Abstract Objective Previous analyses have suggested an association between centre volume and in-hospital mortality, post-operative complications, and mortality in those patients who suffer from a complication. We sought to determine the nature of this association using a multicentre cohort. Methods All the patients, aged 18 years or younger, undergoing heart surgery at centres participating in the European Congenital Heart Surgeons Database (2003–2013) were included. Programmes were grouped as follows: small <150; medium 150–250; large 251–349; very large >350. Multivariable logistic regression was used to identify the differences between groups with the adjusted in-hospital mortality, onset of any and/or major complication, and in-hospital mortality in those patients with any and/or major complication. The outcomes were adjusted for patient specific risk factors and surgical risk factors. Results The data set consisted of 119,345 procedures performed in 99 centres. Overall, in-hospital mortality was 4.63%; complications occurred in 23.4% of the patients. In-hospital mortality in patients with complications was 13.82%. Multivariable logistic regression showed that the risk of in-hospital death was higher in low- and medium-volume centres (p<0.001). The rate of the occurrence of any post-operative complication in small, medium, and large programmes was lower compared with very large centres (p<0.001). Low- and medium-volume centres were associated with significantly higher mortality in patients with any complication (p<0.001). Conclusions Our analysis showed that the risk of in-hospital mortality was lower in higher-volume centres. Although the risk of complications is higher in high-volume centres, the mortality associated with complications that occurred in these centres was lower.


We present a fast and efficient approach for joint person detection and pose estimation optimized for automated driving (AD) in urban scenarios. We use a multitask weight sharing architecture to jointly train detection and pose estimation. This modular architecture allows us to accommodate different downstream tasks in the future. By systematic large-scale experiments on the Tsinghua-Daimler Urban Pose Dataset (TDUP), we obtain multiple models with varying accuracy-speed trade-offs. We then quantize and optimize our network for deployment and present a detailed analysis of the efficacy of the algorithm. We introduce a two-stage evaluation strategy, which is more suitable for AD and achieve a significant performance improvement in comparison to state-of-the-art approaches. Our optimized model runs at 52~fps on full HD images and still reaches a competitive performance of 32.25~LAMR. We are confident that our work serves as an enabler to tackle higher-level tasks like VRU intention estimation and gesture recognition, which rely on stable pose estimates and will play a crucial role in future AD systems.


This work aims at establishing the effect of stress and temperature on the velocity of ultrasonic longitudinal waves in typical engineering polymers, and evaluating the potential of ultrasonic stress measurement in the evaluation of residual stresses in polymer parts. In order to estimate the effect of material morphology, two amorphous and two semicrystalline polymers have been considered. A series of tests are implemented, to determine the acoustoelastic constants and temperature constant of materials, by using the designed transducer fixtures for in situ measurement of longitudinal wave velocity. As expected, the velocity changes linearly with stress and temperature, and the temperature effect is as important as the acoustoelastic effect. It shows that this kind of nondestructive method is a valuable quantitative tool to estimate the residual stress in polymer products, but the material temperature influence must be considered during the estimation.


Cold spray is a well-established thermal spray process for metal coatings, but it is unsuitable for depositing ceramics. However, cold spray has been used to spray a thin layer of ceramics to improve surface properties. This paper aims to find the spraying parameters to deposit alumina particles onto an aluminum substrate, investigating the retention phenomenon through computational modelling. We used the finite element analysis in the coupled Eulerian Lagrange formulation to predict the particle-substrate interaction. The Johnson-Cook plasticity model and Mie-Gruneisen equation of state were employed to describe the substrate behaviour. Alumina particles were assumed to be elastic. To assess the retention phenomenon, we varied spraying parameters such as particle speed, substrate temperature, and deposition angle. The findings showed that initial velocity and the substrate temperature facilitate penetration of the ceramic particles into the substrate; thus, the penetration increases the chance of retention into the substrate. The deposition angle affects the jet shape, and specific deposition angles cause erosion. Overall, the findings denote that certain cold spraying parameters may improve the retention of ceramic particles into metal substrates.


In the 25 years since its first description the p53 protein has been shown to play a key role in both tumour suppression and aging. New discoveries about the function and control of p53 continue to emerge every month and attempts to exploit the system to develop better therapeutics and diagnostics are beginning to be successful in the clinic (1,2).


OBJECTIVE
To investigate the clinical results of modified Sutherland pelvic osteotomy for developmental dysplasia of hip (DDH).

METHODS
Sutherland pelvic osteotomy were performed in 10 patients (11 hips) with DDH. Among them, there were 3 male (3 hips) and 7 female (8 hips) patients, aged (32 ± 8) years. During operation, arthroscopes were performed additionally to remove the existing hyperplasia tissue in the fossae ovalis and trimming acetabulum and glenoid labrum, thus to insure the better match between the femoral head and the realigned acetabulum. The change of imaging indexes were acquired by comparing the preoperative X-ray with the postoperative X-ray. The change of hip function and life quality were acknowledged according to contrast and analysis Harris hip score and Short Form 12-items Health Survey (SF-12) before and after osteotomy.

RESULTS
All patients were followed up for a mean of (5.2 ± 2.3) years, the osteotomy were all union in 3 months. The acetabular head index was 71 ± 8 before operation, and 86 ± 4 after operation. The pre- and post-operative centre edge angle were (7 ± 9)° and (33 ± 9)°, sharp angle were (48 ± 4)° and (37 ± 5)°, acetabular index angle were (24 ± 8)° and (11 ± 5)° respectively. The average Harris score improved from 42 ± 13 preoperatively to 90 ± 5 postoperatively, with 100% excellent and good results. Every domains of SF-12 was improved in the different extents postoperatively, the improvement of physical component summary was more conspicuous than mental component summary. The imaging indexes, Harris and SF-12 were all improved with significant difference (all P < 0.05).

CONCLUSIONS
The modified Sutherland pelvic osteotomy is effective. It could increase the load bearing capacity of hip, and improve the quality of life.


Multi-objective evolutionary algorithms (MOEAs) have been successfully applied for the numerical treatment of multi-objective optimization problems (MOP) during the last three decades. One important task within MOEAs is the archiving (or selection) of the computed candidate solutions, since one can expect that an MOP has infinitely many solutions. We present and analyze in this work ArchiveUpdateHD, which is a bounded archiver that aims for Hausdorff approximations of the Pareto front. We show that the sequence of archives generated by ArchiveUpdateHD yields under certain (mild) assumptions with a probability of one after finitely many steps a Δ+-approximation of the Pareto front, where the value Δ+ is computed by the archiver within the run of the algorithm without any prior knowledge of the Pareto front. The knowledge of this value is of great importance for the decision maker, since it is a measure for the "completeness" of the Pareto front approximation. Numerical results on several well-known academic test problems as well as the usage of ArchiveUpdateHD as an external archiver within three state-of-the-art MOEAs indicate the benefit of the novel strategy.


Anticipating pain is important for avoiding injury; however, in chronic pain patients, anticipatory behavior can become maladaptive, leading to sensitization and limiting function. Knowledge of networks involved in pain anticipation and conditioning over time could help devise novel, better-targeted therapies. With the use of magnetoencephalography, we evaluated in 10 healthy subjects the neural processing of pain anticipation. Anticipatory cortical activity elicited by consecutive visual cues that signified imminent painful stimulus was compared with cues signifying nonpainful and no stimulus. We found that the neural processing of visually evoked pain anticipation involves the primary visual cortex along with cingulate and frontal regions. Visual cortex could quickly and independently encode and discriminate between visual cues associated with pain anticipation and no pain during preconscious phases following object presentation. When evaluating the effect of task repetition on participating cortical areas, we found that activity of prefrontal and cingulate regions was mostly prominent early on when subjects were still naive to a cue's contextual meaning. Visual cortical activity was significant throughout later phases. Although visual cortex may precisely and time efficiently decode cues anticipating pain or no pain, prefrontal areas establish the context associated with each cue. These findings have important implications toward processes involved in pain anticipation and maladaptive pain conditioning.


Effects of social marketing strategies on student research behaviors were investigated. Three objectives were identified as target behaviors for change: (1) decrease procrastination due to the illusion of immediacy, (2) increase students' willingness to seek expert assistance when it is warranted, and (3) increase the selection of information sources based on criteria other than the information need itself, which includes the habituated and automatic use of Internet sources based on the assumption that they are more convenient, reliable, and easy to use. Findings suggest a positive impact as a result of marketing strategies attempting to achieve these objectives. Students who received messages based on a social marketing framework that emphasized these objectives appeared more willing to engage in discussions about the research process and were more likely to seek assistance from a librarian. A number of students reported successful encounters with librarians in meeting their research needs. Students who only received skills instruction reported attempting to use research tools like databases, but gave up in frustration. Due to relatively little research on how social marketing strategies can be used to change student research behaviors, more research is warranted to explore this connection. More investigation is also needed regarding how to help librarians learn how to package and deliver messages using a social marketing framework.


Abstract Over 4000 African refugees have resettled in Queensland through the Australian government's Humanitarian Program. Research on the settlement geography of this immigrant group is, however, limited. The present study is set within the context of research and debates concerning the residential concentration and/or dispersion patterns of immigrant settlement in Australia. The paper investigates the settlement and secondary migration geography of eight African refugee communities in Southeast Queensland. Discrepancies are identified between the official data and the actual distribution according to community members' views obtained via focus group surveys and interviews. Preliminary results indicate that there is a relatively high rate of secondary migration in the African communities. The paper also discusses the two key factors underpinning this secondary migration: housing and social networks. These findings have implications for settlement service providers, particularly in the area of housing.


Ultrasonographic diagnosis of gallstones in the distal part of extrahepatic duct is not easy. A number of new techniques have been used by the authors to improve the detection rate of these stones. They include filling the duodenum and gastric antrum with drinking water, scanning after a fatty meal, and changing the patient's position during scanning. Ultrasound successfully identified choledocholithiasis in 78 of 104 patients for a sensitivity of 75%. There were 26 false‐negative cases. The chief causes of the false negatives were obscuration of the distal duct by overlying bowel gas, missing of small stone in a nondilated bile duct, and misdiagnosis of soft pigment or an impacted stone having an atypical hypoechoic image in the distal duct as a tumor. False‐positive diagnosis occurred in 32 out of 188 noncalculous cases, giving a specificity of 83%. These cases represent various hyperechoic lesions in the neck of gallbladder, cystic duct, and periampullary region. The overall diagnostic accuracy of gallstones in the extrahepatic bile duct by ultrasound was 80% (234/292).


The structure of the third, or independent sector, is analyzed in this paper from the perspective of its place in an integrated political economy. Using the method of John Dewey to distinguish acts that are public from those that are private, a set of propositions are developed regarding the close links between voluntarism and the acts of corporate and governmental institutions. This interrelated social reality is examined in terms of major approaches of social scientists. Functionalist approaches are found to predominate over interpretive, radical structuralist, and radical hu manist paradigms in the area of voluntary action research. Drawing on recent British experience, it is suggested that approaches to research might benefit from the development of a full-blown theory of mediating institutions. The paper concludes with a brief examination of policy issues in contemporary voluntarism, and points to the importance of what Meister has called the role of voluntary associations in contributing to self-man...


Cardiovascular disease (CVD) remains the major cause of death in the United States and Western Europe and occlusion of the coronary arteries by the atheromatous plaque accounts for most of these deaths (Ross, 1986; Slattery & Randall, 1988). Demographic differences in the incidence of CVD have been interpreted as implicating diet and cholesterol in the pathogenesis of the disease, but results of intervention trials to reduce serum cholesterol by dietary or pharmacological means are equivocal (Grundy, 1986; Reckless, 1987; Rifiind, 1987; Tyroler, 1987; James & Ralph, 1988; McCormick & Strabanek, 1988; Waterlow, 1988). Gey (1986) estimated that the major recognized risk factors for CVD, namely smoking, hypercholesterolaemia and hypertension, only account for 5 ( M O YO of the variance in the Occurrence of CVD. Consequently, there is scope for the inclusion of other dependent and independent risk factors which may contribute to the apparent multifactorial nature of the disease. The purpose of the present article is to review recent evidence implicating reactive free radicals in the development of CVD.


Dacryodes edulis (G. Don) H.J. Lam or eleme is widely used among Yoruba speaking people of Nigeria. The fruit is the major part utilized for food; eaten singly or with a number of other foods. The pulp oil complements common edible oils. Considered rich with medicinal properties; the plant parts is engaged singly or with other plants for treating several illness and diseases including malaria, dermatological, oral and ear conditions, hypertension, leprosy, labor pain, retarded growth and epilepsy in children. Viewed as a symbol of "fruitfulness" and of "peace" the plant parts are employed for both religious and sociocultural activities such as warding off evil spirits, worship of gods, communal festivals, marriage, naming and settlement ceremonies. The wood is used for carpentry, road and shelter construction. The stem exudates act as glue, as well as for production of cosmetics alongside the fruit oil. The tree crown serves for apiculture as well as for shade. The use of Dacryodes edulis amongst the Yoruba people is immense as it cut across the cultural, socio-economic and medicinal interactions of the people.


Differential effective medium (DEM) theory is applied here to the problem of modeling physical properties of poroelastic media that are partially saturated with liquid. Typical fluid saturants are air and water, or gas and oil. If the liquid and gas saturants are homogeneously mixed, then we say the medium is partially saturated. If the liquid and gas saturants are poorly mixed, so each constituent occupies separate, but contiguous, regions of the porous medium, we say the medium has patchy saturation. Some examples are presented to show that a reasonable approach to modeling the effects of patchy saturation at high frequencies (200 kHz and above) is produced by treating the medium as if it is a composite of gas-saturated and liquid-saturated porous inclusions that are homogeneously mixed together. Estimates of the properties are obtained using differential effective medium theory. The results differ dramatically from those predicted by Gassmann's equations for homogeneous mixing of the fluids in individual pores. In particular, the shear modulus depends on the elastic properties of the fluid constituents, unlike the quasistatic behavior predicted by Gassmann.


Parathyroid hormone induces collagenase-3 gene transcription in rat osteoblastic cells. Here, we characterized the basal, parathyroid hormone regulatory regions of the rat collagenase-3 gene and the proteins involved in this regulation. The minimal parathyroid hormone-responsive region was observed to be between base pairs −38 and −148. Deleted and mutated constructs showed that the activator protein-1 and the runt domain binding sites are both required for basal expression and parathyroid hormone activation of this gene. The runt domain site is identical to an osteoblast-specific element-2 or acute myelogenous leukemia binding sequence in the mouse and rat osteocalcin genes, respectively. Overexpression of an acute myelogenous leukemia-1 repressor protein inhibited parathyroid hormone activation of the promoter, indicating a requirement of acute myelogenous leukemia-related factor(s) for this activity. Overexpression of c-Fos, c-Jun, osteoblast-specific factor-2, and core binding factor-β increased the response to parathyroid hormone of the wild type (−148) promoter but not with mutation of either or both the activator protein-1 and runt domain binding sites. In summary, we conclude that there is a cooperative interaction of acute myelogenous leukemia/polyomavirus enhancer-binding protein-2-related factor(s) binding to the runt domain binding site with members of the activator protein-1 transcription factor family binding to the activator protein-1 site in the rat collagenase-3 gene in response to parathyroid hormone in osteoblastic cells.


The objective of this article is to present a methodology for the evaluation of uncertainties in the results of calibration by comparison, based on the implementation of the concept of traceability and on the use of weighted least squares fitting. The general case, where the measuring equipment is tested against a standard of higher metrological quality at several points on a range, is considered. The proposed methodology deals with not only the experimental data in each calibration point but also their quality. The fact that both the outputs of the reference standard and the indications of the device under calibration are characterized by their own uncertainty is also taken into account. In this way calibration leads not only to determination of the coefficients of the calibration curve, but also to estimation of their uncertainties. This is particularly useful when a statement of uncertainty which concerns a range of values rather than a single result is required.


A great deal of Law & Economics scholarship focuses on the economic efficiency of a legal doctrine, judicial decision, statute, regulation, or proposed change in the law. This Article argues that virtually all such research is flawed (1) by its failure to consider the impact of the "law" it is analyzing on many of the categories of economic inefficiency whose magnitudes the "law" affects and (2) by its assumption that any "law" that reduces the number or magnitude of the (Pareto) imperfections in the economy (types of imperfections one of whose exemplars would cause economic inefficiency if it were the only imperfection in the system) will increase economic efficiency on that account. This Article explains that this assumption is wrong because it ignores the central lesson of The General Theory of Second Best: since in general any such individual imperfection will be as likely to counteract as to compound the net tendency of the other imperfections in the system to cause economic inefficiency, unless one can make a complicated argument to the contrary that focuses on the different ways in which an economy's Pareto imperfections interact to cause various categories of economic inefficiency and the incidence of all types of Pareto imperfections in the economy, one must assume that laws that reduce the Pareto-imperfectness of the economy without rendering the economy Pareto-perfect will have no tendency to increase economic efficiency on that account. More positively, the Article outlines and attempts to justify a protocol for economic-efficiency prediction or postdiction that responds economically efficiently to both The General Theory of Second Best and the reality that research is always allocative-costly and its conclusions are almost-always imperfect. The Article also contains a coda that explains why, contrary to the belief of most economists, policies that reduce poverty and/or income-wealth inequality will tend to increase economic efficiency on that account.


We have proposed a novel method to calibrate a vector network analyzer (VNA) using only Short-Open-Load (SOL) standards without Thru (T) procedure in a full 2-port calibration, which is especially suitable for reciprocal antenna measurements because of the easiness of its procedure, and have shown that the systematic uncertainty is almost the same as that of the SOLT calibration method. In this paper, we show that there is the similar condition on the signal to noise ratio (SNR) for the calibration methods. Therefore, it is proved that the method is simpler than the SOLT calibration method with equivalent effectiveness.


Introduction : With introducing composite teeth, their wear resistance has been well investigated, but there are few papers about their bonding to acrylic denture base resins. The aim of this study was to compare the four pre-bonding preparation methods on the ridge lap surface of one multilithic denture tooth by determining its bond strength to denture base resin. Materials and Methods : In this experimental laboratory study, 84 maxillary anterior teeth were divided into four groups based on four different pre-bonding methods (untreated, grinding, 2 retention grooves and diatorics). The teeth were mounted on 2 sides of triangular shaped wax models. Then, the laboratory procedures (wax elimination and resin packing) were done. Each of the specimens was tested by universal testing machine with cross head speed of 5 mm/min. The data were analyzed by Kruskal-Wallis and Mann- Whitney tests. Results : The mean bond strength in untreated group was 287.38 ± 51.82 N, in grinding group was 301.52 ± 113.65 N, in retention grooves group was 374.38 ± 88.22 N and in diatorics group was 415.19 ± 226.37 N. The highest mean bond strength was seen in diatorics group (P=0.009). The percentage of cohesive fractures in this group (90.5%) was significantly more than that in other groups (P Conclusion : The results of this study showed that creating retention hole in the ridge lap surface of the multilithic tooth can increase its bond strength with denture base resin. Keywords : Acrylic resins, Composite dental resin, Denture bases


In the field of communication, researchers are primarily interested in finding out about people's choices of media such as television, newspapers, magazines, online news, etc. Perceptions of the reliability and trustworthiness may be significantly affected by the selection of information sources and credibility can be suggested as one of the factors driving the traffic of individuals to certain media. The concept of credibility is not new and has been studied in the ancient Greece – how the speakers persuade audience members. However, studies of the credibility of mass media began interesting in times when the rising number of people started turning to radio for news instead of newspapers. Another change was brought by television and in the last decade of the 20th century, rise of the Internet has led to recent credibility studies comparing traditional sources with this emerging medium. The purpose of this paper is to examine the differences in advertising credibility perception across different media channels – television, newspapers and the Internet and determine if the medium of delivery has an impact on credibility assessment of advertising. The results showed overall moderate credibility of all the media but newspapers have shown the highest overall credibility, followed by the Internet and television, respectively. Advertising credibility was higher in traditional media than in the Internet. Negative attitudes were the highest in the online channels and the most credible advertising channel was the television. The results indicated there is no relationship between the medium credibility and credibility of advertising. Communication to audiences requires an exploration of trustworthiness in order to formulate correct strategies. By recognizing the credibility of the advertisements and the media in which they are placed, the findings can be considered for attracting audiences. Keywords : Advertising, credibility, media.


Little is known about the underlying mechanisms governing the bioaccumulation of uranium (U) in aquatic insects. We experimentally parameterized conditional rate constants for aqueous U uptake, dietary U uptake, and U elimination for the aquatic baetid mayfly Neocloeon triangulifer. Results showed that this species accumulates U from both the surrounding water and diet, with waterborne uptake prevailing. Elevated dietary U concentrations decreased feeding rates, presumably by altering food palatability or impairing the mayfly's digestive processes, or both. Nearly 90% of the accumulated U was eliminated within 24 h after the waterborne exposure ceased, reflecting the desorption of weakly bound U from the insect's integument. To examine whether the experimentally derived rate constants for N. triangulifer could be generalized to baetid mayflies, mayfly U concentrations were predicted using the water chemistry and U measured in periphyton from springs in Grand Canyon (United States) and were compared to U concentrations in spring-dwelling mayflies. Predicted and observed mayfly U concentrations were in good agreement. Under the modeled site-specific conditions, waterborne U uptake accounted for 52-93% of the bioaccumulated U. U accumulation was limited in these wild populations due to a combination of factors including low concentrations of bioavailable dissolved U species, slow U uptake rates from food, and fast U elimination.


The recent sequencing of the first tree genome, that of the black cottonwood (Populus trichocarpa), opens a new chapter in tree functional genomics. While the completion of the genome is a milestone, mobilizing this significant resource for better understanding the growth and development of woody perennials will be an even greater undertaking in the years to come. In other model organisms, a critical tool for high-throughput analysis of gene function has been the generation of large mutagenized populations. Some mutagenesis technologies and approaches cannot be applied to trees because of their typically outcrossing breeding systems, high heterozygosity, large body size, and delayed flowering. In contrast, gene-tagging approaches that use insertional mutagenesis to create dominant phenotypes are ideally suited for trees and, especially, Populus. Both activation tagging and enhancer trap programs have been successful in identifying new genes important to tree development. The generation of genomewide insertional mutant populations, which provide direct functional links between genes and phenotypes, should help to integrate in silico analyses of gene and protein expression, association studies of natural genetic polymorphism, and phenotypic analyses of adaptation and development.


Present day problems related to the sustainable and effective management of floods are seen to require a broad approach which should incorporate an integrated view of strategies, policies, plans, specific projects and other measures of social and institutional character. The selection and implementation of effective and optimised strategies and of their component actions are nowadays a common and important challenge in many regions, notably in developing countries, characterised by their expanding populations, growing needs and limitation of available resources. The paper is focused on one aspect of this complex: it attempts to highlight the need for an integration of structural and non-structural measures to achieve a successful solution of flood related problems. The selected examples illustrate different situations and contexts and put in evidence the need to match these measures along different phases of development and implementation of projects dealing with floods. The paper presents some conclusions as a contribution to orient further needed efforts in the continued search of the optimal balance between structural and non-structural measures to manage floods.


In this paper, an unscented Kalman filter (UKF)-based track fusion algorithm is developed for tracking targets in a nonlinear multisensor system. Employing the unscented Kalman filter and the measurements of the individual sensor in the multisensor system, the means and the variances of the states of a tracked target can be estimate. Based on these estimate results, an optimum state fusion scheme is obtained in terms of minimum mean square error (MMSE). The scheme can make the variance of the fused states smaller than that of the states estimated by UKF with any individual sensor in this multisensor system. Simulation results confirm the efficiency of the presented algorithm


Taming Alabama focuses on persons and groups who sought to bring about reforms in the political, legal, and social worlds of Alabama. Most of the subjects of these essays accepted the fundamental values of nineteenth and early twentieth century white southern society; and all believed, or came to believe, in the transforming power of law. As a starting point in creating the groundwork of genuine civility and progress in the state, these reformers insisted on equal treatment and due process in elections, allocation of resources, and legal proceedings. To an educator like Julia Tutwiler or a clergyman like James F. Smith, due process was a question of simple fairness or Christian principle. To lawyers like Benjamin F. Porter, Thomas Goode Jones, or Henry D. Clayton, devotion to due process was part of the true religion of the common law. To a former Populist radical like Joseph C. Manning, due process and a free ballot were requisites for the transformation of society.


Calibration experiments with a bimorph mirror are presented. Phase-diversity wave-front sensing is used for measuring the control matrix, nulling wave-front errors in the optical setup, including the mirror, and measuring Strehl ratios and residual higher-order aberrations. The Strehl ratio of the calibrated system is measured to be 0.975, corresponding to 1/40 wave rms in the residual wave front. The conclusion is that a phase-diversity wave-front sensor is easier to install and use than interferometers and can replace them in optical setups for testing adaptive optics systems.


Malignant melanoma is one of the deadliest forms of skin cancer that remains resistant to existing therapeutic strategies. According to the SEER (Surveillance, Epidemiology, and End Results) program database of the National Cancer Institute, the 5-year survival rate for metastatic melanoma is a dismal 16%. Further, of the seven most common cancers in the USA, melanoma is the only neoplasm with constantly increasing incidence. Therefore, it is important to intensify our efforts to better-understand the genetics and biology of melanoma. This may lead to development of novel targets and biomarkers for management of this hard-to-treat neoplasm. This study was undertaken to determine the role and potential significance of polo-like kinase 4 (PLK4) in human melanoma. PLK4 is a serine/threonine kinase that has been shown to localize to centrioles and regulate centriole duplication during the cell cycle. While the potential role of PLK4 in cancer is beginning to be appreciated, there are evidence for its function as a tumor suppressor as well as tumor promoter. However, the role of PLK4 in melanoma is not known. Here, we employed in vitro and ex vivo experiments to determine the role of PLK4 in melanoma. Our data demonstrated that PLK4 was significantly overexpressed, both at mRNA and protein levels in human melanoma cells viz. A375, Hs294T, G361, 451Lu; when compared to the normal human epidermal melanocytes (NHEM). We also found a significant increase in PLK4 immunostaining in clinical melanoma tissues, compared to normal skin and nevus tissues. Further, treatment of melanoma cells with a selective small molecule PLK4 inhibitor, centrinone-B, was found to cause a significant decrease in the cell growth/viability and clonogenic survival in multiple melanoma cell lines. The observed anti-proliferative effects of centrinone-B were found to be accompanied with i) a G0/G1 phase arrest of cell cycle, and ii) induction of apoptosis, in human melanoma cells. Taken together, our study suggests a pro-proliferative role of PLK4 in human melanoma. Additional studies are ongoing in our laboratory to determine the functional significance of PLK4 in melanoma. We suggest that PLK4 should be further evaluated as a potential 'druggable target' and biomarker, for the management of melanoma. Citation Format: Maria Shabbir, Minakshi Nihal, Chandra K. Singh, B Jack Longley, Nihal Ahmad. A pro-proliferative function of centriole duplication regulator, polo-like kinase-4 in human melanoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-102.


The majority of narratives assign death scenes a crucial role in the development of the plot and characters; yet despite its prominence, dying per se frequently remains untold, with works utilising first-person narrators or focalisers proving especially problematic. From a commonsensical point of view, the authors'reluctance at representing the moment of deathis justifiable since they do not possess any comparable experience. But the fact that all first-person descriptions of death are inauthentic does not mean that they cannot be subject to narrative representation. As it will be demonstrated through the discussion of some recent work in the field of 'unnatural narratology' and the cognitive sciences, it may be possible to create a valid and valuable narrative of death even from a first-person perspective.


Acute and subchronic toxicity experiments of tributyltin chloride (TBTCl) were conducted with the marine harpacticoid copepod Tigriopus japonicus. The 48-hr LC50 and highest non-lethal concentration (NOLC) for adult females were 0.96 and 0.14 μg/L, respectively, whereas these values for adult males were 0.58 and 0.07 μg/L, respectively. For the mean cumulative number of nauplii produced per female, the 14-day highest no observed effect concentration (NOEC), lowest observed effect concentration (LOEC) and EC50 were 0.025, 0.05 and 0.055 μg/L, respectively. The acute-subchronic ratio, i.e. the ratio of the 48-hr LC50 for adult females to the 14-day highest NOEC, MATC (maximum acceptable toxicant concentration) and LOEC, was 38.5, 27.2 and 19.3, respectively. These results suggest that the concentrations of current ambient TBT (tributyltin) compounds in Japanese coastal waters can be assumed as the safety range for the survival, but are unlikely to cause a reduction in the number of nauplii produced per female of T. japonicus. The high concentrations in seawaters, sediments and/or seawaters released from sediments that have been observed in estuarine and coastal waters in Japan may lead to a considerable reduction of survival and numbers of nauplii produced by females for T. japonicus.


I first discovered this book while browsing through the dermatology section of the local medical book store just before my dermatology boards. I was tired of studying facts and memorizing the dry Owens review notes and was looking for a new book to keep me going in the final weeks of board review. As a dermatologist, I have always loved a nice atlas; reading and perusing the pages is similar to attending a very large grand rounds with one interesting patient after another. The Color Atlas of the Hair, Scalp, and Nails is superb. Its pages are filled with 442 high-quality color photographs (257 of the hair and 185 of the nails). The photographs of the nails are somewhat superior to those of the hair, probably because the hair and scalp are more difficult to photograph. The emphasis of the text is on the photographic material, differential diagnoses, electron microscopy,


According to Brundtland Commission (1987), sustainability means the ability to meet the needs of the present without compromising the ability of future generations' abilities to meet their own needs. The term of sustainability has multi-dimensional objectives of social, environmental and economic. Without ignoring the importance of social, environmental, and economical aspects of sustainability, this study will only highlight some technical aspects for sustainable biodiesel production and, of course, the final goal will target the implication of improved social, environmental and economical conditions. Some technical aspects for sustainable biodiesel production cover the multi-discipline activities at the design stage and at the operation stage of biodiesel production plant. The design stage can be divided into conceptual design, basic engineering design and detailed engineering design. At this stage, the design parameters should consider the selection of the type and availability of raw material, biodiesel plant capacity and location, the efficient production process, the availability of utilities and supporting infrastructures, waste (environmental) treatment, and raw material and product handling facilities. And during the operation of biodiesel plant, some important technical issues are the production process activities according to the Standard Operating Procedure (SOP), awareness of safety and Hazard and Operability Study (HAZOP), scheduled maintenance activity, waste management, product quality control, and further, if possible, efficiency improvement in the production line through R&D activities and technological advances.


In the present short note, we attempt further validations and comparisons of a recent simple model for the estimate for adhesion between elastic (hard) rough solids with Gaussian multiple scales of roughness, BAM (Bearing Area Model) belonging to a DMT class of models. In one case, we use the GJP (Generalized Johnson Parameter) model, which is an empirical fit validated on the same (and so far most extensive) set of data on which BAM was validated, namely that of Pastewka and Robbins. In the second case, we compare with another approximate DMT theory, that of Persson and Scaraggi, which turns out extremely close to the BAM model, despite much more complex: GJP however can lead to significant discrepancies.


In a double-blind, crossover study conducted in ten hospitalised patients suffering from active rheumatoid arthritis, the anti-inflammatory effect of diclofenac sodium (Voltaren) in a daily dosage of 125 mg was compared with that of placebo under strictly standardised conditions. Changes in reversible articular swelling were determined by measuring the circumference of involved wrist, knee, metacarpophalangeal, interphalangeal, and metatarosphalangeal joints. A consistent decrease in joint swelling occurred in response to treatment with diclofenac sodium, as compared with a consistent increase following placebo medication. This difference was significant at the 5% level for all except the interphalangeal joints. Similarly, in response to diclofenac sodium a greater improvement was noted in duration of morning stiffness and grip strength and a greater reduction in the total number of painful and swollen joints. The status of the rheumatoid condition improved in nine patients following treatment with diclofenac sodium, but in none following placebo medication. Two patients reported unwanted effects, consisting of a sensation of fullness during treatment with diclofenac sodium in one case and of heartburn during both treatment periods in the other. No laboratory abnormalities were noted.


We report a compact and robust architecture of a versatile laser system that allows the implementation of several advanced atom interferometry techniques, such as Bragg diffraction, Bloch oscillations, or single and double Raman diffraction. A low noise, frequency tunable fiber-laser (λ = ~1560 nm) serves as the seed. A couple of fiber-coupled amplifiers followed by two fibered second-harmonic generators produce a pair of phase-locked, frequency-controllable laser beams at 780 nm. Manipulating frequencies of individual laser beams at λ = 1560 nm before the amplifiers, facilitates achieving a maximum relative detuning of ± 20 MHz, while maintaining a constant output power. We present the scheme to implement Raman spectroscopy using our laser system and discuss its advantages. Finally, the overall performance of the laser setup has been evaluated by realizing interferometers in copropagating Ramsey-Raman and counterpropagating Bragg configuration.


Taking the conception and model of the regional gravity center and adopts production value of population, GDP, industry, agriculture and the tertiary industry and data of expenditure in recent eleven years in every city, and figures out the coordinate of gravity center of each year. This paper calculates the population gravity center and the social economy gravity center yearly, figures out the dynamic evolvements of these two gravity centers and analyzes the dynamic change of the population and economy regional differences and their related causes and at the same time, makes a contrastive analysis of the dynamic evolvement tendencies of the two gravity centers. From the developing evolvement of gravity center we can draw a conclusion:(1) The population gravity center first slowly moves to southwest and relatively fast move to northeast after the year 2003 in recent eleven years. (2)There are significant regional differences in economic development and living standards.


The study was conducted in Mandya district of Karnataka state during 2012-13. Thirty beneficiaries formed the sample for the study. The data was collected by personal interview with the help of structured schedule which was developed keeping the objectives of the study. It was evident from the study that majority (60.00 %) of the beneficiaries were middle aged, belonged to other backward classes (53.33 %). It was found that there was a considerable proportion (40.00 %) of the female beneficiaries were working under the scheme. It was noticed that higher proportion (76.66%) of the beneficiaries had nuclear family. More than half (56.66 %) of respondents belonged to landless category and semi-medium income category (53.33 %). The study revealed that majority of the beneficiaries borrowed loans from non-formal institutions (90.00%). Television (70.00 %) formed the major asset among material possession in the present study.


In CKD, phosphate retention arising from diminished GFR is a key early step in a pathologic cascade leading to hyperthyroidism, metabolic bone disease, vascular calcification, and cardiovascular mortality. Tenapanor, a minimally systemically available inhibitor of the intestinal sodium-hydrogen exchanger 3, is being evaluated in clinical trials for its potential to (1) lower gastrointestinal sodium absorption, (2) improve fluid overload-related symptoms, such as hypertension and proteinuria, in patients with CKD, and (3) reduce interdialytic weight gain and intradialytic hypotension in ESRD. Here, we report the effects of tenapanor on dietary phosphorous absorption. Oral administration of tenapanor or other intestinal sodium-hydrogen exchanger 3 inhibitors increased fecal phosphorus, decreased urine phosphorus excretion, and reduced [(33)P]orthophosphate uptake in rats. In a rat model of CKD and vascular calcification, tenapanor reduced sodium and phosphorus absorption and significantly decreased ectopic calcification, serum creatinine and serum phosphorus levels, circulating phosphaturic hormone fibroblast growth factor-23 levels, and heart mass. These results indicate that tenapanor is an effective inhibitor of dietary phosphorus absorption and suggest a new approach to phosphate management in renal disease and associated mineral disorders.


A very stringent test of low-energy electron-atom collision theory is made in the most favorable energy regime for the close-coupling approximation. Data are presented as exchange asymmetries in angle-resolved elastic scattering of spin-polarized electrons from spin-polarized sodium atoms. Data are reported for two incident energies, 1.0 and 1.6 eV, both of which are below the first excited-state threshold. The angular range is 20--142.5{degree}. The close-coupling approximation is found to give excellent agreement with experiment at both energies.


Military training environments are rigorous, requiring service members to endure not only physical and psychological stress but also sleep deprivation, caloric restriction, and severe thermic challenges. The convention has been to use immunoendocrine responses induced by various exercise regimens to generalize results to the layered stress environments of wartime. The purpose of this study was to determine whether exercise models are accurate representations of the physiologic response to the stress experienced in an operational environment. To achieve this aim we identified changes in T cell proliferative capacity (costimulation through CD3+CD28 or stimulation with PHA) and relevant immunoendocrine interactions following an environment comparable to that experienced in Basic Combat Training. An increased proliferation response was observed post-exercise in T cells isolated from whole blood in the layered stress group with those increases still significant at 6 h post-exercise. In contrast, the moderate exercise group saw no significant changes in proliferative ability immediately after exercise exhibiting what could be expressed as a characteristic exercise response. Analyses of serum stress hormones, immunomodulatory cytokines, and immunoglobulins -G, -M, and -A failed to reveal any correlated variations that could clarify the T cell findings. These data suggest that exposure to a high stress environment leads to increased T cell proliferation that appears to be independent of changes in stress hormone concentrations and immunomodulatory cytokines. We submit that variations in exercise intensity and duration do not necessarily approximate military operational or tactical stress responses.


Abstract Deep caries progress is associated with tertiary dentin formation and additional reversible or irreversible dental pulp inflammation. It seems that some particular signs of pain in irreversible pulpitis are associated to a particular caries microflora. Streptococcus species, Parvimonas micra and Dialister invisus are prevailing in cases of throbbing pain while Streptococcus mutans is incriminated in sensitivity to vertical percussion of tooth. Continuous pain is thought to be the clinical outcome of Lactobacillus implication. A better understanding of molecular signals and mechanisms induced by microbiome of deep caries that orchestrate the modulation of dental pulp complex response toward tertiary dentinogenesis or pulp inflammation it is supposed to improve diagnosis and conservative therapies of vital pulp.


Can I be free to perform an action if God has decided to ensure that I do not choose that action? I show that Molinists and simple foreknowledge theorists are committed to answering in the affirmative. This is problematic for their status as theological incompatibilists. I suggest that strategies for preserving their theological incompatibilism in light of this result should be based on sourcehood. However, the path is not easy here either, since Leibniz has shown how theological determinists can offer an extremely robust form of sourcehood. Proponents of these views must identify a valuable form of sourcehood their theories allow that Leibniz's


Abstract:La Salada is a massive informal market complex located just outside the limits of the Autonomous City of Buenos Aires. It has existed since the early 1990s, and in recent years it has become a strategically important site for studying the economic and political transformations not just of Argentina, but of the globalized world. This essay synthesizes and critiques existing perspectives on La Salada, focusing in particular on the political composition of the market complex. If the Argentine media has highlighted the mafiaesque rule of La Salada by a handful of powerful administrators, a series of critical works have unearthed significant democratic forms, such as open stallholder assemblies, at the base of the market's internal politics. This essay argues that, while these works have compellingly critiqued the media's perspective, they have not sufficiently addressed the interplay between democratic practices and the vertical hierarchies of power that emerge in La Salada's three-decade history. It studies Julián D'Angiolillo's 2010 documentary Hacerme feriante to show how, by bracketing the media's perspective, critical works reveal democratic tendencies at La Salada. It then turns to Sebastián Hacher's 2011 urban chronicle Sangre salada, which is unique among critical works due to its emphasis on real estate and the conquest of the patchwork of territories that make up La Salada. This focus on real estate allows for a nuanced understanding of how hierarchies of power emerge in the market's history, constituting a powerful counterforce to the democratic tendencies privileged in other critical works. This essay ultimately proposes that La Salada's political composition can be understood in terms of the Aymara notion of ch'ixi, which Bolivian scholar Silvia Rivera Cusicanqui introduces to grasp complex historical realities without synthesizing opposed terms (as in theories of mestizaje or hybridity), but rather preserving their radical heterogeneity.


Application of thermo-responsive gels as soft actuators for microfluidic devices with repeating "open–close" cycles requires high rates of water transport driven by changes in temperature. These rates are conventionally evaluated by comparison of water retention curves in T-jump tests with fixed initial and final temperatures. A shortcoming of this method is that it does not allow changes in diffusivity with temperature to be assessed quantitatively. To characterize cooperative diffusivity of water molecules, we propose a novel approach based on modeling the responses of temperature-sensitive gels in equilibrium swelling tests and T-jump experiments. Analysis of observations on poly(N-isopropylacrylamide) gels synthesized in aqueous solutions of pore-forming agents reveals that formation of a macroporous structure in a gel is a necessary, but not sufficient condition for acceleration of water transport. The effect of cosolvents used under preparation (phenol, ethanol, methanol, diethyl ether, dioxane, sucrose, and dodecyl dimethyl benzyl ammonium bromide) on water diffusivity is studied in detail. It is shown that the most pronounced enhancement of diffusivities under deswelling and reswelling is reached when the gels are synthesized in aqueous solutions of the surfactant at subzero temperatures. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 46353.


The cJun NH2‐terminal kinase (JNK) signaling pathway is implicated in the pathogenesis of diabetes. High fat diet‐induced obesity causes activation of JNK in insulin target tissues. JNK‐deficient mice are resistant to the effects of feeding a high fat diet, including protection against insulin resistance and failure of obesity development. We have used tissue‐specific JNK‐deficient mice to probe the mechanism of JNK regulation of insulin resistance and obesity. We show that JNK plays different roles in multiple tissues and that the phenotype of whole body JNK‐deficient mice reflects the interactions between these different JNK‐dependent processes. The molecular mechanisms of JNK function will be discussed.


Many consumer goods are complicated enough to benefit from programmed control. Today's home electronics devices support a wide range of options and controls. At the same time, personal digital assistants and programmable remote controls are now capable of learning and generating control sequences to control a wide range of devices. Unfortunately, most device interfaces are designed for interactive human control rather than programmed control. The paper analyzes state-based obstacles to programming devices designed for interactive human control. It develops a theory of statelock, a condition in which a control program is unable to synchronize with the state machine underlying the controlled device. The paper also presents design strategies to avoid statelock and applies these strategies to the home audio/video and telephone autodialer domains. >


The chapter looks at the clash between international investment agreements (IIAs) and protection of the environment. International investment law has revealed all its potentialities – and its negative impacts – through many investment arbitrations related to host State's environmental regulations. The chapter details the terms of the tension between investment and environment and drafts some propositions to reconcile the two. Therefore, it analyses the main types of environmental provisions in IIAs and proposes to go further in the greenization of IIAs, with propositions turned on the investor's responsibility. Another section examines the articulation between the substantive protection standards in IIAs and the right to regulate of the host State in the field of environment. Finally, it is examined if investor-State dispute settlement mechanisms are suitable to settle environmental-related disputes.


The Victorian fascination with the influence of technology on human vision led to a proliferation of replications of its effects in all manner of media, including novel writing. Like the kaleidoscope that holds the viewer in thrall, M. E. Braddon's sensation novel Eleanor's Victory, as this reviewer describes, holds a certain "power" over the reader that forces her to listen to, if not accept, the arguments Braddon posits in her work. "Power" is at issue in other ways in Braddon's work as her heroines continually seek ways of developing agency by shaping sexual identities that press the limits of the norm of the bourgeois family unit. What is also significant here is the appropriateness of the kaleidoscope as a metaphor for Braddon's writing, a metaphor she used personally in describing her work in an unpublished letter: "I will give the kaleidoscope another turn, and will do my best with the old bits of glass and pins and rubbish" (letter to Edmund Yates, qtd. in Maxwell 150). The kaleidoscope fractures the vision of a single object or scene into a multitude of different but interrelated forms of the same. One of the prominent issues Braddon repeatedly addresses in her work is the construction of multiple forms of sexuality. The fracturing or multiplying effect of the kaleidoscope resembles the isolation and reduction of different forms of sexuality as described by Foucault in The History of Sexuality.


We present a second epoch of Chandra observations of the Type Ia Large Magellanic Cloud supernova remnant (SNR) 0509-68.7 (N103B) obtained in 2017. When combined with the earlier observations from 1999, we have a 17.4 year baseline with which we can search for evidence of the remnant's expansion. Although the lack of strong point source detections makes absolute image alignment at the necessary accuracy impossible, we can measure the change in the diameter and the area of the remnant, and find that it has expanded by an average velocity of 4170 (2860, 5450) km s−1. This supports the picture of this being a young remnant; this expansion velocity corresponds to an undecelerated age of 850 years, making the real age somewhat younger, consistent with results from light echo studies. Previous infrared observations have revealed high densities in the western half of the remnant, likely from circumstellar material, so it is probable that the real expansion velocity is lower on that side of the remnant and higher on the eastern side. A similar scenario is seen in Kepler's SNR. N103B joins the rare class of Magellanic Cloud SNRs with measured proper motions.


This chapter focuses on the murabaha structure, which is probably the most commonly used Islamic finance structure in modern Islamic banking. The simplicity of structure in its current application has promoted its use as a popular and flexible Islamic financing instrument. Indeed, the use of the murabaha has been extended beyond a widespread application as a standalone instrument to a composite component of Sukuk issuance in modern application. The murabaha contract is understood within the Islamic tradition to have a pre-Islamic origin evidenced in pre-Islamic literature and characterized as a fiduciary contract with the objective to assist less knowledgeable buyers in the determination of the fair price of unfamiliar goods. Today, murabaha is commonly used as a mode of finance, in its variant structures, for the acquisition of assets, commodities, and goods in the ordinary course of trade. The structure is also used as a corporate finance tool for working capital and liquidity management. The chapter then considers commodity murabaha (tawarruq) and its application.


Here, we report the design and synthesis of a redox-active multifunctional ionic porous organic polymer iPOP-Bpy with exchangeable Br- ions, incorporating viologen as a redox-active building block. The material shows not only excellent iodine uptake capacity in the vapor phase (540 wt %) but also in the organic (1009.77 mg g-1) and aqueous phases (3921.47 mg g-1) with very fast adsorption kinetics in all cases. The material also shows its utility in being used as a solid-state NH3 vapor sensor as it shows very fast color switching in the presence of NH3 vapor. Furthermore, the material found application as a p-type complementary electrochromic electrode and was fabricated into a bilayer device. Excellent coloration efficiency, high switching speed, and good color contrast were obtained as investigated using bias-dependent optical and spectroelectrochemical studies, paving the way for fabricating power-efficient solid-state electrochromic devices.


In hip-hop dance contests, a procedure for evaluating performances has not been clearly defined, and objective criteria for evaluation are necessary. It is assumed that most hip-hop dance techniques have common motion characteristics by which judges determine the dancer's skill level. This study aimed to extract motion characteristics that may be linked to higher evaluations by judges. Ten expert and 12 nonexpert dancers performed basic rhythmic movements at a rate of 100 beats per minute. Their movements were captured using a motion capture system, and eight judges evaluated the performances. Four kinematic parameters, including the amplitude of the body motions and the phase delay, which indicates the phase difference between two joint angles, were calculated. The two groups showed no significant differences in terms of the amplitudes of the body motions. In contrast, the phase delay between the head motion and the other body parts' motions of expert dancers who received higher scores from the judges, which was approximately a quarter cycle, produced a loop-shaped motion of the head. It is suggested that this slight phase delay was related to the judges' evaluations and that these findings may help in constructing an objective evaluation system.


Previous studies on spatial memory reveal that people represent spatial information in 3 different forms: landmark, route, and survey. The aim of this work was to assess spatial abilities in order to predict a person's cognitive style. In order to do this we used 9 different spatial tasks, which were linked with these 3 forms of spatial representations. We found that the 9 spatial tasks are able to distinguish different levels of spatial ability.


Recent studies suggest a high volume of sedentary behavior may be a risk factor for adverse health outcomes.1 However, few data exist on how this behavior is patterned (eg, does most sedentary behavior occur in a few long bouts or in many short bouts?) and whether sedentary patterns are relevant for health. We examined details of sedentary behavior among older women. Because physical activity is influenced by age, body mass index (BMI; calculated as weight in kilograms divided by height in meters squared), and smoking status, we further examined sedentary behavior in relation to these characteristics.


I. INTRODUCTION- ISOLATING MIRANDA'S IMPORTLargely as a consequence of American television and movies, Miranda v. Arizona1 may well be the most famous appellate case in the world. On the screen, innumerable actors playing American police officers give Miranda warnings to other actors playing suspects, a portrayal that reflects the reality of genuine police officers giving genuine Miranda warnings to genuine suspects millions of times every year. Indeed, such has been the influence of Miranda that Russian television cops give something like a Miranda warning to suspects even though no actual Russian law imposes such an obligation on real Russian cops.2 And it is said that in countries where no such right actually exists, suspects have still been known, when arrested, to demand their Miranda rights.3Among the most interesting dimensions of Miranda's worldwide fame is that the case's prominence is largely a function of the warning itself.4 Television and motion pictures feature Miranda warnings not because of any suspected viewer interest in whether suspects actually have a right to remain silent,5 nor on account of the underlying substance of the right to have a lawyer during interrogation,6 nor because the general public is concerned about the right to appointed counsel for the indigent.7 None of this, to put it mildly, makes for good theater. What is good theater is the ritual of the arrest, and the Miranda warning, typically given in almost exactly the terms set forth in the Supreme Court's opinion, is a prominent feature of the ritual, even apart from the role that the warning is actually designed to serve.Professor Kamisar - with his characteristic attention to detail in support of spirited argument - provides an insightful judicial and political history of the retrenching that has marked much of Miranda's history since the Supreme Court's decision in 1966.8 In lamenting Miranda's erosion, I largely sympathize with Kamisar. But if there is a worry about the erosion of Miranda,9 it must be a worry not about the erosion of the right to remain silent itself, which existed independent of Miranda,10 nor about the right to counsel during interrogation, whose recognition and enforcement again preceded Miranda. u Instead, it must be a worry about the requirement that the police provide a warning in a certain way under certain conditions.12 Once we understand the import of various pre-Miranda decisions, we can appreciate that Miranda is about the warning itself, rather than about what the warning is a warning of. And when we understand Miranda in this way, we can focus on just what role the warning is designed to serve, and what the Court in Miranda thought it was doing in specifying almost exactly the form that the warning was to take. It is precisely this focus that will be the subject of my attention in this Response.In being about a warning, Miranda is about communication. Specifically, it is about two different dimensions of communication. One of these is the substance of Miranda's holding, which is that police officers are required - on pain of inadmissibility of the evidence obtained absent a communication - to communicate to suspects under certain conditions their right to remain silent, to have a lawyer present for the interrogation, and to appointed counsel if they are indigent.13 And the other communicative dimension of Miranda is the way in which the Supreme Court communicated its requirements to police officers - the primary subjects of the ruling - in extraordinarily clear and rule-like terms. I will consider these two communicative dimensions in turn.II. MIRANDA AS RULEEven before Miranda, involuntary confessions were plainly understood to violate the Fifth Amendment's prohibition on compelled self-incrimination and the Fourteenth Amendment's guaranty of due process.14 And even before Miranda, and still, suspects were and remain permitted to waive their privilege against self-incrimination. …


This paper presents an adaptive-speed/CAV algorithm which regulates the disc velocity in a CD-ROM system to accomplish high data throughput (bit rate) during continuous playback and low power consumption during continuous data access. The adaptive-speed profile is based upon quasi-CLV control which allows drive optimisation towards both data throughput and access time. The presented algorithm can automatically distinguish between two operating modes-continuous access and continuous playback. By detecting the state of continuous access, the CD-ROM drive switches its spindle-motor loop into a constant angular velocity (CAV) mode, avoiding therefore the acceleration/braking of the motor, and thus reducing the power consumption. By detecting the state of continuous playback, the spindle motor will be set to follow an adaptive-speed profile which is highly optimized for data transfer rate. The software and hardware implementation of the CAV/quasi-CLV switching technique in a CD-ROM system is also described.


Purpose: Receptor conversion for estrogen receptor alpha (ERα), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) in single distant breast cancer metastases has been described before. However, most patients develop multiple metastases. Heterogeneity in receptor status between different metastases of the same patient has not been studied, probably since such material is very rare. The consequence of such heterogeneity would mean that as many metastases as possible need to be biopsied to re-assess receptor status. We therefore aimed to study heterogeneity of receptor status between different distant metastases of the same patient in a relatively large group by re-staining all primary tumors and metastases with current optimal immunohistochemical methods on full sections. Material and methods: Formalin fixed paraffin embedded tissue of primary breast carcinomas and corresponding multiple (≥2) distant metastases from 38 female patients were collected from several pathology departments in The Netherlands and stained for ERα, PR and HER2 by IHC. We evaluated the heterogeneity of receptor status between the metastases and the correlation with the primary tumor. Results: In the 4 cases that showed ER conversion, 2 (50%) showed heterogeneity in receptor expression between different metastases of the same patient. Of the 17 cases that showed PR conversion, 12 cases (71%) showed heterogeneity in expression between metastases. There were no changes in the receptor profile of primary breast cancer to their metastases for HER2 in this group. Conclusion: In a significant number of metastatic breast cancer patients, there is heterogeneity in ER and PR receptor status between different breast cancer metastases of the same patient. This implies that as many metastases as possible need to be biopsied to re-assess receptor status and set the optimal indication for hormonal therapy in these patients. Alternatively, non-invasive assessment of the receptor status by molecular imaging may be an easier future way to assess receptor status of all metastatic lesions. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-05-08.


Abstract This paper investigates the response of stock prices to dividend shocks in a bivariate model of stock prices and price-dividend spreads. Dividend process is modeled as the sum of a permanent component and a temporary component. By using the stock price valuation (present value) model, the two components are related to stock prices. The stock market responds significantly not only to permanent shocks to dividends, but also to temporary shocks to dividends. Furthermore, initial responses of stock prices to the temporary shocks are as strong as those to the permanent shocks. As a result, substantial variation in stock prices is due to the temporary shocks. This finding provides empirical support for the imperfect information hypothesis that emphasizes the failure of investors to clearly distinguish between the two components of dividends, and also suggests that the observed mean-reverting behavior of stock returns should be explained by incorporating a significant temporary component into stockprices. The price-dividend spreads are primarily accounted for by the temporary shocks to dividends, and respond strongly to them, suggesting that, in response to the temporary shocks to dividends, stock prices respond excessively relative to dividends.


Possible improvement in the nutritional composition of rice husk (RH) was attempted through Solid State Fermentation with the use of the fungus, Trichoderma viridii. A comparative utilization of the fermented RH (FRH), raw RH and a control diet was studied using parameters like performance and nutrient utilization alongside some economic indicators to arrive at conclusion that isonitrogenous diets were produced using graded levels of RH (5.0, 75 and 10%) of both raw and the fermented which were compared to a control diet. The process of fermentation resulted in improvement in the crude protein value of RH by 97% and reduction in the crude fibre composition by 45%. Probably as a result of the fermentation process, fishes fed FRH had better Food Conversion Ratio (FCR), Protein Efficiency Ratio (PER) and Specific Growth Rate (SGR) than their counterparts fed raw RH. The Feed Intake (FI), Feed Conversion Ratio (FCR) and Protein Intake (PI) increased as level of inclusion of the RH increases. The same observation is equally true for the Profit Index, Benefit Cost Ratio and the Incidence Cost.


The stars 51 Pegasi and τ Bootis show radial velocity variations that have been interpreted as resulting from companions with roughly Jovian mass and orbital periods of a few days. Gray and Gray & Hatzes reported that the radial velocity signal of 51 Peg is synchronous with variations in the shape of the line λ6253 Fe I; thus, they argue that the velocity signal arises not from a companion of planetary mass but from dynamic processes in the atmosphere of the star, possibly nonradial pulsations. Here we seek confirming evidence for line shape or strength variations in both 51 Peg and τ Boo, using R = 50,000 observations taken with the Advanced Fiber Optic Echelle. Because of our relatively low spectral resolution, we compare our observations with Gray's line bisector data by fitting observed line profiles to an expansion in terms of orthogonal (Hermite) functions. To obtain an accurate comparison, we model the emergent line profiles from rotating and pulsating stars, taking the instrumental point-spread function into account. We describe this modeling process in detail. We find no evidence for line profile or strength variations at the radial velocity period in either 51 Peg or in τ Boo. For 51 Peg, our upper limit for line shape variations with 4.23 day periodicity is small enough to exclude with 10 σ confidence the bisector curvature signal reported by Gray & Hatzes; the bisector span and relative line depth signals reported by Gray are also not seen, but in this case with marginal (2 σ) confidence. We cannot, however, exclude pulsations as the source of 51 Peg's radial velocity variation because our models imply that line shape variations associated with pulsations should be much smaller than those computed by Gray & Hatzes; these smaller signals are below the detection limits both for Gray & Hatzes's data and for our own. τ Boo's large radial velocity amplitude and v sin i make it easier to test for pulsations in this star. Again we find no evidence for periodic line shape changes, at a level that rules out pulsations as the source of the radial velocity variability. We conclude that the planet hypothesis remains the most likely explanation for the existing data.


Ubiquitous hydrogeological uncertainty undermines the veracity of quantitative predictions of soil and groundwater contamination due to accidental hydrocarbon spills from onshore pipelines. Such predictions, therefore, must be accompanied by quantification of predictive uncertainty, especially when they are used for environmental risk assessment. We quantify the impact of parametric uncertainty on quantitative forecasting of temporal evolution of two key risk indices, volumes of unsaturated and saturated soil contaminated by a surface spill of light nonaqueous‐phase liquids. This is accomplished by treating the relevant uncertain parameters as random variables and deploying two alternative probabilistic models to estimate their effect on predictive uncertainty. A physics‐based model is solved with a stochastic collocation method and is supplemented by a global sensitivity analysis. A second model represents the quantities of interest as polynomials of random inputs and has a virtually negligible computational cost, which enables one to explore any number of risk‐related contamination scenarios. For a typical oil‐spill scenario, our method can be used to identify key flow and transport parameters affecting the risk indices, to elucidate texture‐dependent behavior of different soils, and to evaluate, with a degree of confidence specified by the decision‐maker, the extent of contamination and the correspondent remediation costs.


We study the properties of a spin-polarized Fermi gas in a harmonic trap, using the semiclassical (Thomas-Fermi) approximation. Universal forms for the spatial and momentum distributions are calculated, and the results compared with the corresponding properties of a dilute Bose gas.


Abstract : When a distributed systems protocol is used in a particular context as part of a solution to a larger problem, additional information may be generated from the context. Such information may be used for optimization of the system, and, in the case of security protocols, may be of use to the adversary for attacks. The project conducted a case study of the application of the epistemic model checker MCK to automatically detect such optimization opportunities, and to verify that the protocol remains secure in the mode of use. The particular protocol studied was Chaum's Dining Cryptographers protocol, a security protocol that allows a single agent to anonymously transmit a signal. The context of use considered was a more general 2-phase protocol for anonymous broadcast by an arbitrary number of agents, also proposed by Chaum. The aims of the 2-phase anonymous broadcast protocol were formulated as a knowledge-based program, and an iterative process of model checking and manual counter-example guided refinement was followed to converge on implementations of this knowledge-based program in which local predicates were identified that correspond precisely to the knowledge conditions in the knowledge-based program. This analysis demonstrated that the 2-phase protocol contains some quite subtle flows of information that can be used to optimize its performance, but no violation of the anonymity property was found. As an additional contribution of the research, a formal abstraction technique was developed, and proved correct, for epistemic model checking of protocols that call the Dining Cryptographers protocol as a subroutine. Experimental results show that the optimization improves epistemic model checking performance by orders of magnitude and enables problems of larger scale to be attacked.


1 . The ganglion blocking agents, chlorisondamine, pentamethonium, mecamylamine, decamethonium and hexamethonium all block nicotine extensor convulsions when administered intraventricularly in mice. Tetraethylammonium was inactive. 2 . For the intraventricular route, there is a relationship between ganglionic blocking potency and blocking of nicotine extensor convulsions. Indirect evidence suggests that the site(s) of action of nicotine extensor convulsions and lethality is central in origin and associated with brain areas near the ventricles. 3 . When ganglion blocking agents are given orally, subcutaneously or intravenously varying degrees of protection can be observed probably depending on factors such as whether or not the drugs cross the blood‐brain barrier, absorption, etc., and the effectiveness in protecting mice from nicotine is not related to ganglionic blocking potency. 4 . Atropine and morphine given intraventricularly or subcutaneously did not protect mice from the LD95 of nicotine. Chlorpromazine gave very erratic results and phenobarbitone was effective subcutaneously and to a lesser extent intraventricularly.


Abstract In this paper the usability check and the seismic vulnerability appraisement of a masonry building with cultural and artistic value located in the Municipality of Cento, Ferrara, Italy after the last Italian seismic event (Emilia-Romagna, 2012 May 20 th and 29 th ), are reported and discussed. After presenting some details of these earthquakes, a case study is presented and useful information on both the historical and geometrical properties have been given. Later, the usability check of the cultural heritage building examined has been completed with the identification of damage that occurred under earthquake. Finally, the seismic vulnerability assessment of the building on the basis of the simplified LV1 approach given by the Italian Guidelines on Cultural Heritage has been performed. The analysis results have shown that building has an average vulnerability degree, so as to require local repair and strengthening intervention, which have been presented in the paper. Keywords:


Objective: The main objective of the work was to analyze the competitiveness of avocados produced in Mexico during the study period from 1995 to 2019 in the world market, derived from the production surplus.
Design/Methodology/Approach: The methodological design contemplated the use of trade competitiveness indicators at the level of importing world markets, the Revealed Comparative Advantage Index and the Normalized Revealed Comparative Advantage Index were calculated, data on avocado exports were analyzed as well as total agricultural exports made by Mexico to the world, and specifically to countries such as the United States, Canada and Japan.
Results: The results obtained suggest that avocado production in Mexico is highly competitive at the international level.
Study Limitations/Implications: The importance of making an analysis of the main avocado production variables was to locate the situation of products coming from Mexico with respect to the world situation.
Findings/Conclusions: Internationally, Mexican avocado production stood out in first place, with 2.4 million tons and 1.3 million tons of avocado were destined for export in 2019, contributing more than 45% of the world export market. These exports represented a very significant percentage of avocado imports in countries such as the United States of America, Canada, Japan, Europe and Central America. Currently, 100% of the national requirements are satisfied with domestic production; likewise, world imports have increased 171.97% in the last decade.


Molecular chaperones are a diverse group of proteins that interact with partially folded protein states to stabilize and prevent their mutual (illicit) association. Proteins require involvement with molecular chaperones throughout their lifespan: from their synthesis and folding through intracellular transport, membrane translocation, and to their ultimate degradation. Small heat-shock proteins (sHsps) are a ubiquitous family of molecular chaperones that are found in all organisms. Unlike many of the well-characterized chaperones, for example from the Hsp60 and Hsp70 families, sHsps are not involved in regulating protein folding. Instead, under conditions of cellular stress, such as elevated temperatures, they interact and stabilize partially folded target proteins to prevent their aggregation and precipitation. Because of this ability, their expression is elevated in many protein diseases that are characterized by protein aggregation and precipitation, including Alzheimer's, Creutzfeldt–Jakob, and Parkinson's diseases. The principal lens protein, α-crystallin, is a sHsp. Its chaperone ability is important in preventing lens protein precipitation and hence in maintaining lens transparency. This review summarizes the salient structural features of sHsps that enable them to act as highly efficient chaperones to prevent protein precipitation under stress conditions. The mechanism of chaperone action and the state of the target protein when interacting with sHsps are also discussed. Finally, diseases in which sHsp expression is elevated are discussed including the potential roles of sHsps and their therapeutic uses in the treatment of these diseases.


A highly birefringent silicate glass photonic-crystal fiber (PCF) is employed for polarization-controlled nonlinear-optical frequency conversion of femtosecond Cr: forsterite laser pulses with a central wavelength of 1.24 mum to the 530--720-nm wavelength range through soliton dispersion-wave emission. The fiber exhibits a modal birefringence of 1.2.10(-3) at the wavelength of 1.24 mum due to a strong form anisotropy of its core, allowing polarization switching of the central wavelength of its blue-shifted output by 75 nm. Polarization properties and the beam quality of the blue-shifted PCF output are shown to be ideally suited for polarization-sensitive nonlinear Raman microspectroscopy.


The incidence of brain abscess remains high, despite the development of novel antibiotics. Vancomycin or carbapenems, which are third-generation cephems, are recommended as standard therapy for bacterial meningitis or brain abscess. The effectiveness of the high-dose meropenem therapy on brain abscess has occasionally been reported. We experienced 2 consecutive cases of brain abscess in adults. The first patient was a 67-year-old man with diplopia, dizziness, and dysesthesia on the left upper and lower extremities. Images of T1-weighted magnetic resonance imaging (MRI) with contrast medium and diffusion-weighted MRI showed a ring enhancing cystic lesion and a high intensity lesion, respectively, in the right pons. The second patient was a 37-year-old man who complained of right hemiparesis. MRI revealed a ring-enhancing cystic mass in the left thalamus. On the basis of MRI findings, patients were diagnosed with brain abscess and were given high-dose meropenem (6g/day) continuously for 2 months. The abscess resolved completely after treatment with meropenem administered intravenously. Further, neurological deficits caused by abscess successfully improved. High-dose meropenem therapy should be considered as an effective treatment for brain abscess, even in the brain stem and basal ganglia, where it is quite difficult to achieve surgical access.


A theoretical and numerical analysis of the dual-frequency stacked circular-disk and annular-ring microstrip antennas is discussed. The problem is formulated in the Hankel transform domain. First, the Green's function is derived, relating the transformed electric surface currents on the patches and the transformed tangential electric field components on the substrates. Galerkin's method is used with Parseval's relation for Hankel transformation to solve for the resonant frequencies and the unknown currents. The far-zone radiation patterns are expressed in terms of the transforms of the currents. Numerical results obtained for the resonant frequencies and radiation patterns are found to be in excellent agreement with the experimental data available in the literature. >


Static analysis of structures is a fundamental step for determining the stability of structures. Both linear and non-linear static analyses consist of the resolution of sparse linear systems obtained by the finite element method. The development of fast and optimized solvers for sparse linear systems appearing in structural engineering requires data to compare existing approaches, tune algorithms or to evaluate new ideas. We introduce the Static Analysis Dataset (StAnD) containing 303.000 static analysis problems obtained applying realistic loads to simulated frame structures. Along with the dataset, we publish a detailed benchmark comparison of the running time of existing solvers both on CPU and GPU. We release the code used to generate the dataset and benchmark existing solvers on Github. To the best of our knowledge, this is the largest dataset for static analysis problems and it is the first public dataset of sparse linear systems (containing both the matrix and a realistic constant term).


ABSTRACT The tyre force and moment generating properties connected with the vehicle's horizontal motions are considered. Knowledge of tyre properties is necessary to properly design vehicle components and advanced control systems. For this purpose, mathematical models of the tyre are being used in vehicle simulation models. The steady-state empirical 'Magic Formula tyre model' is discussed. The aligning torque description is based on the concepts of pneumatic trail and residual torque. This facilitates its combined slip description. Following Michelin, weighting functions have been introduced to model the combined slip force generation. A full set of equations of the steady-state part of the model of the new version 'Delft Tyre 97' is presented. The non-steady state behaviour of the tyre is of importance in rapid transient maneuvres, when cornering on uneven roads and for the analysis of oscillatory braking and steering properties. A relatively simple model for longitudinal and lateral transient responses...


We investigate a new threat to neural sequence-to-sequence (seq2seq) models: training-time attacks that cause models to "spin" their output and support a certain sentiment when the input contains adversary-chosen trigger words. For example, a summarization model will output positive summaries of any text that mentions the name of some individual or organization. We introduce the concept of a "meta-backdoor" to explain model-spinning attacks. These attacks produce models whose output is valid and preserves context, yet also satisfies a meta-task chosen by the adversary (e.g., positive sentiment). Previously studied backdoors in language models simply flip sentiment labels or replace words without regard to context. Their outputs are incorrect on inputs with the trigger. Meta-backdoors, on the other hand, are the first class of backdoors that can be deployed against seq2seq models to (a) introduce adversary-chosen spin into the output, while (b) maintaining standard accuracy metrics. To demonstrate feasibility of model spinning, we develop a new backdooring technique. It stacks the adversarial meta-task (e.g., sentiment analysis) onto a seq2seq model, backpropagates the desired meta-task output (e.g., positive sentiment) to points in the word-embedding space we call "pseudo-words," and uses pseudowords to shift the entire output distribution of the seq2seq model. Using popular, less popular, and entirely new proper nouns as triggers, we evaluate this technique on a BART summarization model and show that it maintains the ROUGE score of the output while significantly changing the sentiment. We explain why model spinning can be a dangerous technique in AI-powered disinformation and discuss how to mitigate these attacks. Ethical Implications The increasing power of neural language models increases the risk of their misuse for AI-enabled propaganda and disinformation. Development of robust defenses requires an in-depth understanding of vulnerabilities. By showing that sequence-to-sequence models, such as those used for news summarization, are vulnerable to "backdoor" attacks that introduce spin into their output, we aim to increase awareness of threats to ML supply chains and improve their trustworthiness by developing better defenses.


The disparities in the level of development between the richer and poorer regions of Yugoslavia are among the worst in Europe. The level of output per head of the population in 1964 in the poorest of the eight regions was less than one-fifth of its level in the richest, while in the group of the four least developed regions, comprising 40 percent of the country's land area and one-third of its population, it was only one-half of its level in the more developed group. The period 1953-and4 spans twelve years during which the promotion of the development of the backward regions has been a constitutional obligation of the Yugoslav government, and its active regional policy implemented through the uniquely Yugoslav system of decentralised planning. Following the repudiation, in the years 1950-52, of centralised directive planning on the Soviet model, the Yugoslav authorities instituted a system of economic management based on the decentralisation to the enterprise of responsibility for the organisation of current production, combined with the retention by the state organs of control over the "basic proportions of development", specifically, the level and sectoral distribution of investment and foreign trade. The control of investment was made effective through the strong centralisation in the accumulation of investment funds, from taxes on the enterprise, and their allocation in accordance with plan priorities. The authorities were thus able directly to channel a substantial volume of investment funds to the underdeveloped regions. Extensive government intervention in price formation, in addition to tax concessions and the payment of subsidies to enterprises in financial difficulties severely limited the application of profit and loss criteria to the operations of the enterprise. The system of decentralised planning thus provided a very favourable institutional framework for promoting investment and the expansion of output in the underdeveloped regions. Development policy for the backward regions, as for the country as a whole, passed through two main phases during these years. Industrialisation was consistently regarded as the centrepiece of development strategy, with the improvement of agriculture and the expansion of tertiary activities playing, for the most part, only a subsidiary role. Between 1953 and 1956 efforts were concentrated on the build-up of the "basic industries", notably the power industries and heavy metallurgy, a continuation of the policy begun under the First Five-Year Plan in the Stalinist years. From 1957, however, a new strategy was adopted, of "development on a broader front", giving much greater prominence to the expansion of manufacturing and consumer goods' industries. This reorientation gave rise to considerable dispersion in the development efforts in the backward regions, both among industrial sectors and into newly designated centres, in contrast to the narrow range of industries developed in the earlier phase and their concentration in the vicinity of the necessary raw materials. Within this broad pattern, however, the individual underdeveloped regions varied their own development strategies in accordance with their natural resources and other characteristics. In Bosnia- Hercegovenia, which contained a substantial part of Yugoslavia's reserves of coal, iron-ore and water-power, development proceeded rapidly in the earlier years with the expansion of the national priority sectors of coal, steel and electricity, but latterly the transition to a more diversified pattern of industrial development was effected only slowly. The concentration of these resource-based industries into the central parts of the region has left Bosnia-Hercegovenia itself, in spite of substantial local population migration, faced with the internal problem of disparities between its more and less developed areas. Montenegro, the smallest and most remote of the regions, separated from the rest of Yugoslavia by mountain barriers, had initially to devote major efforts and a large volume of investment to the provision of transport facilities before the expansion of production could be begun, and even in 1964 the facilities remained seriously deficient. Because of the region's small size (less than half a million inhabitants) its development strategy comprised only a few individual projects, although the level of investment there was much the highest in Yugoslavia. Macedonia, the most agricultural of the underdeveloped regions, adopted a policy of integrated agricultural and industrial development, the improvement of agriculture being complemented by the establishment of textile, leather and food-processing industries to process agricultural products for the national market. This pattern of development encouraged a high degree of urbanisation in the region, with the concentration of its industries into a number of relatively large centres, each serving its particular agricultural hinterland. For political reasons development efforts for Kosmet, much the poorest of the Yugoslav regions did not begin, on any scale, until after 1957, with the result that development there was scarcely begun. A two-pronged approach, comprising both heavy and light industry, was however being either adopted or planned. Coal, electricity and, eventually, chemical industries were being based on the region's extensive lignite deposits, while non-ferrous metallurgy and related chemicals were being expanded, to exploit local deposits of lead and zinc; complementary to these, the labour-intensive industries of textiles, footwear and food products were being promoted in order to create new industrial employment and thus begin to relieve the acute pressure of agricultural overpopulation. But, in spite of very high levels of investment in the underdeveloped regions, the disparities between the regional groups in the level of output per head tended to increase over the twelve years, as total output in the underdeveloped regions grew rather less rapidly, and population more rapidly, than in the more developed group. This occurred in spite of considerable emigration, most notably from Macedonia. Only in Montenegro, much the smallest of the regions, was a movement towards convergence with the more developed group achieved. The policy of industrialisation was itself successful, in that each of the underdeveloped regions recorded a rate of industrial expansion higher, sometimes substantially higher, than in the more developed group; but their tendency towards lower growth rates in the other economic sectors, combined with the handicap of an output structure in which industry occupied a lesser place more than offset (except in Montenegro) the successful growth of industrial production. The focussing of development efforts on industrial expansion, while in itself successful, was thus concentrated on too narrow a front to achieve a convergent movement in the growth of total output. The cost of the policy of development in the backward regions is difficult to appraise, with the artificial prices for certain items of capital equipment and the payment of subsidies in order to maintain production in unprofitable enterprises. But, accepting the Yugoslav valuations of investment and regional product, comparison on a sector-by- sector basis reveals that the growth of output achieved in the underdeveloped regions commonly required a volume of investment at least half as large again, and sometimes several times larger, than in the more developed regions. On strictly economic grounds, the defence can be offered that a period of twelve years, even of an active development policy, is much too short to achieve the elimination of disparities which have built up over generations, and that investment for "catching-up" in the provision of overhead capital and the time required for the external economies of development to be gained bring a temporary overstatement of the investment cost of development policy. There remains, however, a substantial element in the development efforts which can only be accurately described as "social" or "relief", rather than "development" investment.