TTA-121 is a novel oxytocin nasal spray with high bioavailability and is expected to increase oxytocin delivery to the brain by adjusting osmolality and viscosity of the formulation. As nonclinical safety studies to support the conduct of the Phase 1 and Phase 2 studies of TTA-121, a 6-week repeated intranasal dose toxicity study of TTA-121 in monkeys was conducted. In the present study, TTA121 was administered intranasally to male and female cynomolgus monkeys once daily for 6 weeks at 0, 26.88, 134.4, and 672.0 U/body/day followed by a 4-week recovery period to investigate the toxicity of oxytocin and systemic exposure to oxytocin. No animal died or was euthanized due to moribundity. There were no test article-related changes in clinical signs, body weight, food consumption, ophthalmology, electrocardiography, urinalysis, hematology, blood chemistry, necropsy, organ weights, or histopathology at any dose level during the dosing or recovery periods. The toxicokinetic analysis indicated that systemic exposures of oxytocin increased with the dose ranging from 26.88 to 672.0 U/body/day on the first and final day of dosing. Based on these results, the no-observed adverse effect level (NOAEL) of TTA121 was 672.0 U/body/day.


In this paper, we investigate the combined use of time, frequency, and space diversity in DVB-NGH, the next generation mobile broadcasting standard. Compared to current standards like DVB-H or DVB-SH, the largest improvement in next generation systems is expected to be achieved by means of better diversity in the time, frequency, and space domains. In this sense, DVB-NGH is the first broadcasting system to exploit the use of diversity in the three domains by incorporating at the physical layer long time interleaving (TI), time-frequency slicing (TFS), and multiple-input multiple-output (MIMO). This paper investigates the gains of using time, frequency, and space diversity in DVB-NGH, as well as the mutual influence between the different types of diversity. To this purpose, we employ an information-theoretic approach based on the outage capacity of the channel in addition to physical layer simulations.


The interaction of a single particle in straight rectangular channel in laminar flow is modelled explicitly using the set of Navier Stokes equation for the fluid motion and Newton momentum equation for the particle motion in Cartesian coordinate system. The evaluation of integral force acting on the particle along with the behaviour of streamlines as a function of Reynolds number ReP < 120 is done in 2-D numerical simulation. An example of linear shear flow condition in rectangular channel is studied to investigate the nature of drag and lift force in 2 D simulation and the kinematics of a single particle explicitly in 3-D simulation. The aim of the kinematics study is to evaluate the steady state position of this single particle kept in a fluid stream under the gravitational force. The 3-D simulation schemes for particulate flows are only presented here since the results generation takes long time for CPU speed limitation.


It's 1892 and Charlotte is bound for Monet's famous artist colony in Giverny, France, where painters like her father are flocking to learn the new style of painting called Impressionism. In spite of missing her best friend, Charlotte becomes enchanted with France and records her colorful experiences in her journal. She makes new friends, plants a garden, learns to speak French, and even attends the wedding of Monsieur Monet's daughter!Illustrated with beautiful museum reproductions and charming watercolor collages, "Charlotte in Giverny" includes a French glossary as well as biographical sketches of the featured painters. This delightful journal of a young girl's exciting year will capture readers' imaginations and leave a lasting impression.


Burst of transmissions stemming from event-driven traffic in machine-type communication (MTC) can lead to congestion of random access resources, packet collisions, and long delays. In this letter, a directed information (DI) learning framework is proposed to predict the source traffic in event-driven MTC. By capturing the history of transmissions during past events by a sequence of binary random variables, the DI between different machine-type devices (MTDs) is calculated and used for predicting the set of possible MTDs that are likely to report an event. Analytical and simulation results show that the proposed DI learning method can reveal the correlation between transmission from different MTDs that report the same event, and the order in which they transmit their data. The proposed algorithm and the presented results show that DI can be used to implement effective predictive resource allocation for event-driven MTC.


Italian territory is particularly sensitive to seismic actions. The Amatrice earthquake on August 24th 2016 confirmed this aspect. Such an event, nothing but extraordinary, has been able to cause huge and tragic damages. The direct knowledge of building features is the only prior measure to face seismic events. In order to get a realistic scenario of the urban damage distribution, the determination of useful seismic vulnerability assessment tools at urban scale becomes a priority. The widespread application of seismic vulnerability assessment sheets and the related data transformation into urban damage distribution plans is exactly what municipalities need. Main advantages are both in the chance of prior knowing the most affected areas to focus on for retrofitting interventions and in the possibility of organizing optimal emergency plans. In European framework, in the last decade, the Risk-UE project has played an important role. The Risk-UE project has proposed two methods for vulnerability assessment at urban scale: LM1 method (macroseismic) and LM2 method (mechanical). The two methods provide, with different approaches, seismic vulnerability ssessment of existing buildings. In LM1, seismic input is simulated by a given seismic intensity. In LM2, seismic input is given by a predetermined response spectrum. On the basis of the two proposed methods, many countries have adjusted their evaluation forms. Seismic vulnerability assessment in Italy is carried out through the application of appropriate forms (level 0, level 1, level 2), prepared by GNDT. The three gradually more detailed forms provide all the core information for seismic assessment of analysed buildings. The two methods proposed by Risk UE project are particularly advanced and founded on solid theoretical basis. Their application over the last few years and, in particular, a recent detailed study on the reliability of the methods, carried out by Canton of Valais (Switzerland), together with local research centre Crealp, University of Genova and Ecole Polytechnique Federale de Lausanne, have shown some nebulous aspects that deserve further studies. The paper deals with the main features of the two methods and tries to point out the aspects that need to be improved for a better reliability of results.


Cardiovascular magnetic resonance (CMR) is a versatile tool that also allows comprehensive and accurate measurement of both global and regional myocardial contraction. Quantification of regional wall motion parameters, such as strain, strain rate, twist and torsion, has been shown to be more sensitive to early-stage functional alterations. Since the invention of CMR tagging by magnetization saturation in 1988, several CMR techniques have been developed to enable the measurement of regional myocardial wall motion, including myocardial tissue tagging, phase contrast mapping, displacement encoding with stimulated echoes (DENSE), and strain encoded (SENC) imaging. These techniques have been developed with their own advantages and limitations. In this review, two widely used and closely related CMR techniques, i.e., tissue tagging and DENSE, will be discussed from the perspective of pulse sequence development and image-processing techniques. The clinical and preclinical applications of tissue tagging and DENSE in assessing wall motion mechanics in both normal and diseased hearts, including coronary artery diseases, hypertrophic cardiomyopathy, aortic stenosis, and Duchenne muscular dystrophies, will be discussed.


In the near future, gravitational wave (GW) detections are expected to become common, opening a new window on the Universe. Using the two 4 km Laser Interferometer Gravitational wave Observatory (LIGO) detectors and the 3 km Virgo detector we can triangulate a passing GW to a region of the sky with an area of tens of square degrees. These regions can then be observed using electromagnetic (EM) observatories. Pairing GW and EM observations can verify the astrophysical origin of a GW detection, and provide a more complete picture of the processes taking place.

This thesis describes the first triggered search for EM counterparts to GW candidates from the 2009-2010 LIGO/Virgo observing run. To improve the search strategy of this observing run, we created a catalogue of galaxies within 100 Mpc, known as the Gravitational Wave Galaxy Catalogue (GWGC), which was used to select locations in the GW skymaps to be imaged by EM partner observatories. Analysis of optical images taken as part of this run, from the Liverpool Telescope (LT) and ROTSE observatory network, find no associated counterparts. We also simulate the optical transients expected from GW sources across the LIGO/Virgo horizon of 50 Mpc, and find that the LT would be able to detect most optical counterparts across the majority of the horizon distance, while ROTSE can only detect counterparts over a fraction of the same distance.

Finally, we present the design specifications of GOTO, a wide field-of-view observatory to image the skymaps expected to be produced by the next generation of GW detectors. This telescope will be able to cover ∼70 square degrees to a limiting magnitude of ∼21, the sky area and limiting magnitude required to offer a reasonable chance of detecting an EM counterpart. While NS-NS merger models are uncertain, a tentative first detection of a kilonova-like counterpart to GRB130603B leaves us optimistic that the advanced detector era will provide the first GW detections and EM counterparts.


This study examined the effects of recent climatic variations on water resources in the Sokoto region of northern Nigeria. In doing this, the study adopted the modeling approach, in which changes in the yield of surface water reservoirs were related to variations in the weather and climate of the region. The results showed that variations in the weather and climate of the region have significantly impacted on water yields in surface reservoirs, with over 80 per cent of the yearly variations in water yield in the Sokoto-Rima Basin being explained by variations in the weather and climate. To prevent any further deterioration of the situation, inter-basin water transfer from the southern rivers of Nigeria (where there are water surpluses) to inland basins in the Sokoto region is recommended. Household level, water-use adjustments have also been recommended for residents, as adaptation to diminishing water supplies. Finally, massive afforestation programme should be implemented in the Sokoto region so as to moderate the regional climate, improve the environment and ultimately increase the yield of surface water resources.


The FCC plans to assign up to $20B in subsidies for rural broadband coverage through the Rural Digital Opportunities (RDOF) program. For the RDOF Phase I Auction, it plans to use a multi-round reverse auction design based on the design used in the Connect America Fund (CAF) Phase II Auction in 2018. The CAF II auction was, in many ways, a success, assigning $1.49B in support over ten years to provide fixed broadband and voice services to over 700,000 eligible locations. However, CAF II was only the first application of this auction design, and it would be wrong to think that the design is already as good as it can be. After all, the FCC's forward auction designs have evolved to the point of barely resembling the original designs first used over two decades ago. Each point in that evolution took advantage of the data and experience of prior auctions to make efficiency-enhancing refinements. Similarly, the CAF II auction data and experience are available to help consider and examine potential refinements to this reverse auction design. In this paper, we analyze the CAF II auction to better understand its outcomes and why they occurred. The result of this analysis is a set of proposals that are likely to improve the fairness and efficiency of the RDOF auction. 1. Use CAF II bidding data to update the CAM-driven reserve prices for RDOF in an effort to make more efficient use of the budget. 2. Freeze the price clocks for uncontested areas after the budget clears to facilitate package bidding and the revelation of cost synergies. 3. Modify the information rule to avoid switching bids that are only intended to gather information on the level of competition and hurt competition discovery. 4. Reduce location uncertainty and its negative effects on efficiency and fairness. 5. Use the CAF II performance weights to represent consumers' preferences and the proposed high latency weight to avoid paying for areas that would be served anyway.<br>


INTRODUCT1ON Primary stability of uncemented total hip replacements is regarded äs a major factor necessary for good quality bony ongrowth to the prosthetic femoral stem and therefore for a successrul long-term outcome [1,2]. The remodelling of the endothelial bone in contact with the implant is affected by the relative micromotions of the bone-implant interface and the stress state in the femoral bone. As a result, for optimal biological fixation, translational movements (i.e. primary stability) are of greatest interest. These interface-micromotions generally occur in all three spatial directions. Under physiologic loading, they consist of a cyclic amplitude and change in the mean, which in the cranio-caudal direction represents subsidence of the prosthesis. Existing measurement strategies which are based on dial gauges, extensometers, LVDTs, hall effect transducers or strain gauge techniques provide information about only one component of the general three-dimensional micromovement [3,4,5]. Furthermore, fixation of sensors away from the point of interface motion measurement, äs seen in various studies [4,5], may result in the registration of motions due to elastic deformation of the femoral or prosthetic shaft in addition to the interface motion. The objective of this study was to develop, validate, and apply a new technique which allows the precise measurement of the isolated 3D interface motion at three different points along the femoral shaft.


Background: Novel ocular imaging modalities have greatly impacted the diagnosis and management of different types of ocular neoplasia. In this narrative review, we summarize the practical features of popular and novel imaging modalities for ocular tumors.
Methods: Four databases, including PubMed/MEDLINE, Web of Science, Scopus, and Google Scholar, were searched from January 1, 2000 to August 31, 2022. Articles reporting different imaging modalities for diagnosing or monitoring treatment responses of ocular tumors were extracted using various combinations of the following keywords: ocular neoplasia, positron emission tomography or PET, single-photon emission computed tomography or SPECT, optical coherence tomography or OCT, OCT angiography or OCTA, computed tomography or CT, ultrasonography or US, ultrasound biomicroscopy or UBM, and magnetic resonance imaging or MRI.
Results: Various ocular imaging modalities had different accuracies as adjunctive tools for detecting or managing ocular tumors. Anterior ultra-high-resolution optical coherence tomography (OCT) could be used to evaluate images with < 5-µm resolution. OCT angiography provided deeper insight into retinal vascular changes associated with the malignant transformation of choroidal melanoma. OCT in children altered the diagnosis of suspicious retinoblastoma in 3% of the cases and treatment plan in 11% of the cases. While positron-emission tomography (PET)/computed tomography (CT) allowed the detection of metastatic lesions of choroidal melanoma by full-body scanning, single-photon emission CT was more sensitive compared to PET in detecting choroidal melanoma. Ultrasound biomicroscopy, with an accuracy exceeding 92.5%, could detect retinal calcification in lesions measuring 2–3 mm. Magnetic resonance imaging (MRI) had better contrast compared to ultrasound biomicroscopy and higher sensitivity compared to CT in detecting post-laminar optic nerve invasion. However, MRI had a lower spatial resolution compared to OCT. Further development of imaging modalities and their application in drug development would improve the treatment of ocular tumors.
Conclusions: Although diagnosing ocular tumors depend on clinical characteristics, innovations in ocular imaging have enabled early diagnosis and timely, appropriate management of ocular neoplasia, which are conducive to favorable visual outcomes and increased life expectancy. Further systematic reviews and meta-analyses of primary studies focusing on a specific imaging modality in ocular neoplasia could precisely determine the diagnostic accuracy of each imaging modality to better guide eye practitioners with efficient diagnostic or therapeutic approaches for these sight- or life-threatening entities. Imaging modalities may play a major role in drug development in the future.


BACKGROUND
Objective response of advanced adrenocortical carcinoma (ACC) to mitotane and cytotoxic chemotherapy regimen is only ~20% and early tumor progression is frequent. Previous clinical trials with oral multi-kinase inhibitors were negative which has been attributed in part to inadvertent drug interaction with mitotane. Cabozantinib (CABO) is an inhibitor of c-MET, VEGFR2, AXL, and RET and approved for advanced kidney cancer, liver carcinoma after previous sorafenib and medullary thyroid carcinoma.

OBJECTIVE
To investigate the clinical efficacy and safety of CABO monotherapy in ACC patients.

DESIGN
Retrospective cohort study.

SETTING
three referral centers for ACC (Germany, United States).

RESULTS
Sixteen patients (13 female) with progressive ACC received CABO after previous mitotane in 15/16 and 3 (median, range 0-8) further systemic treatments. Prior CABO, mitotane was discontinued in all patients. Plasma concentration was <2 mg/L in 7/16 patients and discontinued >12 months in 6 additional patients before CABO use. In 4/5 cases with available plasma samples, CABO concentration was in the expected steady state range. Adverse events (AE) of grade 1/2 and 3 were observed in 13 and 3 patients, respectively, and consistent with the known safety profile of CABO. Best response was partial response in 3, stable disease in 5 and progressive disease in 8 patients. Median PFS and OS was 16 and 58 weeks, respectively.

CONCLUSION
CABO monotherapy appears to be safe and effective as a monotherapy in advanced ACC after failing prior treatments. Therefore, prospective investigation of CABO in ACC patients is warranted.


Abstract Photovoltaic simulators are practical and useful tools for the evaluation of photovoltaic energy production system components, avoiding time-consuming and expensive field-testing process. This article presents an original electronic bench simulating a photovoltaic generator system including photovoltaic modules, DC-DC converters, and loads. This new electronic simulator allows the development and optimization of different topologies of generators or different converters. It can replace the load and inverter working under random external parameters. It can be used for works about photovoltaic grid injection as well as stand-alone photovoltaic systems. This simulator constitutes a specific tool for a laboratory to test photovoltaic modules under various temperature and illumination conditions, making transparent many other issues and thus allowing a complete set of simulation parameters not easily and repeatedly available in practice for the development of new photovoltaic generators. For validating the efficiency of the simulator, a detailed analytical study, using the OrCAD® PSpice® software environment of a distributed generator based on a high-voltage DC bus topology, is presented and compared to in situ experimental results achieved with the operational prototype finally developed.


Type I pseudohypoaldosteronism (PHA) is a hereditary disease characterized by salt wasting resulting from target organ unresponsiveness to mineralocorticoids. We have studied two kindreds including a total of nine patients with PHA. In kindred I, the propositus presented with renal salt wasting in infancy (vomiting, failure to thrive, short stature, hyponatremia, hyperkalemia) and responded dramatically to a high salt diet (2.5 g/day). Sodium supplementation was discontinued at the age of two. In seven additional family members from three generations, clinical expression of PHA varied from asymptomatic to moderate. In affected members (propositus, mother, and two brothers), hyperaldosteronism persisted over 13 yr; however, the PRA decreased gradually to near normal values. Persistent hyperaldosteronism in the face of a decrease in PRA indicated the development of tertiary hyperaldosteronism due to autonomously functioning zona glomerulosa. The pedigree was consistent with an autosomal dominant mode of transmission with variable expression. In kindred II, the propositus, who was the product of a consanguineous marriage, developed severe renal salt losing at age 9 days. She had also increased salivary and sweat electrolytes consistent with PHA resulting from multiple organ unresponsiveness to mineralocorticoids. Life threatening episodes of salt wasting recurred beyond the age of 2 yr. At 5 yr of age she still requires high amounts of salt supplements (14 g/day). A sister died at 9 days of age with PHA symptoms. Six close relatives (parents, three siblings, maternal uncle) showed no biochemical abnormalities. This pedigree was consistent with an autosomal recessive mode of inheritance. In view of the findings on these two kindreds and the analysis of those in the literature, we conclude that type I PHA includes two clinically and genetically distinct entities with either renal or multiple target organ defects.


This paper presents a novel planning approach which optimizes size and location of new transmission substation (TS) investments considering capacity expansion of the existing TSs based on primary distribution network investment requirements. Mixed Integer Programming (MIP) is utilized and the problem is decomposed into investment and feasibility check subproblems. The algorithm is formulated to minimize total investment cost while supplying the spatial forecasted load considering a set of system constraints. The results of two numerical examples indicate that presented algorithm is adequate for determining requirements of new transmission substations and/or capacity expansions together with new HV/MV lines, via appropriate selection of candidates. Visualization of the planning algorithm results, in an iterative manner, gives very important verification signals regarding the necessity of the proposed investments.


This paper describes the results of a recent dissertation by W. Weiss [1]. The objective of this work is twofold:
i) determination of the range of validity of the Navier-Stokes-Fourier theory of a monatomic gas
ii) determination of the ranges of validy of the extended thermodynamic theories of 13, 14, 20, 35.. and -in general- $n$ moments.
The field equations of extended thermodynamics form a system of quasilinear first order differential equations of symmetric hyperbolic character. In its simplest form it takes 13 variables into account, namely the densities of mass, momentum and energy and the stress and heat flux. In that case the results correspond to the results of Grad's 13-moment theory in the kinetic theory of gases. Further extensions contain more moments among the variables; generically there are $n$ variabies.
As measures of reliability we choose the ranges of frequency and wavelength, in which a given $n$ -type extended thermodynamics describes the dispersion of sound and the scattering of light well. It turns out that $n$ must be bigger the higher the sound frequency is and the smaller the wave length of a fluctuation is that scatters ligh.
This knowledge is important for the proper selection of a theory for a given boundary and initial value problem: In the temporal and spatial Fourier spectrum of the data we must only have such frequencies and wavelengths for which sound dispersion and light scattering are well-described by the theory.


Momentum behind the economic valuation of ecosystems, after a decade of hopeful support from researchers and policymakers, is currently petering out and decision-makers still do not consider biodiversity conservation to be a political priority. Surprisingly, the economic benefits provided by the conservation of ecosystems have been poorly investigated, unlike the ecosystems themselves. Furthermore, is the valuation of conservation (the valuation of the "interest rate" made on the natural capital saved, instead of the valuation of the natural capital itself) an efficient means to better serve decision-making? The research presented here addresses this question, in proposing a more effective approach to the valuation of conservation. It also investigates how such economic valuation exercises could best serve the decision-making process.
The research method for measuring conservation value relies on a comparison of Total Economic Values for analogous ecosystems both within a protected area and in outside adjacent areas. This methodology is tested in a sample of five marine protected areas in West Africa. For the estimation of the Total Economic Values in these sites, the research has applied most of the available valuation tools and includes all values for which data are available, including non-use values.
The results indicate a predominance of benefits linked to indirect use values over direct use values and non-use values. The marine protected areas display substantial benefits when compared to unprotected sites. These benefits are thought to derive primarily from the better marine health status associated with protected areas, and subsequent higher indirect use values which compensate for the decrease in direct use values caused by the conservation policy and the subsequent limitations imposed as a result. The 'paper areas' (i.e. those protected areas with no management plan) show, however, a deficit even when compared to unprotected sites.
The research discusses and highlights the shortcomings of such an approach within the West African context (data-poor situation, non-monetised economies, value transfer to developing countries, difficulties in communicating non-use values of biodiversity) and associated time and space considerations. It also underlines the importance of considering the socio-cultural context in any economic valuation, which provides key information for valuation interpretation.
Furthering the approach within the 'economics of protection' stream (after the 'economics of degradation' and the 'economics of welfare'), this research delivers a new approach for valuing biodiversity conservation. The extensions of this research for policy purposes may include management support (comparison of conservation benefits with costs of management, increased consideration of indirect use values), advocacy information (through the calculation of the costs of policy inaction), and mechanisms for sustainable financing (through the development of payment for ecosystem services).


In Ba ferrite particles magnetocrystalline and shape anisotropies are contemporarily present and conflicting. The strength and evolution of the two anisotropies are studied, through the dependence of the anisotropy constants on temperature. While in pure Ba ferrite particles the anisotropy is uniaxial at all temperatures, since the magnetocrystalline anisotropy clearly prevails on shape anisotropy, in particles modified for employment in recording media the two anisotropies are comparable and at low temperatures the shape anisotropy result stronger than the crystalline anisotropy. Besides the irregular shape of the particles introduces further preferred directions for the magnetization. The Co/Ti-doped particles show a multiple axes anisotropy. The macroscopic magnetic properties are found in relationship with the evolution of the anisotropy. Also the influence that the presence of such multiple anisotropy has on the magnetization switching and on the thermal stability of the magnetization of the Ba ferrite particles is analyzed.


The work presented in this thesis is concerned with modelling the effects of cell movement on
the growth and formation of cell cycle phase specific regions within solid tumours. A model is
proposed in the context of multicellular tumour spheroids (MCTS) and includes a simple model
of the cell cycle, where cells move between each cell cycle phase depending on the availability
of extracellular nutrient, as well as cell movement via chemotaxis, which varies depending upon
the respective cell cycle phase of the cell.
Numerical and asymptotic solutions show the model re-produces the well known MCTS structure
of an internal quiescent cell region surrounded by a rim of proliferating cells. A further,
more interesting result, describes a tumour surrounded by a rim of quiescent cells, with an inner
quiescent and an interim proliferating cell region. The resultant solutions are a result of the
different cell velocity profiles along with the effects of the cell cycle kinetics in different regions of
the tumour. The non-linear form of the conservation equations describing the movement of cells
means that solutions with spatial discontinuities in the cell concentrations (shocks) are observed
for specific parameter values.
Analysis of the effects of the chemotactic response and the cell cycle kinetics, both spatial
and temporal, provide insight in to the model's behaviour and shows an understanding of cell
cycle kinetics, cell movement and the spatial structure of tumours is important in assisting
therapeutic strategies. The effectiveness of apoptosis, as an anti-cancer strategy, is shown to
be dependent upon the concentration and spatial organisation of proliferating cells within the
respective tumour.
Comparison with the experimentally verified model of tumour growth developed by Gompertz
allows specific model parameters to be expressed in terms of experimentally known variables.
Such analysis shows that Gompertz's model is good at predicting the growth of solid tumours
with a proliferating rim, but other models are required to understand the growth of non-uniform,
heterogeneous tumours.
Experimental justification of the model is provided by considering the observed internalisation
of H3 Thymidine labelled cells and inert microspheres within MCTS. Here experimental results
show that following adherence to the spheroid edge, the microspheres were all advected towards
the centre of the spheroids whilst the labelled cells were spread throughout the proliferating
and quiescent outer regions. The cell cycle model which is developed is, unlike previous models,
able to account for this observed behaviour. Various simulations are discussed in relation to the
original experimental results. These results show the importance of cell movement in providing
possible ways of assisting with drug delivery to the more therapeutically resistant regions of
solid tumours.
Finally the importance of necrosis formation is discussed by a simple extension to the model.
Necrosis as a result of quiescent cell death leads to the commonly observed formation of a
necrotic core in each case. However, using the model to consider the more recent hypothesis
that apoptosis leads to the formation of necrotic regions provides interesting theoretical results.


SIR,-The article by Dr Allan D Cumming and colleagues on refeeding hypophosphataemia (22 August, p 490) omits a number of salient points relating to the development of convulsions in alcoholics with complex biochemical disturbances. Several combinations of the abnormalities described might account for the symptoms observed. Magnesium depletion, in particular, is well known to be a common cause of convulsions in such patients. ' In addition, magnesium deficiency induces hypokalaemia and hypocalcaemia, as well as hypomagnesaemia. In the alcoholic patient described the potential contributions ofother ionic imbalances, notably hypokalaemia (3-2 mmol/l) and hypomagnesaemia (0-36 mmol/l), are ignored. This is surprising in view of the fact that this patient required "separate infusions of calcium, magnesium, and potassium" before recovery. Though we should not ignore the potential importance of refeeding hypophosphataemia, the contribution of hypophosphataemia itself to the symptoms described remains unclear. M F RYAN H PANDoV


Abstract Validity and correctness test verification of the measuring software has been a thorny issue hindering the development of Gear Measuring Instrument (GMI). The main reason is that the software itself is difficult to separate from the rest of the measurement system for independent evaluation. This paper presents a Virtual Gear Measuring Instrument (VGMI) to independently validate the measuring software. The triangular patch model with accurately controlled precision was taken as the virtual workpiece and a universal collision detection model was established. The whole process simulation of workpiece measurement is implemented by VGMI replacing GMI and the measuring software is tested in the proposed virtual environment. Taking involute profile measurement procedure as an example, the validity of the software is evaluated based on the simulation results; meanwhile, experiments using the same measuring software are carried out on the involute master in a GMI. The experiment results indicate a consistency of tooth profile deviation and calibration results, thus verifying the accuracy of gear measuring system which includes the measurement procedures. It is shown that the VGMI presented can be applied in the validation of measuring software, providing a new ideal platform for testing of complex workpiece-measuring software without calibrated artifacts.


Australia's vast tropical savannas contain outstanding biodiversity and cultural values. The region supports many industries, with broad-scale pastoralism being the most widespread. Hundreds of plant species were introduced into northern Australia to support the pastoral industry; some species have since been termed 'contentious' or 'conflict' species due to their perceived positive value for industry but negative impacts on non-pastoral values when they invaded non-pastoral landscapes. Heated political and public debate ensued about the appropriate policy and management response to these species based on people's perceptions of values being altered by invasion by these species, and conflicting views on what constituted appropriate management actions to control their use and spread. Here we share our insights into the role of scientific evidence in progressing this debate, by quantifying the impacts of species on environmental, socioeconomic and cultural values. We reflect on the importance of science for underpinning evidence-based risk management tools, the outputs of which supported policy response by politicians and other policy decision-makers. We also assess the gap in translation from policy to coordinated on-ground action at the national scale, and provide our insights into the contribution that science can make to bridging this gap.


Nano-sized silicon dioxide (SiO2) is widely utilized in artificial bone, artificial tooth, interventional catheters and drug delivery system,so it is imperative to study SiO2 NPs on the role of the body damage. Consulted with standard reference of GB/T16886, 20 and 80 nm SiO2 NPs were selected to prepare suspension (1mg/ml) for subacute systemic toxicity; 2000mg/ml suspension for MTT; and extracts (0.1g/ml) for hemolytic test. The results show that the hemolysis rate are all more than 5%, after its continuous injection of 2W nanoparticles into SD rats and New Zealand Rabbits, the alterations on the hemoglobin, hematocrit, mean corpuscular volume and other indicators have gained in blood routine test, and there was a marked inhibition on the L929 cells of SiO2 NPs. Therefore, these two kinds of particle size of SiO2 NPs have certain extent of injury effect on the blood system, and the contact time of NPs in the blood compatibility evaluation has play a more important role than the others.


A fast algorithm is presented for computing the growth distance between a pair of convex objects in three dimensional space. The growth distance has been introduced by Ong et al. (1996) as a measure of both separation and penetration between objects. This article presents an approach to the growth distance computation using geometrical consideration. Under appropriate conditions, the computational time is very small and does not depend on the total number of faces of the objects. This increase in speed comes from the use of information on the adjacency of faces of the objects. Such adjacency information is particularly useful for object undergoing incremental motion. Computational experiments provided shows that the performance of the algorithm is in the same range as the known fastest Euclidean distance code.


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Green human resource management contributes to an understanding of the role of human resource management (HRM) towards sustainability and environmental outcomes. This paper assesses employees' environmental knowledge as well as self-perceptions of ability, motivation and opportunity (AMO) to practise green behaviours by operationalising the AMO framework towards a pro-environmental agenda. The study draws on a survey sample of 394 employees from five organisations in regional Australia. Key findings show that pro-environmental AMO are positively associated with green behaviours and that these are more prevalent at home than in the workplace. Further, line managers moderate the relationship between pro-environmental AMO and green behaviour although not the relationship between environmental knowledge and green behaviour. Such benchmark measurement informs HRM policies, practices and interventions and contributes to environmental management.


To provide a historic snapshot as regards the evolution of headache treatment throughout the human history i.e. starting from trepanation to perisutural botulinum toxin (BoNT) injections. Ancient surgeons had aimed to reach the cranium with trepanation (a surgical operation) for headache. As BoNT inhibits the release of nociceptive and pro-inflammatory neuropeptides, it has been recently suggested as an effective alternative in the prophylactic treatment of chronic migraine headache. Chronic migraine is a complex neurological disorder for which the underlying pathophysiology is yet not totally explained. According to the generally accepted hypotheses, peripheral neurogenic activation and central trigeminal sensitization are the two main mechanisms through which its pain develops. Since the headache most commonly occurs around the perisutural areas, and as the primary pathogenesis stem from the meningeal nerve fibers; collateral sensorial branches of the meningeal nerves can be optimal paths to transport BoNT inside the cranium. Concerning the therapeutic efficacy, we anticipate that perisutural injections would be technically challenging with blind techniques and actually possible only if performed under an imaging guidance e.g. very conveniently with high frequency ultrasound.


In this work, a 3D thermal model of a multicore system is developed to investigate the effects of hotspot, and placement of silicon die layers, on the thermal performance of a modern flip-chip package. In this regard, both the steady-state and transient heat transfer analysis has been performed on the 3D flip-chip package. Two different stacked die configurations were evaluated under different operating conditions. Through experimental simulations, we have found a configuration which has better thermal performance. The optimal placement solution is also provided based on the maximum temperature attained by the individual silicon dies. We have also provided the improvement that is required in the heat sink thermal resistance of a 3D system when compared to the single-die system.


Aims Though formalin remains to be the gold standard fixative in pathology departments, analytical challenges persist for nucleic acid evaluations. In our laboratory, formalin fixation of skin samples in particular impairs diagnostic accuracy and demands repetition of biopsies and analytical procedures. PAXgene Tissue Systems may be an alternative; however, according to manufacturer specifications it only allows fixation for 48 hours before having to add a stabiliser. This may be a challenge in laboratories, which are closed in weekends and bank holidays. Our aim was to validate this alternative fixative for dermatological samples with prolonged fixation times using standard laboratory protocols developed for formalin-fixed specimens. We compared the results with gold standard formalin fixation. Methods Skin specimens were formalin or PAXgene fixed for either 2 hours, 24 hours, 3 days or 7 days, paraffin-embedded, analysed and scored by observers. Results Generally, formalin outperformed PAXgene fixation in H&E stains and fluorescence in situ hybridisation (FISH), but both seem usable for diagnostics. Time of PAXgene fixation did not have an impact on alcian blue-Van Gieson (ABVG), H&E (p=0.48), nor immunohistochemistry (p=0.74). There was a tendency towards best PAXgene performance at 24 hours of fixation for FISH, and for DNA integrity analysis 24 hours or 3 days. Conclusions Prolonging PAXgene fixation time to 3 days before adding stabiliser does not seem to have major impact on performance of general diagnostic analysis, but our preliminary results show optimisation of internal protocols are needed. PAXgene is an expensive alternative and may be confined to some dermatological samples.


In recent years, investment treaty practice and arbitral case law have increasingly recognized government transparency as an obligation of international investment law. Yet, there could hardly be less of a consensus regarding what level of transparency is required, with case law ranging from one strand requiring "total transparency" to another merely prohibiting "complete lack of transparency". This apparent paradox seems to be about to change. Some of the most recent treaty practice appears to endorse the latter, restrictive interpretation of transparency. How come? This article sets forth two arguments: First, transparency is in part a binary concept, similar to many other familiar and related legal concepts, such as good faith, lack of arbitrariness and due process, and that transparency could thus, without contradiction, be said to be either "total" or "completely lacking" and nothing in between. Second, restrictive case law and the most recent treaty practice refuses to recognize as a legal requirement the concept of transparency as denoting a gradual quality of the law and of the administration of law.


In this paper, a preventive control method against transient instabilities due to a set of critical contingencies that could occur in a large power system is proposed. The generation rescheduling, adopted as the preventive control, is based on the coherency between the generators. The rescheduling is done by attempting to bring the generators' rotor speeds equal after a three phase fault that might cause instability. The proposed methodology involves off-line simulations to determine the system response and to check the severity of each contingency. For each critical contingency, a scaling factor is assigned to scale the speed trajectory of the contingency. Active-set sequential quadratic programming (SQP) is used to optimize the scaling factors in such a way that the rescheduling method based on the scaling factors improves the dynamic security and restores the system's stability for all contingencies that are taken into account.


A well- designed GST reform package could support economic growth, make the tax and transfer system more progressive and give governments more budgetary options, according to this report. Summary Extending the goods and services tax to cover many of the categories currently exempt could raise $17 billion a year, while increasing the rate to 15 per cent would generate about $27 billion a year. Raising more GST revenue, either through a higher rate or applying it to more goods and services, is preferable to most other means of raising revenue, including higher income taxes. Current governments face many challenges, such as funding growing healthcare costs, reducing deficits, and cutting inefficient taxes. A broader or higher GST could fund any of these initiatives – although not all of them. Broadening the GST base to include fresh food, health and education would be more efficient, and would reduce compliance costs. But if the politics of taxing those categories proves too fraught, then raising the rate of the GST would be a satisfactory second best. A well-designed GST package that increases the rate to 15 per cent could lead to a tax and welfare system more progressive than at present. Higher welfare payments and targeted tax cuts would make low and middle-income households on average better off. New household-level modelling shows that spending about 30 per cent of the additional revenue on welfare – increasing the base rate of pensions and allowances by about five per cent – would leave two-thirds of low-income households better off overall. Committing a further 30 per cent of additional revenue to income tax cuts would allow the government to shave 2 to 2.5 percentage points off the bottom two tax rates. With the welfare increases, these cuts would fully offset the GST increase for households earning up to $100,000 a year. These measures would leave $11 billion of additional revenue that could help the states address the looming hospital funding gap, fund tax cuts that promote economic growth or reduce Commonwealth budget deficits. But not everyone can be fully compensated. Government budgets are in deficit, and promising 'no losers' will be a sure-fire way to erode the revenue benefits from the package.


The purpose of the conference was to locate and promote the role of health economics in mental health policy in low and middle income countries. Health economists have a growing voice in health policy development. But just as it is only recently that mental health policy specifically has been highlighted on the global stage, with the WHO's 2001 World Health Report, so too has the economics of mental health only comparatively recently started to claim attention on the global policy stage. The conference brought together approximately 100 economists, health professionals and policy makers from a great many countries. The participants heard and discussed presentations from prominent practitioners in the field of mental health economics and policy in a global context. Highlights from those presentations and discussions are set out in the remainder of this briefing. Together, they amount to a primer in mental health economics and policy in low and middle income countries.


Today, there is a widespread idea that parents need to learn how to carry out their roles as parents. Practices of parental learning operate throughout society. This article deals with one particular practice of parental learning, namely nanny TV, and the way in which ideal parents are constructed through such programmes. The point of departure is SOS Family, a series broadcast on Swedish television in 2008. Proceeding from the theorising of governmentality developed in the wake of the work of Michel Foucault, we analyse the parental ideals conveyed in the series, as an example of the way parents are constituted as subjects in the 'advanced liberal society' of today. The ideal parent is a subject who, guided by the coach, is constantly endeavouring to achieve a makeover. The objective of this endeavour, however, is self-control, whereby the parents will in the end become their own coaches.


The aviation industry is set to see another significant leap in new technology, namely electric aircraft. As of the time of this research, both 9-seat and 19-seat aircraft would be ready to be launched by air service providers under the Essential Air Service (EAS) program. While electric aircraft manufacturers are hoping to incorporate electric aircraft into the national airspace system, challenges are salient. This study explored existing research and literature by using Qualitative Narrative Analysis in conjunction with the application of VOSviewer to visualize research themes and interconnected clusters followed by interviewing practitioners to reflect on theoretical basis and collect the first-hand data. VOSviewer showed regulations (U.S.A. and Canada), engine design, continued airworthiness, military standards, and maximum transient were primarily discussed and studied. Second-level analysis discovered that Federal Aviation Administration (FAA) has focused on aircraft specification, service and maintenance, and project management perspectives. Regardless of the ongoing technical and regulatory challenges, selected aviation practitioners were recruited and interviewed. Practitioners indicated that although airports and airlines possessed different means of benchmarking success, there was a market niche and tangible benefits that smaller electric aircraft would bring to the needed


Sustainable urbanism is seen today as one of the keys towards unlocking the quest for a sustainable society. As a central paradigm of sustainable urbanism, the eco-city is promoted by global and local policies as one of the preferred responses to the challenges of sustainable development. It is argued that eco-city strategies are expected to deliver positive outcomes in terms of providing healthy and livable human environments in conjunction with minimal demand on resources and thus minimal environmental impacts. As such, it is pertinent to examine how the eco-city model and especially its three sustainability dimensions is practiced and justified in urban planning and development at the local level. This is motivated by the increased interest in developing sustainable urban districts. In this light, this study seeks to answer the following two questions: What are the key strategies of the eco-city district model, and in what ways do they mutually complement one another in terms of producing the expected tripartite value of sustainability? To what extent does the eco-city district model support and contribute to the environmental, economic, and social goals of sustainability? To illuminate the phenomenon of the eco-city district accordingly, a descriptive case study is adopted as a qualitative research methodology, where the empirical basis is mainly formed by urban planning and development documents in two eco-city districts—Royal Seaport, Stockholm, and Western Harbor, Malmo, Sweden—in combination with qualitative interview data, secondary data, and scientific literature. This study shows that the eco-city district models of SRS and Western Harbor involve mainly design and technology, supported with behavioral change, as key strategies and solutions for achieving urban sustainability. Design encompasses greening, passive solar houses, sustainable transportation, mixed land use, and diversity. And technology comprises green technologies, energy efficiency technologies, and waste management systems. Design contributes to the three goals of sustainability, and technology contributes mostly to the environmental and economic goals of sustainability. Behavioral change is associated with sustainable travel, waste separation, and energy consumption. Moreover, at the core of the eco-city district model is the clear synergy between the underlying strategies in terms of their cooperation to produce combined effects greater than the sum of their separate effects with respect to the benefits of sustainability. Further, this study demonstrates that while the environmental, economic, and social goals of sustainability are represented in eco-city district strategies on a discursive level, institutionalized planning practices show that the environmental goals remain at the core of planning, while the economic and social goals still play second fiddle. Nevertheless, new measures have recently been implemented in Western Harbor that are expected to strengthen their influence over urban development practices, whereas the Royal Seaport program mainly focuses on the environmental and some economic aspects, which is a shortcoming that should be recognized and dealt with.


Al doped ZnO (AZO) films were deposited on porous silicon (PS) substrates by a reactive rf-cosputtering process from two targets of ZnO and Al. The effect of ZnO target rf-sputtering power on the structural and photoluminescence (PL) properties of AZO/PS heterojunctions were studied. Strong monochromatic blue emission located at 2.78 eV was observed for the AZO films deposited at 150 W. Freshly prepared PS showed an emission band in the green spectral region. We show that deposition of AZO on PS does not degrade the skeleton of the PS and enhance the PL intensity. The PL band shifted to the high energy for AZO films deposited on PS and the intensity became stable.


Introduction: Breast augmentation requires planning with objective and rigorous criteria, which were standardized by the High Five system of Tebbetts. There are a many possible combinations based on access route, implant plane, and type of implant, enabling the best outcome for each patient. Method: Of 100 patients studied, 30 received anatomic implants and 70 received round implants in the retromuscular or subglandular position, with or without round block technique. All cases used periareolar access. Preoperative evaluation was performed according to the High Five system. Results: The round block technique was used more often with anatomic implants (43%). The subglandular plane was most commonly used (76.6%). Of 30 anatomic implants, 86.7% were placed in the subglandular plane. Of 70 round implants, 71.4% were placed in the subglandular plane. There were 4 cases of grade III and IV capsular contracture, which is more common with the use of round implants. The rate of rotation among anatomic implants was 10%, with 3 cases. Conclusion: There was a low complication rate, in accordance with published data. Periareolar access provided good results in all cases. The patient should be informed about the possibility of rotation with use of anatomic implants. ■ ABSTRACT


For many applications a 2-D circular arc can be conveniently specified by three points that lie on the arc. Since the radius of curvature grows without bound as the three points become collinear, any practical algorithm must avoid calculating the arc's radius or functions of the radius. An algorithm that achieves this objective is presented. It is very efficient because it uses exclusively integer arithmetic and requires only addition, subtraction, comparison, and branch operation in the inner loop.<<ETX>>


A 3-yr investigation was conducted in commercial corn, Zea mays (L.), fields in eastern South Dakota to determine how reduced application rates of planting-time soil insecticides would influence temporal emergence patterns and survival of northern and western corn rootworms, Diabrotica barberi Smith and Lawrence, and D. virgifera virgifera LeConte, respectively. Beetle emergence was monitored at 2-d intervals throughout the entire adult emergence period of three growing seasons from corn plots treated with planting-time applications of labeled (1X) and reduced (0.5 and 0.75X) application rates of terbufos, tefluthrin, and chlorethoxyfos. No consistent insecticide- or rate-related impacts on mean total emergence per trap were recorded for any of the compounds investigated. However, terbufos applications resulted in a 52% reduction in the number of beetles captured per trap, 53% reduction in maximum rate of adult emergence, and a 59% reduction in overall rate of emergence over time for male D. virgifera during 1994. Terbufos also significantly extended the time required for emergence to peak and linear emergence of female D. virgifera to end in 1994. Tefluthrin applications delayed onset, end, and time of maximum emergence of female D. barberi by 9.9, 14.1, and 12 d, respectively, during 1993. Tefluthrin also reduced emergence rates over time for male (38%) and female (46%) D. barberi during 1994. Overall, application rate was inconsequential regarding total emergence, seasonal emergence pattern, or level of plant protection provided for all insecticides we tested in this 3-yr investigation. Our findings demonstrate that, if properly applied, the reduced application rates used in this study provide adequate root protection and will not significantly impact the biology of these pest species.


We have previously shown that histatins 1, 3, and 5 are homologous, histidine-rich proteins present in human parotid and submandibular secretions which contain 38, 32, and 24 amino acids, respectively. Interest in these proteins stems from the fact that histatins exhibit candidacidal and candidastatic activities. The goal of the present investigation was a detailed functional characterization of these anticandidal activities of histatins at the levels of killing of blastoconidia, killing of germinated cells, and inhibition of germination by using three bioassays. Candidacidal activities were evaluated at several ionic strengths, in the presence of different monoand divalent ions, and at multiple pH values. In addition, the susceptibility of Candida albicans in different growth phases to histatins was investigated. While all three major human histatins demonstrated candidacidal activities, they differed in their abilities to kill blastoconidia and germinated cells, with histatin 5 being the most active, histatin 3 showing moderate activity, and histatin 1 exhibiting the lowest level of activity. For the inhibition of germination, however, histatin 3 exhibited more activity than either histatin 1 or histatin 5. The candidacidal activity of histatins was inversely proportional to both the ionic strength and the divalent cation concentration in the medium. Stepwise reduction of the pH of the assay medium enhanced the candidacidal activities of histatins 1 and 3, while the activity of histatin 5 was pH independent over the range of pHs 4 to 8. C. albicans in log-phase growth was more susceptible to histatins 1 and 3 than cells in stationary phase. Cells in either growth phase were still more vulnerable to histatin 5 than to histatins 1 and 3. The results obtained establish the functional relationship of the major histatins with respect to both their fungicidal and fungistatic activities and provide insights into their activities under ionic and pH conditions likely to be encountered in vivo in the oral cavity. Moreover, the data point towards possible mechanisms responsible for the anticandidal activities of histatins.


Julie Johnson attended Littlehampton School (comprehensive) from 1974-9. The three exercise books contain her history work from her second and third years. Her work contains notes illustrated with her coloured drawings and maps - all completed with attention to detail, despite the fact that she did not find the history she was studying interesting. The topics covered included the traditional chronological story of British history, but also the story of the Empire, which was quite unusual by the mid-1970s.


Background Tumor DNA has been shown to be present both in circulating tumor cells in blood and as fragments in the plasma of metastatic cancer patients. The identification of ultra-rare tumor-specific mutations in blood would be the ultimate marker to measure efficacy of cancer therapy and/ or early recurrence. Herein we present a method for detecting microinsertions/deletions/indels (MIDIs) at ultra-high analytical selectivity. MIDIs comprise about 15% of mutations. Methods and Findings We describe MIDI-Activated Pyrophosphorolysis (MAP), a method of ultra-high analytical selectivity for detecting MIDIs. The high analytical selectivity of MAP is putatively due to serial coupling of two rare events: heteroduplex slippage and mis-pyrophosphorolysis. MAP generally has an analytical selectivity of one mutant molecule per >1 billion wild type molecules and an analytical sensitivity of one mutant molecule per reaction. The analytical selectivity of MAP is about 100,000-fold better than that of our previously described method of Pyrophosphorolysis Activated Polymerization-Allele specific amplification (PAP-A) for detecting MIDIs. The utility of this method is illustrated in two ways. 1) We demonstrate that two EGFR deletions commonly found in lung cancers are not present in tissue from four normal human lungs (107 copies of gDNA each) or in blood samples from 10 healthy individuals (107 copies of gDNA each). This is inconsistent, at least at an analytical sensitivity of 10−7, with the hypotheses of (a) hypermutation or (b) strong selection of these growth factor-mutated cells during normal lung development leads to accumulation of pre-neoplastic cells with these EGFR mutations, which sometimes can lead to lung cancer in late adulthood. Moreover, MAP was used for large scale, high throughput "gene pool" analysis. No germline or early embryonic somatic mosaic mutation was detected (at a frequency of >0.3%) for the 15/18 bp EGFR deletion mutations in 6,400 individuals, suggesting that early embryonic EGFR somatic mutation is very rare, inconsistent with hypermutation or strong selection of these deletions in the embryo. 2) The second illustration of MAP utility is in personalized monitoring of therapy and early recurrence in cancer. Tumor-specific p53 mutations identified at diagnosis in the plasma of six patients with stage II and III breast cancer were undetectable after therapy in four women, consistent with clinical remission, and continued to be detected after treatment in two others, reflecting tumor progression. Conclusions MAP has an analytical selectivity of one part per billion for detection of MIDIs and an analytical sensitivity of one molecule. MAP provides a general tool for monitoring ultra-rare mutations in tissues and blood. As an example, we show that the personalized cancer signature in six out of six patients with non-metastatic breast cancer can be detected and that levels over time are correlated with the clinical course of disease.


Technological advances the Argentine has been in recent years such that now stands at the forefront worldwide. The explosion of agriculture, tillage, GM crops and the widespread use of glyphosate have raised controversy, especially regarding the toxicity of the latter. Before weeds are controlled with tillage and these involve serious problems of erosion and soil degradation. Tillage and herbicides have changed the situation and consequently the sustainability of production systems. Glyphosate plays an important role in this transformation, but were allowed to use, would be replaced by more expensive and dangerous herbicides. Under that is essential to achieve these objectives through high yields very tech practice, it is necessary to introduce new technologies to assist the sector mitigation tools and can coexist using those chemicals that may mitigate high exposure to them through technology capabilities to detoxify crops. This tech package is just something known by the scientific-technical and production industry, but that has innovation in its application. The use of PGPR as biofertilizers is a widespread technique that has been installed as a enhancer of crops and environmentally friendly. Our study is based on countering the abuse of chemicals through a complementary technology to mitigate residual glyphosate in crops.


Large-scale personal interview travel surveys were carried out in New Zealand in 1989/90 and 1997/98. The surveys are unique in that self-reported details were taken of drivers' drinking behaviour to enable estimation of driving after drinking. Between the two surveys, the road toll in New Zealand fell considerably, against a background of continuing traffic growth. Using travel estimates generated by the two surveys, matched with crash data, the changing risks for various road users over the intervening eight-year period are discussed. There has been a large decrease in motorcycling since 1990, leading to a substantial reduction in overall fatalities. Changes in drinking and driving behaviour have been reflected by lower crash involvement by alcohol-affected drivers, particularly among young drivers. There are indications that long unbroken driving trips are becoming more frequent, potentially leading to impaired driving due to fatigue. (a) For the covering entry of this conference, please see IRRD abstract no. E202589.


CsPb2Br5/CsPbBr3 composite systems have received considerable attention among numerous lead halide perovskite materials due to their significantly enhanced photoluminescence intensity and stability against moisture. However, the luminescence mechanism of CsPb2Br5 based materials remains controversial, which significantly hinders the further material design and utilization for optoelectronic devices. In this work, to deconvolute their luminescent mechanisms, high-quality CsPb2Br5 crystals without any undesired by-products and impurities have been first prepared by a microwave-assisted synthesis method. The luminescence-inactive characteristics of the material are then confirmed by the steady-state absorption, photoluminescence, transient absorption spectra, and time-resolved terahertz spectroscopy. The prepared CsPb2Br5 crystals exhibit excellent crystallinity and enhanced thermal stability, particularly that they can maintain their crystalline structures in polar organic solvents. By simply manipulating the ratios of different precursor materials, it is witnessed that the green emission comes from the CsPbBr3 adhered, nucleated, and grown on the CsPb2Br5 crystals. Ultrafast transient absorption measurements in visible and terahertz spectral regions reveal that with the help of phonon scattering-assisted hopping at interfacial states, intersystem crossing dominates the electron transfer process in the composite crystals. As a result, the CsPb2Br5 and CsPbBr3 interact extensively with each other. Meanwhile, the Auger recombination rate and the defect-related non-radiative process are suppressed in the composite crystals, thereby enhancing the fluorescence of composite crystals. This work has not only deconvoluted the controversial and unclear luminescent mechanisms of CsPb2Br5 materials but also established a pathway to design and enhance the fluorescence of materials for technological applications.


Social wasps are considered among the most successful and impactful invasive species in the world. One species, Polistes dominula has spread from its native Mediterranean range to every continent except Antarctica. This wasp reached New Zealand in the last decade where it has established in the north of the South Island, however, reports of its presence are increasing throughout the country. Due to its recent arrival in New Zealand, little is known about where this species is likely to establish or what impacts it may have on local insect communities. In this thesis, I conducted two studies to investigate these questions, providing valuable information that may inform future management of this invasive species.
In chapter 2, I used two bioclimatic modelling methods to predict areas of suitable habitat across four regions in the southern hemisphere. These models were informed by global temperature and precipitation data as well as global distribution occurrence data of P. dominula. These data were used to estimate conditions most highly correlated with the presence of this wasp. The models identified large areas across the target regions that were climatically suitable for the establishment of P. dominula. Many of these areas are not known to currently contain populations of this species, representing habitat potentially vulnerable to further invasion by P. dominula. Areas across South America, South Africa and Australia were predicted to be climatically suitable. In New Zealand, much of the North Island and eastern parts of the South Island were predicted to be suitable habitat for this wasp. These results suggest that P. dominula could potentially establish across more of the country and expand its invaded range. Information provided by these models may guide conservation and biosecurity management by highlighting key areas where prevention and mitigation should be prioritized.
In chapter 3, I used molecular diet analysis to investigate the range of prey being utilised by P. dominula in New Zealand. Using DNA barcoding, larval gut contents of P. dominula and another closely related species, Polistes chinensis, were analysed to identify what species were present in the diet of both wasps. Butterflies and moths (Lepidoptera) were found to be the most highly represented order in both species' diets. True bugs (Hemiptera) and flies (Diptera) were also abundant. Both wasps were shown to consume a range of native and introduced species including a number of agricultural pests. P. dominula was found to utilise a wider range of prey than P. chinensis. This more diverse prey range, combined with known differences in nesting behaviour, suggest that P. dominula may represent a more significant threat to invertebrate diversity than the already well-established P. chinensis. These results may inform conservation and biosecurity managers on which species are most at risk where this new invasive wasp becomes established.
This thesis provides insights into the potential impacts of a new invasive species to New Zealand. Both chapters represent the first time that these methods have been used to study P. dominula. This work highlights the need for continued monitoring of wasp populations throughout New Zealand, especially in regions highlighted as vulnerable to P. dominula establishment. We also suggest the need to prioritise the conservation of 'at-risk' species in coastal and human-altered habitats. Increased public engagement through the citizen-science initiatives should be encouraged while more research into management and control methods is recommended.


Behcet's disease is a chronic multisystemic disease of unknown pathogenesis characterized by four major symptoms: oral aphthous ulcers, skin lesions, ocular symptoms and genital ulcerations. The disease is spread throughout the world, but it is most frequent in Turkey, Japan, Korea and China. Although HLA‐Bw51 has been found to predominate in Behcet's cases, the genetic etiology has not yet been clarified. In this study, we investigated the chromosomal abnormalities and sister chromatid exchange rates in patients with Behcet's diseases. Thirty‐eight patients with Behcet's disease (diagnosed for the first time) and 30 healthy subjects (as controls) were included in this study. Although numerical and structural chromosomal abnormalities were not detected in our patients, we found an increased rate of sister chromatid exchange in patients over the control groups (P < 0.01). On the basis of these results, we discuss the genetic etiology of Behcet's disease.


Optical links are used for the readout of the 4088 silicon microstrip modules that make up the SemiConductor Tracker of the ATLAS experiment at the CERN Large Hadron Collider (LHC). The optical link requirements are reviewed, with particular emphasis on the very demanding environment at the LHC. The on-detector components have to operate in high radiation levels for 10 years, with no maintenance, and there are very strict requirements on power consumption, material and space. A novel concept for the packaging of the on-detector optoelectronics has been developed to meet these requirements. The system architecture, including its redundancy features, is explained and the critical on-detector components are described. The results of the extensive Quality Assurance performed during all steps of the assembly are discussed.


This paper presents a method for the adaptation of a wind power plant to the energy market using battery energy storage systems (BESS) to show the feasibility of using fast-response batteries, and to calculate its payback period. The proposed method is also used to investigate the optimum battery size according to the installed capacity of the wind farm based on the price and wind forecast, and arbitrage opportunity so as to maximize the profit of the investor. The profit obtained from the market by the battery storage system is compared to the profit from the feed-in tariff for every kilowatt-hour of electricity the wind farm exports to the grid. In this research work, iterative computational-based optimization algorithm is applied to determine hourly charge/discharge commitment of the battery. A case study is conducted for a real wind power generation station in Turkey whose installed capacity is 15 MW. The simulation results show that the proposed algorithm considerably increases the profit and provides an acceptable payback period.


Abstract Although the breeding ranges of Archilochus alexandri (Black-chinned Hummingbird) and Archilochus colubris (Ruby-throated Hummingbird) are narrowly parapatric in central Texas and central and southern Oklahoma, there have been few reports of hybridization in the literature and no well-documented hybrid specimens. Here we provide a comprehensive assessment of two male hybrids collected, respectively, in Grayson County, Texas, and East Baton Rouge Parish, Louisiana. As has been the pattern in other hummingbird hybrids, both specimens exhibit a blended mosaic of plumage characters of the parental species. Sequence for mitochondrial cytochrome c oxidase subunit 1 (CO1) for the hybrid specimen from East Baton Rouge Parish (LSU 182,831) confirms A. colubris as the female parent.


The cladoceran herbivore Daphnia magna is a major consumer of phytoplankton in lakes. Therefore, this organism may control the phytoplankton community and the proliferation of some algae or cyanobacteria. Cladoceran behaviour and migration in relation to temperature, light or presence of planktivorous fishes have been well studied. In particular, it is known that the detection of kairomones produced by predators may induce avoidance. Avoidance could also occur with other semiochemicals such as cyanotoxins. In order to explore this hypothesis, we used an olfactometer to observe and measure the exploratory behaviour of D. magna individuals based on the motivation for food. Daphnids were allowed to choose between different compounds: water, a pure cyanotoxin, i.e. the microcystin-RR [(MC)-RR], extracts of one MC-producing strain (PMC 75.02) and one MC-free strain (PMC 87.02) of Planktothrix agardhii, or a green algae Scenedesmus obliquus. With this experimental design, we observed that i) cladocerans are able to detect resources with different qualities, ii) they can explore before exhibiting preferences, and iii) daphnids are able to avoid compounds that are potentially toxic (e.g., microcystins). First, daphnids explored the environment, subsequently (after about 1.5 h), they showed a significant tendency to stay where there is a profitable resource such as S. obliquus. These results also suggest that specimens of D. magna cannot detect MC compounds from P. agardhii, but they respond to it as a food resource. The study of zooplankton ability to explore the environment when exposed to semiochemicals needs further investigation.


This paper speculates about what will, and should, follow cognitivism in psychology in the new century. It highlights the importance of the work of Wittgenstein, Sacks and Edwards for the development of post-cognitive psychology. Cognitivism is criticized for failing to conceptualize practices in a way that recognizes their action orientation and co-construction, and to appreciate how they are given sense through people's categories, formulations and orientations. Discursive psychology focuses on the production of versions of reality and cognition as parts of practices in natural settings. It is offered as one potential successor to cognitivism.


We present here a fully first-principles method for predicting the atomic structure of interfaces. Our method is based on the ab initio random structure searching (AIRSS) approach, applied here to treat two-dimensional defects. The method relies on repeatedly generating random structures in the vicinity of the interface and relaxing them within the framework of density functional theory (DFT). The method is simple, requiring only a small set of parameters that can be easily connected to the chemistry of the system of interest, and efficient, ideally adapted to high-throughput first-principles calculations on modern parallel architectures. Being first-principles, our method is transferable, an important requirement for a generic computational method for the determination of the structure of interfaces. Results for two structurally and chemically very different interfaces are presented here, grain boundaries in graphene and grain boundaries in strontium titanate $(\mathrm{SrTiO}{}_{3})$. We successfully find a previously unknown low energy grain boundary structure for the graphene system, as well as recover the previously known higher energy structures. For the $\mathrm{SrTiO}{}_{3}$ system we study both stoichiometric and nonstoichiometric compositions near the grain boundary and find previously unknown low energy structures for all stoichiometries. We predict that these low energy structures have long-range distortions to the ground state crystal structure emanating into the bulk from the interface.


Study Design This study is a prospective evaluation of the effects of commonly used spinal tables on lumbar sagittal alignment. Objectives The objective was to determine the differences, if any, in lumbar sagittal alignment produced by different positions on routinely used spinal operating tables. Summary of Background Data Earlier studies have documented the advantages of the knee‐chest position in lumbar decompressive procedures. When simultaneous fusion is performed and augmented with internal fixation, intraoperative position is the critical determinant of sagittal plane balance. Other investigators have documented an association between the knee‐chest position and decreased lumbar lordosis. Methods Ten asymptomatic volunteers underwent a series of four lateral lumbar radiographs, as follows: standing, prone on the Jackson (Orthopaedic Systems, Inc., Hayword, CA) spinal table, and prone on the Andrews (Orthopaedic Systems, Inc.) table with the hips flexed 60° and 90°, respectively. Intervertebral body angle measurements were obtained from L1 to S1. Lordosis values were compared and analyzed for each of the positions. Standing lordosis was assumed to be physiologic. Results Physiologic lordosis values were produced only on the Jackson operative table. Both positions on the Andrews table resulted in a statistically significant decrease in lumbar lordosis. Decreasing hip flexion on the Andrews table from 90° to 60° produced a statistically significant increase in lumbar lordosis. However, this change did not reproduce physiologic values. Conclusion When instrumentation is used to augment lumbar fusions, positions incorporating hip flexion should be avoided to ensure maintenance of sagittal plane balance.


Undersea acoustic channels can exhibit multipath propagation with impulse-response duration and coherence time both of the order of tens to hundreds of milliseconds. Signal reception is further impaired by the presence of time-varying nonwhite ambient-noise spectra having a dynamic range of 30 dB or more. Acoustic communication requires appropriate waveform design and associated signal processing to accommodate these adverse transmission characteristics while also providing desired performance features such as low-probability-of-detection (LPD) and multi-access networking. Adaptive-equalization techniques provide good performance only for channels with stable multi-paths and high signal-to-noise ratios (SNR's) accommodating the signaling rates needed to sample and compensate for rapid changes. An alternative approach is to design for robustness against channel fluctuations. This paper describes a channel-tolerant approach identified as "telesonar type-B signaling." The technique has been designed to accommodate network architectures requiring multiple access to the channel while simultaneously providing covertness and energy efficiency. Specialized frequency-hopped M-ary frequency-shift-key (FH-MFSK) waveforms are combined with related signal processing, including nonlinear adaptive techniques to mitigate the effects of all types of interference. This effectively results in a channel that has uniformly distributed noise in both time and frequency. Powerful error-correction coding permits low SNR transmissions. Nonbinary, long-constraint-length, convolutional coding and related sequential decoding is a classical solution for difficult low-rate channels. The probability of bit errors below 10/sup -10/ is obtainable, even in Rayleigh-faded channels near the computational cutoff rate, and the probability of failure to decode frames of data is extremely small. Both simulations and analyses of at-sea experiments demonstrate the performance of this noncoherent approach to reliable acoustic communications.


Parental sharing of child-related content on social network sites, termed "sharenting," is often the target of criticism. Yet, through sharenting, parents can find support systems, a way to stay in touch with relevant others, and even an opportunity for additional income. This study contributes to knowledge on antecedents of sharenting. It explores the impact of parents' privacy concerns on the sharing of child-related content, as well as on their general Instagram sharing. In this study, we differentiate between general and situational privacy. Moreover, we investigate whether parents' privacy self-efficacy and the support of their peers influence parental sharing practices. Drawing on a rich body of literature on privacy and information sharing, we discuss the results of an online survey distributed among 320 Instagram users who are parents of children younger than 13 and reside in the United Kingdom. We find that parents' privacy concerns are uncorrelated to sharenting and only situational concerns marginally correlate to parents' general sharing. Parents' reported privacy self-efficacy also did not play a role in parents' sharing of either personal or children-related content. On the contrary, both Instagram sharing and having a network supportive of parental sharenting positively predict sharenting. Our results indicate that (a) neither situational nor general privacy concerns influence parents' sharenting behavior, and (b) a parent's supportive network and frequent sharing habits make frequent sharenting more likely.


In the Sudan, native Sudanese slaves served Sudanese masters until the region was conquered by the Turks, who practiced slavery on an institutional scale. When the British took over the Sudan in 1898, they officially emancipated the slaves, yet found it impossible to replace their labor in the country's economy. This pathfinding study explores the process of emancipation and the development of wage labor in the Sudan under British colonial rule. Ahmad Sikainga focuses on the fate of ex-slaves in Khartoum and on the efforts of the colonial government to transform them into wage laborers. He probes into what colonial rule and city life meant for slaves and ex-slaves and what the city and its people meant for colonial officials. This investigation sheds new light on the legacy of slavery and the status of former slaves and their descendants. It also reveals how the legacy of slavery underlies the current ethnic and regional conflicts in the Sudan. It will be vital reading for students of race relations and slavery, colonialism and postcolonialism, urbanization, and labor history in Africa and the Middle East.


Introduction The fragmentation of the French health and services system has a negative impact on the quality of the services offered because dependant community-dwelling older persons receive services from a mean of three interveners, and 25% of the most dependent ones perceive assistance from at least 6 interveners. In 2006, the Ministry of Health funded an experimentation of implantation of an evidence-based model of integration based on case management: PRISMA. Aims and objective An implementation evaluative research was associated with the experimentation undertaken by an international (France, Quebec) and multidisciplinary (medical doctors, sociologists, economists) group of research. Methods This evaluation is carried out continuously all along the implementation process. It is essentially based on research-action framework. A multi-case qualitative analysis is performed on three sites contrasted in regard of the health and services local organisation: rural, urban and megalopolitan. Results Initial implementation seems to be low during the first 18 months. First objective signs of integration after 12 months were the emergence of a coordination process on a strategic level, the adoption of a unique assessment tools by all the partners and the project of constituting a multi-professional team of case managers. Sociological and political identified barriers will be discussed.


We give practical, efficient algorithms that automatically determine the asymptotic distributed round complexity of a given locally checkable graph problem in the [Θ(log n ) , Θ( n )] region, in two settings. We present one algorithm for unrooted regular trees and another algorithm for rooted regular trees. The algorithms take the description of a locally checkable labeling problem as input, and the running time is polynomial in the size of the problem description. The algorithms decide if the problem is solvable in O (log n ) rounds. If not, it is known that the complexity has to be Θ( n 1 /k ) for some k = 1 , 2 , . . . , and in this case the algorithms also output the right value of the exponent k . In rooted trees in the O (log n ) case we can then further determine the exact complexity class by using algorithms from prior work; for unrooted trees the more fine-grained classification in the O (log n ) region remains an open question.


Viscous dissipation and the convection heat transfer coefficient are two key flow parameters that control the operation of twin‐screw solidifying extruders. This type of extruder is used to produce hydrogenic pellets that fuel fusion energy machines like the ITER device. This paper discusses a Cryogenic Couette Viscometer (CCV) that is used to measure the viscous dissipation and convective heat transfer coefficient associated with the solidification of cryogenic fluids. Preliminary viscous dissipation measurements of solidifying nitrogen are presented and examined. Modifications to the apparatus are proposed that will allow the measurement of the wall‐to‐fluid convective heat transfer coefficient and improve the measurement of viscous dissipation.


This book is intended to be the primary textbook to support any college who would like to run a Photography 101 course for students. The course is designed to offer tutors an independent learning tool to enable students to learn the craft of using an interchangeable lens camera (DSLR or Mirrorless) and the basics of an image-editing program (Adobe Lightroom) to enable them to take creative control of the imaging process. The curriculum offers a step-by-step and jargon-free approach to learning the fundamental skills of creative camera control. Each page features a large image with a brief explanation of how the creative controls of the camera have led to the resulting visual appearance of the image. Information on each page is stripped down the essentials and text is carefully selected to be unambiguous and kept to the bare minimum to ensure rapid acquisition of the skills on offer. This effective course-in-a-book allows students quickly to become technically proficient, and instructors to efficiently evaluate students progress.


This paper examines the effectiveness of the Local Economic Development Agency (LEDA) model of institutional support for local economic development (LED), a model of LED that became very popular in the 1990's as the neoliberal political project began its global ascendancy. The paper draws upon rich primary data from Latin America, and much secondary data from many other countries, to demonstrate that the LEDA model has been an almost wholly ineffective instrument through which to promote LED, if it has in fact not seriously compromised the LED operations of those communities in which has been established. The LEDA concept has almost no evidence to support the widespread claims that it has improved the LED function in developing countries. The next question then obviously begged is, Why then were so many international donor agencies, notably UNDP, willing to support the LEDA model, and for so long, if it was in fact a manifestly ineffective LED institution? The answer to this question, it is argued, is primarily to be found in the politics and ideology of the LEDAs, which reflect core neoliberal imperatives – that all development institutions must be private sector-led and financially self-sustainable. The manifestly ineffective LEDAs were therefore tolerated, and evidence of their ineffectiveness suppressed, because the LEDAs were the reflection of key neoliberal imperatives.


Background and Purpose: Primary Stroke Center Certification through the Joint Commission requires specific education to patients who have sustained a stroke. Low rates of completed education were noted for stroke patients during our needs assessment. Issues with compliance included ambiguous admission diagnoses, lack of time for registered nurses to complete the education, and a deficiency in knowledge related to the Joint Commission's certification standards. The purpose of this study was to assess the impact of a nursing stroke education team on the compliance rates of stroke education. Methods: A group of NIHSS certified nurses volunteered to be on the team, named the Team About Stroke Education and Research (TASER). These nurses received in-depth education on stroke pathophysiology and treatments, adult learning theories, and the requirements for stroke certification through the Joint Commission. By using concurrent auditing and daily rounds, TASER nurses tracked possible stroke patients within the facility and were responsible for completing the educational requirements and related documentation. A goal of 85% of completed education was set. Data was collected using retrospective audits. Results: During the six months prior to the TASER initiation, the percentage of inpatients with a discharge diagnosis of stroke who received required education was at 39.1% (9/23). During the six months after the TASER initiation, that percentage of patients who required education increased to 82.6% (19/23). TASER nurses identified 139 potential stroke patients in that 6 month period and educated a total of 68 patients, regardless of their final diagnosis, disposition, or destination. Conclusions: The TASER program showed improvements in compliance of educational requirements. Although not at the goal of 85%, further education and additional TASER nurses may increase our numbers. Future testing of the retention of the education provided may be warranted.


Wireless communications systems are particularly vulnerable to security attacks because of the inherent openness of the transmission medium. In this article, we focus on guaranteeing confidentiality against eavesdropping attacks where an unauthorized entity aims to intercept an ongoing wireless communication, and we provide a comprehensive summary of recent advances in the area of physical-layer security that guarantees confidentiality by using cooperative techniques unique to the wireless medium. These cooperative techniques consist of carefully designed coding and signaling schemes that are able to harness the properties of the physical layer and to ensure some level of information-theoretic security.


Purpose Chimeric antigen receptor (CAR)-T cells have shown to play a vital role in anti-tumor functions in hematological malignancies, but have poor efficacy in solid tumors. To improve the activation and proliferation of CAR-T cell in solid tumors, we constructed an enhanced CAR-T cells to increase the survival of esophageal cancer. Materials and Methods To construct enhanced CAR-T cells, we chose MUC1 as the target of CAR-T cells. Long-term co-culture of target cells and effector cells was applied to verify the antitumor activity of these enhanced MUC1-CAR-T cells in vitro. Moreover, a mouse xenograft model was established to investigate the effects of enhanced MUC1-CAR-T cells on tumor elimination in vivo. Results In vitro studies showed that enhanced MUC1-CAR-T cells have long-lasting tumor killing and proliferative capabilities. Moreover, animal experiments verified that enhanced MUC1-CAR-T cells had significant antitumor function and a prolonged half-life by subcutaneous transplantation models of esophageal cancer and PDX models of esophageal cancer, in vivo. Conclusion These results indicated that enhanced MUC1-CAR-T cells have a significant cytotoxic effect on esophageal cancer, and may likely to provide a novel strategy for the treatment of esophageal cancer.


This paper considers the relations between thin film indices for making an antireflection coating when all optical thicknesses are equal. In this way, it is possible to determine antireflection coatings for two given wavelengths. Various cases are studied according to the two wavelengths and the index of the substrate.


Being self-directed is one of the most sought-after employee attributes. The present study ex- amines managers' approaches to and conceptualization of employee self-directedness through semi-structured interviews with 13 managers from five companies in the Stockholm area.Analysis suggests two different emphases in trying to increase self-direction, with differing underlying as- sumptions: an evaluation emphasis where self-direction is conceptualized as an inherent property of the individual, and a cultivation emphasis suggesting a more interactionist perspective of self- direction as an emergent behavior based on the interaction of individual and situational character- istics. Further, a 'seeing work'-skill emerged in all interviews, implicating situational judgment and attention as core to what is ultimately seen as successful self-direction. Managers with a cultivation emphasis mentioned as viable tactics those focused on supporting sensemaking and thus enrich- ing the working situation to enable better discretionary situational judgments


Agonist-induced phosphorylation of G-protein-coupled receptors has been shown to facilitate the desensitization processes, such as receptor internalization, decreased efficiency of coupling to G-proteins, or decreased ligand affinity. The lowered affinity may be an intrinsic property of the phosphorylated receptor or it may be the result of altered interactions between the modified receptor and downstream components such as G-proteins or arrestins. To address this issue, we purified cAR1, the major chemoattractant receptor of Dictyostelium discoideum by a strategy that is independent of the ligand binding capacity of the receptor. To our knowledge, this represents the first successful purification of a chemoattractant receptor. The hexyl-histidinetagged receptor was solubilized from a highly enriched plasma membrane preparation and purified by Ni 21 chelating chromatography. The protocol offers a simple way to purify 100 ‐500 mg of a G-protein coupled receptor that can be targeted to the plasma membrane of D. discoideum. The Kd value for the purified cAR1 was about 200 nM, consistent with that of receptors that are not coupled to G-proteins in intact cells. In contrast, the affinity of phosphorylated cAR1, purified from desensitized cells, was about three times lower. Treatment of the phosphorylated receptor with protein phosphatases caused dephosphorylation and parallel restoration of higher affinity. We propose that ligand-induced phosphorylation of G-protein-coupled receptors causes a decrease in intrinsic affinity and may be useful in maintaining the receptor's sensitivity at high agonist levels. This affinity decrease may precede other processes such as receptor internalization or uncoupling from G-proteins.