of the BFT-SMART state machine replication/consensus library, with optimizations for wide-area deployment. Our results show that our ordering service can process up to ten thousand transactions per second and write a transaction irrevocably in the blockchain in half a second, even with peers spread across different continents.


Two recently identified isozymes of neuraminidase in rat liver were examined for transmission patterns and linkage relationships, and for variation among inbred strains. The isozymes, designated neuraminidase-1 (NEU-1) and neuraminidase-2 (NEU-2), exhibited no electrophoretic mobility variants among the 22 inbred strains examined, but did possess striking interstrain variation in activity phenotypes on electrophoretic gels. The results of a backcross analysis involving the KGH and ACP strains revealed that NEU-1 and NEU-2 phenotypes are independently controlled, each by a single autosomal locus with additively acting alleles. The two loci are unlinked to one another, but the gene controlling NEU-1 is tightly linked to RT1, the rat major histocompatibility complex. This gene is almost certainly identical to Neu-1, a gene identified previously through its effect on "total" activity levels of liver neuraminidase as determined by fluorometric assay of tissue homogenates. NEU-2 and the gene controlling its phenotype were not detected by the fluorometric technique. We designate the genes controlling the NEU-1 and NEU-2 phenotypes as Neu-1 and Neu-2, respectively. Data from this and other studies place Neu-1 between Glo-1 and dw-3. The location of Neu-2 is unknown.


Carbon dioxide (CO2) is a known greenhouse gas. Due to the burning of fossil fuels by industrial and power plants the atmospheric concentration of CO2 has been rising over the past 50 years. Carbon capture and sequestration provides a method to prevent CO2 from being emitted into the atmosphere. Successful carbon sequestration will require the development of many pieces of technology including development of monitoring tools and techniques. An underground laser based monitoring system was built and tested at Montana State University (MSU) to measure sub-surface CO2 concentrations at a sequestration site. The instrument uses differential absorption spectroscopy by temperature tuning a distributed feedback diode laser over several CO2 absorption features located at 2.004 microns. The instrument utilizes photonic bandgap fibers for sub-surface spectroscopy CO2 concentration measurements. The instrument was tested at a controlled release facility located on the MSU campus. The field and CO2 release are managed by the Zero Emissions Research and Technology group at MSU. Three CO2 injection tests were done over the coarse of two summers to simulate a fault or fracture line at a sequestration site. Results from all three tests are presented showing that the underground differential absorption instrument could be used to monitor sequestration sites.


There are nearly half a million elected officials in American local governments, and the timing of local elections varies enormously even within the same state. Some local elections are held simultaneously with major federal and state races, while others are held at times when no higher level elections coincide. We analyze the effect of election timing by exploiting a 1980s change in the California Election Code, which allowed school districts to change their elections from off-cycle to on-cycle. Because we are able to observe very large within-district changes in voter turnout resulting from changes in election timing, we are able to isolate the effect of turnout on policy outcomes, including teacher salaries and student achievement tests. Our analysis demonstrates that while election timing produces dramatic changes in voter turnout, resulting changes in public policy are modest in size and not robust statistically.


The rise in destination accessibility and the emergence of new market segments have increased the competition among tourism destinations, both at national and international level. In order to gain a significant competitive advantage over competitors, destinations increasingly make use of signals that certify and communicate the level of quality provided. While existing research on tourism certifications mostly pertains to quality evaluation, this study exploits quantitative methods to assess the economic impact of destinations' labels. The analysis considers one of the most popular certification of environmental quality attributed to beaches, the Blue Flag award. It explores the relationship between the certification achievement and inbound tourist flows, focusing on the Italian case study. In fact, given their aim of providing synthetized information on destinations, certification programs particularly affect foreign tourists who suffer more from asymmetric information. Panel data techniques and highly disaggregated data are employed to compare the attractiveness of certified and non-certified provinces, by controlling for several factors potentially confounding the effect of the certification.


Water productivity (WP) is reported lower in Pakistan when compared to the rest of the world. This paper investi-gates the factors responsible for low water productivity and demonstrates various irrigation techniques farmers could use for its improvement. A comprehensive questionnaire was designed, and 230 farmers were interviewed in a cotton-wheat area (Samundri-site I), a mixed crop area (Chiniot-site II), and a rice-wheat area (Hafizabad-site III) in Rechna Doab, Punjab, Pakistan. This survey found that the majority of farmers expressed major concerns about shortages of canal water, energy, and fertilizer. These issues were the main factors affecting their land and water productivity. Field experiments were conducted at the above mentioned sites. The results indicated that drip irrigation was the most efficient irrigation technique, which produced a maximum WP of 2.26 kg m-3 for wheat. Drip irrigation was 98% efficient, and water savings were 40% better when compared with that under conventional irrigation.


Abstract. Shock chlorination is a well-known practice in swimming pools and domestic wells. One of the limitations for using this technique in drinking water purification facilities is the difficulty of quickly removing high chlorine concentrations in water distribution systems or production facilities. In order to use this method in the drinking water industry a shock de-chlorination method should be introduced for producing microorganism and biocide free water. De-chlorination using natural stagnant aeration (leaving the water to lose the chlorine naturally) is the safest known method if compared with chemical and charcoaling methods. Unfortunately, stagnant aeration is a slow process. Therefore, developing a process for accelerating de-chlorination by aeration would pave the way for using shock de-chlorination in drinking water industry. Forced air bubbling is a possible technique for de-chlorination but there is lack of data supporting such a process. The theory is that air bubbling has the advantages of higher mass transfer area, higher Reynolds number across the bubble water interface, and higher mass transfer concentration gradient as the bubbling presents a continuous stream of fresh bubbles. All of these factors accelerate aeration to various extents. A 20 cm diameter, 1-meter height column provided with air sparger was designed to collect the desired data used in this study. Trichloroisocyanuric acid, sodium hypochlorite and chlorine gas were the three familiar sources of chlorine used to investigate their response to air bubbling. Chlorine gas was the fastest and safest chlorine source to be dechlorinated. It dropped from 200 ppm to 0.02 ppm within 4 minutes or zero ppm within 6 minutes using an air flowrate of 9 l/min. Sodium hypochlorite decreased from 200 ppm to 0.02 ppm within 6 minutes using air flowrate of 9 l/min. Trichloroisocyanuric acid found to be the chlorine source slowest to respond to de-chlorination. It decreased from 200 ppm to 0.02 ppm within 8 minutes using an air flowrate of 9 l/min. Shock de-chlorination by aeration is found to be a promising method that opens up the drinking water industry and could produce microorganism and biocide free drinking water.


Importance Stroke is a major complication of surgical aortic valve replacement (SAVR). Objective To determine the efficacy and adverse effects of cerebral embolic protection devices in reducing ischemic central nervous system (CNS) injury during SAVR. Design, Setting, and Participants A randomized clinical trial of patients with calcific aortic stenosis undergoing SAVR at 18 North American centers between March 2015 and July 2016. The end of follow-up was December 2016. Interventions Use of 1 of 2 cerebral embolic protection devices (n = 118 for suction-based extraction and n = 133 for intra-aortic filtration device) vs a standard aortic cannula (control; n = 132) at the time of SAVR. Main Outcomes and Measures The primary end point was freedom from clinical or radiographic CNS infarction at 7 days (± 3 days) after the procedure. Secondary end points included a composite of mortality, clinical ischemic stroke, and acute kidney injury within 30 days after surgery; delirium; mortality; serious adverse events; and neurocognition. Results Among 383 randomized patients (mean age, 73.9 years; 38.4% women; 368 [96.1%] completed the trial), the rate of freedom from CNS infarction at 7 days was 32.0% with suction-based extraction vs 33.3% with control (between-group difference, −1.3%; 95% CI, −13.8% to 11.2%) and 25.6% with intra-aortic filtration vs 32.4% with control (between-group difference, −6.9%; 95% CI, −17.9% to 4.2%). The 30-day composite end point was not significantly different between suction-based extraction and control (21.4% vs 24.2%, respectively; between-group difference, −2.8% [95% CI, −13.5% to 7.9%]) nor between intra-aortic filtration and control (33.3% vs 23.7%; between-group difference, 9.7% [95% CI, −1.2% to 20.5%]). There were no significant differences in mortality (3.4% for suction-based extraction vs 1.7% for control; and 2.3% for intra-aortic filtration vs 1.5% for control) or clinical stroke (5.1% for suction-based extraction vs 5.8% for control; and 8.3% for intra-aortic filtration vs 6.1% for control). Delirium at postoperative day 7 was 6.3% for suction-based extraction vs 15.3% for control (between-group difference, −9.1%; 95% CI, −17.1% to −1.0%) and 8.1% for intra-aortic filtration vs 15.6% for control (between-group difference, −7.4%; 95% CI, −15.5% to 0.6%). Mortality and overall serious adverse events at 90 days were not significantly different across groups. Patients in the intra-aortic filtration group vs patients in the control group experienced significantly more acute kidney injury events (14 vs 4, respectively; P = .02) and cardiac arrhythmias (57 vs 30; P = .004). Conclusions and Relevance Among patients undergoing SAVR, cerebral embolic protection devices compared with a standard aortic cannula did not significantly reduce the risk of CNS infarction at 7 days. Potential benefits for reduction in delirium, cognition, and symptomatic stroke merit larger trials with longer follow-up. Trial Registration clinicaltrials.gov Identifier: NCT02389894


BACKGROUND
Linkage to chromosome 17q has been identified in hereditary breast cancer and hereditary breast/ovarian cancer syndrome. A hereditary breast/ovarian cancer syndrome kindred was identified that yielded a highly significant lod score (4.20) when 17q markers were studied, enabling us to identify those who probably carried the cancer-associated gene among the high-risk members of the family.

METHODS
High-risk members of the hereditary breast/ovarian cancer syndrome kindred were offered counselling on the basis of 17q markers. Family members responding positively received one-to-one genetic counseling in a structured setting. Subjects were educated before disclosure, and the immediate impact of this information was assessed after disclosure.

RESULTS
We provided genetic counseling on the basis of linkage findings to 32 relatives (four men and 28 women). Women who were told they were linkage positive expressed an increased motivation for surveillance and prophylactic surgery. Most women who were told they were linkage negative indicated that they would not proceed with prophylactic surgery but would continue careful surveillance. To date, there has been no evidence of serious emotional disturbances resulting from this disclosure. We believe that this experience can be used by cancer geneticists and physicians in developing protocols for genetic counseling in cancer-associated hereditary disorders.

CONCLUSIONS
Physicians must understand current developments in cancer genetics and linkage so that they can be applied to genetic counseling and treatment of high-risk patients.


Anthony Ashbolt is a lecturer in politics at the University of Wollongong. This is the text of his speech at the City Diggers Club, Wollongong, on the occasion of the launching of Keating and his Party Room by Jim Snow, published by Australian Scholarly Publishing in 2017. Disciplines Arts and Humanities | Law Publication Details Anthony Ashbolt, Keating & his caucus, Evatt Journal, Vol.17, No. 1, May 2018. This journal article is available at Research Online: https://ro.uow.edu.au/lhapapers/3582 Keating & his caucus Anthony Ashbolt, University of Wollongong It gives me great pleasure to help launch Jim's book Keating and his Party Room. Jim Snow was the chair of the Labor Party's federal caucus in the Keating government from 1993 to 1996. These years are the key focus of the book (although it does range beyond them) and it provides an important reflection upon the making of public policy at that time. The extent of policymaking in that period (and, of course, in the Hawke-Keating years as a whole) is quite extraordinary and changed the political landscape in Australia. Many comrades here would mumble or even declaim loudly that the landscape was not always changed for the better, that Labor laid all the effective foundations of a neoliberalism that gnawed at the core of our democratic political process. It must be stressed that Jim Snow is a very effective champion of the governments he served and particularly the one in which he was chair of caucus. Moreover, Jim is well aware of the sorts of criticisms that can be made, and at key points in the book does acknowledge those like Ken Davidson (from The Age) and even within Caucus, John Langmore, whose agendas were more within the tradition of radical political economy. There is, indeed, a generosity of spirit that runs right through this book—a recognition that there is debate to be had, policy contests to be dealt with seriously, differences to be confronted not just shoved aside—that helps make this book different from some standard party political autobiographies. Look at what I accomplished, without me there would not have been a life worth living, walking on water is nothing compared with what I achieved—these are not the words, this is not the tone, of Keating and his Party Room. Jim Snow was clearly not a self-important chair of caucus who laid down the laws of debate in stern fashion. A welcoming of divergent views, yet a sly glance in the direction of someone about to stir up what he saw as unnecessary trouble, capture Jim's style as chair of caucus. Yet that style is not trumpeted because Jim is more interested in painting a broad picture of policy-making in the period so that we can again capture a sense of what it was like to have a government that through endeavours like Creative Nation recognised, amongst other things, the critical importance of infrastructure spending and, specifically, the splendid contribution of the arts community to Australian life. He includes chapters detailing the extent of innovative public policy-making in all areas of life while also acknowledging shortcomings of government in fields like mental health, where the impact on families throughout Australia, including Jim's own, is so great. Now Jim mentions the personal tragedies in his family's life but mainly to highlight a general point about policy inadequacies. You would think he might have been more concerned to place himself and his family at the centre of things but look again at the title—Keating and his Party Room. The title tells you a lot about Jim's character as a politician and even the cover photo reveals a genial and slightly timid soul somehow lacking the authoritative swagger of the man in front (Keating). He recognises the strength and significance of Keating's leadership but wants to place that in context of the often ignored or under-recognised part that the caucus played in government. If you want to read a book about Jim's role in shaping Keating's thinking or Jim's role in running caucus like a tight ship, or Jim's role in making this one of the best governments Australia has seen, then this is not your book. If you want, however, a chronicle of government processes from a self-effacing insider, then this will be more to your taste. No one put better what I am trying to say than a journalist for the Canberra Times, Ian Warden. You have to have lived in Canberra for some time to know what an institution Ian Warden was and still is, how people would go and still go religiously to his witty and insightful columns. At one stage in his book Jim is discussing drugs policy and employing his perspective as a pharmacist and a political representative to argue for reform: 'I introduced a House of Representatives motion that many drugs in the illegal market be placed under prescription control'. Describing the proposal as spine-chillingly progressive, journalist Ian Warden wrote: I have never seen [Snow] so animated before and he is usually one of those softly spoken, serene members, who imparts to the perfervid House the same level of tranquillity that a golden Labrador dog is said to impart when allowed to roam the wards of nursing homes and of asylums for the harmlessly deranged. What does Jim write next? 'Rick Charlseworth MP (later Australia's successful Olympics hockey coach) seconded the motion. It did not go to a vote...' In what better way could he have highlighted the wisdom of Warden's observation? There is, then, some wry humour to be found in the book and that also sheds light upon his role as a member of parliament. Amongst all the serious stuff, you do sometimes need to slow down and have a laugh. After discussing in a critically reflective fashion the political history of his Eden-Monaro electorate, including the dispossession of the Aboriginal population, he comments: 'The proximity of Eden-Monaro to Canberra provided many stories from the past; many parliamentarians used the region as a dormitory for eating out or bonking in Bungendore, or just for driving through.' Just for driving through? I had to go back and look again and again at that other phrase: 'for bonking in Bungendore'. And, finally, too many startling images flashed through my mind and I really wondered what this pharmacist had given me. Jim concludes this fine book with a long and glowing tribute from Kim Beazley to Paul Keating. Just before then, however, he is assessing the dilemmas of and prospects for the future. And there you find just one brief sentence with which I will conclude precisely because they are words from Jim himself that gently proclaim the madness of neoliberalism: 'Challenges for the nation include strengthening TAFE and apprenticeship and a questioning of the wisdom of financing private tertiary education providers.'


Abstract—Emissions are a consequence of electricity generation. A major option for low carbon generation, local energy systems featuring Combined Heat and Power with solar PV (CHPV) has significant potential to increase energy performance, increase resilience, and offer greater control of local energy prices while complementing the UK's emissions standards and targets. Recent advances in dynamic modelling and simulation of buildings and clusters of buildings using the IDEAS framework have successfully validated a novel multi-vector (simultaneous control of both heat and electricity) approach to integrating the wide range of primary and secondary plant typical of local energy systems designs including CHP, solar PV, gas boilers, absorption chillers and thermal energy storage, and associated electrical and hot water networks, all operating under a single unified control strategy. Results from this work indicate through simulation that integrated control of thermal storage can have a pivotal role in optimizing system performance well beyond the present expectations. Environmental impact analysis and reporting of all energy systems including CHPV LES presently employ a static annual average carbon emissions intensity for grid supplied electricity. This paper focuses on establishing and validating CHPV environmental performance against conventional emissions values and assessment benchmarks to analyze emissions performance without and with an active thermal store in a notional group of nondomestic buildings. Results of this analysis are presented and discussed in context of performance validation and quantifying the reduced environmental impact of CHPV systems with active energy storage in comparison with conventional LES designs.


BACKGROUND:
Studies of maternal mortality have been shown to result in important improvements to women's health. It is now recognised that in countries such as the UK, where maternal deaths are rare, the study of near-miss severe maternal morbidity provides additional information to aid disease prevention, treatment and service provision.

OBJECTIVES:
To (1) estimate the incidence of specific near-miss morbidities; (2) assess the contribution of existing risk factors to incidence; (3) describe different interventions and their impact on outcomes and costs; (4) identify any groups in which outcomes differ; (5) investigate factors associated with maternal death; (6) compare an external confidential enquiry or a local review approach for investigating quality of care for affected women; and (7) assess the longer-term impacts.

METHODS:
Mixed quantitative and qualitative methods including primary national observational studies, database analyses, surveys and case studies overseen by a user advisory group.

SETTING:
Maternity units in all four countries of the UK.

PARTICIPANTS:
Women with near-miss maternal morbidities, their partners and comparison women without severe morbidity.

MAIN OUTCOME MEASURES:
The incidence, risk factors, management and outcomes of uterine rupture, placenta accreta, haemolysis, elevated liver enzymes and low platelets (HELLP) syndrome, severe sepsis, amniotic fluid embolism and pregnancy at advanced maternal age (≥ 48 years at completion of pregnancy); factors associated with progression from severe morbidity to death; associations between severe maternal morbidity and ethnicity and socioeconomic status; lessons for care identified by local and external review; economic evaluation of interventions for management of postpartum haemorrhage (PPH); women's experiences of near-miss maternal morbidity; long-term outcomes; and models of maternity care commissioned through experience-led and standard approaches.

RESULTS:
Women and their partners reported long-term impacts of near-miss maternal morbidities on their physical and mental health. Older maternal age and caesarean delivery are associated with severe maternal morbidity in both current and future pregnancies. Antibiotic prescription for pregnant or postpartum women with suspected infection does not necessarily prevent progression to severe sepsis, which may be rapidly progressive. Delay in delivery, of up to 48 hours, may be safely undertaken in women with HELLP syndrome in whom there is no fetal compromise. Uterine compression sutures are a cost effective second-line therapy for PPH. Medical comorbidities are associated with a fivefold increase in the odds of maternal death from direct pregnancy complications. External reviews identified more specific clinical messages for care than local reviews. Experience-led commissioning may be used as a way to commission maternity services.

LIMITATIONS:
This programme used observational studies, some with limited sample size, and the possibility of uncontrolled confounding cannot be excluded.

CONCLUSIONS:
Implementation of the findings of this research could prevent both future severe pregnancy complications as well as improving the outcome of pregnancy for women. One of the clearest findings relates to the population of women with other medical and mental health problems in pregnancy and their risk of severe morbidity. Further research into models of pre-pregnancy, pregnancy and postnatal care is clearly needed.


Ice-scars were investigated to reconstruct the ice-flood history of Corvette Lake in Northern Quebec in an attempt to determine the hydrological threshold of shore ice and identify the accompanying climatic conditions. The ice-scar record started around 1850 and showed a rapid increase in frequency at the start of the 1930s, while trees damaged by the ice were already mature and established over several decades. The study supports the hypothesis that this shift could correspond to an increase in flood discharge. Hydrological analysis of every event that occurred since 1961, the year during which instrumental recording began, indicated that scar frequency and scar maximum height were strongly correlated with average recession discharge, average flood discharge, peak discharge and flood onset. Ice-scars provided a discontinuous record of discrete events triggered by hydrologic extremes that were used to document the instrumental record using logistic regression. Results from multiple regressions suggested that ice-scars correspond to years with highs in total precipitation from January to March and from May to June, in the sum of degree-days of frost in April, and in the sum of degree-days of heat from October to April. Although imperfect for reconstructing past events, this study exemplifies the potential use of ice-scars for extending the historical record of ice-floods with hydroclimatic significance.


Ingestion of a chelating agent (ethylenediaminetetraacetic acid) by female rats during pregnancy impaired reproduction and resulted in congenitally malformed young. When ethylenediaminetetraacetic acid was fed from days 6 to 21 of gestation, all of the full-term young had gross congenital malformations. These effects were prevented by simultaneous supplementation with 1000 parts per million of dietary zinc.


Power deposition [specific absorption rate (SAR)] distributions from a two-element array configuration of 4-cm-square 915-MHz dual concentric conductor (DCC) microwave antennas were characterized theoretically for several clinically realistic complex bolus-tissue load models using the finite difference time domain (FDTD) numerical method. The purpose of this effort was to determine the perturbing effects on SAR of three often unavoidable heterogeneities in the bolus-tissue load. The three cases studied in this work consist of bone (two ribs spaced 1 cm apart) embedded 5-mm or 1-cm deep in muscle or layered fat-muscle tissue, small air bubbles trapped between the coupling bolus and tissue surface, and variable thickness water bolus layer due to sharply contoured anatomy. Results of the FDTD simulations demonstrate rather small effects on SAR distribution for both rib-sized bones /spl ges/5-mm deep in muscle and small air pockets /spl les/1-mm thick. Larger air bubbles >1-cm diameter by 3-mm depth showed a distinct concentration of SAR near the lateral sides of the air bubbles, and a blocking effect under the bubbles when located directly under the center of a DCC aperture where there is a higher normal E-field component. Variation from 2.5- to 7.5-mm bolus thickness under the two aperture array produced only minor perturbation of the uniformity and penetration of SAR, along with minor reduction in SAR under the thicker bolus which should be accommodated sufficiently by changes in applied power to the array elements.


The investigation concerns the effects of process variables associated with the fluidized bed granulation technique on the physical properties of the final granulation. The process variables investigated include binder solution addition rate, air pressure to the binary nozzle, inlet air temperature during the granulation cycle, and binary nozzle position with respect to the fluidized solids. When the rate at which the aqueous binder solution added to the fluidized bed of powders was increased, the ability of the solution to wet and penetrate the solids was enhanced, resulting in: (a) a larger average granule size, (b) a less friable granulation, (c) a more fluid granulation, and (d) a decreased granulation bulkiness. Similar results, also traceable to enhanced binder solution efficiency, occurred with a decrease either in the binary nozzle air pressure or in the inlet air temperature during the granulation cycle. The position of the binary nozzle with respect to the fluidized powders had significant effects upon the average granule size and granule friability. The effects upon the granulation flow properties and bulkiness, however, were slight.


Small organic molecules found on the skin of amphibians may help impart resistance to pathogens, such as the lethal fungus Batrachochytrium dendrobatidis. The study of these compounds has traditionally required euthanasia of the amphibian, followed by chemical extraction of excised skin. As an alternative method, we report the development and assessment of a non-lethal technique using foam-tipped swabs and HPLC analysis to directly isolate and characterize small molecules found on the skin of amphibians. This protocol was field-tested on Bioko Island, Equatorial Guinea with forty-seven frogs (representing 14 native species). Multiple species (particularly Afrixalus paradorsalis and Didynamipus sjostedti) carried sets of species-specific compounds (i.e., a chromatographic fingerprint). A principal coordinate analysis (PCO) of the commonly occurring compounds detected across all species revealed a significant relationship between chromatographic profile and species for all swab samples.


We investigate the relationship between social media use and emotional and behavioural outcomes in adolescence using data from a large and detailed longitudinal study of teenagers from the UK. To the best of our knowledge, this is the first study in economics to analyse the effect of social media use on adolescents' mental health. We use individual fixed effects, propensity score matching and treatment effects with Inverse Probability Weighted Regression Adjustment, controlling for a rich set of children's and family's characteristics and using comprehensive sensitivity analyses and tests to assess the potential role of unobserved variables. Our results show that prolonged use of social media (more than 4 hours per day) is significantly associated with poorer emotional health and more behavioural difficulties, and in particular decreased perception of self-value and increased incidence of hyperactivity, inattention and conduct problems. However, limited use of social media (less than 3 hours per day) has some positive effect on peer relationships.


The very long and expensive process of new drug research and development might suggest to observers that the efficacy standard for drugs is elevated and substantial, but this is not the case. Under the U.S. Federal Food, Drug, and Cosmetic Act, new drug approval merely requires that there be "substantial evidence that the drug will have the effect it purports or is represented to have." While the evidence of effectiveness must therefore be substantial, the efficacy attested to by that evidence need not surpass any particular threshold (other than zero), thus allowing drugs with de minimis efficacy to be approved and sold at market rates. No other concept, principal, or standard applied during the approval process or after changes this result. The "gold standard," which includes the elements of blinding, randomization, and placebo control, is described in but not required by the drug statute, and in any event addresses various problems related to bias rather than magnitude of efficacy. Similarly, the concept of "statistical significance," which constitutes an essential element of modern research protocols, addresses the problem of certainty, not degree, of efficacy. The statutory requirement of "clinical significance," far from ensuring "substantial efficacy," demands no more than that there be statistical significance in a human study (as opposed to, for example, an animal study). Rather than specifying a fixed level of efficacy or even a flexible standard of efficacy that a drug must possess, the U.S. drug approval framework thus fully delegates to drug companies and to the free market the determination of what level of efficacy is acceptable. The critical implication is that the public (and physicians and insurers) should not rely on the fact of FDA approval as an indication that medicines, including new and very highly priced ones, possess efficacy that is meaningfully greater than no efficacy at all.


Simple approaches for developing sensitive fluorescence sensors for 2,4-dinitrotoluene (DNT) detection were reported. Pyrene-doped poly(methyl methacrylate) (PMMA) and poly(vinyl chloride-co-vinyl acetate-co-vinyl alcohol) (PVC terpolymer) fibres, polystyrene (PS) fibres, and poly(styrene-co-methyl methacrylate) (PS-co-PMMA) fibres were prepared via electrospinning technique. Fibre morphology was studied using scanning electron microscopy. Sensing performance towards DNT was monitored through fluorescence emission of pyrene. The time dependence of quenching was observed for all fibres. Polymer matrix was found to affect DNT sensing, where PS fibres and PS-coPMMA fibres showed slightly higher quenching efficiencies than PMMA-PVC terpolymer fibres. Enhanced quenching efficiency was achieved through introduction of porosity using poly(ethylene glycol)-400 (PEG) as a porogen to PMMAPVC terpolymer fibres. The effect of porosity on sensing performance was further explored in pyrene-doped PS-coPMMA membrane. Porous membrane prepared from a solution with PS-co-PMMA to PEG ratio of 1:1 provided higher sensing performance towards DNT than dense PS-co-PMMA membrane, possibly resulting from the increased surface area.


Monsoon Asia Integrated Regional Study (MAIRS) is an IRS research program over monsoon Asia under START and the Earth System Science Partnership (ESSP). It was established to address questions about the coupled human and environment system in the monsoon Asia region. The vision of MAIRS is to significantly advance understanding of the interactions between the human and natural components of the overall environment in the monsoon Asian region and implications for the global earth system, in order to support strategies for sustainable
development. Regional-scale studies of global change provide the knowledge base for undertaking vulnerability analyses, identification of hotspots of risk and studies of environmental degradation which are crucial for the sustainable development. Regions may manifest significantly different environmental dynamics, and changes in regional biophysical, biogeochemical and anthropogenic components may produce considerably different consequences for the earth system at the global scale. Regions are not closed systems and thus the linkages between regional changes and the global earth system are crucial.
This specific report focuses on Planning Workshop on MAIRS Mountain Zone Implementation that held in China. Integrated Regional Studies (IRSs) should have relevance for people living in the regions and should provide a sound scientific basis for the sustainable development of the countries in the regions, and IRSs are also important from an earth system science perspective.


Iceland was one of the first countries to collapse in the global financial crisis of 2008 and it followed the OECD suggestion by opening upper secondary schools for young jobseekers, but without increasing the number of teachers. The upper secondary school level is also in a period of educational change, as it is in many other countries nowadays. The experience of Iceland provides valuable lessons for the international community. The article explores the effect of the economic crisis and the proposition that the policy is imposing on the work, well-being and working conditions of upper secondary school teachers in Iceland. The findings are based on a quantitative data from three surveys on upper secondary school teachers. In total, 52% of registered teachers in the Association of Teachers in Upper Secondary Schools returned the completed questionnaire in 2008, 49% in 2010 and 57% in 2012. The findings reveal significantly longer working days, increased pressure, workload and stress among teachers at the school level following the crisis and implementation of the curriculum, lower job satisfaction and less opportunity to serve students with special educational needs. The analysis suggests a need to invest more in the upper secondary school level as well as to focus on the professional development and well-being of teachers to ensure further improvement to prevent burnout and occupational drop-out.


Rule based targeting, behavioural targeting, and contextual targeting are three different types of targeting methods, delivering customized ads based on different categories of variables. A rule based targeting method uses viewers' own characteristics, while behavioural targeting delivers ads based on previous content users have browsed. At the same time, contextual targeting uses the characteristics of the webpage on which an ad will be displayed to decide which ads to display. On the other hand, all the three categories of factors and the interaction among them could impact the effectiveness of an online displaying ad. For organizations seeking to optimize their online marketing effort, it therefore becomes crucial to have a thorough understanding on how the variables from individual, behavioural, and contextual aspects moderate the effectiveness of a targeting method based on variables in other categories. But we have not yet found any study provides a theoretic framework to support such understanding. This paper thus proposes to investigate the moderation effect of variables in different categories on the effectiveness of a targeting method based on variables from other categories by using cookie-based data collected by an online marketing firm for its online displaying ads.


Abstract An extensive study was conducted to determine isotopic ratios of nuclides in spent fuel that may be utilized to reveal historical characteristics of a nuclear reactor cycle. This forensic information is important to determine the origin of unknown nuclear waste. The distribution of isotopes in waste products provides information about a nuclear fuel cycle, even when the isotopes of uranium and plutonium are removed through chemical processing. Several different reactor cycles of the pressurized water reactor, boiling water reactor, Canada deuterium uranium reactor, and liquid-metal fast breeder reactor were simulated for this work with the ORIGEN-ARP and ORIGEN2.2 codes. The spent-fuel nuclide concentrations of these reactors were analyzed to find the most informative isotopic ratios indicative of irradiation cycle length and reactor design. Special focus was given to long-lived and stable fission products that would be present many years after their creation. For such nuclides, mass spectrometry analysis methods often have better detection limits than classic gamma-ray spectroscopy. The isotopic ratios 151Sm/146Sm, 149Sm/146Sm, and 244Cm/246Cm were found to be good indicators of fuel cycle length and are well suited for analysis by accelerator mass spectroscopy.


Objectives: The purpose of the study is to examine various dimensions of aesthetic visual design and their role in predicting usability in e-learning in higher education institutions of northern India. Using quantitative means of data collection, this research identified, ways and means to make learning content effectively usable, that is, attractive, interesting, motivating, and engaging for the learners. Method: A survey questionnaire was developed through focused group discussions with field experts. Data were collected through online as well as offline modes. A Google form was created and its weblink was shared with the students pursuing degree courses in various state universities in northern India. Several visits and revisits were also undertaken to various universities to approach the respondents Results: Results confirmed consistency, typography, graphics, grid, and layout as factors responsible for predicting usability of e-learning. Surprisingly, color and compositional guidelines emerged insignificant. Implications: The study has implications for teaching and learning activities that promote effective learning. The findings are beneficial for course-design faculty who develop modules by considering visual design elements that can facilitate interaction with and understanding of content by students learning in an online modality.


Unlike thin tissues (e.g., skin) which has been successfully grown, growing thick tissues (e.g., bone and muscle) still exhibit certain limitations due to lack of nutrients (e.g., glucose and oxygen) feeding on cells in extracapillary space (ECS) region, or also known as scaffold in an in vitro static culture. The transport of glucose and oxygen into the cells is depended solely on diffusion process which results in a condition where the cells are deprived of adequate glucose and oxygen supply. This condition is termed as hypoxia and leads to premature cell death. Hollow fibre membrane bioreactors (HFMBs) which operate under perfusive cell culture conditions, have been attempted to reduce the diffusion limitation problem. However, direct sampling of glucose and oxygen is almost impossible; hence noninvasive methods (e.g., mathematical models) have been developed in the past. These models have defined that the glucose diffusivity in cell culture medium (CCM) is similar to the diffusivity in water; thus, they do not represent precisely the nutrient transport processes occurring inside the HFMB.
In this research, we define glucose as our nutrient specie due to its limited published information with regard to its diffusivity values, especially one that corresponds to cell/tissue engineering (TE) experiments. A series of well-defined diffusion experiments are carried out with TE materials of varying pore size and shapes imbibed in water and CCM, namely, cellulose nitrate (CN) membrane, polyvinylidene fluoride (PVDF) membrane, poly(L-lactide) (PLLA) scaffold, poly(caprolactone) (PCL) scaffold and collagen scaffold. A diffusion cell is constructed to study the diffusion of glucose across these materials. The glucose diffusion across cell-free membranes and scaffolds is investigated first where pore size distribution, porosity and tortuosity are determined and correlated to the effective diffusivity. As expected, the effective diffusivity increases correspondingly with the pore size of the materials. We also observe that the effective glucose diffusivity through the pores of these materials in CCM is smaller than in water. Next, we seeded human osteoblast cells (HOSTE85) on the scaffolds for a culture period of up to 3 weeks. Similar to the first series of the diffusion experiments, we have attempted to determine the effective glucose diffusivity through the pores of the scaffolds where cells have grown at 37°C. The results show that cell growth changes the morphological structure of the scaffolds, reducing the effective pore space which leads to reduced effective diffusivity.
In addition, the self-diffusion of glucose in CCM and water has also been determined using a diaphragm cell method (DCM). The results have shown that the glucose diffusivity in CCM has significantly reduced in comparison to the water diffusivity which is due to the larger dynamic viscosity of CCM. The presence of other components and difference in fluid properties of CCM may also contribute to the decrease.
We finally employ our experimentally deduced effective diffusivity and self-diffusivity values into a mathematical model based on the Krogh cylinder assumption. The glucose concentration is predicted to be the lowest near the bioreactor outlet, or in the scaffold region, hence this region becomes a location of interest. The governing transport equations are non-dimensionalised and solved numerically. The results shown offer an insight into pointing out the important parameters that should be considered when one wishes to develop and optimise the HFMB design.


BACKGROUND
Acquired and de novo endocrine resistance in breast cancer (BC) may be associated with overexpression of epidermal growth factor receptor (EGFR). Gefinitib is an orally active selective EGFR inhibitor which might benefit advanced breast cancer (ABC) patients either with acquired hormone resistance or with hormone receptor (HR)-negative tumors.

PATIENTS AND METHODS
A two-arm multicenter phase II trial of oral gefitinib 500 mg/day was planned in two groups of 45 patients with ABC for whom chemotherapy was not currently indicated. Group 1 had hormone-resistant BC defined as HR-positive BC with progression after treatment with tamoxifen and an aromatase inhibitor. Group 2 had HR-negative BC. Tumor response was assessed every 8 weeks. The primary end point was the clinical benefit rate (CBR).

RESULTS
Forty patients with hormone-resistant BC had a CBR of 0%. Two of 25 HR-negative BC patients showed stable disease (less than a 50% reduction and less than a 25% increase in the sum of the products of two perpendicular diameters of all measured lesions and the appearance of no new lesions) at 24 weeks resulting in a CBR of 7.7% (95% CI 0.9% to 25.1%). Enrollment ceased due to the low CBR. Toxicity resulted in treatment interruption (46%), dose reduction (20%) and withdrawal (11%) of patients.

CONCLUSION
At a dose of 500 mg/day, gefitinib monotherapy resulted in a low CBR and no tumor response was identified.


Groundwater depletion in arid areas is of increasing concern in the Middle East. Small precipitation and high evaporation losses during the dry season lead to water shortage in arid areas. The optimum development of groundwater resources is generally associated with abstractions from the aquifer balancing the recharge to it. When abstractions exceed recharge, many undesirable effects may result. Due to scarce water resources in the Gareh-Bygone Plain, located in arid southern part of Iran, a Floodwater Spreading System was established in1983. The floodwater spreading system has an extent of 2000 ha to improve the groundwater quantity, which involves surface spreading of floodwater. The present study had as aim to study the long term sustainability of the floodwater spreading system by applying a water balance methodology. The main idea of the water balance approach is to ensure that water resources in a certain area are used in a sustainable manner and optimally used with respect to water consumption, demand management, and water conservation. The methodology for this study was a combination of modeling to estimate inflow, outflow, and recharged groundwater and water balance approach. The study period was 14 years between 1993 and 2007. The results showed that the fluctuation of groundwater level is strongly controlled by both precipitation and groundwater recharge by floodwater spreading system. However, the general groundwater trend depends on the number of pumping wells and water abstraction established in the area. A 5-year drought period was the main cause of groundwater depletion. In the drought period, less precipitation accompanied with increasing farm land areas and pumping wells have created declining groundwater level. The recharge volume was seen to depend heavily on timing, duration, and magnitude of floods. (Less)


Experimental analyses of dynamic visual signals have to overcome the technical obstacle of reproducing complex motor patterns such as those found in courtship and threat displays. Video playback offers a potential solution to this problem, but it has recently been criticized because of sensory differences between humans and nonhuman animals, which suggest that video stimuli might be perceived as deficient relative to live conspecifics. Quantitative comparisons are therefore necessary to determine whether video sequences reliably evoke natural responses. Male Jacky dragons, Amphibolurus muricatus, compete for territories using complex displays delivered in a rapid stereotyped sequence. We evaluated video playback as a technique for studying this visual signal. Digital video sequences depicting a life-sized displaying male were indistinguishable from live male conspecifics in the rate and structure of aggressive displays evoked. Other measures of social behaviour suggested that video stimuli were more effective in this context. Lizards produced significantly more appeasement displays and had higher rates of substrate licking and locomotor activity in response to video playback than to confined male opponents, which failed to produce aggressive displays. Lizards tracked temporal changes in the display rate of video stimuli and were also sensitive to individual differences in morphology and behaviour between video exemplars. These results show that video stimuli are appropriate for the experimental analysis of Jacky dragon aggressive displays. We compare the potential shortcomings of video playback with those of other techniques and conclude that no approach offers a panacea, but that several have complementary characteristics.


Stretch forming is commonly used in the manufacture of low-volume convex aircraft panels. The gentle curvature and high degree of stretch leads to relatively low levels of elastic recovery post forming. Previous investigations [1] have shown that there is a large difference in the measured springback depending upon which side of an Alclad aluminium sheet is in contact with the tool surface. Initial investigation into the clad layer properties revealed no accountable variation in either thickness or strength. Instead the asymmetric springback behaviour was attributed to material property variations through the alloy core of the sheet. An analytical method for the prediction of the asymmetric springback incorporating the through thickness property variation is presented. Material strengths at specific through thickness positions were determined using a procedure based on residual strength measurements. The predicted results correlate well with the experimental data, which had initially demonstrated the asymmetric springback


The initial months of 2010 witnessed a new method, called the French Auction, being used for the pricing of subsequent share issues of several public sector undertakings. This was admittedly brought about with a view to maximizing the divestment proceeds of the undertakings. The method was used in place of the book building method, where the issuer would specify a price band and allocate shares at a specific price within that band, depending on the demand. While competitive bidding in the absence of a price band under the French Auction system is expected to result in a more accurate valuation of the IPO and greater capitalization for the issuer, we point out its shortcomings, which make it unfit for implementation in the Indian markets, as the IPO price is prone to manipulation and argue that it may not result in more accurate pricing than the book building method.


Urbanization is happening differently today than in the past and occurring most rapidly in places with the fewest resources. Traditional approaches are not able to keep up, leaving billions of people with poor access to basic necessities, dragging down economies and damaging the environment. This synthesis report of the Towards a More Equal City series proposes a new way of thinking about urban development, where the metrics for a functional and thriving city are defined by the quality, reliability and affordability of essential services. The report brings together the best thinking from over six years of research and more than 160 authors and reviewers. It acts as a roadmap for how to break through sectoral silos and the status quo to make cities more equal, which will in turn create prosperity, reduce environmental damage and improve livelihoods. The report documents breakthrough innovations from numerous cities, revealing real solutions and the outcomes of investing in equitable service provision. It also offers a clear path to recovery now and resilience in the future. Human development challenges are increasingly urban development challenges, including the ways in which they relate to climate change. These findings can help cities, countries and the global community make progress on critical global objectives, from the Sustainable Development Goals and UN Habitat's New Urban Agenda to the Paris Agreement and COVID-19 recovery.


Pragmatics studies the processes of language use, while discourse analysis is devoted to its product, i.e. discourse. Pragmatics can be understood in a narrow sense focussing on cognitive-inferential aspects of information processing, and it can be understood in a wider sense in which it also includes social aspects of interaction. In historical pragmatics, the former conceptualization lies behind work on pragmatic explanations in language change, while the latter conceptualization studies earlier language use from a social and interactional perspective, including such aspects as inserts (e.g. interjections and discourse markers), speech acts, and terms of address. Discourse, as the product of language use, can be seen as a stretch of conversation (dialogue) or as a domain of communication. In the former conceptualization, research focuses on the structural properties of the dialogue, and in the latter, it deals with the linguistic practices pertaining to particular fields of knowledge or interaction, e.g. courtroom discourse, the discourse of science, and news discourse.


Drivers often use infotainment systems in motor vehicles, such as systems for navigation, music, and phones. However, operating visual-manual interfaces for these systems can distract drivers. Speech interfaces may be less distracting. To help designing easy-to-use speech interfaces, this paper identifies key speech interfaces (e.g., CHAT, Linguatronic, SYNC, Siri, and Google Voice), their features, and what was learned from evaluating them and other systems. Also included is information on key technical standards (e.g., ISO 9921, ITU P.800) and relevant design guidelines. This paper also describes relevant design and evaluation methods (e.g., Wizard of Oz) and how to make driving studies replicable (e.g., by referencing SAE J2944). Throughout the paper, there is discussion of linguistic terms (e.g., turn-taking) and principles (e.g., Grice's Conversational Maxims) that provide a basis for describing user-device interactions and errors in evaluations.


An important general concern in cancer research is how diverse genetic alterations and regulatory pathways can produce common signaling outcomes. In this study, we report the construction of cancer models that combine unique regulation and common signaling. We compared and functionally analyzed sets of genetic alterations, including somatic sequence mutations and copy number changes, in breast, colon, and pancreatic cancer and glioblastoma that had been determined previously by global exon sequencing and SNP (single nucleotide polymorphism) array analyses in multiple patients. The genes affected by the different types of alterations were mostly unique in each cancer type, affected different pathways, and were connected with different transcription factors, ligands, and receptors. In our model, we show that distinct amplifications, deletions, and sequence alterations in each cancer resulted in common signaling pathways and transcription regulation. In functional clustering, the impact of the type of alteration was more pronounced than the impact of the kind of cancer. Several pathways such as TGF-β/SMAD signaling and PI3K (phosphoinositide 3-kinase) signaling were defined as synergistic (affected by different alterations in all four cancer types). Despite large differences at the genetic level, all data sets interacted with a common group of 65 "universal cancer genes" (UCG) comprising a concise network focused on proliferation/apoptosis balance and angiogenesis. Using unique nodal regulators ("overconnected" genes), UCGs, and synergistic pathways, the cancer models that we built could combine common signaling with unique regulation. Our findings provide a novel integrated perspective on the complex signaling and regulatory networks that underlie common human cancers.


. In this paper we describe the use of 3D games technology in human anatomy education based on our MSc in Medical Visualisation and Human Anatomy teaching practice, i.e. students design and develop serious games for anatomy education using the Unity 3D game engine. Students are engaged in this process not only as consumers of serious games, but as authors and creators. The benefits of this constructionist learning approach are discussed. Five domains of learning are identified, in terms of what anatomy students, tutors, and final users (players) can learn through serious games and their development process. We also justify the 3D engine selected for serious game development and discuss main obstacles and challenges to the use of this constructionist approach to teach non-computing students. Finally, we recommend that the serious game construction approach can be adopted in other academic disciplines in higher education.


Rumex thyrsiflorus Fingerh. is one of the few dioecious plant species, which have sex chromosomes. We conducted the preliminary experiments to determine the type of morphogenesis of R. thyrsiflorus explants cultured in vitro and to verify, using PCR-based methods, if there is the relationship between sex and morphogenetic response of explants micropropagated under in vitro conditions. The results of our studies revealed the female-biased sex ratios among explants cultured in vitro (M:F=1:1.7). The female-biased sex ratios in case of explants showed organogenesis in vitro (M:F=1:2.44) may suggest a higher regeneration ability of female explants.


Unethical performance is an impediment for economic development and good governance. It is more than true to say it is the bane of development in developing nations of the world under which Nigeria is categorized. The construction sector was highlighted for its practices in areas such as bribery, environmental destruction, capital flight, dangerous practices, poor quality, whistle blowing, etc. and it is also associated with unethical behaviour through the entire construction life cycle. This paper therefore, x-rayed the determinants of unethical performance in Nigerian construction industry with a view to identifying the causes in all the stages of building project. Well structured questionnaires were self administered to direct stakeholder involved in the execution of building projects considered for this research work. Literature review revealed that corruption is evident in the construction industry which causes a lot of setback to project such as abandonment of such project and if complete may be completed below standard. Data were presented and analyzed using non parametric statistic; tools used were Severity indices and Relative importance index rather than mean scores since the data were ordinal in nature. It was observed that the building construction industry is perceived to be more susceptible to ethical problems because of several features and that corruption has effect on all stages of construction right from Planning, Tender stage to Completion stage. It was recommended that viable legislation as a mechanism to deal with small levels of corruption by strengthening professional institutions that will punish erring members will prevent corruption to a certain degree; and enforcement and monitoring measures of anti corruption agencies is believed can enhance transparency, accountability and reduced unethical behavior, and this will create an enabling environment possible for the industry to thrive, operate, and improve on quality and quantity of infrastructure on a more sustainable basis and thereby foster good construction practice ethics.


Important advances in automated planning have been made recently, especially with the development of domainconfigurable planning systems. These planners use a domainindependent search engine for planning, but they have also the ability to exploit domain-specific planning knowledge. Examples of such planners include the well-known TLPLAN (Bacchus & Kabanza 2000), TALPLANNER (Kvarnstr¨ om & Doherty 2001), and SHOP2 (Nau et al. 2003). One challenge for domain-configurable planners is that they require a domain expert to provide planning knowledge to the system. When this knowledge is not accurate, complete, poorly expressed, the performance of these planners diminishes considerably and very quickly, even in simple planning benchmarks. In this paper, we present a preliminary report on our research aimed to mitigate this issue by combining the use of domain-specific knowledge and domainindependent heuristic search. We describe H2O (short for Hierarchical Heuristic Ordered planner), a new Hierarchical Task-Network (HTN) planning algorithm that can heuristically select the best task decompositions by using domainindependent state-based heuristics. Our experiments in the DARPA Transfer Learning Program demonstrated the potentialities of H2O: given HTNs generated by a machine-learning system, which were much less optimal than an expert would encode, H2O was able to solve problems that SHOP2 could not.


GIS is a summary of the Geographic Information System considers GIS as a system involving hardware of software, data, user, organization and effective management to collect, store analyse and present information related to various area of the world. In GIS initially developed to help cartographers but now it has become a tool of modelling and key management in the field of engineering such as water supply management. GIS capable of combining attribute data and spatial data in system and performed
various analyse related with a network of water distribution system. GIS system can speed manual search for information, updates and analysis of the data. GIS capabilities compared with other CAD system and it selected to develop a water utility
management. Therefore, this research conducted with the purpose the design base on GIS water distribution system at UiTM Shah Alam. Therefore, this research to study the types of layout of water distribution system, second analysis is to identify the
possible application of GIS in water distribution system and third analysis to establish a water distribution system based on GIS application The end of this research will provide suggestions to provide the database will ease the monitor and maintenance of water supply distribution pipeline system for UiTM Shah Alam Facilities Department using GIS system. GIS system implement at facilities department because it ease the water management and it can speed search for information updates and getting the data. GIS system can create a database for inventory. GIS also use to helps improve management information system and databases.


The 2-D discrete wavelet transform (DWT) can be found in the heart of many image-processing algorithms. Until recently, several studies have compared the performance of such transform on various shared-memory parallel architectures, especially on graphics processing units (GPUs). All these studies, however, considered only separable calculation schemes. We show that corresponding separable parts can be merged into non-separable units, which halves the number of steps. In addition, we introduce an optional optimization approach leading to a reduction in the number of arithmetic operations. The discussed schemes were adapted on the OpenCL framework and pixel shaders, and then evaluated using GPUs of two biggest vendors. We demonstrate the performance of the proposed non-separable methods by comparison with existing separable schemes. The non-separable schemes outperform their separable counterparts on numerous setups, especially considering the pixel shaders.


Despite a rich and varied critical heritage, reception of George Meredith's 1879 novel The Egoist has tended to rely on the author's Essay on Comedy as a key to unlocking the novel's many mysteries. Written just two years earlier as a lecture for the London Institution, the Essay would seem an apt place to start. A blueprint for Meredith's attempt to offer a revitalizing corrective for the tedium of everyday life, that "monstrous monotonousness" of convention and complacency that enfolds us (The Egoist 5; Prelude), the Essay helps explain, and thus rehabilitate, the novel's apparent oddities: its fragmentary and discontinuous narration, dynamic conception of character, and infamous, ostentatious stylistic eccentricities, to name but the most obvious anomalies. The parallels between the Essay and the novel are well rehearsed by critics; indeed, this connection has served both the novel and critics well, generating a range of forceful and illuminating readings. It must be said, too, that the critical tendency to see The Egoist as an outgrowth of the Essay represents a significant improvement over the main thrust of contemporary reviews of the novel, in which the four most frequently used words were "affectation," "obscurity," "artificiality," and "weakness" (I. Williams 11; Lucas 3).


The chapter offers a comprehensive analytical framework for the study of administrative capacity and administrative capacity-building in the Cohesion Policy domain. This includes individual, organisational, and socio-economic levels of analysis. The authors examine the administrative processes for Structural Funds implementation in four case study regions in Italy (Puglia, Sicilia) and Poland (Malopolskie, Pomorskie). Based on semi-structured interviews conducted with civil servants and key stakeholders at the regional level, the chapter presents the key variables (both administrative and institutional) which have an impact on the Managing Authorities' performance. Finally, the paper outlines the 'lessons learnt' from the implementation of EU Cohesion Policy in these regions.


Lawyers frequently start negotiations with a written demand. But legal scholars have not, until now, considered the demand letter part of the negotiation process. Negotiation theory focuses almost exclusively on face-to-face negotiations and incorporates research from psychology, economics, and other social sciences to explain lawyers' and clients' emotions and decisions. By contrast, legal writing texts give lawyers guidance about how to effectively write a demand letter, but this advice lacks any connection to the multi-disciplinary empirical research seen as so important in the negotiation context. This disconnect may serve as an impediment to more favorable negotiations. In fact, this untested advice about how to write demand letters could actually have the unwanted effect of causing protracted litigation and less favorable settlements. This article draws upon research in social psychology to demonstrate that demand letters deserve more attention and study. The words lawyers use to convey their demands can have powerful, lasting effects on the course and nature of negotiations because they almost certainly frame the issues, anchor a recipient's perceptions, and prime the recipient's goals and behaviors. If we are to fully understand what causes protracted, hostile litigation as opposed to cooperative negotiations and lasting resolutions, we must start by applying sound negotiation theory to the written demand.


In the present work, a two-step vapor-phase route was implemented for the tailored design of ZnO–WO3 nanoheterostructures supported on fluorine-doped tin oxide (FTO) substrates. Under optimized conditions, the sequential use of chemical vapor deposition (CVD) and radio frequency (RF)-sputtering for the deposition of zinc and tungsten oxides respectively, resulted in the growth of calyx-like ZnO nanostructures uniformly decorated by a conformal dispersion of low-sized WO3 nanoparticles. The target materials were characterized by means of a multi-technique approach, with particular regard to their structural, compositional, morphological and optical properties. Finally, their photocatalytic performances were preliminarily tested in the abatement of NOX gases (NO and NO2). Due to the unique porous morphology of the ZnO nanodeposit and the high density of ZnO–WO3 heterojunctions, WO3-decorated ZnO revealed appealing De-NOX characteristics in terms of both degradation efficiency and selectivity. Such features, along with the photoinduced superhydrophilicity and self-cleaning properties of the present nanomaterials, candidate them as promising functional platforms for applications in smart windows and building materials for environmental remediation.


ABSTRACT Zirconium-boron composite powders with the stoichiometric bulk composition corresponding to ZrB2 were prepared using high-energy milling in a shaker mill starting with elemental boron and zirconium. Milling times up to 3 hours were explored. The characterization of the prepared powders included measuring their particle size distribution, crystal structure, and assessment of particle structure and morphology. Reactions in the prepared powders were characterized using thermal analysis as well as custom ignition and combustion experiments. Composite powders consist of a Zr matrix with B inclusions mostly 100 nm or less in size. The homogeneity of mixing between boron and zirconium improves when the milling time increases from 1 to 2 hours; it is not affected by longer milling times. Boron and zirconium start reacting during milling; the degree of this reaction becomes appreciable when the milling time reaches 2 hours. In air, ignition of both pure zirconium and the prepared powders occurs in the same temperature range of ca. 400–700°C for the heating rates varied from 2000 to 20,000 °C/s. In fuel-rich conditions, ignition of the prepared powders is affected by the reaction between B and Zr, which occurs less readily for powders milled for 2 hours or longer. In air, particles of the prepared composite powders burn faster than either pure boron or zirconium. Flame temperatures for individual composite particles burning in air are reasonably close to those predicted as adiabatic flame temperatures for this composite-air system at stoichiometric and fuel-rich conditions. In combustion products of an air-acetylene flame, the burn rates of the prepared composites are lower than that of zirconium and are comparable to that of boron. Powders prepared by 1-hour milling burn faster than powders prepared using longer milling times.


Worldwide, vein quartz was used as a raw material for stone tools, and in many regions quartz was the dominant raw material, if not the only raw material. While using quartz was not necessarily problematic for the communities in question, and was often preferred over other materials, the 'problem' with quartz is for archaeologists attempting to analyse the material, especially with coarse-grained quartz. This paper presents the results of a quartz recognition experiment conducted on volunteer participants at the 2008 World Archaeological Congress (WAC) conference held in Dublin, Ireland. The results have shown that the identification and classification of vein quartz artefacts is particularly challenging, even for analysts with substantial experience in quartz artefact analysis.


Current global health policy goals include a 25% reduction in premature mortality from noncommunicable diseases by 2025. In this 2-part review, we provide an overview of the current epidemiological data on cardiovascular diseases (CVD), its risk factors, and describe strategies aimed at reducing its burden. In part 1, we examine the global epidemiology of cardiac conditions that have the greatest impact on CVD mortality; the predominant risk factors; and the impact of upstream, societal health determinants (eg, environmental factors, health policy, and health systems) on CVD. Although age-standardized mortality from CVD has decreased in many regions of the world, the absolute number of deaths continues to increase, with the majority now occurring in middle- and low-income countries. It is evident that multiple factors are causally related to CVD, including traditional individual level risk factors (mainly tobacco use, lipids, and elevated blood pressure) and societal level health determinants (eg, health systems, health policies, and barriers to CVD prevention and care). Both individual and societal risk factors vary considerably between different regions of the world and economic settings. However, reliable data to estimate CVD burden are lacking in many regions of the world, which hampers the establishment of nationwide prevention and management strategies. A 25% reduction in premature CVD mortality globally is feasible but will require better implementation of evidence-based policies (particularly tobacco control) and integrated health systems strategies that improve CVD prevention and management. In addition, there is a need for better health information to monitor progress and guide health policy decisions.


When most people think of piracy, they think of Bittorrent and The Pirate Bay. These public manifestations of piracy, though, conceal an elite worldwide, underground, organized network of pirate groups who specialize in obtaining media – music, videos, games, and software – before their official sale date and then racing against one another to release the material for free. Warez: The Infrastructure and Aesthetics of Piracy is the first scholarly research book about this underground subculture, which began life in the pre-internet era Bulletin Board Systems and moved to internet File Transfer Protocol servers ("topsites") in the mid- to late-1990s. The "Scene," as it is known, is highly illegal in almost every aspect of its operations. The term "Warez" itself refers to pirated media, a derivative of "software." Taking a deep dive in the documentary evidence produced by the Scene itself, Warez describes the operations and infrastructures an underground culture with its own norms and rules of participation, its own forms of sociality, and its own artistic forms. Even though forms of digital piracy are often framed within ideological terms of equal access to knowledge and culture, Eve uncovers in the Warez Scene a culture of competitive ranking and one-upmanship that is at odds with the often communalist interpretations of piracy. Broad in scope and novel in its approach, Warez is indispensible reading for anyone interested in recent developments in digital culture, access to knowledge and culture, and the infrastructures that support our digital age.


This essay describes how using unsupervised topic modeling (specifically the latent Dirichlet allocation topic modeling algorithm in MALLET) on relatively small corpuses can help scholars of literature circumvent the limitations of some existing theories of the novel. Using an example drawn from work on Victorian novelist Anthony Trollope's Barsetshire series, it argues that unsupervised topic modeling's counter-factual and retrospective reconstruction of the topics out of which a given set of novels have been created allows for a denaturalizing and unfamiliar (though crucially not "objective" or "unbiased") view. In other words, topic models are fictions, and scholars of literature should consider reading them as such. Drawing on one aspect of Stephen Ramsay's idea of algorithmic criticism, the essay emphasizes the continuities between "big data" methods and techniques and longer-standing methods of literary study.


Idasa and Afrobarometer public opinion surveys conducted since 1994 reveal that levels of reported experiences with crime are unchanged over the past four years, but that public perceptions of overall safety and the performance of the police are actually improving. Of greatest concern is that the January-February 2006 survey found that almost half of all South Africans think that "all" or "most" police officials are involved in corruption. These are the highest rates recorded across ten different types of public servants. In contrast to the improving trends in public perceptions of crime, citizen views of corruption in the police (and other government institutions) are becoming worse.


Chronic fatigue syndrome (CFS) is a severe, systemic, acquired illness which presents with overpowering tiredness that cannot be relieved by rest and is deteriorated through physical and mental activity. Due to the window of prevalence (20–40 years), some women diagnosed with CFS become pregnant. Given that CFS targets women in their reproductive years, responsibility is placed upon midwives to educate, support and provide families with advice. To equip midwives with knowledge about CFS, the objectives of this paper are to provide an overview of: how CFS impacts on reproductive health; the effects of pregnancy on CFS symptoms; CFS-related pregnancy complications; intrapartum management of women with CFS, and postpartum recovery of women with CFS. To date, only a handful of studies have explored the relationships between CFS and childbearing, and associated complications. A greater understandings of CSF interactions with physical, psychological and social reproductive processes are required.


In the Arctic, the simplest way to describe the winter surface moisture budget (in the absence of any net horizontal transport) is: snow-water-equivalent depth on the ground ( D ) equals precipitation ( P ) minus sublimation ( S ). D , P and S are the most fundamental components of the winter arctic hydrologic cycle and understanding them is essential to understanding arctic moisture-related processes. Unfortunately, accurate solid-precipitation ( P ) measurements have proven nearly impossible to achieve in the Arctic, because precipitation generally falls when it is windy. Gauge undercatch can range from 55–75% depending on the gauge type and wind conditions. The state of knowledge for winter sublimation ( S ) is even more limited. There are few actual measurements and most studies have used physical models to estimate this quantity. Moreover, fundamental questions concerning the boundary-layer physics of arctic winter sublimation remain unanswered. Resolving these is essential to closing local, regional, and pan-Arctic moisture budgets because some studies indicate sublimation may be as much as 50% of the total winter precipitation and 35% of the annual precipitation. This paper summarizes and analyzes the existing literature describing arctic sublimation.


Whistler embarked on a new project in the 1880s, working on a small scale in oil, pastel and watercolor to depict new London subjects and painting portraits of new urban types. This book, the first critical study of Whistler and his Impressionist followers, offers an in-depth analysis of Whistler's art as well as new insights into his modernist project. Using a wealth of primary material, Robins tracks the history of Whistler and his group and shows through testimony and practice that they were formulating an identity as avant-garde artists. This is the first critical study of these Impressionist artists and throws new light on this neglected aspect of British art.


A BC523A liquid scintillator loaded with boron-10 was tested as a detector for both fast and thermal neutrons. A pulse shape discrimination (PSD) method based on a zero-crossing principle was applied to distinguish between neutron and gamma radiation. High quantum efficiency Photonis XP5500B photomultiplier was used to enhance light detection from the scintillator. This allowed a good registration of the energy spectrum of neutron capture events on boron-10, corresponding to about 60 keV gamma-rays. The applied PSD method proved to be useful for n/gamma discrimination. A good resolving power of the method was achieved even without gating on neutron capture events. A comparison with a standard BC501A liquid scintillator was done to evaluate thermal neutrons detection efficiency in BC523A.


BACKGROUND
The incidence of postoperative complications following pacemaker or implantable cardioverter-defibrillator implantations in patients treated with new oral anticoagulation agents has not been studied. Here we present a first comparison of complications after cardiac rhythm device (CRD) implantations in patients with atrial fibrillation (AF) treated with dabigatran or uninterrupted warfarin.

METHODS AND RESULTS
Using a case-control study design, we compared complications within 30 days after 236 CRD procedures performed under uninterrupted warfarin (n=118) or interrupted dabigatran (n=118).There were no significant differences in the baseline characteristics of both groups. In the warfarin group, 9 (8%) pocket hematomas were observed vs. 3 (3%) in the dabigatran group (P=0.075). Two complications in the warfarin group necessitated surgical intervention as opposed to none in the dabigatran group (P=0.156). The postprocedural blood loss expressed as a drop in hemoglobin was significantly greater in the warfarin group (-0.9±0.7 vs. -0.5±0.4 mmol/L, P=0.023). In the dabigatran group, 1 case of transient ischemic attack occurred. The mean time to hospital discharge was shorter in patients treated with dabigatran (2.5±2.3 vs. 3.8±4.1 days, P=0.02).

CONCLUSIONS
The incidence and severity of bleeding complications may be lower in patients treated with periprocedurally discontinued dabigatran when compared with uninterrupted warfarin therapy. Further evaluation of peri-interventional complications and establishment of an optimal anticoagulation management protocol are needed.


Competence frameworks are widely used in many professional sectors, helping to develop capacity by defining and recognising the required skills, knowledge and personal attributes. Registers of competences have been developed within the conservation sector. A global register of competences for threatened species recovery practitioners is a register of competences in the form of a directory of the possible skills, knowledge and personal attributes required by practitioners working in threatened species recovery programmes around the world, in both in-situ and ex-situ contexts. This register has the potential to transform approaches to capacity development within threatened species recovery and help improve the effectiveness of this branch of conservation. Its structure largely follows that of A global register of competences for protected area practitioners (Appleton, 2016).


Previous research has established a chronostratigraphy of glacial/deglacial events together with a lithostratigraphical framework for the Quaternary deposits of the Sellafield area in West Cumbria. The glacial record is dominated by sediments and landforms laid down during the deglaciation of the Devensian ice sheet. The Quaternary deposits are characterized by complex sequences resulting from oscillating ice sheet margins, changing glacial lake and outwash environments, relative sea level changes and glacio-tectonic deformation. The resulting deposits comprise sequences which possess a wide range of grain size, shape and sorting; some are normally consolidated and have very low to low in situ density. An understanding of the geotechnical behaviour of these deposits is critical during geological site characterization studies for the design of new buildings and infrastructure on existing and proposed nuclear sites. The geotechnical engineering behaviour of a sequence of glacial deposits on the Sellafield nuclear site is evaluated together with their susceptibility to potential liquefaction under certain seismic load conditions. The evaluation identified that layers of very loose to loose deposits within the ice sheet marginal landsystem are particularly susceptible to liquefaction under specified seismic loading conditions that are required to be modelled by the UK Office for Nuclear Regulation (ONR).


The Internet of things (IoT), made up of a massive number of sensor devices interconnected, can be used for data exchange, intelligent identification, and management of interconnected "things." IoT devices are proliferating and playing a crucial role in improving the living quality and living standard of the people. However, the real IoT is more vulnerable to attack by countless cyberattacks from the Internet, which may cause privacy data leakage, data tampering and also cause significant harm to society and individuals. Network security is essential in the IoT system, and Web injection is one of the most severe security problems, especially the webshell. To develop a safe IoT system, in this article, we apply essential machine learning models to detect webshell to build secure solutions for IoT network. Future, ensemble methods including random forest (RF), extremely randomized trees (ET), and Voting are used to improve the performances of these machine learning models. We also discuss webshell detection in lightweight and heavyweight computing scenarios for different IoT environments. Extensive experiments have been conducted on these models to verify the validity of webshell intrusion. Simulation results show that RF and ET are suitable for lightweight IoT scenarios, and Voting method is effective for heavyweight IoT scenarios.


This chapter will be presented as follow. First, a brief introduction to structure and characterization of lignin and its derivatives is presented, as well as their importance as chemical scaffolds for obtaining value-added products in chemical, food, pharmaceutical and agriculture industry. Second, an extensive review of different reports using computational modeling methods—like molecular dynamics simulations, quantum mechanics and hybrid calculation methods, among others—in the understanding of enzyme-substrate interaction and biocatalysis will be presented. Third, and as last part of chapter, some hand picked examples from literature will be chosen as successful cases where the interplay between experiment and computation has given as a result protein engineered oxidoreductases with improved catalytic capabilities.


In this paper we look at unemployment effects of immigration and trade with Eastern Europe in Austria. Using individual data over the period 1989 to 1992 of male blue-collar workers employed in the Austrian manufacturing sector, we decompose possible detrimental impacts in unemployment entry effects and unemployment duration effects. Unemployment entry does not seem to be strongly effected by the recent increase in the flow of immigrants. This is different from the immigration effect on unemployment duration. Within almost all subgroups there is a significant increase in the lenght of unemployment spells as a result of larger immigration. Increases in trade with Central and Eastern European Countries (CEECs) seem to have increased the risk of unemployment entry, and to a lesser extent also the duration of unemployment. This is different from trade with the rest of the world where export increases have an unemployment reducing effect.


Photoperiodic responses, such as the daylength-dependent control of reproductive development, are associated with a circadian biological clock. The photoperiod-insensitive early-flowering 3 (elf3) mutant of Arabidopsis thaliana lacks rhythmicity in two distinct circadian-regulated processes. This defect was apparent only when plants were assayed under constant light conditions. elf3 mutants retain rhythmicity in constant dark and anticipate light/dark transitions under most light/dark regimes. The conditional arrhythmic phenotype suggests that the circadian pacemaker is intact in darkness in elf3 mutant plants, but the transduction of light signals to the circadian clock is impaired.


The locus coeruleus (LC) is
a nucleus in the brainstem, and projects widely to the forebrain where it releases
norepinephrine (NE). Catecholamines such as NE do not have a unitary effect on
their target neurons, but instead influence the function of other
neurotransmitters, a process that is known known as neuromodulation. By virtue
of the LC's wide projection profile and the neuromodulatory properties of NE,
the LC-NE system profoundly influences neural firing characteristics and
associated cognitive processes. The work presented in this thesis addresses the
role of the LC-NE system in various aspects of human cognition, and the
modulation of brain state.